What Matters

Proton pump inhibitors (PPIs) are one of the most widely prescribed drugs on the planet. PPIs have alleviated the long since forgotten clinical challenge of antacid-resistant and H₂-receptor agonist–resistant GERD or dyspepsia. Few of us may continue to “ramp up” GERD or dyspepsia treatment, settling instead on the PPI quick-fix so we can move onto other clinical issues. Based upon claims database data, patients who take prescription PPIs usually stay on therapy for an average of about 6 months. That’s all? Many clinicians have patients who are on these medications for years. With several PPIs now available in the generic form, it has become easier for us to maintain these medications. But what are the harms of this approach?

CDC/D. Holdeman

Last week, the Food and Drug Administration released a report that drew conclusions about data that have been accumulating for some time: PPIs are associated with an increased risk for Clostridium difficile-associated diarrhea. 

The FDA reviewed data from the Adverse Event Reporting System (AERS) and the medical literature. The lion’s share of the cases involved older patients with chronic medical conditions or patients who were taking antibiotics. More compelling, perhaps, were the 23 studies demonstrating a higher risk with PPI use compared to no PPI exposure. Notably, this information adds to the labeling information for prescription PPIs, which also lists an increased risk for osteoporosis and bone fracture and hypomagnesemia.

So what does this mean for our practice? I think the onus is on us to assess patient need for PPIs in order to prevent unintended consequences from their long-term use in patients who may not need them. Clinicians should individualize the “need” assessment. This could be done on a trial basis with PPI discontinuation or use of a “step-down” medication such as an H₂RA or antacid.

Proton pump inhibitors (PPIs) are one of the most widely prescribed drugs on the planet. PPIs have alleviated the long since forgotten clinical challenge of antacid-resistant and H₂-receptor agonist–resistant GERD or dyspepsia. Few of us may continue to “ramp up” GERD or dyspepsia treatment, settling instead on the PPI quick-fix so we can move onto other clinical issues. Based upon claims database data, patients who take prescription PPIs usually stay on therapy for an average of about 6 months. That’s all? Many clinicians have patients who are on these medications for years. With several PPIs now available in the generic form, it has become easier for us to maintain these medications. But what are the harms of this approach?

CDC/D. Holdeman

Last week, the Food and Drug Administration released a report that drew conclusions about data that have been accumulating for some time: PPIs are associated with an increased risk for Clostridium difficile-associated diarrhea. 

The FDA reviewed data from the Adverse Event Reporting System (AERS) and the medical literature. The lion’s share of the cases involved older patients with chronic medical conditions or patients who were taking antibiotics. More compelling, perhaps, were the 23 studies demonstrating a higher risk with PPI use compared to no PPI exposure. Notably, this information adds to the labeling information for prescription PPIs, which also lists an increased risk for osteoporosis and bone fracture and hypomagnesemia.

So what does this mean for our practice? I think the onus is on us to assess patient need for PPIs in order to prevent unintended consequences from their long-term use in patients who may not need them. Clinicians should individualize the “need” assessment. This could be done on a trial basis with PPI discontinuation or use of a “step-down” medication such as an H₂RA or antacid.

Proton pump inhibitors (PPIs) are one of the most widely prescribed drugs on the planet. PPIs have alleviated the long since forgotten clinical challenge of antacid-resistant and H₂-receptor agonist–resistant GERD or dyspepsia. Few of us may continue to “ramp up” GERD or dyspepsia treatment, settling instead on the PPI quick-fix so we can move onto other clinical issues. Based upon claims database data, patients who take prescription PPIs usually stay on therapy for an average of about 6 months. That’s all? Many clinicians have patients who are on these medications for years. With several PPIs now available in the generic form, it has become easier for us to maintain these medications. But what are the harms of this approach?

CDC/D. Holdeman

Last week, the Food and Drug Administration released a report that drew conclusions about data that have been accumulating for some time: PPIs are associated with an increased risk for Clostridium difficile-associated diarrhea. 

The FDA reviewed data from the Adverse Event Reporting System (AERS) and the medical literature. The lion’s share of the cases involved older patients with chronic medical conditions or patients who were taking antibiotics. More compelling, perhaps, were the 23 studies demonstrating a higher risk with PPI use compared to no PPI exposure. Notably, this information adds to the labeling information for prescription PPIs, which also lists an increased risk for osteoporosis and bone fracture and hypomagnesemia.

So what does this mean for our practice? I think the onus is on us to assess patient need for PPIs in order to prevent unintended consequences from their long-term use in patients who may not need them. Clinicians should individualize the “need” assessment. This could be done on a trial basis with PPI discontinuation or use of a “step-down” medication such as an H₂RA or antacid.

No preventable cause of death and disability kills more of our patients than cigarette smoking. Smoking will kill one billion people this century worldwide. Despite the high stakes of this addiction, we as practitioners frequently feel de-energized by the prospect of reviewing treatment options for smokers interested in quitting knowing that relapse is the most likely outcome. Virtually no time is spent on smokers who do not express a desire to quit. When we hear a negative response to the question, “Do you want to quit” we quickly move on to the next task at hand.

