University of Colorado: Annual Internal Medicine Program

ESTES PARK, COLO. – S-adenosylmethionine doesn’t crack the annual top-10 lists of the most widely used supplements in complementary and alternative medicine surveys. But unlike other far more popular products, the supplement is supported by randomized trial evidence of efficacy for osteoarthritis, depression, and fibromyalgia.

Indeed, s-adenosylmethionine (SAMe) is "buzz worthy," Dr. Lisa Corbin declared at the update in internal medicine sponsored by the University of Colorado.

The Natural Medicines Comprehensive Database, which she considers the best available source of physician information on supplements, rates SAMe as "likely effective" for depression and osteoarthritis, and "possibly effective" for fibromyalgia, noted Dr. Corbin, medical director of the Center for Integrative Medicine and a general internist at the University of Colorado, Aurora.

The Natural Medicines Comprehensive Database is subscription funded and eschews financial support from industry. The organization is famously tough in its efficacy ratings. "Likely effective" is about as good as it gets. Take, for example, hypertension. Nothing included in the natural medicines database has earned the coveted "effective" rating for treatment of hypertension, and a single item is listed as "likely effective": namely, the Dietary Approaches to Stop Hypertension, or DASH diet – which is backed by the National Institutes of Health.

SAMe is a naturally occurring homocysteine derivative present in all living human cells. Its synthesis is related to vitamin B₁₂/folate metabolism, and SAMe serves as an essential methyl donor in cellular metabolism.

The mechanism of SAMe’s antidepressant effect involves boosting norepinephrine and dopamine as well as increased serotonin turnover. Neuroimaging studies and EEGs show changes in patients on SAMe similar to those seen with conventional antidepressant medications.

An early meta-analysis of many small studies concluded SAMe was superior to placebo, with an efficacy equivalent to that of tricyclics, the state-of-the-art antidepressant medications of that era (Acta Neurol. Scand. Suppl. 1994;154:7-14).

More recently, investigators at Massachusetts General Hospital, Boston, conducted a double-blind randomized trial in 73 adults with major depressive disorder, all with an inadequate response to adequately dosed serotonin reuptake inhibitors. They continued on their antidepressant and were randomized to add-on placebo or SAMe at 400 mg twice daily, increased after 2 weeks to 800 mg twice daily.

The response rate as defined by a greater than 50% improvement in Hamilton Rating Scale for Depression scores after 6 weeks was 36% in the SAMe group, more than twice the rate in the placebo arm. Remission as defined by a HAM-D score below seven occurred in 26% of the SAMe group, compared with 12% of controls. Both between-group differences were statistically significant.

The investigators calculated the number needed to treat (NNT) as six in order to obtain one additional clinical response more than with placebo plus a serotonin reuptake inhibitor. The NNT for one additional remission was seven (Am. J. Psychiatry 2010;167:942-8).

"Those are actually pretty good NNTs," Dr. Corbin observed.

She said no major safety issues have been cited with SAMe. At higher doses, however, it has been associated with gastrointestinal side effects, headache, and loss of appetite.

"I think the financial toxicity is a potential issue," she quipped.

She urges her patients who are interested in trying dietary supplements to seek out those with "USP Verified" displayed prominently on the label. That designation signals that the product meets rigorous United States Pharmacopeia quality standards. However, SAMe is not a big seller, and no USP standards have been set for it. So she recommends that patients scan the shelves and select a SAMe product marketed by a company with USP labels on plenty of their other, more common supplements.

"That way, you know that in general this manufacturer is making decent products, so that’s where I’d spend my money," Dr. Corbin said.

She reported having no financial interests relevant to her presentation.

ESTES PARK, COLO. – S-adenosylmethionine doesn’t crack the annual top-10 lists of the most widely used supplements in complementary and alternative medicine surveys. But unlike other far more popular products, the supplement is supported by randomized trial evidence of efficacy for osteoarthritis, depression, and fibromyalgia.

Indeed, s-adenosylmethionine (SAMe) is "buzz worthy," Dr. Lisa Corbin declared at the update in internal medicine sponsored by the University of Colorado.

The Natural Medicines Comprehensive Database, which she considers the best available source of physician information on supplements, rates SAMe as "likely effective" for depression and osteoarthritis, and "possibly effective" for fibromyalgia, noted Dr. Corbin, medical director of the Center for Integrative Medicine and a general internist at the University of Colorado, Aurora.

The Natural Medicines Comprehensive Database is subscription funded and eschews financial support from industry. The organization is famously tough in its efficacy ratings. "Likely effective" is about as good as it gets. Take, for example, hypertension. Nothing included in the natural medicines database has earned the coveted "effective" rating for treatment of hypertension, and a single item is listed as "likely effective": namely, the Dietary Approaches to Stop Hypertension, or DASH diet – which is backed by the National Institutes of Health.

SAMe is a naturally occurring homocysteine derivative present in all living human cells. Its synthesis is related to vitamin B₁₂/folate metabolism, and SAMe serves as an essential methyl donor in cellular metabolism.

The mechanism of SAMe’s antidepressant effect involves boosting norepinephrine and dopamine as well as increased serotonin turnover. Neuroimaging studies and EEGs show changes in patients on SAMe similar to those seen with conventional antidepressant medications.

An early meta-analysis of many small studies concluded SAMe was superior to placebo, with an efficacy equivalent to that of tricyclics, the state-of-the-art antidepressant medications of that era (Acta Neurol. Scand. Suppl. 1994;154:7-14).

More recently, investigators at Massachusetts General Hospital, Boston, conducted a double-blind randomized trial in 73 adults with major depressive disorder, all with an inadequate response to adequately dosed serotonin reuptake inhibitors. They continued on their antidepressant and were randomized to add-on placebo or SAMe at 400 mg twice daily, increased after 2 weeks to 800 mg twice daily.

The response rate as defined by a greater than 50% improvement in Hamilton Rating Scale for Depression scores after 6 weeks was 36% in the SAMe group, more than twice the rate in the placebo arm. Remission as defined by a HAM-D score below seven occurred in 26% of the SAMe group, compared with 12% of controls. Both between-group differences were statistically significant.

The investigators calculated the number needed to treat (NNT) as six in order to obtain one additional clinical response more than with placebo plus a serotonin reuptake inhibitor. The NNT for one additional remission was seven (Am. J. Psychiatry 2010;167:942-8).

"Those are actually pretty good NNTs," Dr. Corbin observed.

She said no major safety issues have been cited with SAMe. At higher doses, however, it has been associated with gastrointestinal side effects, headache, and loss of appetite.

"I think the financial toxicity is a potential issue," she quipped.

She urges her patients who are interested in trying dietary supplements to seek out those with "USP Verified" displayed prominently on the label. That designation signals that the product meets rigorous United States Pharmacopeia quality standards. However, SAMe is not a big seller, and no USP standards have been set for it. So she recommends that patients scan the shelves and select a SAMe product marketed by a company with USP labels on plenty of their other, more common supplements.

"That way, you know that in general this manufacturer is making decent products, so that’s where I’d spend my money," Dr. Corbin said.

She reported having no financial interests relevant to her presentation.

ESTES PARK, COLO. – S-adenosylmethionine doesn’t crack the annual top-10 lists of the most widely used supplements in complementary and alternative medicine surveys. But unlike other far more popular products, the supplement is supported by randomized trial evidence of efficacy for osteoarthritis, depression, and fibromyalgia.

Indeed, s-adenosylmethionine (SAMe) is "buzz worthy," Dr. Lisa Corbin declared at the update in internal medicine sponsored by the University of Colorado.

The Natural Medicines Comprehensive Database, which she considers the best available source of physician information on supplements, rates SAMe as "likely effective" for depression and osteoarthritis, and "possibly effective" for fibromyalgia, noted Dr. Corbin, medical director of the Center for Integrative Medicine and a general internist at the University of Colorado, Aurora.

The Natural Medicines Comprehensive Database is subscription funded and eschews financial support from industry. The organization is famously tough in its efficacy ratings. "Likely effective" is about as good as it gets. Take, for example, hypertension. Nothing included in the natural medicines database has earned the coveted "effective" rating for treatment of hypertension, and a single item is listed as "likely effective": namely, the Dietary Approaches to Stop Hypertension, or DASH diet – which is backed by the National Institutes of Health.

SAMe is a naturally occurring homocysteine derivative present in all living human cells. Its synthesis is related to vitamin B₁₂/folate metabolism, and SAMe serves as an essential methyl donor in cellular metabolism.

The mechanism of SAMe’s antidepressant effect involves boosting norepinephrine and dopamine as well as increased serotonin turnover. Neuroimaging studies and EEGs show changes in patients on SAMe similar to those seen with conventional antidepressant medications.

An early meta-analysis of many small studies concluded SAMe was superior to placebo, with an efficacy equivalent to that of tricyclics, the state-of-the-art antidepressant medications of that era (Acta Neurol. Scand. Suppl. 1994;154:7-14).

More recently, investigators at Massachusetts General Hospital, Boston, conducted a double-blind randomized trial in 73 adults with major depressive disorder, all with an inadequate response to adequately dosed serotonin reuptake inhibitors. They continued on their antidepressant and were randomized to add-on placebo or SAMe at 400 mg twice daily, increased after 2 weeks to 800 mg twice daily.

The response rate as defined by a greater than 50% improvement in Hamilton Rating Scale for Depression scores after 6 weeks was 36% in the SAMe group, more than twice the rate in the placebo arm. Remission as defined by a HAM-D score below seven occurred in 26% of the SAMe group, compared with 12% of controls. Both between-group differences were statistically significant.

The investigators calculated the number needed to treat (NNT) as six in order to obtain one additional clinical response more than with placebo plus a serotonin reuptake inhibitor. The NNT for one additional remission was seven (Am. J. Psychiatry 2010;167:942-8).

"Those are actually pretty good NNTs," Dr. Corbin observed.

She said no major safety issues have been cited with SAMe. At higher doses, however, it has been associated with gastrointestinal side effects, headache, and loss of appetite.

"I think the financial toxicity is a potential issue," she quipped.

She urges her patients who are interested in trying dietary supplements to seek out those with "USP Verified" displayed prominently on the label. That designation signals that the product meets rigorous United States Pharmacopeia quality standards. However, SAMe is not a big seller, and no USP standards have been set for it. So she recommends that patients scan the shelves and select a SAMe product marketed by a company with USP labels on plenty of their other, more common supplements.

"That way, you know that in general this manufacturer is making decent products, so that’s where I’d spend my money," Dr. Corbin said.

She reported having no financial interests relevant to her presentation.

ESTES PARK, COLO. – Beta-blockers may be underprescribed in the setting of chronic obstructive pulmonary disease, yet overused in the early treatment of acute myocardial infarction, recent surprising evidence suggests.

Cardiovascular disease and COPD are closely intertwined through the effects of smoking. Yet the notion of prescribing beta-blockers in patients with COPD challenges the conventional wisdom. Most physicians avoid the practice, even in patients with concomitant cardiovascular disease, because of worries about triggering bronchospasm and perhaps blocking the bronchodilating benefits of beta-agonist inhaler therapy.

©2008 Elsevier Ltd. All rights reserved.

But data from a Scottish retrospective cohort study strongly suggest these concerns are misplaced, asserted Dr. Mel L. Anderson, chief of the hospital medicine section and associate chief of the medical service at the Denver VA Medical Center.

The NHS Tayside Respiratory Disease Information System (TARDIS) is a disease-specific database developed 11 years ago to help Scottish primary care physicians and pulmonologists manage patients with COPD. The TAYSIDE investigators recently reported on 5,977 patients above age 50 with confirmed COPD who were followed for a mean of 4.4 years. The study population included 819 patients on beta-blockers, nearly 90% of which were relatively cardioselective agents such as bisoprolol or atenolol.

In a matched propensity score analysis, patients on a beta-blocker plus various combinations of respiratory medications had a 22% decreased risk of all-cause mortality and a 50% reduction in the risk of hospitalizations for COPD during the follow-up period. The mortality benefit associated with beta-blocker therapy proved independent of the presence or absence of overt cardiovascular disease, as similar reductions were seen in deaths due to COPD and to MI (BMJ 2011;342:d2549]).

"Yes, this is an observational study and so you have to worry about selection bias, but if anything, it should at least make you feel comfortable that it’s safe to offer beta-blocker therapy to COPD patients, provided you’re sure they don’t have asthma," Dr. Anderson said at a conference on internal medicine sponsored by the University of Colorado.

He also highlighted another emerging issue with regard to beta-blockers, this one involving their widespread inappropriate use in the early treatment of MI in patients with one or more risk factors for cardiogenic shock.

Investigators utilized the American College of Cardiology registry known as ACTION Registry-GWTG to study outcomes in 34,661 patients with ST elevation MI (STEMI) and non-ST-segment MI (non-STEMI) who received beta-blocker therapy within the first 24 hours after MI presentation at 291 participating U.S. hospitals. The registry is part of the ACC’s National Cardiovascular Data Registry.

The relevant ACC/American Heart Association Guidelines for Unstable Angina/Non-STEMI (J. Am. Coll. Cardiol. 2007;50:e1-e157) and STEMI (J. Am. Coll. Cardiol. 2008;51:210-47) recommend caution in giving beta-blockers in the first 24 hours in patients with risk factors for cardiogenic shock. Yet in the ACTION Registry-GWTG study, 45% of the STEMI patients treated with early beta-blockers and 63% of early beta-blocker recipients with non-STEMI had one or more cardiogenic shock risk factors identified in the guidelines on the basis of findings in the earlier COMMIT (Clopidogrel and Metoprolol in Myocardial Infarction Trial) study (Lancet 2005;366:1,622-32).

Moreover, the ACTION Registry data demonstrated that early beta-blocker therapy in patients with risk factors for cardiogenic shock was associated with significantly worse outcomes. For example, the combined rate of in-hospital cardiogenic shock or death was 1.3% in beta-blocker recipients with no shock risk factors, 4.8% in those with one of the risk factors, and 8.1% in those with two or more (Am. Heart J. 2011;161:864-70).

The cardiogenic shock risk factors that grew out of the COMMIT study are age greater than 70 years, systolic blood pressure below 120 mm Hg at presentation, a heart rate in excess of 110 bpm, and 12 hours or longer since symptom onset in STEMI patients.

"I bring this to your attention because these risk factors are not going to jump out at you. They fit a lot of the patients we see, but statistically they have an excess risk for cardiogenic shock, and you should either not use beta-blockers early or be incredibly careful in doing so in those patients," Dr. Anderson advised.

Asked by a concerned audience member how physicians who decline to prescribe a beta-blocker for patients with acute coronary syndrome and one or more shock risk factors can avoid taking a hit for noncompliance with a Joint Commission and Medicare core performance indicator, the hospitalist replied that the key is to avoid "early" use of the medication in patients with cardiogenic shock risk factors. Once 24 hours have gone by and the patient has been stabilized and has better blood flow to the heart, prescribing a beta-blocker may well be appropriate.

Dr. Anderson reported having no financial conflicts.

ESTES PARK, COLO. – Beta-blockers may be underprescribed in the setting of chronic obstructive pulmonary disease, yet overused in the early treatment of acute myocardial infarction, recent surprising evidence suggests.

Cardiovascular disease and COPD are closely intertwined through the effects of smoking. Yet the notion of prescribing beta-blockers in patients with COPD challenges the conventional wisdom. Most physicians avoid the practice, even in patients with concomitant cardiovascular disease, because of worries about triggering bronchospasm and perhaps blocking the bronchodilating benefits of beta-agonist inhaler therapy.

©2008 Elsevier Ltd. All rights reserved.

But data from a Scottish retrospective cohort study strongly suggest these concerns are misplaced, asserted Dr. Mel L. Anderson, chief of the hospital medicine section and associate chief of the medical service at the Denver VA Medical Center.

The NHS Tayside Respiratory Disease Information System (TARDIS) is a disease-specific database developed 11 years ago to help Scottish primary care physicians and pulmonologists manage patients with COPD. The TAYSIDE investigators recently reported on 5,977 patients above age 50 with confirmed COPD who were followed for a mean of 4.4 years. The study population included 819 patients on beta-blockers, nearly 90% of which were relatively cardioselective agents such as bisoprolol or atenolol.

In a matched propensity score analysis, patients on a beta-blocker plus various combinations of respiratory medications had a 22% decreased risk of all-cause mortality and a 50% reduction in the risk of hospitalizations for COPD during the follow-up period. The mortality benefit associated with beta-blocker therapy proved independent of the presence or absence of overt cardiovascular disease, as similar reductions were seen in deaths due to COPD and to MI (BMJ 2011;342:d2549]).

"Yes, this is an observational study and so you have to worry about selection bias, but if anything, it should at least make you feel comfortable that it’s safe to offer beta-blocker therapy to COPD patients, provided you’re sure they don’t have asthma," Dr. Anderson said at a conference on internal medicine sponsored by the University of Colorado.

He also highlighted another emerging issue with regard to beta-blockers, this one involving their widespread inappropriate use in the early treatment of MI in patients with one or more risk factors for cardiogenic shock.

Investigators utilized the American College of Cardiology registry known as ACTION Registry-GWTG to study outcomes in 34,661 patients with ST elevation MI (STEMI) and non-ST-segment MI (non-STEMI) who received beta-blocker therapy within the first 24 hours after MI presentation at 291 participating U.S. hospitals. The registry is part of the ACC’s National Cardiovascular Data Registry.

