Nortriptyline effective for smoking cessation

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BACKGROUND: Despite public health campaigns and recommendations from national organizations for clinicians to encourage smoking cessation, only 2.5% of all smokers succeed in abstaining for 1 year. Currently, bupropion (Zyban) is an antidepressant approved by the FDA as an aid in smoking cessation. This study evaluated the safety and efficacy of another antidepressant, nortriptyline (Pamelor), in smokers enrolled in a smoking support group.

POPULATION STUDIED: Patients were participating in a hospital-based smoking support group in Brazil. They were in good general health, aged 18 to 65 years, and smoked more than 15 cigarettes per day. Degree of nicotine dependence was determined by the Fagerstrom questionnaire. Patients were excluded if they were depressed as determined by the Beck Depression Inventory or had a history of other psychiatric syndromes, cardiovascular disease, glaucoma, urinary retention, thyroid disease, or epilepsy, or were pregnant or breast-feeding. Patients could not be receiving nicotine replacement therapy or have taken antidepressants, benzodiazepines, or antipsychotic agents during the past month. Of 144 patients who completed the study, most were women.

STUDY DESIGN AND VALIDITY: Patients were randomly assigned to receive either placebo or nortriptyline, increased at weekly intervals from 25 to 75 mg daily. Patients and clinicians were blinded to assigned treatment. During the 6-week treatment, all patients participated in weekly group therapy supervised by the same psychiatrist. Group therapy was based on cognitive-behavioral therapy. Follow-up abstinence rates were evaluated 6 months after the treatment period.

OUTCOMES MEASURED: Success was defined as cessation of smoking 1 week after the end of the treatment period. The rate of abstinence was also determined 6 months after the end of the study.

RESULTS: Patients receiving nortriptyline were less likely to report smoking in the week after the treatment period (55.9% vs 23.7% in the placebo group, P < .001, numbers needed to treat [NNT]=3). After 6 months of follow-up, 20.6% of patients receiving nortriptyline and 5.3% of patients receiving placebo reported to be free from nicotine use (P < .012, NNT=7). Patients most likely to respond had low nicotine dependence (Fagerstrom score less than 7 out of a possible 10) and were younger than 50 years.

 

RECOMMENDATIONS FOR CLINICAL PRACTICE

Nortriptyline (Pamelor), in combination with weekly behavioral therapy, is effective in helping highly motivated smokers to quit. The medication may be an alternative for patients who cannot tolerate or do not benefit from bupropion. Given the high motivation of the group and the extensive behavioral therapy they also received, results are not likely to be as good in typical practice.

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Peter J. Carek, MD, MS
Department of Family Medicine Medical University of South Carolina, Charleston

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Peter J. Carek, MD, MS
Department of Family Medicine Medical University of South Carolina, Charleston

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Lori M. Dickerson, PharmD, BCPS
Peter J. Carek, MD, MS
Department of Family Medicine Medical University of South Carolina, Charleston

ABSTRACT

BACKGROUND: Despite public health campaigns and recommendations from national organizations for clinicians to encourage smoking cessation, only 2.5% of all smokers succeed in abstaining for 1 year. Currently, bupropion (Zyban) is an antidepressant approved by the FDA as an aid in smoking cessation. This study evaluated the safety and efficacy of another antidepressant, nortriptyline (Pamelor), in smokers enrolled in a smoking support group.

POPULATION STUDIED: Patients were participating in a hospital-based smoking support group in Brazil. They were in good general health, aged 18 to 65 years, and smoked more than 15 cigarettes per day. Degree of nicotine dependence was determined by the Fagerstrom questionnaire. Patients were excluded if they were depressed as determined by the Beck Depression Inventory or had a history of other psychiatric syndromes, cardiovascular disease, glaucoma, urinary retention, thyroid disease, or epilepsy, or were pregnant or breast-feeding. Patients could not be receiving nicotine replacement therapy or have taken antidepressants, benzodiazepines, or antipsychotic agents during the past month. Of 144 patients who completed the study, most were women.

STUDY DESIGN AND VALIDITY: Patients were randomly assigned to receive either placebo or nortriptyline, increased at weekly intervals from 25 to 75 mg daily. Patients and clinicians were blinded to assigned treatment. During the 6-week treatment, all patients participated in weekly group therapy supervised by the same psychiatrist. Group therapy was based on cognitive-behavioral therapy. Follow-up abstinence rates were evaluated 6 months after the treatment period.

OUTCOMES MEASURED: Success was defined as cessation of smoking 1 week after the end of the treatment period. The rate of abstinence was also determined 6 months after the end of the study.