In a recently published study, investigators conducted a systematic review to examine the effect of single, minimal (less than 10 minutes long) interventions delivered by physicians to patients who were not selected for their motivation to quit (Addiction 2011 Dec 16.PubMed PMID: 22175545). The findings suggest that offering advice to stop smoking and assistance increases the number of quit attempts and abstinence rates. Offering support for quitting motivates an additional 50% of people to try to quit regardless of their willingness to quit. Offering nicotine replacement therapy increased long-term abstinence rates among this population. The authors conclude that giving advice to stop smoking would increase the number of people stopping smoking by one for every 21 people advised. Offering assistance would increase this by one for every 7 people offered assistance. Once again, this is regardless of the motivation to quit.

So what does this mean for our practice? This evidence suggests that we can change the conversation from starting out with “Are you interested in quitting?” Regardless of a smoker’s interest to quit, we should not ask, but tell them they need to quit to improve their health and offer them nicotine replacement therapy and behavioral counseling (e.g., refer to 1800QUITNOW). Instead of feeling hopeless in the face of a tough addiction, we should feel empowered by the finding that our advice and assistance will increase quit attempts and abstinence rates, regardless of whether patients initially want to quit or not.

Dr. Ebbert is professor of medicine at the Mayo Clinic in Rochester, Minn. He has received grants from the National Institutes of Health and Pfizer to conduct studies of interventions for tobacco use and has served as a consultant to GlaxoSmithKline, manufacturer of nicotine replacement products.

No preventable cause of death and disability kills more of our patients than cigarette smoking. Smoking will kill one billion people this century worldwide. Despite the high stakes of this addiction, we as practitioners frequently feel de-energized by the prospect of reviewing treatment options for smokers interested in quitting knowing that relapse is the most likely outcome. Virtually no time is spent on smokers who do not express a desire to quit. When we hear a negative response to the question, “Do you want to quit” we quickly move on to the next task at hand.

In a recently published study, investigators conducted a systematic review to examine the effect of single, minimal (less than 10 minutes long) interventions delivered by physicians to patients who were not selected for their motivation to quit (Addiction 2011 Dec 16.PubMed PMID: 22175545). The findings suggest that offering advice to stop smoking and assistance increases the number of quit attempts and abstinence rates. Offering support for quitting motivates an additional 50% of people to try to quit regardless of their willingness to quit. Offering nicotine replacement therapy increased long-term abstinence rates among this population. The authors conclude that giving advice to stop smoking would increase the number of people stopping smoking by one for every 21 people advised. Offering assistance would increase this by one for every 7 people offered assistance. Once again, this is regardless of the motivation to quit.

So what does this mean for our practice? This evidence suggests that we can change the conversation from starting out with “Are you interested in quitting?” Regardless of a smoker’s interest to quit, we should not ask, but tell them they need to quit to improve their health and offer them nicotine replacement therapy and behavioral counseling (e.g., refer to 1800QUITNOW). Instead of feeling hopeless in the face of a tough addiction, we should feel empowered by the finding that our advice and assistance will increase quit attempts and abstinence rates, regardless of whether patients initially want to quit or not.

Dr. Ebbert is professor of medicine at the Mayo Clinic in Rochester, Minn. He has received grants from the National Institutes of Health and Pfizer to conduct studies of interventions for tobacco use and has served as a consultant to GlaxoSmithKline, manufacturer of nicotine replacement products.

No preventable cause of death and disability kills more of our patients than cigarette smoking. Smoking will kill one billion people this century worldwide. Despite the high stakes of this addiction, we as practitioners frequently feel de-energized by the prospect of reviewing treatment options for smokers interested in quitting knowing that relapse is the most likely outcome. Virtually no time is spent on smokers who do not express a desire to quit. When we hear a negative response to the question, “Do you want to quit” we quickly move on to the next task at hand.

In a recently published study, investigators conducted a systematic review to examine the effect of single, minimal (less than 10 minutes long) interventions delivered by physicians to patients who were not selected for their motivation to quit (Addiction 2011 Dec 16.PubMed PMID: 22175545). The findings suggest that offering advice to stop smoking and assistance increases the number of quit attempts and abstinence rates. Offering support for quitting motivates an additional 50% of people to try to quit regardless of their willingness to quit. Offering nicotine replacement therapy increased long-term abstinence rates among this population. The authors conclude that giving advice to stop smoking would increase the number of people stopping smoking by one for every 21 people advised. Offering assistance would increase this by one for every 7 people offered assistance. Once again, this is regardless of the motivation to quit.

So what does this mean for our practice? This evidence suggests that we can change the conversation from starting out with “Are you interested in quitting?” Regardless of a smoker’s interest to quit, we should not ask, but tell them they need to quit to improve their health and offer them nicotine replacement therapy and behavioral counseling (e.g., refer to 1800QUITNOW). Instead of feeling hopeless in the face of a tough addiction, we should feel empowered by the finding that our advice and assistance will increase quit attempts and abstinence rates, regardless of whether patients initially want to quit or not.

Dr. Ebbert is professor of medicine at the Mayo Clinic in Rochester, Minn. He has received grants from the National Institutes of Health and Pfizer to conduct studies of interventions for tobacco use and has served as a consultant to GlaxoSmithKline, manufacturer of nicotine replacement products.