The relevant ACC/American Heart Association Guidelines for Unstable Angina/Non-STEMI (J. Am. Coll. Cardiol. 2007;50:e1-e157) and STEMI (J. Am. Coll. Cardiol. 2008;51:210-47) recommend caution in giving beta-blockers in the first 24 hours in patients with risk factors for cardiogenic shock. Yet in the ACTION Registry-GWTG study, 45% of the STEMI patients treated with early beta-blockers and 63% of early beta-blocker recipients with non-STEMI had one or more cardiogenic shock risk factors identified in the guidelines on the basis of findings in the earlier COMMIT (Clopidogrel and Metoprolol in Myocardial Infarction Trial) study (Lancet 2005;366:1,622-32).

Moreover, the ACTION Registry data demonstrated that early beta-blocker therapy in patients with risk factors for cardiogenic shock was associated with significantly worse outcomes. For example, the combined rate of in-hospital cardiogenic shock or death was 1.3% in beta-blocker recipients with no shock risk factors, 4.8% in those with one of the risk factors, and 8.1% in those with two or more (Am. Heart J. 2011;161:864-70).

The cardiogenic shock risk factors that grew out of the COMMIT study are age greater than 70 years, systolic blood pressure below 120 mm Hg at presentation, a heart rate in excess of 110 bpm, and 12 hours or longer since symptom onset in STEMI patients.

"I bring this to your attention because these risk factors are not going to jump out at you. They fit a lot of the patients we see, but statistically they have an excess risk for cardiogenic shock, and you should either not use beta-blockers early or be incredibly careful in doing so in those patients," Dr. Anderson advised.

Asked by a concerned audience member how physicians who decline to prescribe a beta-blocker for patients with acute coronary syndrome and one or more shock risk factors can avoid taking a hit for noncompliance with a Joint Commission and Medicare core performance indicator, the hospitalist replied that the key is to avoid "early" use of the medication in patients with cardiogenic shock risk factors. Once 24 hours have gone by and the patient has been stabilized and has better blood flow to the heart, prescribing a beta-blocker may well be appropriate.

Dr. Anderson reported having no financial conflicts.

ESTES PARK, COLO. – Beta-blockers may be underprescribed in the setting of chronic obstructive pulmonary disease, yet overused in the early treatment of acute myocardial infarction, recent surprising evidence suggests.

Cardiovascular disease and COPD are closely intertwined through the effects of smoking. Yet the notion of prescribing beta-blockers in patients with COPD challenges the conventional wisdom. Most physicians avoid the practice, even in patients with concomitant cardiovascular disease, because of worries about triggering bronchospasm and perhaps blocking the bronchodilating benefits of beta-agonist inhaler therapy.

©2008 Elsevier Ltd. All rights reserved.

But data from a Scottish retrospective cohort study strongly suggest these concerns are misplaced, asserted Dr. Mel L. Anderson, chief of the hospital medicine section and associate chief of the medical service at the Denver VA Medical Center.

The NHS Tayside Respiratory Disease Information System (TARDIS) is a disease-specific database developed 11 years ago to help Scottish primary care physicians and pulmonologists manage patients with COPD. The TAYSIDE investigators recently reported on 5,977 patients above age 50 with confirmed COPD who were followed for a mean of 4.4 years. The study population included 819 patients on beta-blockers, nearly 90% of which were relatively cardioselective agents such as bisoprolol or atenolol.

In a matched propensity score analysis, patients on a beta-blocker plus various combinations of respiratory medications had a 22% decreased risk of all-cause mortality and a 50% reduction in the risk of hospitalizations for COPD during the follow-up period. The mortality benefit associated with beta-blocker therapy proved independent of the presence or absence of overt cardiovascular disease, as similar reductions were seen in deaths due to COPD and to MI (BMJ 2011;342:d2549]).

"Yes, this is an observational study and so you have to worry about selection bias, but if anything, it should at least make you feel comfortable that it’s safe to offer beta-blocker therapy to COPD patients, provided you’re sure they don’t have asthma," Dr. Anderson said at a conference on internal medicine sponsored by the University of Colorado.

He also highlighted another emerging issue with regard to beta-blockers, this one involving their widespread inappropriate use in the early treatment of MI in patients with one or more risk factors for cardiogenic shock.

Investigators utilized the American College of Cardiology registry known as ACTION Registry-GWTG to study outcomes in 34,661 patients with ST elevation MI (STEMI) and non-ST-segment MI (non-STEMI) who received beta-blocker therapy within the first 24 hours after MI presentation at 291 participating U.S. hospitals. The registry is part of the ACC’s National Cardiovascular Data Registry.

The relevant ACC/American Heart Association Guidelines for Unstable Angina/Non-STEMI (J. Am. Coll. Cardiol. 2007;50:e1-e157) and STEMI (J. Am. Coll. Cardiol. 2008;51:210-47) recommend caution in giving beta-blockers in the first 24 hours in patients with risk factors for cardiogenic shock. Yet in the ACTION Registry-GWTG study, 45% of the STEMI patients treated with early beta-blockers and 63% of early beta-blocker recipients with non-STEMI had one or more cardiogenic shock risk factors identified in the guidelines on the basis of findings in the earlier COMMIT (Clopidogrel and Metoprolol in Myocardial Infarction Trial) study (Lancet 2005;366:1,622-32).

Moreover, the ACTION Registry data demonstrated that early beta-blocker therapy in patients with risk factors for cardiogenic shock was associated with significantly worse outcomes. For example, the combined rate of in-hospital cardiogenic shock or death was 1.3% in beta-blocker recipients with no shock risk factors, 4.8% in those with one of the risk factors, and 8.1% in those with two or more (Am. Heart J. 2011;161:864-70).

The cardiogenic shock risk factors that grew out of the COMMIT study are age greater than 70 years, systolic blood pressure below 120 mm Hg at presentation, a heart rate in excess of 110 bpm, and 12 hours or longer since symptom onset in STEMI patients.

"I bring this to your attention because these risk factors are not going to jump out at you. They fit a lot of the patients we see, but statistically they have an excess risk for cardiogenic shock, and you should either not use beta-blockers early or be incredibly careful in doing so in those patients," Dr. Anderson advised.

Asked by a concerned audience member how physicians who decline to prescribe a beta-blocker for patients with acute coronary syndrome and one or more shock risk factors can avoid taking a hit for noncompliance with a Joint Commission and Medicare core performance indicator, the hospitalist replied that the key is to avoid "early" use of the medication in patients with cardiogenic shock risk factors. Once 24 hours have gone by and the patient has been stabilized and has better blood flow to the heart, prescribing a beta-blocker may well be appropriate.

Dr. Anderson reported having no financial conflicts.

ESTES PARK, COLO. – Topping Dr. Jeffrey I. Wallace’s pantheon of peeves in prescribing for the elderly are:

• Megestrol acetate (Megace): These are widely prescribed in older patients who aren’t eating well and are experiencing failure to thrive. But the randomized trials with 6- to 12-month followup clearly show that any modest benefit achieved in terms of weight gain takes 2-3 months of therapy. And megestrol acetate is a progestational agent associated with increased risk of thrombotic events and a possible increase in mortality.

"The data on Megace really look terrible. I much prefer using mirtazapine to increase appetite in a patient with even a hint of depression. I’d probably use medical marijuana in the form of Marinol [dronabinol] before I’d use Megace," declared Dr. Wallace at an update in internal medicine sponsored by the University of Colorado, Denver, where he is a professor of medicine.

• Oral iron more than once daily: "I see patients in the nursing homes all the time who’ve been discharged from the hospital by the surgeons on T.I.D. (three times a day) iron," according to the geriatrician.

Absorption of iron is an active process occurring in the duodenum and jejunum. By taking once-daily iron, a patient gets roughly 75% of all the iron that can possibly be absorbed in a day. Moving up to B.I.D. iron, that figure rises to 90%, and T.I.D. dosing bumps up another 5%.

"So each time, I get a little more iron absorbed. The problem is I get a lot more GI side effects. Most of the geriatric patients I see after they get out of the hospital aren’t feeling good already – and now I’m going to make them constipated and give them some dyspepsia and decreased appetite? It’s just not worth it; you don’t get much more bang for the buck. I’m pretty much a stickler to always take the iron down to once a day," he said.

A tip: Oral iron requires an acid environment to be absorbed well. A patient who has had a GI bleed or is at increased risk because of chronic NSAID therapy is likely to be on a proton pump inhibitor, which will interfere with iron absorption. "Have the patient take the iron with some orange juice or vitamin C to help absorption. The data isn’t all that good that it makes much difference, but it’s worth a try," according to the geriatrician.

• Muscle relaxants: These medications are sedating; cause anticholinergic side effects and are linked to an increased risk of falls; and are of questionable efficacy.

"It used to be that if you were 65 or 70 [years old] and came to the ED with back pain, everyone walked out of there with Flexeril [cyclobenzaprine] or some variant thereof. Our ED at the university pretty much doesn’t hand out muscle relaxants anymore. They’re not really pain pills; the data are terrible in terms of helping pain. For run-of-the-mill back pain, I’d rather give an older patient an opiate than a muscle relaxant. So unless you have a definitive muscle spasm, treat the pain with pain pills," he urged at the conference.

He reported having no financial conflicts.

ESTES PARK, COLO. – Topping Dr. Jeffrey I. Wallace’s pantheon of peeves in prescribing for the elderly are:

• Megestrol acetate (Megace): These are widely prescribed in older patients who aren’t eating well and are experiencing failure to thrive. But the randomized trials with 6- to 12-month followup clearly show that any modest benefit achieved in terms of weight gain takes 2-3 months of therapy. And megestrol acetate is a progestational agent associated with increased risk of thrombotic events and a possible increase in mortality.

"The data on Megace really look terrible. I much prefer using mirtazapine to increase appetite in a patient with even a hint of depression. I’d probably use medical marijuana in the form of Marinol [dronabinol] before I’d use Megace," declared Dr. Wallace at an update in internal medicine sponsored by the University of Colorado, Denver, where he is a professor of medicine.

• Oral iron more than once daily: "I see patients in the nursing homes all the time who’ve been discharged from the hospital by the surgeons on T.I.D. (three times a day) iron," according to the geriatrician.

Absorption of iron is an active process occurring in the duodenum and jejunum. By taking once-daily iron, a patient gets roughly 75% of all the iron that can possibly be absorbed in a day. Moving up to B.I.D. iron, that figure rises to 90%, and T.I.D. dosing bumps up another 5%.

"So each time, I get a little more iron absorbed. The problem is I get a lot more GI side effects. Most of the geriatric patients I see after they get out of the hospital aren’t feeling good already – and now I’m going to make them constipated and give them some dyspepsia and decreased appetite? It’s just not worth it; you don’t get much more bang for the buck. I’m pretty much a stickler to always take the iron down to once a day," he said.

A tip: Oral iron requires an acid environment to be absorbed well. A patient who has had a GI bleed or is at increased risk because of chronic NSAID therapy is likely to be on a proton pump inhibitor, which will interfere with iron absorption. "Have the patient take the iron with some orange juice or vitamin C to help absorption. The data isn’t all that good that it makes much difference, but it’s worth a try," according to the geriatrician.

• Muscle relaxants: These medications are sedating; cause anticholinergic side effects and are linked to an increased risk of falls; and are of questionable efficacy.

"It used to be that if you were 65 or 70 [years old] and came to the ED with back pain, everyone walked out of there with Flexeril [cyclobenzaprine] or some variant thereof. Our ED at the university pretty much doesn’t hand out muscle relaxants anymore. They’re not really pain pills; the data are terrible in terms of helping pain. For run-of-the-mill back pain, I’d rather give an older patient an opiate than a muscle relaxant. So unless you have a definitive muscle spasm, treat the pain with pain pills," he urged at the conference.

He reported having no financial conflicts.

ESTES PARK, COLO. – Topping Dr. Jeffrey I. Wallace’s pantheon of peeves in prescribing for the elderly are:

• Megestrol acetate (Megace): These are widely prescribed in older patients who aren’t eating well and are experiencing failure to thrive. But the randomized trials with 6- to 12-month followup clearly show that any modest benefit achieved in terms of weight gain takes 2-3 months of therapy. And megestrol acetate is a progestational agent associated with increased risk of thrombotic events and a possible increase in mortality.

"The data on Megace really look terrible. I much prefer using mirtazapine to increase appetite in a patient with even a hint of depression. I’d probably use medical marijuana in the form of Marinol [dronabinol] before I’d use Megace," declared Dr. Wallace at an update in internal medicine sponsored by the University of Colorado, Denver, where he is a professor of medicine.

• Oral iron more than once daily: "I see patients in the nursing homes all the time who’ve been discharged from the hospital by the surgeons on T.I.D. (three times a day) iron," according to the geriatrician.

Absorption of iron is an active process occurring in the duodenum and jejunum. By taking once-daily iron, a patient gets roughly 75% of all the iron that can possibly be absorbed in a day. Moving up to B.I.D. iron, that figure rises to 90%, and T.I.D. dosing bumps up another 5%.

"So each time, I get a little more iron absorbed. The problem is I get a lot more GI side effects. Most of the geriatric patients I see after they get out of the hospital aren’t feeling good already – and now I’m going to make them constipated and give them some dyspepsia and decreased appetite? It’s just not worth it; you don’t get much more bang for the buck. I’m pretty much a stickler to always take the iron down to once a day," he said.

A tip: Oral iron requires an acid environment to be absorbed well. A patient who has had a GI bleed or is at increased risk because of chronic NSAID therapy is likely to be on a proton pump inhibitor, which will interfere with iron absorption. "Have the patient take the iron with some orange juice or vitamin C to help absorption. The data isn’t all that good that it makes much difference, but it’s worth a try," according to the geriatrician.

• Muscle relaxants: These medications are sedating; cause anticholinergic side effects and are linked to an increased risk of falls; and are of questionable efficacy.

"It used to be that if you were 65 or 70 [years old] and came to the ED with back pain, everyone walked out of there with Flexeril [cyclobenzaprine] or some variant thereof. Our ED at the university pretty much doesn’t hand out muscle relaxants anymore. They’re not really pain pills; the data are terrible in terms of helping pain. For run-of-the-mill back pain, I’d rather give an older patient an opiate than a muscle relaxant. So unless you have a definitive muscle spasm, treat the pain with pain pills," he urged at the conference.

He reported having no financial conflicts.

ESTES PARK, COLO. – As a geriatrician with several decades of experience, Dr. Jeffrey I. Wallace is particularly loath to see three things prescribed in older patients: megestrol acetate, oral iron more than once daily, or muscle relaxants.

While he considers those three prescriptions to be especially egregious because the at-best tiny potential benefits are so clearly overshadowed by the sizeable downside risks, other agents on his personal ‘just say no’ list for the elderly include chronic NSAIDs, benzodiazepines, chronic proton pump inhibitors, sedating antihistamines, and first-generation tricyclic antidepressants, said Dr. Wallace at an update in internal medicine sponsored by the University of Colorado, Denver, where he is a professor of medicine.

Learn more about three of the most popular, inappropriate prescriptions for the elderly.

Those agents, with the sole exception of more-than-once-daily oral iron, are among the 53 medications or medication classes included on the recently overhauled Beers list of potentially inappropriate medications in older adults published by the American Geriatrics Society (2012 [doi:10.1111/j.1532-5415.2012.03923.x]). Dr. Wallace has some issues with the list.

"My problem with the Beers list is that most of us have some patients taking a drug that’s on that list because they didn’t respond to the first three drugs we used, yet we can’t get rid of the Beers list drug because they really need treatment. And I’m telling you, there are quality assurance measures that will ding us for that," the physician explained.

He has similar reservations about the STOPP/START criteria developed by an expert panel in Ireland (Int. J. Clin. Pharmacol. Ther. 2008; 46:72-83) and the Healthcare Effectiveness Data and Information Set (HEDIS) list.

"It’s good to be aware of what’s on those lists – the attorneys are aware of them – but if a drug you’re using is on a list and it’s your fourth choice because the first three didn’t work, then you should feel OK," he continued.

Rather than slavishly trying to steer clear of drugs on the Beers or other "potentially inappropriate drug" lists, Dr. Wallace’s preference in his own daily medical practice is to incorporate the "Good Palliative–Geriatric Practice" algorithm (Arch. Intern. Med. 2010;170:1648-54). This tool, developed by Israeli geriatricians in an effort to reduce rampant polypharmacy and inappropriate medications in the elderly, challenges the clinician at multiple points to consider whether an individual patient really needs to be on a particular drug at a given dose. The algorithm has been shown in multiple small controlled trials to improve key outcomes, including hospitalization and mortality.

For example, in a study of 190 patients on a baseline average of 7.1 drugs at six Israeli nursing homes, application of the algorithm in 119 patients led to discontinuation of an average of 2.8 drugs each. The 1-year rates of acute hospitalization and mortality were 12% and 21%, respectively, in the group where the algorithm was applied, compared with 30% and 45% in the control group, making the point that when it comes to prescribing for the elderly, less is often more (Isr. Med. Assoc. J. 2007;9:430-4).

More recently, a study in 70 Israeli geriatric outpatients on an average of 7.7 medications at baseline showed that application of the Good Palliative–Geriatric Practice algorithm resulted in discontinuation of an average of 4.9 drugs, with no significant increase in morbidity or mortality during a mean follow-up of 19 months. A total of 88% of patients who discontinued drugs reported a global improvement in their health (Arch. Intern. Med. 2010;170:1648-54).