RESULTS: Patients receiving nortriptyline were less likely to report smoking in the week after the treatment period (55.9% vs 23.7% in the placebo group, P < .001, numbers needed to treat [NNT]=3). After 6 months of follow-up, 20.6% of patients receiving nortriptyline and 5.3% of patients receiving placebo reported to be free from nicotine use (P < .012, NNT=7). Patients most likely to respond had low nicotine dependence (Fagerstrom score less than 7 out of a possible 10) and were younger than 50 years.

 

RECOMMENDATIONS FOR CLINICAL PRACTICE

Nortriptyline (Pamelor), in combination with weekly behavioral therapy, is effective in helping highly motivated smokers to quit. The medication may be an alternative for patients who cannot tolerate or do not benefit from bupropion. Given the high motivation of the group and the extensive behavioral therapy they also received, results are not likely to be as good in typical practice.

ABSTRACT

BACKGROUND: Despite public health campaigns and recommendations from national organizations for clinicians to encourage smoking cessation, only 2.5% of all smokers succeed in abstaining for 1 year. Currently, bupropion (Zyban) is an antidepressant approved by the FDA as an aid in smoking cessation. This study evaluated the safety and efficacy of another antidepressant, nortriptyline (Pamelor), in smokers enrolled in a smoking support group.

POPULATION STUDIED: Patients were participating in a hospital-based smoking support group in Brazil. They were in good general health, aged 18 to 65 years, and smoked more than 15 cigarettes per day. Degree of nicotine dependence was determined by the Fagerstrom questionnaire. Patients were excluded if they were depressed as determined by the Beck Depression Inventory or had a history of other psychiatric syndromes, cardiovascular disease, glaucoma, urinary retention, thyroid disease, or epilepsy, or were pregnant or breast-feeding. Patients could not be receiving nicotine replacement therapy or have taken antidepressants, benzodiazepines, or antipsychotic agents during the past month. Of 144 patients who completed the study, most were women.

STUDY DESIGN AND VALIDITY: Patients were randomly assigned to receive either placebo or nortriptyline, increased at weekly intervals from 25 to 75 mg daily. Patients and clinicians were blinded to assigned treatment. During the 6-week treatment, all patients participated in weekly group therapy supervised by the same psychiatrist. Group therapy was based on cognitive-behavioral therapy. Follow-up abstinence rates were evaluated 6 months after the treatment period.

OUTCOMES MEASURED: Success was defined as cessation of smoking 1 week after the end of the treatment period. The rate of abstinence was also determined 6 months after the end of the study.

RESULTS: Patients receiving nortriptyline were less likely to report smoking in the week after the treatment period (55.9% vs 23.7% in the placebo group, P < .001, numbers needed to treat [NNT]=3). After 6 months of follow-up, 20.6% of patients receiving nortriptyline and 5.3% of patients receiving placebo reported to be free from nicotine use (P < .012, NNT=7). Patients most likely to respond had low nicotine dependence (Fagerstrom score less than 7 out of a possible 10) and were younger than 50 years.

 

RECOMMENDATIONS FOR CLINICAL PRACTICE

Nortriptyline (Pamelor), in combination with weekly behavioral therapy, is effective in helping highly motivated smokers to quit. The medication may be an alternative for patients who cannot tolerate or do not benefit from bupropion. Given the high motivation of the group and the extensive behavioral therapy they also received, results are not likely to be as good in typical practice.

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Are new antihypertensive agents better than old antihypertensive agents in preventing cardiovascular complications?

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Are new antihypertensive agents better than old antihypertensive agents in preventing cardiovascular complications?

ABSTRACT

BACKGROUND: It has not been established whether antihypertensive agents provide a benefit beyond their blood pressure lowering effects. The investigators conducted a meta-analysis to determine whether old or new antihypertensive agents are more effective in preventing cardiovascular complications.

POPULATION STUDIED: The investigators included 9 studies enrolling 62,605 middle-aged patients (53-76 years) with a mean blood pressure at entry ranging from 145 to 194 mm Hg systolic and 83 to 106 mm Hg diastolic. The proportion of women ranged from 22% to 67%, and the proportion of patients with cardiovascular complications and diabetes varied (4% to 45% and 4% to 100%, respectively).

STUDY DESIGN AND VALIDITY: The meta-analysis compared older antihypertensive agents (β-blockers and diuretics) with new antihypertensive agents (angiotensin-converting enzyme [ACE] inhibitors, calcium channel blockers, and (β-blockers) for the prevention of cardiovascular complications. All studies were randomized controlled trials, published in peer-reviewed journals, included an assessment of blood pressure and cardiovascular events, were at least 2 years in duration, and enrolled at least 100 patients.