Screening for osteoporosis by assessing bone mineral density (BMD) has become an integral part of the care we provide to our older patients. Medicare pays for dual-energy x-ray absorptiometry (DXA) screening every two years or more frequently if the procedure is determined to be medically necessary. Based on my discussions with colleagues, however, striking heterogeneity clearly exists in the frequency with which we obtain BMDs. How frequently do we really need to screen?

In a recent report in the New England Journal of Medicine, the Study of Osteoporotic Fractures Research Group provides clinicians with refreshingly helpful data to inform our practices (N Engl J Med. 2012;366:225-33). In a cohort of 4,957 women two transitions were evaluated: 1) from normal BMD to osteoporosis; and 2) from osteopenia to osteoporosis. The BMD “testing interval” was defined as the estimated time for 10% of women to make the transition to osteoporosis before having a hip or clinical vertebral fracture, with adjustments for estrogen use and clinical factors. Participants were stratified into normal BMD (T score, −1.00 or higher), mild osteopenia (T score −1.01 to −1.49), moderate osteopenia (T score −1.50 to −1.99), and advanced osteopenia (T score −2.00 to −2.49). The estimated BMD testing interval was 16.8 years (95% confidence interval [CI] 11.5 to 24.6) for women with normal BMD, 17.3 years (95% CI 13.9 to 21.5) for women with mild osteopenia, 4.7 years (95% CI, 4.2 to 5.2) for women with moderate osteopenia, and 1.1 years (95% CI, 1.0 to 1.3) for women with advanced osteopenia. Within a given T-score, the transition from osteopenia to osteoporosis was longer for women of younger age, higher BMI, and estrogen use. Table 3 provides an excellent reference tool for tailoring screening intervals for our patients. When the testing interval was redefined for 20% of women to make the transition from osteopenia to osteoporosis, the time estimates were 80% longer.

These findings provide some rationale, evidence-based guidelines upon which we can base our testing intervals. This will help us do our part to avoid breaking the bank in the interest of avoiding breaking a bone.

Dr. Ebbert reported having no relevant conflicts of interest.

Screening for osteoporosis by assessing bone mineral density (BMD) has become an integral part of the care we provide to our older patients. Medicare pays for dual-energy x-ray absorptiometry (DXA) screening every two years or more frequently if the procedure is determined to be medically necessary. Based on my discussions with colleagues, however, striking heterogeneity clearly exists in the frequency with which we obtain BMDs. How frequently do we really need to screen?

In a recent report in the New England Journal of Medicine, the Study of Osteoporotic Fractures Research Group provides clinicians with refreshingly helpful data to inform our practices (N Engl J Med. 2012;366:225-33). In a cohort of 4,957 women two transitions were evaluated: 1) from normal BMD to osteoporosis; and 2) from osteopenia to osteoporosis. The BMD “testing interval” was defined as the estimated time for 10% of women to make the transition to osteoporosis before having a hip or clinical vertebral fracture, with adjustments for estrogen use and clinical factors. Participants were stratified into normal BMD (T score, −1.00 or higher), mild osteopenia (T score −1.01 to −1.49), moderate osteopenia (T score −1.50 to −1.99), and advanced osteopenia (T score −2.00 to −2.49). The estimated BMD testing interval was 16.8 years (95% confidence interval [CI] 11.5 to 24.6) for women with normal BMD, 17.3 years (95% CI 13.9 to 21.5) for women with mild osteopenia, 4.7 years (95% CI, 4.2 to 5.2) for women with moderate osteopenia, and 1.1 years (95% CI, 1.0 to 1.3) for women with advanced osteopenia. Within a given T-score, the transition from osteopenia to osteoporosis was longer for women of younger age, higher BMI, and estrogen use. Table 3 provides an excellent reference tool for tailoring screening intervals for our patients. When the testing interval was redefined for 20% of women to make the transition from osteopenia to osteoporosis, the time estimates were 80% longer.

These findings provide some rationale, evidence-based guidelines upon which we can base our testing intervals. This will help us do our part to avoid breaking the bank in the interest of avoiding breaking a bone.

Dr. Ebbert reported having no relevant conflicts of interest.

Screening for osteoporosis by assessing bone mineral density (BMD) has become an integral part of the care we provide to our older patients. Medicare pays for dual-energy x-ray absorptiometry (DXA) screening every two years or more frequently if the procedure is determined to be medically necessary. Based on my discussions with colleagues, however, striking heterogeneity clearly exists in the frequency with which we obtain BMDs. How frequently do we really need to screen?