Dr. Wallace tries hard to limit older patients to a maximum of six drugs. It can be tough because so many elderly patients have multiple comorbid conditions. But studies show that when elderly patients are on more than six medications, the rate of adverse drug reactions shoots up exponentially. With eight drugs, the chance of a drug-drug interaction is nearly 100%.

Interestingly, he noted, a landmark national study of emergency hospitalizations for adverse drug reactions in the elderly found that only 1.2% of the admissions involved drugs considered high risk because they were on the 2003 version of the Beers criteria or the HEDIS list. Two-thirds of all adverse drug reactions severe enough to lead to hospitalization after an emergency department (ED) visit involved warfarin, diabetes medications, or oral antiplatelet agents (N. Engl. J. Med. 2011;365:2002-12).

An annual or semiannual office visit devoted specifically to a medications review by the patient’s primary care physician or a skilled pharmacist is an excellent way to optimize therapy. Drug plans are willing to pay for it.

An acute hospitalization or trip to the ED provides a good opportunity for another physician to take a critical look at an older patient’s medications.

"I used to get cranky when a hospitalist would take one of my patients who I’ve been taking care of for 10 years and say, ‘Gee, Wallace – this is a dumb drug for this patient; I’m stopping the Fosamax.’ I’d reply, ‘I know the patient; don’t mess with him.’ But more and more, as I look at the literature, I’m thinking that when a patient is in the hospital or the ED, it’s a great time to cut back. I would urge those of you who are hospitalists to do that for reasons of adherence and safety. The data are out there to support you. Just let us know what you’ve done," the geriatrician said.

One of the key means of reducing polypharmacy in the elderly involves avoidance of what’s been called "the prescribing cascade." This cascade occurs when an adverse effect of one drug gets misinterpreted as a new medical condition, for which a second drug is dutifully prescribed.

"This happens all the time," according to Dr. Wallace.

Examples: A patient on hydrochlorothiazide experiences rising uric acid levels, is diagnosed with gout, and put on allopurinol; had he simply been switched to another antihypertensive agent, he’d still be on one drug instead of two for two diseases. Or a patient on chronic daily NSAID therapy develops rising blood pressure as a drug side effect, gets labeled hypertensive, and goes on antihypertensive medications. Or a patient on donepezil or another cholesterase inhibitor reports an increased frequency of urination because of the drug’s effects on the bladder; in response, tolterodine is prescribed.

Three years ago, the cholinesterase inhibitors used in treating dementia were linked to a previously unrecognized increased risk of bradycardia. In a large Canadian study, these medications were associated with a 69% increased rate of emergency department visits for symptomatic bradycardia, a 76% increase in syncope, a 49% greater likelihood of permanent pacemaker implantation, and an 18% increased risk of hip fracture (Arch. Intern. Med. 169: 867-73).

"We didn’t know about this until 2009. I grew up using donepezil in the 1990s when I was a fellow. We were using it all the time and no one thought about bradycardia. It wasn’t in our differential," Dr. Wallace recalled. "I’m sure patients passed out and got pacemakers as an unrecognized drug side effect. My question is this: We think we’re smart, but what else do we not know, especially with newer agents coming along?"

Dr. Wallace reported having no financial conflicts.

ESTES PARK, COLO. – As a geriatrician with several decades of experience, Dr. Jeffrey I. Wallace is particularly loath to see three things prescribed in older patients: megestrol acetate, oral iron more than once daily, or muscle relaxants.

While he considers those three prescriptions to be especially egregious because the at-best tiny potential benefits are so clearly overshadowed by the sizeable downside risks, other agents on his personal ‘just say no’ list for the elderly include chronic NSAIDs, benzodiazepines, chronic proton pump inhibitors, sedating antihistamines, and first-generation tricyclic antidepressants, said Dr. Wallace at an update in internal medicine sponsored by the University of Colorado, Denver, where he is a professor of medicine.

Learn more about three of the most popular, inappropriate prescriptions for the elderly.

Those agents, with the sole exception of more-than-once-daily oral iron, are among the 53 medications or medication classes included on the recently overhauled Beers list of potentially inappropriate medications in older adults published by the American Geriatrics Society (2012 [doi:10.1111/j.1532-5415.2012.03923.x]). Dr. Wallace has some issues with the list.

"My problem with the Beers list is that most of us have some patients taking a drug that’s on that list because they didn’t respond to the first three drugs we used, yet we can’t get rid of the Beers list drug because they really need treatment. And I’m telling you, there are quality assurance measures that will ding us for that," the physician explained.

He has similar reservations about the STOPP/START criteria developed by an expert panel in Ireland (Int. J. Clin. Pharmacol. Ther. 2008; 46:72-83) and the Healthcare Effectiveness Data and Information Set (HEDIS) list.

"It’s good to be aware of what’s on those lists – the attorneys are aware of them – but if a drug you’re using is on a list and it’s your fourth choice because the first three didn’t work, then you should feel OK," he continued.

Rather than slavishly trying to steer clear of drugs on the Beers or other "potentially inappropriate drug" lists, Dr. Wallace’s preference in his own daily medical practice is to incorporate the "Good Palliative–Geriatric Practice" algorithm (Arch. Intern. Med. 2010;170:1648-54). This tool, developed by Israeli geriatricians in an effort to reduce rampant polypharmacy and inappropriate medications in the elderly, challenges the clinician at multiple points to consider whether an individual patient really needs to be on a particular drug at a given dose. The algorithm has been shown in multiple small controlled trials to improve key outcomes, including hospitalization and mortality.

For example, in a study of 190 patients on a baseline average of 7.1 drugs at six Israeli nursing homes, application of the algorithm in 119 patients led to discontinuation of an average of 2.8 drugs each. The 1-year rates of acute hospitalization and mortality were 12% and 21%, respectively, in the group where the algorithm was applied, compared with 30% and 45% in the control group, making the point that when it comes to prescribing for the elderly, less is often more (Isr. Med. Assoc. J. 2007;9:430-4).

More recently, a study in 70 Israeli geriatric outpatients on an average of 7.7 medications at baseline showed that application of the Good Palliative–Geriatric Practice algorithm resulted in discontinuation of an average of 4.9 drugs, with no significant increase in morbidity or mortality during a mean follow-up of 19 months. A total of 88% of patients who discontinued drugs reported a global improvement in their health (Arch. Intern. Med. 2010;170:1648-54).

Dr. Wallace tries hard to limit older patients to a maximum of six drugs. It can be tough because so many elderly patients have multiple comorbid conditions. But studies show that when elderly patients are on more than six medications, the rate of adverse drug reactions shoots up exponentially. With eight drugs, the chance of a drug-drug interaction is nearly 100%.

Interestingly, he noted, a landmark national study of emergency hospitalizations for adverse drug reactions in the elderly found that only 1.2% of the admissions involved drugs considered high risk because they were on the 2003 version of the Beers criteria or the HEDIS list. Two-thirds of all adverse drug reactions severe enough to lead to hospitalization after an emergency department (ED) visit involved warfarin, diabetes medications, or oral antiplatelet agents (N. Engl. J. Med. 2011;365:2002-12).

An annual or semiannual office visit devoted specifically to a medications review by the patient’s primary care physician or a skilled pharmacist is an excellent way to optimize therapy. Drug plans are willing to pay for it.

An acute hospitalization or trip to the ED provides a good opportunity for another physician to take a critical look at an older patient’s medications.

"I used to get cranky when a hospitalist would take one of my patients who I’ve been taking care of for 10 years and say, ‘Gee, Wallace – this is a dumb drug for this patient; I’m stopping the Fosamax.’ I’d reply, ‘I know the patient; don’t mess with him.’ But more and more, as I look at the literature, I’m thinking that when a patient is in the hospital or the ED, it’s a great time to cut back. I would urge those of you who are hospitalists to do that for reasons of adherence and safety. The data are out there to support you. Just let us know what you’ve done," the geriatrician said.

One of the key means of reducing polypharmacy in the elderly involves avoidance of what’s been called "the prescribing cascade." This cascade occurs when an adverse effect of one drug gets misinterpreted as a new medical condition, for which a second drug is dutifully prescribed.

"This happens all the time," according to Dr. Wallace.

Examples: A patient on hydrochlorothiazide experiences rising uric acid levels, is diagnosed with gout, and put on allopurinol; had he simply been switched to another antihypertensive agent, he’d still be on one drug instead of two for two diseases. Or a patient on chronic daily NSAID therapy develops rising blood pressure as a drug side effect, gets labeled hypertensive, and goes on antihypertensive medications. Or a patient on donepezil or another cholesterase inhibitor reports an increased frequency of urination because of the drug’s effects on the bladder; in response, tolterodine is prescribed.

Three years ago, the cholinesterase inhibitors used in treating dementia were linked to a previously unrecognized increased risk of bradycardia. In a large Canadian study, these medications were associated with a 69% increased rate of emergency department visits for symptomatic bradycardia, a 76% increase in syncope, a 49% greater likelihood of permanent pacemaker implantation, and an 18% increased risk of hip fracture (Arch. Intern. Med. 169: 867-73).

"We didn’t know about this until 2009. I grew up using donepezil in the 1990s when I was a fellow. We were using it all the time and no one thought about bradycardia. It wasn’t in our differential," Dr. Wallace recalled. "I’m sure patients passed out and got pacemakers as an unrecognized drug side effect. My question is this: We think we’re smart, but what else do we not know, especially with newer agents coming along?"

Dr. Wallace reported having no financial conflicts.

ESTES PARK, COLO. – As a geriatrician with several decades of experience, Dr. Jeffrey I. Wallace is particularly loath to see three things prescribed in older patients: megestrol acetate, oral iron more than once daily, or muscle relaxants.

While he considers those three prescriptions to be especially egregious because the at-best tiny potential benefits are so clearly overshadowed by the sizeable downside risks, other agents on his personal ‘just say no’ list for the elderly include chronic NSAIDs, benzodiazepines, chronic proton pump inhibitors, sedating antihistamines, and first-generation tricyclic antidepressants, said Dr. Wallace at an update in internal medicine sponsored by the University of Colorado, Denver, where he is a professor of medicine.

Learn more about three of the most popular, inappropriate prescriptions for the elderly.

Those agents, with the sole exception of more-than-once-daily oral iron, are among the 53 medications or medication classes included on the recently overhauled Beers list of potentially inappropriate medications in older adults published by the American Geriatrics Society (2012 [doi:10.1111/j.1532-5415.2012.03923.x]). Dr. Wallace has some issues with the list.

"My problem with the Beers list is that most of us have some patients taking a drug that’s on that list because they didn’t respond to the first three drugs we used, yet we can’t get rid of the Beers list drug because they really need treatment. And I’m telling you, there are quality assurance measures that will ding us for that," the physician explained.

He has similar reservations about the STOPP/START criteria developed by an expert panel in Ireland (Int. J. Clin. Pharmacol. Ther. 2008; 46:72-83) and the Healthcare Effectiveness Data and Information Set (HEDIS) list.

"It’s good to be aware of what’s on those lists – the attorneys are aware of them – but if a drug you’re using is on a list and it’s your fourth choice because the first three didn’t work, then you should feel OK," he continued.

Rather than slavishly trying to steer clear of drugs on the Beers or other "potentially inappropriate drug" lists, Dr. Wallace’s preference in his own daily medical practice is to incorporate the "Good Palliative–Geriatric Practice" algorithm (Arch. Intern. Med. 2010;170:1648-54). This tool, developed by Israeli geriatricians in an effort to reduce rampant polypharmacy and inappropriate medications in the elderly, challenges the clinician at multiple points to consider whether an individual patient really needs to be on a particular drug at a given dose. The algorithm has been shown in multiple small controlled trials to improve key outcomes, including hospitalization and mortality.

For example, in a study of 190 patients on a baseline average of 7.1 drugs at six Israeli nursing homes, application of the algorithm in 119 patients led to discontinuation of an average of 2.8 drugs each. The 1-year rates of acute hospitalization and mortality were 12% and 21%, respectively, in the group where the algorithm was applied, compared with 30% and 45% in the control group, making the point that when it comes to prescribing for the elderly, less is often more (Isr. Med. Assoc. J. 2007;9:430-4).

More recently, a study in 70 Israeli geriatric outpatients on an average of 7.7 medications at baseline showed that application of the Good Palliative–Geriatric Practice algorithm resulted in discontinuation of an average of 4.9 drugs, with no significant increase in morbidity or mortality during a mean follow-up of 19 months. A total of 88% of patients who discontinued drugs reported a global improvement in their health (Arch. Intern. Med. 2010;170:1648-54).

Dr. Wallace tries hard to limit older patients to a maximum of six drugs. It can be tough because so many elderly patients have multiple comorbid conditions. But studies show that when elderly patients are on more than six medications, the rate of adverse drug reactions shoots up exponentially. With eight drugs, the chance of a drug-drug interaction is nearly 100%.

Interestingly, he noted, a landmark national study of emergency hospitalizations for adverse drug reactions in the elderly found that only 1.2% of the admissions involved drugs considered high risk because they were on the 2003 version of the Beers criteria or the HEDIS list. Two-thirds of all adverse drug reactions severe enough to lead to hospitalization after an emergency department (ED) visit involved warfarin, diabetes medications, or oral antiplatelet agents (N. Engl. J. Med. 2011;365:2002-12).

An annual or semiannual office visit devoted specifically to a medications review by the patient’s primary care physician or a skilled pharmacist is an excellent way to optimize therapy. Drug plans are willing to pay for it.

An acute hospitalization or trip to the ED provides a good opportunity for another physician to take a critical look at an older patient’s medications.

"I used to get cranky when a hospitalist would take one of my patients who I’ve been taking care of for 10 years and say, ‘Gee, Wallace – this is a dumb drug for this patient; I’m stopping the Fosamax.’ I’d reply, ‘I know the patient; don’t mess with him.’ But more and more, as I look at the literature, I’m thinking that when a patient is in the hospital or the ED, it’s a great time to cut back. I would urge those of you who are hospitalists to do that for reasons of adherence and safety. The data are out there to support you. Just let us know what you’ve done," the geriatrician said.

One of the key means of reducing polypharmacy in the elderly involves avoidance of what’s been called "the prescribing cascade." This cascade occurs when an adverse effect of one drug gets misinterpreted as a new medical condition, for which a second drug is dutifully prescribed.

"This happens all the time," according to Dr. Wallace.

Examples: A patient on hydrochlorothiazide experiences rising uric acid levels, is diagnosed with gout, and put on allopurinol; had he simply been switched to another antihypertensive agent, he’d still be on one drug instead of two for two diseases. Or a patient on chronic daily NSAID therapy develops rising blood pressure as a drug side effect, gets labeled hypertensive, and goes on antihypertensive medications. Or a patient on donepezil or another cholesterase inhibitor reports an increased frequency of urination because of the drug’s effects on the bladder; in response, tolterodine is prescribed.

Three years ago, the cholinesterase inhibitors used in treating dementia were linked to a previously unrecognized increased risk of bradycardia. In a large Canadian study, these medications were associated with a 69% increased rate of emergency department visits for symptomatic bradycardia, a 76% increase in syncope, a 49% greater likelihood of permanent pacemaker implantation, and an 18% increased risk of hip fracture (Arch. Intern. Med. 169: 867-73).

"We didn’t know about this until 2009. I grew up using donepezil in the 1990s when I was a fellow. We were using it all the time and no one thought about bradycardia. It wasn’t in our differential," Dr. Wallace recalled. "I’m sure patients passed out and got pacemakers as an unrecognized drug side effect. My question is this: We think we’re smart, but what else do we not know, especially with newer agents coming along?"

Dr. Wallace reported having no financial conflicts.

ESTES PARK, COLO. – Rational combination therapy is often the answer for the acute treatment of migraine attacks not successfully relieved by a triptan alone, according to Dr. Chantal O’Brien, a neurologist at the University of Colorado, Denver.

The goal is to identify a combination regimen that addresses both the central and peripheral pathways involved in the headaches. When successful, this strategy aborts the headache and reduces the rate of headache recurrence hours later, she said at a conference on internal medicine sponsored by the University of Colorado.

©Getty Images

One rational combination therapy is a triptan and a nonsteroidal anti-inflammatory drug (NSAID), with an antinausea medication added as needed. Various combinations of drugs in these medication classes have been shown effective in the treatment of refractory migraine in multiple randomized studies in recent years.

Dr. O’Brien cited as one example a Harvard University study of 28 patients exhibiting migraine with the associated cutaneous pain and tenderness known as allodynia. Half received subcutaneous sumatriptan 4 hours after their attack was underway. All continued to have pain 2 hours later, at which point they received intravenous ketorolac. Seventy-one percent were free of head pain and allodynia within 60 minutes after ketorolac infusion.

The other half of the subjects received intravenous ketorolac monotherapy 4 hours after onset of the attack; 64% were pain- and allodynia-free within 60 minutes (Headache 2005;45:850-61).

This approach is readily adaptable to primary care settings, albeit with administration of the NSAID by routes other than intravenous infusion.

"I have quite a few patients who actually present to their primary care physician’s office for IM ketorolac when they’ve gone past that stage of response to their triptan agents. And they’ve had good success with that," according to the neurologist.

The ketorolac dose is a single 10-mg IM injection followed by 10 mg orally every 4-6 hours as needed to a maximum of 40 mg per day.

A far more convenient, fast-acting alternative that received Food and Drug Administration approval for acute migraine several years ago is solubilized diclofenac (Cambia). The patient can mix the diclofenac powder in a glass of water and drink it down for quick absorption.