OUTCOMES MEASURED: The researchers determined cardiovascular mortality, cardiovascular events, fatal and nonfatal stroke, fatal and nonfatal myocardial infarction (MI), fatal and nonfatal congestive heart failure (CHF) rates with old versus new antihypertensive agents.

RESULTS: The new antihypertensive agents were as effective as the old antihypertensive agents in the prevention of cardiovascular mortality, fatal and nonfatal stroke, and fatal and nonfatal MI. Calcium channel blockers provided more reduction in the risk of stroke than the older antihypertensive agents (absolute risk reduction [ARR]=13.5%, P <.03; number needed to treat [NNT]=7) but were associated with an increase in risk of fatal and nonfatal MI (absolute risk increase [ARI]=19.2%, P <.01; number needed to harm [NNH]=5). Older antihypertensive agents were more effective in preventing cardiovascular events (ARR=11.2%, P <.001; NNT=9). Newer antihypertensive agents were less effective in preventing fatal and nonfatal CHF (ARI=52.4%, P <.001; NNH=2), but this result was attributed to the higher risk of events with the (β-blocker doxazosin compared with the diuretic, chlorthalidone, in the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial.

RECOMMENDATIONS FOR CLINICAL PRACTICE

This study confirms that blood pressure control reduces the risk of cardiovascular complications in patients with hypertension. As a group, newer antihypertensive agents are as effective as the older antihypertensive agents in the prevention of cardiovascular mortality, fatal and nonfatal stroke, and fatal and nonfatal MI. However, the (β-blockers and diuretics are more effective in preventing cardiovascular events than ACE inhibitors and calcium channel blockers. Considering that (β-blockers and diuretics are much less expensive than the newer antihypertensive agents, they should remain first line in the treatment of hypertension.

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Peter J. Carek, MD, MS
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Peter J. Carek, MD, MS
Department of Family Medicine Charleston, South Carolina

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ABSTRACT

BACKGROUND: It has not been established whether antihypertensive agents provide a benefit beyond their blood pressure lowering effects. The investigators conducted a meta-analysis to determine whether old or new antihypertensive agents are more effective in preventing cardiovascular complications.

POPULATION STUDIED: The investigators included 9 studies enrolling 62,605 middle-aged patients (53-76 years) with a mean blood pressure at entry ranging from 145 to 194 mm Hg systolic and 83 to 106 mm Hg diastolic. The proportion of women ranged from 22% to 67%, and the proportion of patients with cardiovascular complications and diabetes varied (4% to 45% and 4% to 100%, respectively).

STUDY DESIGN AND VALIDITY: The meta-analysis compared older antihypertensive agents (β-blockers and diuretics) with new antihypertensive agents (angiotensin-converting enzyme [ACE] inhibitors, calcium channel blockers, and (β-blockers) for the prevention of cardiovascular complications. All studies were randomized controlled trials, published in peer-reviewed journals, included an assessment of blood pressure and cardiovascular events, were at least 2 years in duration, and enrolled at least 100 patients.

OUTCOMES MEASURED: The researchers determined cardiovascular mortality, cardiovascular events, fatal and nonfatal stroke, fatal and nonfatal myocardial infarction (MI), fatal and nonfatal congestive heart failure (CHF) rates with old versus new antihypertensive agents.

RESULTS: The new antihypertensive agents were as effective as the old antihypertensive agents in the prevention of cardiovascular mortality, fatal and nonfatal stroke, and fatal and nonfatal MI. Calcium channel blockers provided more reduction in the risk of stroke than the older antihypertensive agents (absolute risk reduction [ARR]=13.5%, P <.03; number needed to treat [NNT]=7) but were associated with an increase in risk of fatal and nonfatal MI (absolute risk increase [ARI]=19.2%, P <.01; number needed to harm [NNH]=5). Older antihypertensive agents were more effective in preventing cardiovascular events (ARR=11.2%, P <.001; NNT=9). Newer antihypertensive agents were less effective in preventing fatal and nonfatal CHF (ARI=52.4%, P <.001; NNH=2), but this result was attributed to the higher risk of events with the (β-blocker doxazosin compared with the diuretic, chlorthalidone, in the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial.

RECOMMENDATIONS FOR CLINICAL PRACTICE

This study confirms that blood pressure control reduces the risk of cardiovascular complications in patients with hypertension. As a group, newer antihypertensive agents are as effective as the older antihypertensive agents in the prevention of cardiovascular mortality, fatal and nonfatal stroke, and fatal and nonfatal MI. However, the (β-blockers and diuretics are more effective in preventing cardiovascular events than ACE inhibitors and calcium channel blockers. Considering that (β-blockers and diuretics are much less expensive than the newer antihypertensive agents, they should remain first line in the treatment of hypertension.