In a recent report in the New England Journal of Medicine, the Study of Osteoporotic Fractures Research Group provides clinicians with refreshingly helpful data to inform our practices (N Engl J Med. 2012;366:225-33). In a cohort of 4,957 women two transitions were evaluated: 1) from normal BMD to osteoporosis; and 2) from osteopenia to osteoporosis. The BMD “testing interval” was defined as the estimated time for 10% of women to make the transition to osteoporosis before having a hip or clinical vertebral fracture, with adjustments for estrogen use and clinical factors. Participants were stratified into normal BMD (T score, −1.00 or higher), mild osteopenia (T score −1.01 to −1.49), moderate osteopenia (T score −1.50 to −1.99), and advanced osteopenia (T score −2.00 to −2.49). The estimated BMD testing interval was 16.8 years (95% confidence interval [CI] 11.5 to 24.6) for women with normal BMD, 17.3 years (95% CI 13.9 to 21.5) for women with mild osteopenia, 4.7 years (95% CI, 4.2 to 5.2) for women with moderate osteopenia, and 1.1 years (95% CI, 1.0 to 1.3) for women with advanced osteopenia. Within a given T-score, the transition from osteopenia to osteoporosis was longer for women of younger age, higher BMI, and estrogen use. Table 3 provides an excellent reference tool for tailoring screening intervals for our patients. When the testing interval was redefined for 20% of women to make the transition from osteopenia to osteoporosis, the time estimates were 80% longer.

These findings provide some rationale, evidence-based guidelines upon which we can base our testing intervals. This will help us do our part to avoid breaking the bank in the interest of avoiding breaking a bone.

Dr. Ebbert reported having no relevant conflicts of interest.

Most of us are familiar with the relationship between diuretics and increased uric acid levels potentially precipitating attacks of gout. Perhaps fewer recall that beta blockers also increase uric acid levels. In contrast, calcium channel blockers (CCBs) and losartan have been observed to decrease serum uric acid levels. This begs the question: Do CCBs and losartan reduce the incidence of gout attacks? Unfortunately, no randomized trials have been conducted to evaluate this.

However, a very large case-control study was published recently (BMJ. 2012;344:d8190) exploring the benefit of these drug classes for preventing gout attacks. Using an impressive computerized medical record database including 4 million patients entered by U.K. general practitioners, investigators conducted a case-control study of adults, aged 20 to 89 years, to determine the relationship between antihypertensives and gout. Incident cases of gout (n = 24,768) were ascertained in individuals having a gout attack after an initial diagnosis and were matched with 50,000 controls. The antihypertensives evaluated included diuretics, beta blockers, CCBs, ACE-inhibitors, losartan, and non-losartan angiotensin receptor blockers (ARBs). Results were adjusted for covariates. Hypertension itself was associated with a higher relative risk for incident gout (RR 1.75; 95% CI: 1.69-1.82). CCBs were associated with a lower risk of incident gout (RR 0.87; 95% CI: 0.82-0.93). Increasing duration and dose of medication further reduced the risk. Losartan also was associated with a reduced risk of developing gout (RR 0.81; 95% CI: 0.70 to 0.94). In contrast, current use of diuretics, beta blockers, ACE-inhibitors, and non-losartan ARBs among those with hypertension were all associated with an increased risk of incident gout. Findings were similar among patients without hypertension and among those on anti-gout medications.

Since the majority of patients with gout have hypertension, most of these patients will eventually be taking an antihypertensive. Data from this study would suggest that the selection of antihypertensive is an important consideration for avoiding future gout attacks. Similarly to how we might select an ACE-I/ARB for the treatment of hypertension in patients with diabetes for renoprotection, we should consider selecting losartan and CCB’s in patients with gout to prevent future attacks.

Dr. Ebbert reported having no relevant conflicts of interest.

Most of us are familiar with the relationship between diuretics and increased uric acid levels potentially precipitating attacks of gout. Perhaps fewer recall that beta blockers also increase uric acid levels. In contrast, calcium channel blockers (CCBs) and losartan have been observed to decrease serum uric acid levels. This begs the question: Do CCBs and losartan reduce the incidence of gout attacks? Unfortunately, no randomized trials have been conducted to evaluate this.

However, a very large case-control study was published recently (BMJ. 2012;344:d8190) exploring the benefit of these drug classes for preventing gout attacks. Using an impressive computerized medical record database including 4 million patients entered by U.K. general practitioners, investigators conducted a case-control study of adults, aged 20 to 89 years, to determine the relationship between antihypertensives and gout. Incident cases of gout (n = 24,768) were ascertained in individuals having a gout attack after an initial diagnosis and were matched with 50,000 controls. The antihypertensives evaluated included diuretics, beta blockers, CCBs, ACE-inhibitors, losartan, and non-losartan angiotensin receptor blockers (ARBs). Results were adjusted for covariates. Hypertension itself was associated with a higher relative risk for incident gout (RR 1.75; 95% CI: 1.69-1.82). CCBs were associated with a lower risk of incident gout (RR 0.87; 95% CI: 0.82-0.93). Increasing duration and dose of medication further reduced the risk. Losartan also was associated with a reduced risk of developing gout (RR 0.81; 95% CI: 0.70 to 0.94). In contrast, current use of diuretics, beta blockers, ACE-inhibitors, and non-losartan ARBs among those with hypertension were all associated with an increased risk of incident gout. Findings were similar among patients without hypertension and among those on anti-gout medications.

Since the majority of patients with gout have hypertension, most of these patients will eventually be taking an antihypertensive. Data from this study would suggest that the selection of antihypertensive is an important consideration for avoiding future gout attacks. Similarly to how we might select an ACE-I/ARB for the treatment of hypertension in patients with diabetes for renoprotection, we should consider selecting losartan and CCB’s in patients with gout to prevent future attacks.