Alternatively, naproxen sodium is more rapidly absorbed than other oral NSAIDs, such as ibuprofen or ketoprofen. The dose is 220-550 mg, with a maximum of 1,100 mg in 24 hours.

Dr. O’Brien explained that the current understanding of migraine without aura is that it’s a condition of neuronal hyperexcitability. The pathophysiology is complex. The initiating event occurs centrally in the brainstem. Once this central generator is activated, it initiates two peripheral pain mechanisms in the meninges: vasodilation of meningeal blood vessels and neurogenic inflammation. Pain signals from the periphery ascend to the trigeminal nucleus caudalis in the brainstem, at which point central sensitization occurs. This is a state of neuronal hyperexcitability, and triptans are often unable to quell it.

Triptans address the peripheral migraine pathway by preventing release of calcitonin gene–related peptide, an extremely potent endogenous vasodilator that also activates mast cells, triggering release of histamine, serotonin, and proinflammatory cytokines such as interleukin-6 and tumor necrosis factor-alpha. But if the triptan is unable to curb this process and ascending pain signals activate the trigeminal nucleus caudalis, it’s game on: The resultant central sensitization is beyond the reach of that medication class.

In contrast, NSAIDs tackle central sensitization by addressing the increased levels of cyclooxygenase present in the spinal cord, she continued.

Another rational combination therapy is an ergot plus an NSAID. Like the triptans, ergots address the key peripheral target, calcitonin gene–related peptide. Migranal is a dihydroergotamine available in formulations for subcutaneous injection and as a nasal spray. An investigational, orally inhaled dihydroergotamine known as Levadex is thought to be close to marketing approval.

Dr. O’Brien reported having no relevant financial conflicts.

ESTES PARK, COLO. – Rational combination therapy is often the answer for the acute treatment of migraine attacks not successfully relieved by a triptan alone, according to Dr. Chantal O’Brien, a neurologist at the University of Colorado, Denver.

The goal is to identify a combination regimen that addresses both the central and peripheral pathways involved in the headaches. When successful, this strategy aborts the headache and reduces the rate of headache recurrence hours later, she said at a conference on internal medicine sponsored by the University of Colorado.

©Getty Images

One rational combination therapy is a triptan and a nonsteroidal anti-inflammatory drug (NSAID), with an antinausea medication added as needed. Various combinations of drugs in these medication classes have been shown effective in the treatment of refractory migraine in multiple randomized studies in recent years.

Dr. O’Brien cited as one example a Harvard University study of 28 patients exhibiting migraine with the associated cutaneous pain and tenderness known as allodynia. Half received subcutaneous sumatriptan 4 hours after their attack was underway. All continued to have pain 2 hours later, at which point they received intravenous ketorolac. Seventy-one percent were free of head pain and allodynia within 60 minutes after ketorolac infusion.

The other half of the subjects received intravenous ketorolac monotherapy 4 hours after onset of the attack; 64% were pain- and allodynia-free within 60 minutes (Headache 2005;45:850-61).

This approach is readily adaptable to primary care settings, albeit with administration of the NSAID by routes other than intravenous infusion.

"I have quite a few patients who actually present to their primary care physician’s office for IM ketorolac when they’ve gone past that stage of response to their triptan agents. And they’ve had good success with that," according to the neurologist.

The ketorolac dose is a single 10-mg IM injection followed by 10 mg orally every 4-6 hours as needed to a maximum of 40 mg per day.

A far more convenient, fast-acting alternative that received Food and Drug Administration approval for acute migraine several years ago is solubilized diclofenac (Cambia). The patient can mix the diclofenac powder in a glass of water and drink it down for quick absorption.

Alternatively, naproxen sodium is more rapidly absorbed than other oral NSAIDs, such as ibuprofen or ketoprofen. The dose is 220-550 mg, with a maximum of 1,100 mg in 24 hours.

Dr. O’Brien explained that the current understanding of migraine without aura is that it’s a condition of neuronal hyperexcitability. The pathophysiology is complex. The initiating event occurs centrally in the brainstem. Once this central generator is activated, it initiates two peripheral pain mechanisms in the meninges: vasodilation of meningeal blood vessels and neurogenic inflammation. Pain signals from the periphery ascend to the trigeminal nucleus caudalis in the brainstem, at which point central sensitization occurs. This is a state of neuronal hyperexcitability, and triptans are often unable to quell it.

Triptans address the peripheral migraine pathway by preventing release of calcitonin gene–related peptide, an extremely potent endogenous vasodilator that also activates mast cells, triggering release of histamine, serotonin, and proinflammatory cytokines such as interleukin-6 and tumor necrosis factor-alpha. But if the triptan is unable to curb this process and ascending pain signals activate the trigeminal nucleus caudalis, it’s game on: The resultant central sensitization is beyond the reach of that medication class.

In contrast, NSAIDs tackle central sensitization by addressing the increased levels of cyclooxygenase present in the spinal cord, she continued.

Another rational combination therapy is an ergot plus an NSAID. Like the triptans, ergots address the key peripheral target, calcitonin gene–related peptide. Migranal is a dihydroergotamine available in formulations for subcutaneous injection and as a nasal spray. An investigational, orally inhaled dihydroergotamine known as Levadex is thought to be close to marketing approval.

Dr. O’Brien reported having no relevant financial conflicts.

ESTES PARK, COLO. – Rational combination therapy is often the answer for the acute treatment of migraine attacks not successfully relieved by a triptan alone, according to Dr. Chantal O’Brien, a neurologist at the University of Colorado, Denver.

The goal is to identify a combination regimen that addresses both the central and peripheral pathways involved in the headaches. When successful, this strategy aborts the headache and reduces the rate of headache recurrence hours later, she said at a conference on internal medicine sponsored by the University of Colorado.

©Getty Images

One rational combination therapy is a triptan and a nonsteroidal anti-inflammatory drug (NSAID), with an antinausea medication added as needed. Various combinations of drugs in these medication classes have been shown effective in the treatment of refractory migraine in multiple randomized studies in recent years.

Dr. O’Brien cited as one example a Harvard University study of 28 patients exhibiting migraine with the associated cutaneous pain and tenderness known as allodynia. Half received subcutaneous sumatriptan 4 hours after their attack was underway. All continued to have pain 2 hours later, at which point they received intravenous ketorolac. Seventy-one percent were free of head pain and allodynia within 60 minutes after ketorolac infusion.

The other half of the subjects received intravenous ketorolac monotherapy 4 hours after onset of the attack; 64% were pain- and allodynia-free within 60 minutes (Headache 2005;45:850-61).

This approach is readily adaptable to primary care settings, albeit with administration of the NSAID by routes other than intravenous infusion.

"I have quite a few patients who actually present to their primary care physician’s office for IM ketorolac when they’ve gone past that stage of response to their triptan agents. And they’ve had good success with that," according to the neurologist.

The ketorolac dose is a single 10-mg IM injection followed by 10 mg orally every 4-6 hours as needed to a maximum of 40 mg per day.

A far more convenient, fast-acting alternative that received Food and Drug Administration approval for acute migraine several years ago is solubilized diclofenac (Cambia). The patient can mix the diclofenac powder in a glass of water and drink it down for quick absorption.

Alternatively, naproxen sodium is more rapidly absorbed than other oral NSAIDs, such as ibuprofen or ketoprofen. The dose is 220-550 mg, with a maximum of 1,100 mg in 24 hours.

Dr. O’Brien explained that the current understanding of migraine without aura is that it’s a condition of neuronal hyperexcitability. The pathophysiology is complex. The initiating event occurs centrally in the brainstem. Once this central generator is activated, it initiates two peripheral pain mechanisms in the meninges: vasodilation of meningeal blood vessels and neurogenic inflammation. Pain signals from the periphery ascend to the trigeminal nucleus caudalis in the brainstem, at which point central sensitization occurs. This is a state of neuronal hyperexcitability, and triptans are often unable to quell it.

Triptans address the peripheral migraine pathway by preventing release of calcitonin gene–related peptide, an extremely potent endogenous vasodilator that also activates mast cells, triggering release of histamine, serotonin, and proinflammatory cytokines such as interleukin-6 and tumor necrosis factor-alpha. But if the triptan is unable to curb this process and ascending pain signals activate the trigeminal nucleus caudalis, it’s game on: The resultant central sensitization is beyond the reach of that medication class.

In contrast, NSAIDs tackle central sensitization by addressing the increased levels of cyclooxygenase present in the spinal cord, she continued.

Another rational combination therapy is an ergot plus an NSAID. Like the triptans, ergots address the key peripheral target, calcitonin gene–related peptide. Migranal is a dihydroergotamine available in formulations for subcutaneous injection and as a nasal spray. An investigational, orally inhaled dihydroergotamine known as Levadex is thought to be close to marketing approval.

Dr. O’Brien reported having no relevant financial conflicts.

ESTES PARK, COLO. – Largely overlooked in all the hubbub over the new oral anticoagulants and their evolving role in stroke prevention in patients with atrial fibrillation has been an unrelated significant change in the 2012 American College of Chest Physicians guidelines on antithrombotic therapy.

The latest ACCP guidelines chart a new course in managing patients with a CHADS2 score of 0 – that is, those patients under age 75 with none of the major risk factors included in the CHADS2 rating system. For the first time, the recommended antithrombotic regimen in such patients is ... nothing.

That’s right. Nada. Not aspirin, not aspirin plus clopidogrel, not warfarin or its new alternatives.

"For patients with AF, including those with paroxysmal AF, who are at low risk of stroke ... the expert panel suggests no therapy rather than antithrombotic therapy," the guidelines state (CHEST 2012;141[Suppl. 2]:7S-47S).

The American College of Chest Physicians (ACCP) expert panel was influenced by calculations that 1 year of prophylactic aspirin in patients with a CHADS2 score of 0 may prevent 2 nonfatal strokes per 1,000 treated patients at the expense of 3 additional nonfatal major extracranial bleeding events.

This is an evolution of therapy. Earlier editions of the ACCP guidelines recommended aspirin in patients under age 65 with a CHADS2 score of 0, and either aspirin or warfarin in those aged 65-75 years, noted Dr. Kathryn Hassell, a hematologist and professor of medicine at the University of Colorado, Denver.

The CHADS2 scoring system assigns 1 point each for atrial fibrillation (AF) patients who have Congestive heart failure, Hypertension, Age of 75 years or more, or Diabetes mellitus, and 2 points for a history of Stroke or TIA.

The 2012 ACCP guidelines recommend that patients with a CHADS2 score of 1 or more receive oral anticoagulation, with the novel agent dabigatran (Pradaxa) favored over warfarin. For patients who are not oral anticoagulation therapy candidates, combination prophylaxis with aspirin and clopidogrel is recommended.

The ACCP’s recommendation for preferential use of dabigatran over warfarin has become controversial. Dabigatran was the first of the new anticoagulants to come to the market. It did so with much fanfare on the basis of its far greater convenience, as well as its small, but statistically significant reductions in stroke or systemic embolism and intracranial hemorrhage compared with warfarin in the randomized, 18,000-plus patient RE-LY trial (N. Engl. J. Med. 2009;361:1139-51).

But then came a December 2011 Food and Drug Administration safety announcement of postmarketing reports of serious bleeding events in patients on dabigatran, along with a recommendation to assess renal function prior to treatment and adjust the dabigatran dosing depending upon the creatinine clearance rate.

FDA warnings are always a boon to the legal profession. The TV airwaves are now filled with commercials for ‘The Pradaxa Side Effects Lawyer,’ whose zingy motto is, "Over 130,000 clients can’t be wrong."

Serious bleeding problems arose because physicians aren’t used to thinking about creatinine clearance when anticoagulating patients for AF, Dr. Hassell said at a conference on internal medicine sponsored by the University of Colorado. Creatinine clearance is simply not an issue for warfarin, whose clearance is unaffected by renal function. In contrast, dabigatran’s elimination is 80% renal. Clearance of the drug is considerably slowed in the elderly, even the healthy elderly. And neither the pharmaceutical company nor the FDA did a good job initially of getting the word out to physicians regarding the short list of drug interactions with dabigatran, she said.

"Many of the cardiologists I work with were surprised to learn dabigatran even has drug interactions," she recalled at the conference.

Strong inducers of dabigatran metabolism include St. John’s wort, rifampin, carbamazepine, and phenytoin. "You think you’re giving a full dose of dabigatran to patients on one of those drugs, but you’re not," the hematologist observed.

On the other hand, patients on a strong inhibitor of dabigatran metabolism, such as verapamil, experience rising blood concentrations of the anticoagulant, setting them up for severe bleeding.

Rivaroxaban (Xarelto), the other novel oral anticoagulant marketed in the United States, also is cleared predominantly by the kidneys. Dr. Hassell said she’s looking forward to the widely expected eventual approval of a third oral agent, apixaban, which has only 25% renal elimination, meaning it’s likely to be better tolerated than dabigatran or rivaroxaban in patients having a glomerular filtration rate (GFR) on the low side.

The new anticoagulants share a number of attractive characteristics that make them "a huge step forward" compared with warfarin, Dr. Hassell said. Their onset of activity is 2-4 hours rather than the days it takes for warfarin to build up in the patient’s system. There are no interactions with leafy green vegetables or any other foods. No monitoring of INR (International Normalized Ratio) is required or even possible; all humans take the same once-daily dose provided they’re not renally impaired or on an interacting drug. The potential drug interactions are relatively few in number.

Moreover, key clinical outcomes are modestly, but significantly, better than with warfarin, as demonstrated in a recent meta-analysis of three pivotal randomized clinical trials of dabigatran, rivaroxaban, and apixaban involving nearly 45,000 patients. Compared with warfarin, the new agents collectively showed reductions of 22% in the risk of stroke or systemic embolism, 13% in the risk of vascular mortality, 12% in all-cause mortality, and 51% in intracranial hemorrhage, all of which were significant. In addition, there were nonsignificant trends for less major bleeding and more GI bleeding (Am. J. Cardiol. 2012;110:453-60).

Nonetheless, Dr. Hassell isn’t prepared to routinely substitute the new agents for warfarin. She’s waiting to see reports of more extensive experience with them in everyday clinical practice. For the time being, the patients in her practice who get one of the new anticoagulants instead of warfarin are those with normal renal function, low bleeding risk, unstable INRs on warfarin, and reasonably good medication adherence, and who are not taking any of the interacting drugs.

She sticks with warfarin in patients with a GFR below about 60 mL/minute or a stable INR in therapeutic range a great deal of the time. If they’re at high bleeding risk they get warfarin, which is readily reversible, unlike the novel anticoagulants. If they have problems with adherence, warfarin is the best option because missing a dose of warfarin causes less harm; loss of activity occurs within 12-24 hours with the new agents. And if Dr. Hassell thinks she wants to monitor the degree of anticoagulation by measuring INR, as in a patient with a history of multiple bleeding or clotting events, warfarin is the sole option.

She reported having no financial conflicts.

ESTES PARK, COLO. – Largely overlooked in all the hubbub over the new oral anticoagulants and their evolving role in stroke prevention in patients with atrial fibrillation has been an unrelated significant change in the 2012 American College of Chest Physicians guidelines on antithrombotic therapy.

The latest ACCP guidelines chart a new course in managing patients with a CHADS2 score of 0 – that is, those patients under age 75 with none of the major risk factors included in the CHADS2 rating system. For the first time, the recommended antithrombotic regimen in such patients is ... nothing.

That’s right. Nada. Not aspirin, not aspirin plus clopidogrel, not warfarin or its new alternatives.

"For patients with AF, including those with paroxysmal AF, who are at low risk of stroke ... the expert panel suggests no therapy rather than antithrombotic therapy," the guidelines state (CHEST 2012;141[Suppl. 2]:7S-47S).

The American College of Chest Physicians (ACCP) expert panel was influenced by calculations that 1 year of prophylactic aspirin in patients with a CHADS2 score of 0 may prevent 2 nonfatal strokes per 1,000 treated patients at the expense of 3 additional nonfatal major extracranial bleeding events.

This is an evolution of therapy. Earlier editions of the ACCP guidelines recommended aspirin in patients under age 65 with a CHADS2 score of 0, and either aspirin or warfarin in those aged 65-75 years, noted Dr. Kathryn Hassell, a hematologist and professor of medicine at the University of Colorado, Denver.

The CHADS2 scoring system assigns 1 point each for atrial fibrillation (AF) patients who have Congestive heart failure, Hypertension, Age of 75 years or more, or Diabetes mellitus, and 2 points for a history of Stroke or TIA.

The 2012 ACCP guidelines recommend that patients with a CHADS2 score of 1 or more receive oral anticoagulation, with the novel agent dabigatran (Pradaxa) favored over warfarin. For patients who are not oral anticoagulation therapy candidates, combination prophylaxis with aspirin and clopidogrel is recommended.

The ACCP’s recommendation for preferential use of dabigatran over warfarin has become controversial. Dabigatran was the first of the new anticoagulants to come to the market. It did so with much fanfare on the basis of its far greater convenience, as well as its small, but statistically significant reductions in stroke or systemic embolism and intracranial hemorrhage compared with warfarin in the randomized, 18,000-plus patient RE-LY trial (N. Engl. J. Med. 2009;361:1139-51).

But then came a December 2011 Food and Drug Administration safety announcement of postmarketing reports of serious bleeding events in patients on dabigatran, along with a recommendation to assess renal function prior to treatment and adjust the dabigatran dosing depending upon the creatinine clearance rate.