ABSTRACT

BACKGROUND: It has not been established whether antihypertensive agents provide a benefit beyond their blood pressure lowering effects. The investigators conducted a meta-analysis to determine whether old or new antihypertensive agents are more effective in preventing cardiovascular complications.

POPULATION STUDIED: The investigators included 9 studies enrolling 62,605 middle-aged patients (53-76 years) with a mean blood pressure at entry ranging from 145 to 194 mm Hg systolic and 83 to 106 mm Hg diastolic. The proportion of women ranged from 22% to 67%, and the proportion of patients with cardiovascular complications and diabetes varied (4% to 45% and 4% to 100%, respectively).

STUDY DESIGN AND VALIDITY: The meta-analysis compared older antihypertensive agents (β-blockers and diuretics) with new antihypertensive agents (angiotensin-converting enzyme [ACE] inhibitors, calcium channel blockers, and (β-blockers) for the prevention of cardiovascular complications. All studies were randomized controlled trials, published in peer-reviewed journals, included an assessment of blood pressure and cardiovascular events, were at least 2 years in duration, and enrolled at least 100 patients.

OUTCOMES MEASURED: The researchers determined cardiovascular mortality, cardiovascular events, fatal and nonfatal stroke, fatal and nonfatal myocardial infarction (MI), fatal and nonfatal congestive heart failure (CHF) rates with old versus new antihypertensive agents.

RESULTS: The new antihypertensive agents were as effective as the old antihypertensive agents in the prevention of cardiovascular mortality, fatal and nonfatal stroke, and fatal and nonfatal MI. Calcium channel blockers provided more reduction in the risk of stroke than the older antihypertensive agents (absolute risk reduction [ARR]=13.5%, P <.03; number needed to treat [NNT]=7) but were associated with an increase in risk of fatal and nonfatal MI (absolute risk increase [ARI]=19.2%, P <.01; number needed to harm [NNH]=5). Older antihypertensive agents were more effective in preventing cardiovascular events (ARR=11.2%, P <.001; NNT=9). Newer antihypertensive agents were less effective in preventing fatal and nonfatal CHF (ARI=52.4%, P <.001; NNH=2), but this result was attributed to the higher risk of events with the (β-blocker doxazosin compared with the diuretic, chlorthalidone, in the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial.

RECOMMENDATIONS FOR CLINICAL PRACTICE

This study confirms that blood pressure control reduces the risk of cardiovascular complications in patients with hypertension. As a group, newer antihypertensive agents are as effective as the older antihypertensive agents in the prevention of cardiovascular mortality, fatal and nonfatal stroke, and fatal and nonfatal MI. However, the (β-blockers and diuretics are more effective in preventing cardiovascular events than ACE inhibitors and calcium channel blockers. Considering that (β-blockers and diuretics are much less expensive than the newer antihypertensive agents, they should remain first line in the treatment of hypertension.

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Are new antihypertensive agents better than old antihypertensive agents in preventing cardiovascular complications?
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Are all b-blockers equally effective in reducing mortality after acute myocardial infarction (AMI)?

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Are all b-blockers equally effective in reducing mortality after acute myocardial infarction (AMI)?

BACKGROUND: The impact of b-blockers on survival after AMI has been well demonstrated in multiple randomized controlled trials. However, differences among specific b-blockers have not been evaluated. Because b-blockers differ in b-receptor selectivity and lipophilicity, researchers and clinicians have postulated variations in efficacy due to these properties. Also, clinicians are often hesitant to use b-blockers in certain patient populations with comorbid conditions, despite the known benefit after AMI. This study was designed to compare the effectiveness of 3 b-blockers (atenolol, metoprolol, and propranolol) on survival after AMI. Atenolol and metoprolol are cardioselective b-blockers; metoprolol and propranolol are lipophilic agents.

POPULATION STUDIED: Data were obtained from the Cooperative Cardiovascular Project (CCP), a database of acute care hospital claims for Medicare patients with AMI from 1994 to 1995 (n=201,752). Of this group, 69,338 patients (34%) were prescribed b-blockers, and they comprise the population for this study. Patients were elderly (mean age = approximately 73 years), 45% men, primarily white, and had comorbidities, including illness (ie, diabetes mellitus and chronic obstructive pulmonary disease) for which b-blocker use is often considered a relative contraindication. The mean systolic blood pressure was 146 mm Hg; heart rate was 81 to 83 beats per minute; and ejection fraction was 46% to 48%.