Dr. Ebbert reported having no relevant conflicts of interest.

Most of us are familiar with the relationship between diuretics and increased uric acid levels potentially precipitating attacks of gout. Perhaps fewer recall that beta blockers also increase uric acid levels. In contrast, calcium channel blockers (CCBs) and losartan have been observed to decrease serum uric acid levels. This begs the question: Do CCBs and losartan reduce the incidence of gout attacks? Unfortunately, no randomized trials have been conducted to evaluate this.

However, a very large case-control study was published recently (BMJ. 2012;344:d8190) exploring the benefit of these drug classes for preventing gout attacks. Using an impressive computerized medical record database including 4 million patients entered by U.K. general practitioners, investigators conducted a case-control study of adults, aged 20 to 89 years, to determine the relationship between antihypertensives and gout. Incident cases of gout (n = 24,768) were ascertained in individuals having a gout attack after an initial diagnosis and were matched with 50,000 controls. The antihypertensives evaluated included diuretics, beta blockers, CCBs, ACE-inhibitors, losartan, and non-losartan angiotensin receptor blockers (ARBs). Results were adjusted for covariates. Hypertension itself was associated with a higher relative risk for incident gout (RR 1.75; 95% CI: 1.69-1.82). CCBs were associated with a lower risk of incident gout (RR 0.87; 95% CI: 0.82-0.93). Increasing duration and dose of medication further reduced the risk. Losartan also was associated with a reduced risk of developing gout (RR 0.81; 95% CI: 0.70 to 0.94). In contrast, current use of diuretics, beta blockers, ACE-inhibitors, and non-losartan ARBs among those with hypertension were all associated with an increased risk of incident gout. Findings were similar among patients without hypertension and among those on anti-gout medications.

Since the majority of patients with gout have hypertension, most of these patients will eventually be taking an antihypertensive. Data from this study would suggest that the selection of antihypertensive is an important consideration for avoiding future gout attacks. Similarly to how we might select an ACE-I/ARB for the treatment of hypertension in patients with diabetes for renoprotection, we should consider selecting losartan and CCB’s in patients with gout to prevent future attacks.

Dr. Ebbert reported having no relevant conflicts of interest.

There’s little controversy surrounding the use of aspirin for the prevention of cardiovascular events in patients with established disease. By contrast, there’s far more smoke than light regarding the issue of aspirin for primary prevention. We all commonly face the proverbial “handle-on-the-doorknob” question, “Should I be taking aspirin?” from patients without established cardiovascular disease. Such interactions tax us to recall our most recently-attended CME meeting to try and remember what the general mood of clinicians was on this issue.

A recent large meta-analysis (Arch Intern Med.2012;Jan 9 [doi:10.1001/archinternmed.2011.626]) will inform these conversations in the year ahead. In this study, investigators conducted a meta-analysis of studies that had at least one year of follow-up and at least 1,000 participants. Nine trials involving a total of more than 100,000 patients were included. Aspirin was associated with a reduction in cardiovascular (CVD) events attributable primarily to the nonfatal MI. No effect of aspirin was observed on fatal MI, stroke, CVD death or cancer mortality. A 70% increase in bleeding events was observed with a 30% increase in the risk of clinically significant bleeding events, defined as fatal bleeding from any site, cerebrovascular or retinal bleeding, bleeding from hollow viscus, bleeding requiring hospitalization and/or transfusion, or study-defined major bleeding regardless of source. The number needed to treat for nonfatal MI was 162 compared to the number needed to harm for nontrivial bleed of 73.

The data suggest that for every two patients to whom we recommend aspirin to prevent a nonfatal MI we will have two clinically significant bleeding events. Perhaps the authors are correct in suggesting that aspirin may add little extra value to CVD risk reduction efforts that aggressively target lipid levels, blood pressure, and tobacco use behaviors. But we can’t ignore the aspirin question because patients want to know what to do and, commonly, the justification for it. In patients at low risk for CVD events, aspirin prophylaxis may make them bleed. But let us not throw the baby out with the bathwater because among higher risk patients, the data are strong that aspirin may prevent a heart attack and some patients may place high value on this prevention. For those in the middle, perhaps creative aspirin dosing, such as every-other-day, could be explored. 

There’s little controversy surrounding the use of aspirin for the prevention of cardiovascular events in patients with established disease. By contrast, there’s far more smoke than light regarding the issue of aspirin for primary prevention. We all commonly face the proverbial “handle-on-the-doorknob” question, “Should I be taking aspirin?” from patients without established cardiovascular disease. Such interactions tax us to recall our most recently-attended CME meeting to try and remember what the general mood of clinicians was on this issue.