FDA warnings are always a boon to the legal profession. The TV airwaves are now filled with commercials for ‘The Pradaxa Side Effects Lawyer,’ whose zingy motto is, "Over 130,000 clients can’t be wrong."

Serious bleeding problems arose because physicians aren’t used to thinking about creatinine clearance when anticoagulating patients for AF, Dr. Hassell said at a conference on internal medicine sponsored by the University of Colorado. Creatinine clearance is simply not an issue for warfarin, whose clearance is unaffected by renal function. In contrast, dabigatran’s elimination is 80% renal. Clearance of the drug is considerably slowed in the elderly, even the healthy elderly. And neither the pharmaceutical company nor the FDA did a good job initially of getting the word out to physicians regarding the short list of drug interactions with dabigatran, she said.

"Many of the cardiologists I work with were surprised to learn dabigatran even has drug interactions," she recalled at the conference.

Strong inducers of dabigatran metabolism include St. John’s wort, rifampin, carbamazepine, and phenytoin. "You think you’re giving a full dose of dabigatran to patients on one of those drugs, but you’re not," the hematologist observed.

On the other hand, patients on a strong inhibitor of dabigatran metabolism, such as verapamil, experience rising blood concentrations of the anticoagulant, setting them up for severe bleeding.

Rivaroxaban (Xarelto), the other novel oral anticoagulant marketed in the United States, also is cleared predominantly by the kidneys. Dr. Hassell said she’s looking forward to the widely expected eventual approval of a third oral agent, apixaban, which has only 25% renal elimination, meaning it’s likely to be better tolerated than dabigatran or rivaroxaban in patients having a glomerular filtration rate (GFR) on the low side.

The new anticoagulants share a number of attractive characteristics that make them "a huge step forward" compared with warfarin, Dr. Hassell said. Their onset of activity is 2-4 hours rather than the days it takes for warfarin to build up in the patient’s system. There are no interactions with leafy green vegetables or any other foods. No monitoring of INR (International Normalized Ratio) is required or even possible; all humans take the same once-daily dose provided they’re not renally impaired or on an interacting drug. The potential drug interactions are relatively few in number.

Moreover, key clinical outcomes are modestly, but significantly, better than with warfarin, as demonstrated in a recent meta-analysis of three pivotal randomized clinical trials of dabigatran, rivaroxaban, and apixaban involving nearly 45,000 patients. Compared with warfarin, the new agents collectively showed reductions of 22% in the risk of stroke or systemic embolism, 13% in the risk of vascular mortality, 12% in all-cause mortality, and 51% in intracranial hemorrhage, all of which were significant. In addition, there were nonsignificant trends for less major bleeding and more GI bleeding (Am. J. Cardiol. 2012;110:453-60).

Nonetheless, Dr. Hassell isn’t prepared to routinely substitute the new agents for warfarin. She’s waiting to see reports of more extensive experience with them in everyday clinical practice. For the time being, the patients in her practice who get one of the new anticoagulants instead of warfarin are those with normal renal function, low bleeding risk, unstable INRs on warfarin, and reasonably good medication adherence, and who are not taking any of the interacting drugs.

She sticks with warfarin in patients with a GFR below about 60 mL/minute or a stable INR in therapeutic range a great deal of the time. If they’re at high bleeding risk they get warfarin, which is readily reversible, unlike the novel anticoagulants. If they have problems with adherence, warfarin is the best option because missing a dose of warfarin causes less harm; loss of activity occurs within 12-24 hours with the new agents. And if Dr. Hassell thinks she wants to monitor the degree of anticoagulation by measuring INR, as in a patient with a history of multiple bleeding or clotting events, warfarin is the sole option.

She reported having no financial conflicts.

ESTES PARK, COLO. – Largely overlooked in all the hubbub over the new oral anticoagulants and their evolving role in stroke prevention in patients with atrial fibrillation has been an unrelated significant change in the 2012 American College of Chest Physicians guidelines on antithrombotic therapy.

The latest ACCP guidelines chart a new course in managing patients with a CHADS2 score of 0 – that is, those patients under age 75 with none of the major risk factors included in the CHADS2 rating system. For the first time, the recommended antithrombotic regimen in such patients is ... nothing.

That’s right. Nada. Not aspirin, not aspirin plus clopidogrel, not warfarin or its new alternatives.

"For patients with AF, including those with paroxysmal AF, who are at low risk of stroke ... the expert panel suggests no therapy rather than antithrombotic therapy," the guidelines state (CHEST 2012;141[Suppl. 2]:7S-47S).

The American College of Chest Physicians (ACCP) expert panel was influenced by calculations that 1 year of prophylactic aspirin in patients with a CHADS2 score of 0 may prevent 2 nonfatal strokes per 1,000 treated patients at the expense of 3 additional nonfatal major extracranial bleeding events.

This is an evolution of therapy. Earlier editions of the ACCP guidelines recommended aspirin in patients under age 65 with a CHADS2 score of 0, and either aspirin or warfarin in those aged 65-75 years, noted Dr. Kathryn Hassell, a hematologist and professor of medicine at the University of Colorado, Denver.

The CHADS2 scoring system assigns 1 point each for atrial fibrillation (AF) patients who have Congestive heart failure, Hypertension, Age of 75 years or more, or Diabetes mellitus, and 2 points for a history of Stroke or TIA.

The 2012 ACCP guidelines recommend that patients with a CHADS2 score of 1 or more receive oral anticoagulation, with the novel agent dabigatran (Pradaxa) favored over warfarin. For patients who are not oral anticoagulation therapy candidates, combination prophylaxis with aspirin and clopidogrel is recommended.

The ACCP’s recommendation for preferential use of dabigatran over warfarin has become controversial. Dabigatran was the first of the new anticoagulants to come to the market. It did so with much fanfare on the basis of its far greater convenience, as well as its small, but statistically significant reductions in stroke or systemic embolism and intracranial hemorrhage compared with warfarin in the randomized, 18,000-plus patient RE-LY trial (N. Engl. J. Med. 2009;361:1139-51).

But then came a December 2011 Food and Drug Administration safety announcement of postmarketing reports of serious bleeding events in patients on dabigatran, along with a recommendation to assess renal function prior to treatment and adjust the dabigatran dosing depending upon the creatinine clearance rate.

FDA warnings are always a boon to the legal profession. The TV airwaves are now filled with commercials for ‘The Pradaxa Side Effects Lawyer,’ whose zingy motto is, "Over 130,000 clients can’t be wrong."

Serious bleeding problems arose because physicians aren’t used to thinking about creatinine clearance when anticoagulating patients for AF, Dr. Hassell said at a conference on internal medicine sponsored by the University of Colorado. Creatinine clearance is simply not an issue for warfarin, whose clearance is unaffected by renal function. In contrast, dabigatran’s elimination is 80% renal. Clearance of the drug is considerably slowed in the elderly, even the healthy elderly. And neither the pharmaceutical company nor the FDA did a good job initially of getting the word out to physicians regarding the short list of drug interactions with dabigatran, she said.

"Many of the cardiologists I work with were surprised to learn dabigatran even has drug interactions," she recalled at the conference.

Strong inducers of dabigatran metabolism include St. John’s wort, rifampin, carbamazepine, and phenytoin. "You think you’re giving a full dose of dabigatran to patients on one of those drugs, but you’re not," the hematologist observed.

On the other hand, patients on a strong inhibitor of dabigatran metabolism, such as verapamil, experience rising blood concentrations of the anticoagulant, setting them up for severe bleeding.

Rivaroxaban (Xarelto), the other novel oral anticoagulant marketed in the United States, also is cleared predominantly by the kidneys. Dr. Hassell said she’s looking forward to the widely expected eventual approval of a third oral agent, apixaban, which has only 25% renal elimination, meaning it’s likely to be better tolerated than dabigatran or rivaroxaban in patients having a glomerular filtration rate (GFR) on the low side.

The new anticoagulants share a number of attractive characteristics that make them "a huge step forward" compared with warfarin, Dr. Hassell said. Their onset of activity is 2-4 hours rather than the days it takes for warfarin to build up in the patient’s system. There are no interactions with leafy green vegetables or any other foods. No monitoring of INR (International Normalized Ratio) is required or even possible; all humans take the same once-daily dose provided they’re not renally impaired or on an interacting drug. The potential drug interactions are relatively few in number.

Moreover, key clinical outcomes are modestly, but significantly, better than with warfarin, as demonstrated in a recent meta-analysis of three pivotal randomized clinical trials of dabigatran, rivaroxaban, and apixaban involving nearly 45,000 patients. Compared with warfarin, the new agents collectively showed reductions of 22% in the risk of stroke or systemic embolism, 13% in the risk of vascular mortality, 12% in all-cause mortality, and 51% in intracranial hemorrhage, all of which were significant. In addition, there were nonsignificant trends for less major bleeding and more GI bleeding (Am. J. Cardiol. 2012;110:453-60).

Nonetheless, Dr. Hassell isn’t prepared to routinely substitute the new agents for warfarin. She’s waiting to see reports of more extensive experience with them in everyday clinical practice. For the time being, the patients in her practice who get one of the new anticoagulants instead of warfarin are those with normal renal function, low bleeding risk, unstable INRs on warfarin, and reasonably good medication adherence, and who are not taking any of the interacting drugs.

She sticks with warfarin in patients with a GFR below about 60 mL/minute or a stable INR in therapeutic range a great deal of the time. If they’re at high bleeding risk they get warfarin, which is readily reversible, unlike the novel anticoagulants. If they have problems with adherence, warfarin is the best option because missing a dose of warfarin causes less harm; loss of activity occurs within 12-24 hours with the new agents. And if Dr. Hassell thinks she wants to monitor the degree of anticoagulation by measuring INR, as in a patient with a history of multiple bleeding or clotting events, warfarin is the sole option.

She reported having no financial conflicts.

ESTES PARK, COLO. – Nonpharmacologic therapy is as important as medications in successful management of fibromyalgia, yet the nondrug interventions are greatly underutilized, Dr. Sterling G. West asserted at a conference on internal medicine sponsored by the University of Colorado.

"Nonpharmacologic therapy has to be used. If you don’t, you won’t get near the success rate you will by combining it with pharmacotherapy," said Dr. West, professor of medicine and a rheumatologist at the University of Colorado, Aurora.

©shutterstock.com

The core elements of nonpharmacologic therapy for this challenging disorder are education, exercise, sleep hygiene, psychological support, and stress management.

Two educational websites he recommends for his fibromyalgia patients are www.fmaware.org and www.knowfibro.com.

"You’ll find they get 20% better just knowing what they’re dealing with," according to Dr. West.

He particularly likes www.knowfibro.com. "It basically tells patients that it’s up to them to get better. They can’t just lay back and say, ‘Give me disability.’ They have to participate and actively try to improve," the rheumatologist explained.

The emphasis with regard to exercise needs to be on aerobic activity. Patients must understand the importance of exercising on their bad as well as good days, and that their pain may initially get worse as they become more active.

Fibromyalgia patients are exquisitely sensitive to medications and their side effects. The same is true for exercise. As with drug prescriptions, the exercise prescription has to start low and build up gradually. A good rule of thumb is to begin with 15 minutes of physical activity per day, increasing it by 5 minutes per day each week until reaching 30 minutes per day. The intensity is gradually boosted to the moderate range, or 75% of maximum heart rate. For patients who find land-based exercise too painful at first, warm water exercise is a good alternative. The Arthritis Foundation sponsors pool-based warm water exercise programs in every state that are available to fibromyalgia patients.

Sleep apnea is quite common in patients with fibromyalgia, many of whom aren’t particularly overweight. It needs to be addressed as part of the comprehensive treatment of this pain disorder, Dr. West continued.

The need to involve a skilled psychologist often becomes apparent at a physician’s initial encounter with a fibromyalgia patient. Two questions Dr. West always asks as part of his history taking are, "What do you do to cope with your pain?" and "Do you think your pain will ever get better?"

"If a patient answers no to that second question, you know you’re in big trouble because the patient is catastrophizing. That means you need to elicit the help of a psychologist with expertise in pain to help you deal with this. Your patient is going to need their help in addition to the things you’re going to do," he explained.

Another situation where a psychologist’s help is essential is in the fibromyalgia patient with early-life trauma in the form of sexual and/or physical abuse. Often patients with the most severe fibromyalgia have such a history.

"The patient may have never previously been asked about early-life trauma. If you’re going to unroof that scab, you’d better have someone in the background who can help you," Dr. West advised.

Strong evidence supports the utility of cognitive-behavioral therapy in improving pain, fatigue, physical function, and mood.

An estimated 6 million American adults have fibromyalgia, making this disorder more common than gout.

The current view of fibromyalgia is that it’s an afferent processing disorder leading to central and peripheral amplification of pain pathways and additional somatic complaints. It features increased excitation at the level of the dorsal horn nuclei and inhibition of descending pathways responsible for diffuse noxious inhibitory control. Insight into the neurotransmitters involved has led to more rational use of medications.

Nonetheless, the clinical trial data for drug therapy point to effect sizes that are "modest at best" for all drug classes, he observed, adding that "30% to 40% of patients get 40% to 50% relief of their pain; that’s what you can tell patients they can expect. But those are averages. You’ll have patients who respond well to their medicine and others who won’t respond at all. You can’t tell which ones are going to respond well and which aren’t until you try them. You try a drug, and, if it doesn’t work, you try something different, and you keep on until you find what works best," Dr. West said.

The strongest evidence of efficacy exists for the Food and Drug Administration–approved drugs duloxetine, milnacipran, and pregabalin, along with the off-label agents venlafaxine, gabapentin, cyclobenzaprine, and the tricyclic antidepressants. All of those off-label drugs are supported by a body of literature supporting effectiveness, and they make for good alternatives when patients can’t afford the approved drugs, which are invariably more costly, he said.

The numbers-needed-to-treat to achieve a 30% reduction in pain have been calculated at 7.2 for duloxetine, 8.6 for pregabalin, and 19 for milnacipran.

"All of these patients with fibromyalgia come to us with pain," Dr. West noted. "I choose their medications based on what their chief complaint is."

For example, a fibromyalgia patient who presents with pain, prominent fatigue, and depressed mood is a good candidate for duloxetine (Cymbalta), which fortuitously is also approved for osteoarthritis pain. A patient who complains of pain, cognitive dysfunction or "fibrofog," and fatigue may do well with milnacipran (Savella) starting at 12.5 mg in the morning with food, titrated upward by 12.5 mg per week to a maximum of 50 mg b.i.d. Pain with sleep disturbance is a symptom cluster that often responds well to pregabalin (Lyrica), dosed at 50 mg with food before bed, increased by 25 mg/day weekly to at least 150 mg/day before a morning dose is added, with a ceiling of 225 mg b.i.d..

Tramadol is supported by "modest" evidence of efficacy as an add-on niche medication for patients with substantial pain despite their baseline medications, the rheumatologist continued. Its efficacy in fibromyalgia is not through its better-known mu-opioid receptor agonist effect, but rather through the mechanism of serotonin-norepinephrine reuptake inhibition. Dr. West said that he starts tramadol at 25 mg/day and increases it weekly to a maximum of 100 mg four times daily.

Rational combination therapies utilizing different mechanisms of action and that are backed by supporting efficacy data include milnacipran plus pregabalin, venlafaxine and gabapentin, and fluoxetine and either amitriptyline or cyclobenzaprine, the rheumatologist continued.

Nearly all the medications recommended for treatment of fibromyalgia other than pregabalin and gabapentin modulate serotonin. That means patients need to be monitored for the development of suicidal ideation as well as serotonin syndrome. A simple way to check for emergent serotonin syndrome is to regularly evaluate the patient’s deep tendon reflexes.

"If a patient suddenly becomes much more hyper-reflexive, you need to start dialing it down because you’re putting them at risk for serotonin syndrome," Dr. West cautioned.

It’s evident that many physicians are struggling with the use of medications to treat patients with fibromyalgia. "There’s a gap between the evidence and what medications are actually prescribed in practice," Dr. West observed.

This gap was highlighted by data from the REFLECTIONS study, presented at last year’s annual scientific meeting of the American Pain Society. REFLECTIONS is an Eli Lilly–sponsored longitudinal study of 1,700 fibromyalgia patients and 91 physicians. The physicians collectively prescribed 186 different medications to treat individuals with fibromyalgia. Only about one-quarter of the physicians used one of the FDA-approved drugs. Opioids and nonsteroidal anti-inflammatory drugs were used just as frequently, even though these medications have zero evidence of efficacy in fibromyalgia and experts agree they are of no help.

Dr. West reported having no financial conflicts.

ESTES PARK, COLO. – Nonpharmacologic therapy is as important as medications in successful management of fibromyalgia, yet the nondrug interventions are greatly underutilized, Dr. Sterling G. West asserted at a conference on internal medicine sponsored by the University of Colorado.

"Nonpharmacologic therapy has to be used. If you don’t, you won’t get near the success rate you will by combining it with pharmacotherapy," said Dr. West, professor of medicine and a rheumatologist at the University of Colorado, Aurora.

©shutterstock.com

The core elements of nonpharmacologic therapy for this challenging disorder are education, exercise, sleep hygiene, psychological support, and stress management.

Two educational websites he recommends for his fibromyalgia patients are www.fmaware.org and www.knowfibro.com.

"You’ll find they get 20% better just knowing what they’re dealing with," according to Dr. West.

He particularly likes www.knowfibro.com. "It basically tells patients that it’s up to them to get better. They can’t just lay back and say, ‘Give me disability.’ They have to participate and actively try to improve," the rheumatologist explained.