A recent large meta-analysis (Arch Intern Med.2012;Jan 9 [doi:10.1001/archinternmed.2011.626]) will inform these conversations in the year ahead. In this study, investigators conducted a meta-analysis of studies that had at least one year of follow-up and at least 1,000 participants. Nine trials involving a total of more than 100,000 patients were included. Aspirin was associated with a reduction in cardiovascular (CVD) events attributable primarily to the nonfatal MI. No effect of aspirin was observed on fatal MI, stroke, CVD death or cancer mortality. A 70% increase in bleeding events was observed with a 30% increase in the risk of clinically significant bleeding events, defined as fatal bleeding from any site, cerebrovascular or retinal bleeding, bleeding from hollow viscus, bleeding requiring hospitalization and/or transfusion, or study-defined major bleeding regardless of source. The number needed to treat for nonfatal MI was 162 compared to the number needed to harm for nontrivial bleed of 73.

The data suggest that for every two patients to whom we recommend aspirin to prevent a nonfatal MI we will have two clinically significant bleeding events. Perhaps the authors are correct in suggesting that aspirin may add little extra value to CVD risk reduction efforts that aggressively target lipid levels, blood pressure, and tobacco use behaviors. But we can’t ignore the aspirin question because patients want to know what to do and, commonly, the justification for it. In patients at low risk for CVD events, aspirin prophylaxis may make them bleed. But let us not throw the baby out with the bathwater because among higher risk patients, the data are strong that aspirin may prevent a heart attack and some patients may place high value on this prevention. For those in the middle, perhaps creative aspirin dosing, such as every-other-day, could be explored. 

There’s little controversy surrounding the use of aspirin for the prevention of cardiovascular events in patients with established disease. By contrast, there’s far more smoke than light regarding the issue of aspirin for primary prevention. We all commonly face the proverbial “handle-on-the-doorknob” question, “Should I be taking aspirin?” from patients without established cardiovascular disease. Such interactions tax us to recall our most recently-attended CME meeting to try and remember what the general mood of clinicians was on this issue.

A recent large meta-analysis (Arch Intern Med.2012;Jan 9 [doi:10.1001/archinternmed.2011.626]) will inform these conversations in the year ahead. In this study, investigators conducted a meta-analysis of studies that had at least one year of follow-up and at least 1,000 participants. Nine trials involving a total of more than 100,000 patients were included. Aspirin was associated with a reduction in cardiovascular (CVD) events attributable primarily to the nonfatal MI. No effect of aspirin was observed on fatal MI, stroke, CVD death or cancer mortality. A 70% increase in bleeding events was observed with a 30% increase in the risk of clinically significant bleeding events, defined as fatal bleeding from any site, cerebrovascular or retinal bleeding, bleeding from hollow viscus, bleeding requiring hospitalization and/or transfusion, or study-defined major bleeding regardless of source. The number needed to treat for nonfatal MI was 162 compared to the number needed to harm for nontrivial bleed of 73.

The data suggest that for every two patients to whom we recommend aspirin to prevent a nonfatal MI we will have two clinically significant bleeding events. Perhaps the authors are correct in suggesting that aspirin may add little extra value to CVD risk reduction efforts that aggressively target lipid levels, blood pressure, and tobacco use behaviors. But we can’t ignore the aspirin question because patients want to know what to do and, commonly, the justification for it. In patients at low risk for CVD events, aspirin prophylaxis may make them bleed. But let us not throw the baby out with the bathwater because among higher risk patients, the data are strong that aspirin may prevent a heart attack and some patients may place high value on this prevention. For those in the middle, perhaps creative aspirin dosing, such as every-other-day, could be explored. 

Vitamin supplementation for health benefits is widespread among patients in our clinical practices. Data emerging from randomized trials have indicated that vitamin supplementation may not be beneficial in some cases (e.g., vitamin E for stroke), and harmful in others (e.g. beta-carotene and vitamin A for lung cancer prevention in smokers). Vitamin D is the most recent darling of vitamin fever, and the evidence has reliably been pointing to a positive effect on health. The salutary effects of vitamin D on cardiovascular disease are likely related to its ability to decrease inflammation. But should all patients be taking vitamin D?

Evidence published recently in the American Journal of Cardiology (Am J Cardiol. 2011 Oct 12. Epub ahead of print) suggests that vitamin D may not turn out to be a panacea for everybody. In this study, investigators evaluated data from the National Health and Nutrition Examination Survey (NHANES), an ongoing sample assessing the nutritional status of U.S.-based adults. The NHANES collects surveys and serum samples, and the current study evaluated the relationship between vitamin D [25-hydroxyvitamin D = 25(OH)D] and C-reactive protein (an inflammatory marker) blood concentrations from 15,167 individuals. The median serum concentration of vitamin D was 21 ng/mL. Below this median serum level, an inverse relationship was observed between vitamin D and CRP levels. Above the median serum vitamin D level, a direct relationship was observed between vitamin D and CRP levels. The authors concluded that vitamin D levels above the population median might be pro-inflammatory.

More research needs to be conducted to quantify the risks incurred by supplementing vitamin D in patients with normal concentrations of vitamin D. At the very least, this study may warrant having discussions with our patients about taking what we would consider high doses of vitamin D. Obtaining serum concentrations of vitamin D is a common clinical practice and might be a good place to start these discussions. Among patients who, for example, have osteoporosis and cardiovascular disease, we may need to make tradeoffs between the risks and benefits of vitamin D supplementation. For now, we should balance these risks by encouraging our patients implement “everything in moderation.” 