The emphasis with regard to exercise needs to be on aerobic activity. Patients must understand the importance of exercising on their bad as well as good days, and that their pain may initially get worse as they become more active.

Fibromyalgia patients are exquisitely sensitive to medications and their side effects. The same is true for exercise. As with drug prescriptions, the exercise prescription has to start low and build up gradually. A good rule of thumb is to begin with 15 minutes of physical activity per day, increasing it by 5 minutes per day each week until reaching 30 minutes per day. The intensity is gradually boosted to the moderate range, or 75% of maximum heart rate. For patients who find land-based exercise too painful at first, warm water exercise is a good alternative. The Arthritis Foundation sponsors pool-based warm water exercise programs in every state that are available to fibromyalgia patients.

Sleep apnea is quite common in patients with fibromyalgia, many of whom aren’t particularly overweight. It needs to be addressed as part of the comprehensive treatment of this pain disorder, Dr. West continued.

The need to involve a skilled psychologist often becomes apparent at a physician’s initial encounter with a fibromyalgia patient. Two questions Dr. West always asks as part of his history taking are, "What do you do to cope with your pain?" and "Do you think your pain will ever get better?"

"If a patient answers no to that second question, you know you’re in big trouble because the patient is catastrophizing. That means you need to elicit the help of a psychologist with expertise in pain to help you deal with this. Your patient is going to need their help in addition to the things you’re going to do," he explained.

Another situation where a psychologist’s help is essential is in the fibromyalgia patient with early-life trauma in the form of sexual and/or physical abuse. Often patients with the most severe fibromyalgia have such a history.

"The patient may have never previously been asked about early-life trauma. If you’re going to unroof that scab, you’d better have someone in the background who can help you," Dr. West advised.

Strong evidence supports the utility of cognitive-behavioral therapy in improving pain, fatigue, physical function, and mood.

An estimated 6 million American adults have fibromyalgia, making this disorder more common than gout.

The current view of fibromyalgia is that it’s an afferent processing disorder leading to central and peripheral amplification of pain pathways and additional somatic complaints. It features increased excitation at the level of the dorsal horn nuclei and inhibition of descending pathways responsible for diffuse noxious inhibitory control. Insight into the neurotransmitters involved has led to more rational use of medications.

Nonetheless, the clinical trial data for drug therapy point to effect sizes that are "modest at best" for all drug classes, he observed, adding that "30% to 40% of patients get 40% to 50% relief of their pain; that’s what you can tell patients they can expect. But those are averages. You’ll have patients who respond well to their medicine and others who won’t respond at all. You can’t tell which ones are going to respond well and which aren’t until you try them. You try a drug, and, if it doesn’t work, you try something different, and you keep on until you find what works best," Dr. West said.

The strongest evidence of efficacy exists for the Food and Drug Administration–approved drugs duloxetine, milnacipran, and pregabalin, along with the off-label agents venlafaxine, gabapentin, cyclobenzaprine, and the tricyclic antidepressants. All of those off-label drugs are supported by a body of literature supporting effectiveness, and they make for good alternatives when patients can’t afford the approved drugs, which are invariably more costly, he said.

The numbers-needed-to-treat to achieve a 30% reduction in pain have been calculated at 7.2 for duloxetine, 8.6 for pregabalin, and 19 for milnacipran.

"All of these patients with fibromyalgia come to us with pain," Dr. West noted. "I choose their medications based on what their chief complaint is."

For example, a fibromyalgia patient who presents with pain, prominent fatigue, and depressed mood is a good candidate for duloxetine (Cymbalta), which fortuitously is also approved for osteoarthritis pain. A patient who complains of pain, cognitive dysfunction or "fibrofog," and fatigue may do well with milnacipran (Savella) starting at 12.5 mg in the morning with food, titrated upward by 12.5 mg per week to a maximum of 50 mg b.i.d. Pain with sleep disturbance is a symptom cluster that often responds well to pregabalin (Lyrica), dosed at 50 mg with food before bed, increased by 25 mg/day weekly to at least 150 mg/day before a morning dose is added, with a ceiling of 225 mg b.i.d..

Tramadol is supported by "modest" evidence of efficacy as an add-on niche medication for patients with substantial pain despite their baseline medications, the rheumatologist continued. Its efficacy in fibromyalgia is not through its better-known mu-opioid receptor agonist effect, but rather through the mechanism of serotonin-norepinephrine reuptake inhibition. Dr. West said that he starts tramadol at 25 mg/day and increases it weekly to a maximum of 100 mg four times daily.

Rational combination therapies utilizing different mechanisms of action and that are backed by supporting efficacy data include milnacipran plus pregabalin, venlafaxine and gabapentin, and fluoxetine and either amitriptyline or cyclobenzaprine, the rheumatologist continued.

Nearly all the medications recommended for treatment of fibromyalgia other than pregabalin and gabapentin modulate serotonin. That means patients need to be monitored for the development of suicidal ideation as well as serotonin syndrome. A simple way to check for emergent serotonin syndrome is to regularly evaluate the patient’s deep tendon reflexes.

"If a patient suddenly becomes much more hyper-reflexive, you need to start dialing it down because you’re putting them at risk for serotonin syndrome," Dr. West cautioned.

It’s evident that many physicians are struggling with the use of medications to treat patients with fibromyalgia. "There’s a gap between the evidence and what medications are actually prescribed in practice," Dr. West observed.

This gap was highlighted by data from the REFLECTIONS study, presented at last year’s annual scientific meeting of the American Pain Society. REFLECTIONS is an Eli Lilly–sponsored longitudinal study of 1,700 fibromyalgia patients and 91 physicians. The physicians collectively prescribed 186 different medications to treat individuals with fibromyalgia. Only about one-quarter of the physicians used one of the FDA-approved drugs. Opioids and nonsteroidal anti-inflammatory drugs were used just as frequently, even though these medications have zero evidence of efficacy in fibromyalgia and experts agree they are of no help.

Dr. West reported having no financial conflicts.

ESTES PARK, COLO. – Nonpharmacologic therapy is as important as medications in successful management of fibromyalgia, yet the nondrug interventions are greatly underutilized, Dr. Sterling G. West asserted at a conference on internal medicine sponsored by the University of Colorado.

"Nonpharmacologic therapy has to be used. If you don’t, you won’t get near the success rate you will by combining it with pharmacotherapy," said Dr. West, professor of medicine and a rheumatologist at the University of Colorado, Aurora.

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The core elements of nonpharmacologic therapy for this challenging disorder are education, exercise, sleep hygiene, psychological support, and stress management.

Two educational websites he recommends for his fibromyalgia patients are www.fmaware.org and www.knowfibro.com.

"You’ll find they get 20% better just knowing what they’re dealing with," according to Dr. West.

He particularly likes www.knowfibro.com. "It basically tells patients that it’s up to them to get better. They can’t just lay back and say, ‘Give me disability.’ They have to participate and actively try to improve," the rheumatologist explained.

The emphasis with regard to exercise needs to be on aerobic activity. Patients must understand the importance of exercising on their bad as well as good days, and that their pain may initially get worse as they become more active.

Fibromyalgia patients are exquisitely sensitive to medications and their side effects. The same is true for exercise. As with drug prescriptions, the exercise prescription has to start low and build up gradually. A good rule of thumb is to begin with 15 minutes of physical activity per day, increasing it by 5 minutes per day each week until reaching 30 minutes per day. The intensity is gradually boosted to the moderate range, or 75% of maximum heart rate. For patients who find land-based exercise too painful at first, warm water exercise is a good alternative. The Arthritis Foundation sponsors pool-based warm water exercise programs in every state that are available to fibromyalgia patients.

Sleep apnea is quite common in patients with fibromyalgia, many of whom aren’t particularly overweight. It needs to be addressed as part of the comprehensive treatment of this pain disorder, Dr. West continued.

The need to involve a skilled psychologist often becomes apparent at a physician’s initial encounter with a fibromyalgia patient. Two questions Dr. West always asks as part of his history taking are, "What do you do to cope with your pain?" and "Do you think your pain will ever get better?"

"If a patient answers no to that second question, you know you’re in big trouble because the patient is catastrophizing. That means you need to elicit the help of a psychologist with expertise in pain to help you deal with this. Your patient is going to need their help in addition to the things you’re going to do," he explained.

Another situation where a psychologist’s help is essential is in the fibromyalgia patient with early-life trauma in the form of sexual and/or physical abuse. Often patients with the most severe fibromyalgia have such a history.

"The patient may have never previously been asked about early-life trauma. If you’re going to unroof that scab, you’d better have someone in the background who can help you," Dr. West advised.

Strong evidence supports the utility of cognitive-behavioral therapy in improving pain, fatigue, physical function, and mood.

An estimated 6 million American adults have fibromyalgia, making this disorder more common than gout.

The current view of fibromyalgia is that it’s an afferent processing disorder leading to central and peripheral amplification of pain pathways and additional somatic complaints. It features increased excitation at the level of the dorsal horn nuclei and inhibition of descending pathways responsible for diffuse noxious inhibitory control. Insight into the neurotransmitters involved has led to more rational use of medications.

Nonetheless, the clinical trial data for drug therapy point to effect sizes that are "modest at best" for all drug classes, he observed, adding that "30% to 40% of patients get 40% to 50% relief of their pain; that’s what you can tell patients they can expect. But those are averages. You’ll have patients who respond well to their medicine and others who won’t respond at all. You can’t tell which ones are going to respond well and which aren’t until you try them. You try a drug, and, if it doesn’t work, you try something different, and you keep on until you find what works best," Dr. West said.

The strongest evidence of efficacy exists for the Food and Drug Administration–approved drugs duloxetine, milnacipran, and pregabalin, along with the off-label agents venlafaxine, gabapentin, cyclobenzaprine, and the tricyclic antidepressants. All of those off-label drugs are supported by a body of literature supporting effectiveness, and they make for good alternatives when patients can’t afford the approved drugs, which are invariably more costly, he said.

The numbers-needed-to-treat to achieve a 30% reduction in pain have been calculated at 7.2 for duloxetine, 8.6 for pregabalin, and 19 for milnacipran.

"All of these patients with fibromyalgia come to us with pain," Dr. West noted. "I choose their medications based on what their chief complaint is."

For example, a fibromyalgia patient who presents with pain, prominent fatigue, and depressed mood is a good candidate for duloxetine (Cymbalta), which fortuitously is also approved for osteoarthritis pain. A patient who complains of pain, cognitive dysfunction or "fibrofog," and fatigue may do well with milnacipran (Savella) starting at 12.5 mg in the morning with food, titrated upward by 12.5 mg per week to a maximum of 50 mg b.i.d. Pain with sleep disturbance is a symptom cluster that often responds well to pregabalin (Lyrica), dosed at 50 mg with food before bed, increased by 25 mg/day weekly to at least 150 mg/day before a morning dose is added, with a ceiling of 225 mg b.i.d..

Tramadol is supported by "modest" evidence of efficacy as an add-on niche medication for patients with substantial pain despite their baseline medications, the rheumatologist continued. Its efficacy in fibromyalgia is not through its better-known mu-opioid receptor agonist effect, but rather through the mechanism of serotonin-norepinephrine reuptake inhibition. Dr. West said that he starts tramadol at 25 mg/day and increases it weekly to a maximum of 100 mg four times daily.

Rational combination therapies utilizing different mechanisms of action and that are backed by supporting efficacy data include milnacipran plus pregabalin, venlafaxine and gabapentin, and fluoxetine and either amitriptyline or cyclobenzaprine, the rheumatologist continued.

Nearly all the medications recommended for treatment of fibromyalgia other than pregabalin and gabapentin modulate serotonin. That means patients need to be monitored for the development of suicidal ideation as well as serotonin syndrome. A simple way to check for emergent serotonin syndrome is to regularly evaluate the patient’s deep tendon reflexes.

"If a patient suddenly becomes much more hyper-reflexive, you need to start dialing it down because you’re putting them at risk for serotonin syndrome," Dr. West cautioned.

It’s evident that many physicians are struggling with the use of medications to treat patients with fibromyalgia. "There’s a gap between the evidence and what medications are actually prescribed in practice," Dr. West observed.

This gap was highlighted by data from the REFLECTIONS study, presented at last year’s annual scientific meeting of the American Pain Society. REFLECTIONS is an Eli Lilly–sponsored longitudinal study of 1,700 fibromyalgia patients and 91 physicians. The physicians collectively prescribed 186 different medications to treat individuals with fibromyalgia. Only about one-quarter of the physicians used one of the FDA-approved drugs. Opioids and nonsteroidal anti-inflammatory drugs were used just as frequently, even though these medications have zero evidence of efficacy in fibromyalgia and experts agree they are of no help.

Dr. West reported having no financial conflicts.

ESTES PARK, COLO. – Perhaps the least-known finding of the landmark Women’s Health Initiative was the complete failure of a structured low-fat diet intervention to lower the risks of coronary heart disease, stroke, or colon cancer.

"This has gotten very little press. But the results made me very happy because it gave me one less thing to worry about, which is eating a low-fat diet. It doesn’t seem to have the same magnitude of effect in women as it does in men," Dr. Nanette Santoro said at a conference on internal medicine sponsored by the University of Colorado.

The Women’s Health Initiative Randomized Controlled Dietary Modification Trial involved 48,835 postmenopausal women aged 50-79 at 40 U.S. centers who were randomized 40/60 to a low-fat diet intervention or a control group.

During a mean follow-up of 8.1 years, the diet intervention and control groups didn’t show any significant differences in rates of coronary heart disease (hazard ratio, 0.97); stroke (1.02); or cardiovascular disease (0.98) (JAMA 2006;295:655-66).

Similarly, the event-rate curves for cardiovascular outcomes as well as for colon cancer in the intervention and control arms were virtually identical the entire time, with no hint of either early or late benefit for the low-fat diet (JAMA 2006;295:643-54).

There was a nonsignificant trend for less invasive breast cancer in the low-fat diet group, where the annualized incidence rate was 0.42%, a 9% relative risk reduction compared with the 0.45% rate in controls (JAMA 2006;295:629-42).

"So if there’s any possible benefit to a low-fat diet, there might be some for breast cancer," commented Dr. Santoro, professor and chair of the department of ob.gyn. at the university.

The diet intervention entailed an intensive behavioral modification program with 18 group sessions during year 1 and quarterly maintenance sessions thereafter, with supplemental individualized contact. The goal was to reduce dietary fat intake by boosting consumption of fruits and vegetables to at least five servings daily, along with at least six servings of grains daily. Weight loss goals weren’t part of the study, which was designed in the 1990s before the obesity epidemic was apparent.

The intervention was effective in terms of accomplishing lasting dietary change. At baseline, fat accounted for about 38% of total daily energy intake. After 1 year, this figure dropped to 24% in the diet intervention arm. At year 6, fat accounted for 29% of daily energy intake in the diet group compared with 37% in controls, a difference Dr. Santoro called "huge" in light of the enormous number of participants and the women’s diverse ethnicities and backgrounds.

The intervention group averaged 3.6 servings per day of fruits and vegetables at baseline and 4.9 by year 6, compared with 3.8 in controls. Efforts to increase consumption of grains were unsuccessful, however. The intervention group averaged 4.7 servings per day at baseline and 4.3 at year 6, compared with 3.8 in controls.

The Women’s Health Initiative Randomized Controlled Dietary Modification Trial was funded by the National Heart, Lung, and Blood Institute. Dr. Santoro reported that she has a research grant from Bayer.

ESTES PARK, COLO. – Perhaps the least-known finding of the landmark Women’s Health Initiative was the complete failure of a structured low-fat diet intervention to lower the risks of coronary heart disease, stroke, or colon cancer.

"This has gotten very little press. But the results made me very happy because it gave me one less thing to worry about, which is eating a low-fat diet. It doesn’t seem to have the same magnitude of effect in women as it does in men," Dr. Nanette Santoro said at a conference on internal medicine sponsored by the University of Colorado.

The Women’s Health Initiative Randomized Controlled Dietary Modification Trial involved 48,835 postmenopausal women aged 50-79 at 40 U.S. centers who were randomized 40/60 to a low-fat diet intervention or a control group.

During a mean follow-up of 8.1 years, the diet intervention and control groups didn’t show any significant differences in rates of coronary heart disease (hazard ratio, 0.97); stroke (1.02); or cardiovascular disease (0.98) (JAMA 2006;295:655-66).

Similarly, the event-rate curves for cardiovascular outcomes as well as for colon cancer in the intervention and control arms were virtually identical the entire time, with no hint of either early or late benefit for the low-fat diet (JAMA 2006;295:643-54).

There was a nonsignificant trend for less invasive breast cancer in the low-fat diet group, where the annualized incidence rate was 0.42%, a 9% relative risk reduction compared with the 0.45% rate in controls (JAMA 2006;295:629-42).

"So if there’s any possible benefit to a low-fat diet, there might be some for breast cancer," commented Dr. Santoro, professor and chair of the department of ob.gyn. at the university.

The diet intervention entailed an intensive behavioral modification program with 18 group sessions during year 1 and quarterly maintenance sessions thereafter, with supplemental individualized contact. The goal was to reduce dietary fat intake by boosting consumption of fruits and vegetables to at least five servings daily, along with at least six servings of grains daily. Weight loss goals weren’t part of the study, which was designed in the 1990s before the obesity epidemic was apparent.