Vitamin supplementation for health benefits is widespread among patients in our clinical practices. Data emerging from randomized trials have indicated that vitamin supplementation may not be beneficial in some cases (e.g., vitamin E for stroke), and harmful in others (e.g. beta-carotene and vitamin A for lung cancer prevention in smokers). Vitamin D is the most recent darling of vitamin fever, and the evidence has reliably been pointing to a positive effect on health. The salutary effects of vitamin D on cardiovascular disease are likely related to its ability to decrease inflammation. But should all patients be taking vitamin D?

Evidence published recently in the American Journal of Cardiology (Am J Cardiol. 2011 Oct 12. Epub ahead of print) suggests that vitamin D may not turn out to be a panacea for everybody. In this study, investigators evaluated data from the National Health and Nutrition Examination Survey (NHANES), an ongoing sample assessing the nutritional status of U.S.-based adults. The NHANES collects surveys and serum samples, and the current study evaluated the relationship between vitamin D [25-hydroxyvitamin D = 25(OH)D] and C-reactive protein (an inflammatory marker) blood concentrations from 15,167 individuals. The median serum concentration of vitamin D was 21 ng/mL. Below this median serum level, an inverse relationship was observed between vitamin D and CRP levels. Above the median serum vitamin D level, a direct relationship was observed between vitamin D and CRP levels. The authors concluded that vitamin D levels above the population median might be pro-inflammatory.

More research needs to be conducted to quantify the risks incurred by supplementing vitamin D in patients with normal concentrations of vitamin D. At the very least, this study may warrant having discussions with our patients about taking what we would consider high doses of vitamin D. Obtaining serum concentrations of vitamin D is a common clinical practice and might be a good place to start these discussions. Among patients who, for example, have osteoporosis and cardiovascular disease, we may need to make tradeoffs between the risks and benefits of vitamin D supplementation. For now, we should balance these risks by encouraging our patients implement “everything in moderation.” 

Vitamin supplementation for health benefits is widespread among patients in our clinical practices. Data emerging from randomized trials have indicated that vitamin supplementation may not be beneficial in some cases (e.g., vitamin E for stroke), and harmful in others (e.g. beta-carotene and vitamin A for lung cancer prevention in smokers). Vitamin D is the most recent darling of vitamin fever, and the evidence has reliably been pointing to a positive effect on health. The salutary effects of vitamin D on cardiovascular disease are likely related to its ability to decrease inflammation. But should all patients be taking vitamin D?

Evidence published recently in the American Journal of Cardiology (Am J Cardiol. 2011 Oct 12. Epub ahead of print) suggests that vitamin D may not turn out to be a panacea for everybody. In this study, investigators evaluated data from the National Health and Nutrition Examination Survey (NHANES), an ongoing sample assessing the nutritional status of U.S.-based adults. The NHANES collects surveys and serum samples, and the current study evaluated the relationship between vitamin D [25-hydroxyvitamin D = 25(OH)D] and C-reactive protein (an inflammatory marker) blood concentrations from 15,167 individuals. The median serum concentration of vitamin D was 21 ng/mL. Below this median serum level, an inverse relationship was observed between vitamin D and CRP levels. Above the median serum vitamin D level, a direct relationship was observed between vitamin D and CRP levels. The authors concluded that vitamin D levels above the population median might be pro-inflammatory.

More research needs to be conducted to quantify the risks incurred by supplementing vitamin D in patients with normal concentrations of vitamin D. At the very least, this study may warrant having discussions with our patients about taking what we would consider high doses of vitamin D. Obtaining serum concentrations of vitamin D is a common clinical practice and might be a good place to start these discussions. Among patients who, for example, have osteoporosis and cardiovascular disease, we may need to make tradeoffs between the risks and benefits of vitamin D supplementation. For now, we should balance these risks by encouraging our patients implement “everything in moderation.” 

Editor’s Note

Welcome to “What Matters,” a blog about the clinical research that is most likely to affect your practice, patient outcomes, and your bottom line. We know you have too much to read; there are simply too many studies and often too much buzz generated about them to really make sense of it all in a practical, systematic way. Dr. Jon O. Ebbert, professor of medicine at the Mayo Clinic in Rochester, Minn., offers an authoritative view on recent key clinical developments and what they may mean for you. Follow him every week to stay informed and on top of your world.

Elevated LDL cholesterol is an independent risk factor for cardiovascular disease (CVD) and the evidence supporting treatment to lower LDL is clear. Low HDL also is an independent risk factor for CVD. However, guidance is mixed and practice heterogeneous on how clinicians should address low HDL when LDL goals are achieved with statin therapy.

The AIM-HIGH trial recently published evidence on the effect of extended-release niacin among patients with established CVD with low baseline HDL (less than 40 mg/dL) (N. Engl. J. Med. 2011;365:2255-67). Subjects in the experimental group received niacin 1,500-2,000 mg per day plus simvastatin while subjects in the placebo group received a matching subtherapeutic control (50 mg immediate-release niacin) in addition to simvastatin to maintain blinding. Doses of simvastatin were adjusted to achieve a target LDL of 40-80 mg/dL. Subjects could receive ezetimibe to achieve target LDL cholesterol as needed. A very large sample size of 3,414 subjects was randomized. At 2 years, the mean HDL level had increased by 25% to 42 mg/dL in the niacin group and by about 10% to 38 mg/dL in the placebo group. Triglycerides also improved more in the niacin group. Study drug was discontinued in 25% of patients in the niacin group and 20% in the placebo group. No differences were observed in the first event of the composite of death from CVD, nonfatal myocardial infarction, ischemic stroke, hospitalization for acute coronary syndrome, or symptom-driven coronary or cerebral revascularization.

Many clinicians treat HDL as a “secondary target” for reduction of CVD events when LDL goals have already been achieved. Data from this study would suggest that exposing patients to additional risk and cost in an attempt to raise HDL in this setting is not warranted. In light of present data, we are once again reminded to “treat the patient, not a number.”

Editor’s Note

Welcome to “What Matters,” a blog about the clinical research that is most likely to affect your practice, patient outcomes, and your bottom line. We know you have too much to read; there are simply too many studies and often too much buzz generated about them to really make sense of it all in a practical, systematic way. Dr. Jon O. Ebbert, professor of medicine at the Mayo Clinic in Rochester, Minn., offers an authoritative view on recent key clinical developments and what they may mean for you. Follow him every week to stay informed and on top of your world.

Elevated LDL cholesterol is an independent risk factor for cardiovascular disease (CVD) and the evidence supporting treatment to lower LDL is clear. Low HDL also is an independent risk factor for CVD. However, guidance is mixed and practice heterogeneous on how clinicians should address low HDL when LDL goals are achieved with statin therapy.

The AIM-HIGH trial recently published evidence on the effect of extended-release niacin among patients with established CVD with low baseline HDL (less than 40 mg/dL) (N. Engl. J. Med. 2011;365:2255-67). Subjects in the experimental group received niacin 1,500-2,000 mg per day plus simvastatin while subjects in the placebo group received a matching subtherapeutic control (50 mg immediate-release niacin) in addition to simvastatin to maintain blinding. Doses of simvastatin were adjusted to achieve a target LDL of 40-80 mg/dL. Subjects could receive ezetimibe to achieve target LDL cholesterol as needed. A very large sample size of 3,414 subjects was randomized. At 2 years, the mean HDL level had increased by 25% to 42 mg/dL in the niacin group and by about 10% to 38 mg/dL in the placebo group. Triglycerides also improved more in the niacin group. Study drug was discontinued in 25% of patients in the niacin group and 20% in the placebo group. No differences were observed in the first event of the composite of death from CVD, nonfatal myocardial infarction, ischemic stroke, hospitalization for acute coronary syndrome, or symptom-driven coronary or cerebral revascularization.

Many clinicians treat HDL as a “secondary target” for reduction of CVD events when LDL goals have already been achieved. Data from this study would suggest that exposing patients to additional risk and cost in an attempt to raise HDL in this setting is not warranted. In light of present data, we are once again reminded to “treat the patient, not a number.”

Editor’s Note

Welcome to “What Matters,” a blog about the clinical research that is most likely to affect your practice, patient outcomes, and your bottom line. We know you have too much to read; there are simply too many studies and often too much buzz generated about them to really make sense of it all in a practical, systematic way. Dr. Jon O. Ebbert, professor of medicine at the Mayo Clinic in Rochester, Minn., offers an authoritative view on recent key clinical developments and what they may mean for you. Follow him every week to stay informed and on top of your world.

Elevated LDL cholesterol is an independent risk factor for cardiovascular disease (CVD) and the evidence supporting treatment to lower LDL is clear. Low HDL also is an independent risk factor for CVD. However, guidance is mixed and practice heterogeneous on how clinicians should address low HDL when LDL goals are achieved with statin therapy.

The AIM-HIGH trial recently published evidence on the effect of extended-release niacin among patients with established CVD with low baseline HDL (less than 40 mg/dL) (N. Engl. J. Med. 2011;365:2255-67). Subjects in the experimental group received niacin 1,500-2,000 mg per day plus simvastatin while subjects in the placebo group received a matching subtherapeutic control (50 mg immediate-release niacin) in addition to simvastatin to maintain blinding. Doses of simvastatin were adjusted to achieve a target LDL of 40-80 mg/dL. Subjects could receive ezetimibe to achieve target LDL cholesterol as needed. A very large sample size of 3,414 subjects was randomized. At 2 years, the mean HDL level had increased by 25% to 42 mg/dL in the niacin group and by about 10% to 38 mg/dL in the placebo group. Triglycerides also improved more in the niacin group. Study drug was discontinued in 25% of patients in the niacin group and 20% in the placebo group. No differences were observed in the first event of the composite of death from CVD, nonfatal myocardial infarction, ischemic stroke, hospitalization for acute coronary syndrome, or symptom-driven coronary or cerebral revascularization.

Many clinicians treat HDL as a “secondary target” for reduction of CVD events when LDL goals have already been achieved. Data from this study would suggest that exposing patients to additional risk and cost in an attempt to raise HDL in this setting is not warranted. In light of present data, we are once again reminded to “treat the patient, not a number.”