The intervention was effective in terms of accomplishing lasting dietary change. At baseline, fat accounted for about 38% of total daily energy intake. After 1 year, this figure dropped to 24% in the diet intervention arm. At year 6, fat accounted for 29% of daily energy intake in the diet group compared with 37% in controls, a difference Dr. Santoro called "huge" in light of the enormous number of participants and the women’s diverse ethnicities and backgrounds.

The intervention group averaged 3.6 servings per day of fruits and vegetables at baseline and 4.9 by year 6, compared with 3.8 in controls. Efforts to increase consumption of grains were unsuccessful, however. The intervention group averaged 4.7 servings per day at baseline and 4.3 at year 6, compared with 3.8 in controls.

The Women’s Health Initiative Randomized Controlled Dietary Modification Trial was funded by the National Heart, Lung, and Blood Institute. Dr. Santoro reported that she has a research grant from Bayer.

ESTES PARK, COLO. – Perhaps the least-known finding of the landmark Women’s Health Initiative was the complete failure of a structured low-fat diet intervention to lower the risks of coronary heart disease, stroke, or colon cancer.

"This has gotten very little press. But the results made me very happy because it gave me one less thing to worry about, which is eating a low-fat diet. It doesn’t seem to have the same magnitude of effect in women as it does in men," Dr. Nanette Santoro said at a conference on internal medicine sponsored by the University of Colorado.

The Women’s Health Initiative Randomized Controlled Dietary Modification Trial involved 48,835 postmenopausal women aged 50-79 at 40 U.S. centers who were randomized 40/60 to a low-fat diet intervention or a control group.

During a mean follow-up of 8.1 years, the diet intervention and control groups didn’t show any significant differences in rates of coronary heart disease (hazard ratio, 0.97); stroke (1.02); or cardiovascular disease (0.98) (JAMA 2006;295:655-66).

Similarly, the event-rate curves for cardiovascular outcomes as well as for colon cancer in the intervention and control arms were virtually identical the entire time, with no hint of either early or late benefit for the low-fat diet (JAMA 2006;295:643-54).

There was a nonsignificant trend for less invasive breast cancer in the low-fat diet group, where the annualized incidence rate was 0.42%, a 9% relative risk reduction compared with the 0.45% rate in controls (JAMA 2006;295:629-42).

"So if there’s any possible benefit to a low-fat diet, there might be some for breast cancer," commented Dr. Santoro, professor and chair of the department of ob.gyn. at the university.

The diet intervention entailed an intensive behavioral modification program with 18 group sessions during year 1 and quarterly maintenance sessions thereafter, with supplemental individualized contact. The goal was to reduce dietary fat intake by boosting consumption of fruits and vegetables to at least five servings daily, along with at least six servings of grains daily. Weight loss goals weren’t part of the study, which was designed in the 1990s before the obesity epidemic was apparent.

The intervention was effective in terms of accomplishing lasting dietary change. At baseline, fat accounted for about 38% of total daily energy intake. After 1 year, this figure dropped to 24% in the diet intervention arm. At year 6, fat accounted for 29% of daily energy intake in the diet group compared with 37% in controls, a difference Dr. Santoro called "huge" in light of the enormous number of participants and the women’s diverse ethnicities and backgrounds.

The intervention group averaged 3.6 servings per day of fruits and vegetables at baseline and 4.9 by year 6, compared with 3.8 in controls. Efforts to increase consumption of grains were unsuccessful, however. The intervention group averaged 4.7 servings per day at baseline and 4.3 at year 6, compared with 3.8 in controls.

The Women’s Health Initiative Randomized Controlled Dietary Modification Trial was funded by the National Heart, Lung, and Blood Institute. Dr. Santoro reported that she has a research grant from Bayer.

ESTES PARK, COLO. – Adding liothyronine is a reasonable treatment strategy when symptoms of hypothyroidism persist on optimal levothyroxine alone, according to Dr. Michael T. McDermott, professor of medicine and clinical pharmacology and director of endocrinology and diabetes practice at the University of Colorado Hospital, Aurora.

Combination levothyroxine/liothyronine (LT4/LT3) therapy is supported by a biologically plausible mechanism of benefit in symptomatic patients who are biochemically euthyroid on LT4. But it’s a step that belongs near the bottom of the management plan for the difficult hypothyroid patient. It should be considered only after other actions have been taken, including a search for coexisting autoimmune conditions or other medical illnesses, Dr. McDermott said at an update on internal medicine sponsored by the University of Colorado.

Every physician who treats hypothyroidism has patients who experience lingering fatigue, memory problems, and other symptoms even though their on-treatment TSH is in the target range of 0.5-2.0 mU/L. Five published studies underscore just how common this situation is. Dr. McDermott cited as an example a study of 397 hypothyroid patients with a TSH in the goal range; 34% scored in the abnormal range on the short-form General Health Questionnaire and 49% had elevated scores on a thyroid symptom-specific questionnaire (Clin. Endocrinol. [Oxf.] 2002;57:577-85).

These are patients who require further general medical evaluation. Their symptoms may be due to a coexistent autoimmune disease. After all, autoimmune diseases tend to cluster. Indeed, when British investigators did a systematic work-up of 495 patients with Hashimoto’s thyroiditis, they found a 14% prevalence of another autoimmune disease. Leading the way was rheumatoid arthritis, present in 4% of subjects. The Hashimoto’s thyroiditis group also had greater than 10-fold increased relative risks of celiac disease, vitiligo, SLE, and Addison’s disease (Am. J. Med. 2010;183:e1-9).

Alternatively, the patient’s lingering symptoms may be due in part to Hashimoto’s thyroiditis itself rather than to hypothyroidism per se. A study of 426 euthyroid women with goiter undergoing thyroidectomy showed that those with antithyroperoxidase antibodies had higher levels of fatigue, nervousness, and irritability, and lower quality of life (Thyroid 2011;21:161-7).

Dr. McDermott routinely obtains a serum 25 vitamin D measurement in his difficult cases of hypothyroidism, since low vitamin D levels are a common cause of fatigue. He also encourages patients with lingering symptoms to eat a well-balanced diet and get regular exercise and sleep, and he refers them for treatment of depression when indicated.

Only after doing all that, does he consider adding LT3. Combined LT4/LT3 therapy is controversial. The first-ever randomized controlled clinical trial was positive (N. Engl. J. Med. 1999;340:424-9), but it was followed by a spate of negative studies. Some physicians closed the book on this treatment strategy after a meta-analysis of all 11 randomized trials showed combination therapy was without benefit (J. Clin. Endocrinol. Metab. 2006; 91: 2,592-9).

However, more recent work has shown that a relatively common polymorphism of the deiodinase 2 gene known as Thr92Ala may predict less responsiveness of psychological symptoms of hypothyroidism to optimal LT4 monotherapy. Deiodinase 2 is responsible for maintaining brain T3 levels, and there is evidence to indicate that the Thr92Ala polymorphism subtly impairs T4 to T3 conversion in the brain.

In a secondary analysis of a study involving 552 hypothyroid patients randomized to LT4 or LT4/LT3, the prevalence of Thr92Ala homozygosity was 16%, and psychological well being in patients with the deiodinase 2 polymorphism improved significantly more on combination therapy than with LT4 alone (J. Clin. Endocrinol. Metab. 2009;94:1623-9).

The fact that the Thr92Ala polymorphism is present in only 16% of individuals on thyroid hormone therapy might explain why so many randomized trials of LT4 versus combination therapy were negative: With study populations of only 20-141 patients, the trials would have been underpowered to detect a significant difference in treatment effect. Unfortunately, genetic testing for deiodinase polymorphisms is not commercially available, the endocrinologist observed.

When he does resort to combination therapy, Dr. McDermott prescribes it in an LT4:LT3 ratio of 10-14:1 to mimic normal thyroid secretion. He generally has patients take LT3 twice daily, with the second dose no later than about 6 p.m. so it doesn’t interfere with sleep. Once-daily slow-release formulations of LT3 are available in Europe and work very well. Several companies are interested in developing a slow-release LT3 for the United States, which would be a welcome development, according to Dr. McDermott.

Another option, once all else has been tried and failed, is to switch to another brand of LT4, he continued. Some patients may have adverse reactions to the various dyes and fillers contained in LT4 pills. When this is a potential concern, levothyroxine sodium (Tirosint), approved by the Food and Drug Administration a couple of years ago, is an attractive option. The LT4 in Tirosint is contained in oil in a liquid gelcap with no dyes or fillers, differentiating it from all other brand name and generic products, Dr. McDermott noted.

He emphasized the importance of avoiding overtreatment with LT4 in an attempt to improve quality of life in patients with residual symptoms despite a TSH of 0.5-2.0 mU/L. Subclinical hyperthyroidism as defined by a TSH below 0.1 mU/L has been shown to significantly increase the risk of hip and spine fractures, atrial fibrillation, and cardiovascular mortality.

Dr. McDermott reported having no financial conflicts.

ESTES PARK, COLO. – Adding liothyronine is a reasonable treatment strategy when symptoms of hypothyroidism persist on optimal levothyroxine alone, according to Dr. Michael T. McDermott, professor of medicine and clinical pharmacology and director of endocrinology and diabetes practice at the University of Colorado Hospital, Aurora.

Combination levothyroxine/liothyronine (LT4/LT3) therapy is supported by a biologically plausible mechanism of benefit in symptomatic patients who are biochemically euthyroid on LT4. But it’s a step that belongs near the bottom of the management plan for the difficult hypothyroid patient. It should be considered only after other actions have been taken, including a search for coexisting autoimmune conditions or other medical illnesses, Dr. McDermott said at an update on internal medicine sponsored by the University of Colorado.

Every physician who treats hypothyroidism has patients who experience lingering fatigue, memory problems, and other symptoms even though their on-treatment TSH is in the target range of 0.5-2.0 mU/L. Five published studies underscore just how common this situation is. Dr. McDermott cited as an example a study of 397 hypothyroid patients with a TSH in the goal range; 34% scored in the abnormal range on the short-form General Health Questionnaire and 49% had elevated scores on a thyroid symptom-specific questionnaire (Clin. Endocrinol. [Oxf.] 2002;57:577-85).

These are patients who require further general medical evaluation. Their symptoms may be due to a coexistent autoimmune disease. After all, autoimmune diseases tend to cluster. Indeed, when British investigators did a systematic work-up of 495 patients with Hashimoto’s thyroiditis, they found a 14% prevalence of another autoimmune disease. Leading the way was rheumatoid arthritis, present in 4% of subjects. The Hashimoto’s thyroiditis group also had greater than 10-fold increased relative risks of celiac disease, vitiligo, SLE, and Addison’s disease (Am. J. Med. 2010;183:e1-9).

Alternatively, the patient’s lingering symptoms may be due in part to Hashimoto’s thyroiditis itself rather than to hypothyroidism per se. A study of 426 euthyroid women with goiter undergoing thyroidectomy showed that those with antithyroperoxidase antibodies had higher levels of fatigue, nervousness, and irritability, and lower quality of life (Thyroid 2011;21:161-7).

Dr. McDermott routinely obtains a serum 25 vitamin D measurement in his difficult cases of hypothyroidism, since low vitamin D levels are a common cause of fatigue. He also encourages patients with lingering symptoms to eat a well-balanced diet and get regular exercise and sleep, and he refers them for treatment of depression when indicated.

Only after doing all that, does he consider adding LT3. Combined LT4/LT3 therapy is controversial. The first-ever randomized controlled clinical trial was positive (N. Engl. J. Med. 1999;340:424-9), but it was followed by a spate of negative studies. Some physicians closed the book on this treatment strategy after a meta-analysis of all 11 randomized trials showed combination therapy was without benefit (J. Clin. Endocrinol. Metab. 2006; 91: 2,592-9).

However, more recent work has shown that a relatively common polymorphism of the deiodinase 2 gene known as Thr92Ala may predict less responsiveness of psychological symptoms of hypothyroidism to optimal LT4 monotherapy. Deiodinase 2 is responsible for maintaining brain T3 levels, and there is evidence to indicate that the Thr92Ala polymorphism subtly impairs T4 to T3 conversion in the brain.

In a secondary analysis of a study involving 552 hypothyroid patients randomized to LT4 or LT4/LT3, the prevalence of Thr92Ala homozygosity was 16%, and psychological well being in patients with the deiodinase 2 polymorphism improved significantly more on combination therapy than with LT4 alone (J. Clin. Endocrinol. Metab. 2009;94:1623-9).

The fact that the Thr92Ala polymorphism is present in only 16% of individuals on thyroid hormone therapy might explain why so many randomized trials of LT4 versus combination therapy were negative: With study populations of only 20-141 patients, the trials would have been underpowered to detect a significant difference in treatment effect. Unfortunately, genetic testing for deiodinase polymorphisms is not commercially available, the endocrinologist observed.

When he does resort to combination therapy, Dr. McDermott prescribes it in an LT4:LT3 ratio of 10-14:1 to mimic normal thyroid secretion. He generally has patients take LT3 twice daily, with the second dose no later than about 6 p.m. so it doesn’t interfere with sleep. Once-daily slow-release formulations of LT3 are available in Europe and work very well. Several companies are interested in developing a slow-release LT3 for the United States, which would be a welcome development, according to Dr. McDermott.

Another option, once all else has been tried and failed, is to switch to another brand of LT4, he continued. Some patients may have adverse reactions to the various dyes and fillers contained in LT4 pills. When this is a potential concern, levothyroxine sodium (Tirosint), approved by the Food and Drug Administration a couple of years ago, is an attractive option. The LT4 in Tirosint is contained in oil in a liquid gelcap with no dyes or fillers, differentiating it from all other brand name and generic products, Dr. McDermott noted.

He emphasized the importance of avoiding overtreatment with LT4 in an attempt to improve quality of life in patients with residual symptoms despite a TSH of 0.5-2.0 mU/L. Subclinical hyperthyroidism as defined by a TSH below 0.1 mU/L has been shown to significantly increase the risk of hip and spine fractures, atrial fibrillation, and cardiovascular mortality.

Dr. McDermott reported having no financial conflicts.

ESTES PARK, COLO. – Adding liothyronine is a reasonable treatment strategy when symptoms of hypothyroidism persist on optimal levothyroxine alone, according to Dr. Michael T. McDermott, professor of medicine and clinical pharmacology and director of endocrinology and diabetes practice at the University of Colorado Hospital, Aurora.

Combination levothyroxine/liothyronine (LT4/LT3) therapy is supported by a biologically plausible mechanism of benefit in symptomatic patients who are biochemically euthyroid on LT4. But it’s a step that belongs near the bottom of the management plan for the difficult hypothyroid patient. It should be considered only after other actions have been taken, including a search for coexisting autoimmune conditions or other medical illnesses, Dr. McDermott said at an update on internal medicine sponsored by the University of Colorado.

Every physician who treats hypothyroidism has patients who experience lingering fatigue, memory problems, and other symptoms even though their on-treatment TSH is in the target range of 0.5-2.0 mU/L. Five published studies underscore just how common this situation is. Dr. McDermott cited as an example a study of 397 hypothyroid patients with a TSH in the goal range; 34% scored in the abnormal range on the short-form General Health Questionnaire and 49% had elevated scores on a thyroid symptom-specific questionnaire (Clin. Endocrinol. [Oxf.] 2002;57:577-85).

These are patients who require further general medical evaluation. Their symptoms may be due to a coexistent autoimmune disease. After all, autoimmune diseases tend to cluster. Indeed, when British investigators did a systematic work-up of 495 patients with Hashimoto’s thyroiditis, they found a 14% prevalence of another autoimmune disease. Leading the way was rheumatoid arthritis, present in 4% of subjects. The Hashimoto’s thyroiditis group also had greater than 10-fold increased relative risks of celiac disease, vitiligo, SLE, and Addison’s disease (Am. J. Med. 2010;183:e1-9).

Alternatively, the patient’s lingering symptoms may be due in part to Hashimoto’s thyroiditis itself rather than to hypothyroidism per se. A study of 426 euthyroid women with goiter undergoing thyroidectomy showed that those with antithyroperoxidase antibodies had higher levels of fatigue, nervousness, and irritability, and lower quality of life (Thyroid 2011;21:161-7).

Dr. McDermott routinely obtains a serum 25 vitamin D measurement in his difficult cases of hypothyroidism, since low vitamin D levels are a common cause of fatigue. He also encourages patients with lingering symptoms to eat a well-balanced diet and get regular exercise and sleep, and he refers them for treatment of depression when indicated.

Only after doing all that, does he consider adding LT3. Combined LT4/LT3 therapy is controversial. The first-ever randomized controlled clinical trial was positive (N. Engl. J. Med. 1999;340:424-9), but it was followed by a spate of negative studies. Some physicians closed the book on this treatment strategy after a meta-analysis of all 11 randomized trials showed combination therapy was without benefit (J. Clin. Endocrinol. Metab. 2006; 91: 2,592-9).

However, more recent work has shown that a relatively common polymorphism of the deiodinase 2 gene known as Thr92Ala may predict less responsiveness of psychological symptoms of hypothyroidism to optimal LT4 monotherapy. Deiodinase 2 is responsible for maintaining brain T3 levels, and there is evidence to indicate that the Thr92Ala polymorphism subtly impairs T4 to T3 conversion in the brain.

In a secondary analysis of a study involving 552 hypothyroid patients randomized to LT4 or LT4/LT3, the prevalence of Thr92Ala homozygosity was 16%, and psychological well being in patients with the deiodinase 2 polymorphism improved significantly more on combination therapy than with LT4 alone (J. Clin. Endocrinol. Metab. 2009;94:1623-9).

The fact that the Thr92Ala polymorphism is present in only 16% of individuals on thyroid hormone therapy might explain why so many randomized trials of LT4 versus combination therapy were negative: With study populations of only 20-141 patients, the trials would have been underpowered to detect a significant difference in treatment effect. Unfortunately, genetic testing for deiodinase polymorphisms is not commercially available, the endocrinologist observed.

When he does resort to combination therapy, Dr. McDermott prescribes it in an LT4:LT3 ratio of 10-14:1 to mimic normal thyroid secretion. He generally has patients take LT3 twice daily, with the second dose no later than about 6 p.m. so it doesn’t interfere with sleep. Once-daily slow-release formulations of LT3 are available in Europe and work very well. Several companies are interested in developing a slow-release LT3 for the United States, which would be a welcome development, according to Dr. McDermott.

Another option, once all else has been tried and failed, is to switch to another brand of LT4, he continued. Some patients may have adverse reactions to the various dyes and fillers contained in LT4 pills. When this is a potential concern, levothyroxine sodium (Tirosint), approved by the Food and Drug Administration a couple of years ago, is an attractive option. The LT4 in Tirosint is contained in oil in a liquid gelcap with no dyes or fillers, differentiating it from all other brand name and generic products, Dr. McDermott noted.

He emphasized the importance of avoiding overtreatment with LT4 in an attempt to improve quality of life in patients with residual symptoms despite a TSH of 0.5-2.0 mU/L. Subclinical hyperthyroidism as defined by a TSH below 0.1 mU/L has been shown to significantly increase the risk of hip and spine fractures, atrial fibrillation, and cardiovascular mortality.

Dr. McDermott reported having no financial conflicts.

ESTES PARK, COLO. – Improving the unacceptably low rates of blood pressure control in the two-thirds of Americans older than age 60 years who have hypertension will require physicians to discard some enduring myths and ill-advised treatment approaches, Dr. Philip S. Mehler said at a conference on internal medicine update sponsored by the University of Colorado at Denver, Aurora.

"This is really a winnable battle we have in health care," said Dr. Mehler, professor of medicine at the university and chief medical officer at Denver Health.

Only half of the more than 73 million hypertensive adults have good blood pressure control, according to data from the 2008 NHANES (National Health and Nutrition Examination Survey). To boost that rate, physicians will have to reconsider the following widespread treatment misconceptions:

• Monotherapy is the best initial approach to reducing blood pressure. "The way many of us were trained in the past, you take one blood pressure pill and keep doubling it and tripling it and quadrupling it before you move to another class, because in general we try to treat hypertension with one drug. Now we know, in one of the biggest paradigm shifts in hypertension control, that what we need to do is replace that practice and combine drugs from different classes without necessarily maximizing the dose of any one of those classes. That’s a big change, and it needs to be insinuated in your practice," the internist urged.

Fully 80% of the efficacy of most antihypertensive agents is achieved at 50% of the maximum dose, he said. The one exception to that rule is diuretics. Diuretics are underutilized, as evidenced by the fact that they accounted for only 26% of total blood pressure drugs dispensed in 2010. And they are underdosed as well: Diuretic dosing needs to be increased to optimize diuresis, as volume overload is such a common feature in hypertension.

"The message from JNC7 [Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure], and the message that will be in JNC8, which should finally be out this November, is that a diuretic should be the first or second medication you use in patients with hypertension," Dr. Mehler said.

He noted that a key message in JNC7 is that if a patient’s blood pressure is more than 20/10 mm Hg above goal, treatment should be initiated with two agents, one of which should usually be a thiazide-type diuretic.

• Myth No. 1: Diuretics are interchangeable. There’s a good argument for increased preferential usage of chlorthalidone over hydrochlorothiazide. Dr. Mehler called chlorthalidone "the ideal once-a-day drug" for hypertension because of its pharmacokinetics; it has a half-life of 30 hours, compared with 8 hours for hydrochlorothiazide. A 12.5-mg dose of chlorthalidone is equivalent to 25 mg of hydrochlorothiazide. Potassium wasting occurs in 15%-30% of patients within their first 2 weeks on chlorthalidone. Unfortunately, unlike hydrochlorothiazide, chlorthalidone is not available in any of the convenient combination products.

• Myth No. 2: Beta-blockers are tops. Noting that 22% of blood pressure drug dispensing in 2010 was for beta-blockers, Dr. Mehler commented, "I’m a bit surprised that almost one-quarter of the blood pressure pills prescribed in America are beta-blockers; there’s less and less evidence supporting the use of beta-blockers for pure, garden-variety hypertension."

Beta-blockers are particularly ineffective in treating high blood pressure in the elderly, in whom the disease most often takes the form of isolated systolic hypertension, which results from conduit stiffness, a different mechanism than that of mixed systolic/diastolic hypertension. The best multidrug combinations for isolated systolic hypertension include diuretics; ACE inhibitors or angiotensin receptor blockers; dihydropyridine calcium channel blockers; and an aldosterone antagonist, he said.

• Myth No. 3: There’s no J-curve. Whether or not a J-curve (that is, a level of blood pressure lowering beyond which the mortality risk reverses and starts climbing) exists in hypertension therapy is a long-standing argument. The latest thinking is that there is indeed a J-curve, and that it applies to diastolic – but not to systolic – blood pressure. It is critical to stop intensifying therapy once a patient’s diastolic pressure falls below 65 mm Hg, even if the systolic pressure remains above goal, according to Dr. Mehler.

• Myth No. 4: Salt, schmalt! The average American consumes more than 5 g of sodium per day. American Heart Association guidelines recommend reducing that to 1.5 g.

"Salt restriction is an often overlooked aspect of therapy, but it’s as beneficial as smoking cessation and adding another class of medication to treat hypertension," he asserted.

• Myth No. 5: No hypokalemia means no primary hyperaldosteronism. Resistant hypertension (defined as above-goal blood pressure despite the use of at least three optimally dosed medications from different classes) is present in 35% of hypertensive patients. Primary hyperaldosteronism is the cause of resistant hypertension in 10%-20% cases. In the past, the diagnosis of primary hypoaldosteronism leaned heavily on the presence of hypokalemia. More recently, however, studies demonstrate that normokalemic hypertension is the most common presentation of primary hyperaldosteronism; hypokalemia is present in only 9%-37% of cases, and these tend to be the most severe ones.

Screening for primary hyperaldosteronism is warranted in all patients with resistant hypertension with no other explanation, in those with an abnormal-appearing adrenal gland on CT, and in those with hypokalemia. The combination of a plasma aldosterone–to– plasma renin activity ratio greater than 30, plus an absolute plasma aldosterone concentration above 20 ng/dL, has been shown to have 90% sensitivity and 91% specificity for primary aldosteronism, Dr. Mehler continued.

Most affected patients respond to spironolactone with a marked blood pressure reduction. This drug, which costs pennies per day, is one of just four cardiovascular medications that were developed before 1960 and are still widely used today. The others are digoxin, aspirin, and warfarin, he noted.

Dr. Mehler reported having no financial conflicts.

ESTES PARK, COLO. – Improving the unacceptably low rates of blood pressure control in the two-thirds of Americans older than age 60 years who have hypertension will require physicians to discard some enduring myths and ill-advised treatment approaches, Dr. Philip S. Mehler said at a conference on internal medicine update sponsored by the University of Colorado at Denver, Aurora.

"This is really a winnable battle we have in health care," said Dr. Mehler, professor of medicine at the university and chief medical officer at Denver Health.

Only half of the more than 73 million hypertensive adults have good blood pressure control, according to data from the 2008 NHANES (National Health and Nutrition Examination Survey). To boost that rate, physicians will have to reconsider the following widespread treatment misconceptions:

• Monotherapy is the best initial approach to reducing blood pressure. "The way many of us were trained in the past, you take one blood pressure pill and keep doubling it and tripling it and quadrupling it before you move to another class, because in general we try to treat hypertension with one drug. Now we know, in one of the biggest paradigm shifts in hypertension control, that what we need to do is replace that practice and combine drugs from different classes without necessarily maximizing the dose of any one of those classes. That’s a big change, and it needs to be insinuated in your practice," the internist urged.

Fully 80% of the efficacy of most antihypertensive agents is achieved at 50% of the maximum dose, he said. The one exception to that rule is diuretics. Diuretics are underutilized, as evidenced by the fact that they accounted for only 26% of total blood pressure drugs dispensed in 2010. And they are underdosed as well: Diuretic dosing needs to be increased to optimize diuresis, as volume overload is such a common feature in hypertension.

"The message from JNC7 [Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure], and the message that will be in JNC8, which should finally be out this November, is that a diuretic should be the first or second medication you use in patients with hypertension," Dr. Mehler said.

He noted that a key message in JNC7 is that if a patient’s blood pressure is more than 20/10 mm Hg above goal, treatment should be initiated with two agents, one of which should usually be a thiazide-type diuretic.

• Myth No. 1: Diuretics are interchangeable. There’s a good argument for increased preferential usage of chlorthalidone over hydrochlorothiazide. Dr. Mehler called chlorthalidone "the ideal once-a-day drug" for hypertension because of its pharmacokinetics; it has a half-life of 30 hours, compared with 8 hours for hydrochlorothiazide. A 12.5-mg dose of chlorthalidone is equivalent to 25 mg of hydrochlorothiazide. Potassium wasting occurs in 15%-30% of patients within their first 2 weeks on chlorthalidone. Unfortunately, unlike hydrochlorothiazide, chlorthalidone is not available in any of the convenient combination products.

• Myth No. 2: Beta-blockers are tops. Noting that 22% of blood pressure drug dispensing in 2010 was for beta-blockers, Dr. Mehler commented, "I’m a bit surprised that almost one-quarter of the blood pressure pills prescribed in America are beta-blockers; there’s less and less evidence supporting the use of beta-blockers for pure, garden-variety hypertension."

Beta-blockers are particularly ineffective in treating high blood pressure in the elderly, in whom the disease most often takes the form of isolated systolic hypertension, which results from conduit stiffness, a different mechanism than that of mixed systolic/diastolic hypertension. The best multidrug combinations for isolated systolic hypertension include diuretics; ACE inhibitors or angiotensin receptor blockers; dihydropyridine calcium channel blockers; and an aldosterone antagonist, he said.

• Myth No. 3: There’s no J-curve. Whether or not a J-curve (that is, a level of blood pressure lowering beyond which the mortality risk reverses and starts climbing) exists in hypertension therapy is a long-standing argument. The latest thinking is that there is indeed a J-curve, and that it applies to diastolic – but not to systolic – blood pressure. It is critical to stop intensifying therapy once a patient’s diastolic pressure falls below 65 mm Hg, even if the systolic pressure remains above goal, according to Dr. Mehler.

• Myth No. 4: Salt, schmalt! The average American consumes more than 5 g of sodium per day. American Heart Association guidelines recommend reducing that to 1.5 g.

"Salt restriction is an often overlooked aspect of therapy, but it’s as beneficial as smoking cessation and adding another class of medication to treat hypertension," he asserted.

• Myth No. 5: No hypokalemia means no primary hyperaldosteronism. Resistant hypertension (defined as above-goal blood pressure despite the use of at least three optimally dosed medications from different classes) is present in 35% of hypertensive patients. Primary hyperaldosteronism is the cause of resistant hypertension in 10%-20% cases. In the past, the diagnosis of primary hypoaldosteronism leaned heavily on the presence of hypokalemia. More recently, however, studies demonstrate that normokalemic hypertension is the most common presentation of primary hyperaldosteronism; hypokalemia is present in only 9%-37% of cases, and these tend to be the most severe ones.

Screening for primary hyperaldosteronism is warranted in all patients with resistant hypertension with no other explanation, in those with an abnormal-appearing adrenal gland on CT, and in those with hypokalemia. The combination of a plasma aldosterone–to– plasma renin activity ratio greater than 30, plus an absolute plasma aldosterone concentration above 20 ng/dL, has been shown to have 90% sensitivity and 91% specificity for primary aldosteronism, Dr. Mehler continued.

Most affected patients respond to spironolactone with a marked blood pressure reduction. This drug, which costs pennies per day, is one of just four cardiovascular medications that were developed before 1960 and are still widely used today. The others are digoxin, aspirin, and warfarin, he noted.

Dr. Mehler reported having no financial conflicts.

ESTES PARK, COLO. – Improving the unacceptably low rates of blood pressure control in the two-thirds of Americans older than age 60 years who have hypertension will require physicians to discard some enduring myths and ill-advised treatment approaches, Dr. Philip S. Mehler said at a conference on internal medicine update sponsored by the University of Colorado at Denver, Aurora.

"This is really a winnable battle we have in health care," said Dr. Mehler, professor of medicine at the university and chief medical officer at Denver Health.

Only half of the more than 73 million hypertensive adults have good blood pressure control, according to data from the 2008 NHANES (National Health and Nutrition Examination Survey). To boost that rate, physicians will have to reconsider the following widespread treatment misconceptions:

• Monotherapy is the best initial approach to reducing blood pressure. "The way many of us were trained in the past, you take one blood pressure pill and keep doubling it and tripling it and quadrupling it before you move to another class, because in general we try to treat hypertension with one drug. Now we know, in one of the biggest paradigm shifts in hypertension control, that what we need to do is replace that practice and combine drugs from different classes without necessarily maximizing the dose of any one of those classes. That’s a big change, and it needs to be insinuated in your practice," the internist urged.

Fully 80% of the efficacy of most antihypertensive agents is achieved at 50% of the maximum dose, he said. The one exception to that rule is diuretics. Diuretics are underutilized, as evidenced by the fact that they accounted for only 26% of total blood pressure drugs dispensed in 2010. And they are underdosed as well: Diuretic dosing needs to be increased to optimize diuresis, as volume overload is such a common feature in hypertension.

"The message from JNC7 [Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure], and the message that will be in JNC8, which should finally be out this November, is that a diuretic should be the first or second medication you use in patients with hypertension," Dr. Mehler said.

He noted that a key message in JNC7 is that if a patient’s blood pressure is more than 20/10 mm Hg above goal, treatment should be initiated with two agents, one of which should usually be a thiazide-type diuretic.

• Myth No. 1: Diuretics are interchangeable. There’s a good argument for increased preferential usage of chlorthalidone over hydrochlorothiazide. Dr. Mehler called chlorthalidone "the ideal once-a-day drug" for hypertension because of its pharmacokinetics; it has a half-life of 30 hours, compared with 8 hours for hydrochlorothiazide. A 12.5-mg dose of chlorthalidone is equivalent to 25 mg of hydrochlorothiazide. Potassium wasting occurs in 15%-30% of patients within their first 2 weeks on chlorthalidone. Unfortunately, unlike hydrochlorothiazide, chlorthalidone is not available in any of the convenient combination products.

• Myth No. 2: Beta-blockers are tops. Noting that 22% of blood pressure drug dispensing in 2010 was for beta-blockers, Dr. Mehler commented, "I’m a bit surprised that almost one-quarter of the blood pressure pills prescribed in America are beta-blockers; there’s less and less evidence supporting the use of beta-blockers for pure, garden-variety hypertension."

Beta-blockers are particularly ineffective in treating high blood pressure in the elderly, in whom the disease most often takes the form of isolated systolic hypertension, which results from conduit stiffness, a different mechanism than that of mixed systolic/diastolic hypertension. The best multidrug combinations for isolated systolic hypertension include diuretics; ACE inhibitors or angiotensin receptor blockers; dihydropyridine calcium channel blockers; and an aldosterone antagonist, he said.

• Myth No. 3: There’s no J-curve. Whether or not a J-curve (that is, a level of blood pressure lowering beyond which the mortality risk reverses and starts climbing) exists in hypertension therapy is a long-standing argument. The latest thinking is that there is indeed a J-curve, and that it applies to diastolic – but not to systolic – blood pressure. It is critical to stop intensifying therapy once a patient’s diastolic pressure falls below 65 mm Hg, even if the systolic pressure remains above goal, according to Dr. Mehler.

• Myth No. 4: Salt, schmalt! The average American consumes more than 5 g of sodium per day. American Heart Association guidelines recommend reducing that to 1.5 g.

"Salt restriction is an often overlooked aspect of therapy, but it’s as beneficial as smoking cessation and adding another class of medication to treat hypertension," he asserted.

• Myth No. 5: No hypokalemia means no primary hyperaldosteronism. Resistant hypertension (defined as above-goal blood pressure despite the use of at least three optimally dosed medications from different classes) is present in 35% of hypertensive patients. Primary hyperaldosteronism is the cause of resistant hypertension in 10%-20% cases. In the past, the diagnosis of primary hypoaldosteronism leaned heavily on the presence of hypokalemia. More recently, however, studies demonstrate that normokalemic hypertension is the most common presentation of primary hyperaldosteronism; hypokalemia is present in only 9%-37% of cases, and these tend to be the most severe ones.

Screening for primary hyperaldosteronism is warranted in all patients with resistant hypertension with no other explanation, in those with an abnormal-appearing adrenal gland on CT, and in those with hypokalemia. The combination of a plasma aldosterone–to– plasma renin activity ratio greater than 30, plus an absolute plasma aldosterone concentration above 20 ng/dL, has been shown to have 90% sensitivity and 91% specificity for primary aldosteronism, Dr. Mehler continued.

Most affected patients respond to spironolactone with a marked blood pressure reduction. This drug, which costs pennies per day, is one of just four cardiovascular medications that were developed before 1960 and are still widely used today. The others are digoxin, aspirin, and warfarin, he noted.

Dr. Mehler reported having no financial conflicts.