STUDY DESIGN AND VALIDITY: This study was a retrospective chart review of hospital claims data submitted to Medicare. Survival data were based on Social Security records and were reported to be 99% accurate at 60 days. Outcomes of patients prescribed different b-blockers were compared on the basis of demographic and clinical variables. The investigators emphasized comparing the magnitude of difference between groups, given that the enormous size of the database could allow for statistical but inconsequential differences among b-blockers. Obvious limitations to this study are the lack of randomization and the use of data collected from medical records, although the authors stated that the data were very complete. Also, b-blockers prescribed in the hospital may have been changed after discharge, and these data were not collected.

OUTCOMES MEASURED: Outcomes included 1- and 2-year mortality adjusted for age, race, sex, length of hospital stay, severity of illness, type of AMI, cardiovascular interventions (ie, angioplasty, bypass surgery, thrombolytics), various comorbidities (ie, diabetes, congestive heart failure, chronic obstructive pulmonary disease, asthma), and medication use (ie, angiotensin-converting enzyme inhibitors, calcium channel blockers).

RESULTS: Sixty-five percent (n=44,865) of the CCP patients were given metoprolol; 25% (n=17,411) received atenolol; and 6% (n=4236) were given propranolol in the CCP. No other b-blocker was prescribed for more than 1% of the patients. Adjusted 1-year mortality was similar among the patient groups (8.3% for metoprolol, 8.2% for atenolol, 9.6% for propranolol, and 9.2% for other b-blockers). In comparison, adjusted 2-year mortality was similar for the cardioselective b-blockers, metoprolol and atenolol (13.52% vs 13.41%, respectively). Patients discharged while taking propranolol had a slightly increased mortality rate (15.91%), which may have been related to undetected differences in severity of illness at baseline in this group. Compared with metoprolol, patients discharged while taking propranolol had a 15% increased mortality rate at 1 year and an 18% increased mortality rate at 2 years. Overall, survival with all b-blockers was superior to the 23.2% 2-year mortality rate documented in patients not receiving therapy (number needed to treat = 10-14 over 2 years).

RECOMMENDATIONS FOR CLINICAL PRACTICE

Overall, b-blocker therapy in patients following a myocardial infarction produces a substantial decrease in mortality over the following 2 years (13%-15% vs 23%). There is little difference between atenolol and metoprolol in reducing mortality after AMI, despite their different pharmacologic characteristics. Propranolol may be slightly less effective, but all agents resulted in improved survival when compared with patients not receiving b-blockers. Atenolol and metoprolol are both once-daily b-blockers. As atenolol is now available generically, it is considerably less expensive than metoprolol (<$10/month vs $25-$45/month).

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Peter J. Carek, MD, MS
Medical University of South Carolina Charleston E-mail: macfarll@musc.edu

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Medical University of South Carolina Charleston E-mail: macfarll@musc.edu

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Lori M. Dickerson, PharmD, BCPS
Peter J. Carek, MD, MS
Medical University of South Carolina Charleston E-mail: macfarll@musc.edu

BACKGROUND: The impact of b-blockers on survival after AMI has been well demonstrated in multiple randomized controlled trials. However, differences among specific b-blockers have not been evaluated. Because b-blockers differ in b-receptor selectivity and lipophilicity, researchers and clinicians have postulated variations in efficacy due to these properties. Also, clinicians are often hesitant to use b-blockers in certain patient populations with comorbid conditions, despite the known benefit after AMI. This study was designed to compare the effectiveness of 3 b-blockers (atenolol, metoprolol, and propranolol) on survival after AMI. Atenolol and metoprolol are cardioselective b-blockers; metoprolol and propranolol are lipophilic agents.

POPULATION STUDIED: Data were obtained from the Cooperative Cardiovascular Project (CCP), a database of acute care hospital claims for Medicare patients with AMI from 1994 to 1995 (n=201,752). Of this group, 69,338 patients (34%) were prescribed b-blockers, and they comprise the population for this study. Patients were elderly (mean age = approximately 73 years), 45% men, primarily white, and had comorbidities, including illness (ie, diabetes mellitus and chronic obstructive pulmonary disease) for which b-blocker use is often considered a relative contraindication. The mean systolic blood pressure was 146 mm Hg; heart rate was 81 to 83 beats per minute; and ejection fraction was 46% to 48%.

STUDY DESIGN AND VALIDITY: This study was a retrospective chart review of hospital claims data submitted to Medicare. Survival data were based on Social Security records and were reported to be 99% accurate at 60 days. Outcomes of patients prescribed different b-blockers were compared on the basis of demographic and clinical variables. The investigators emphasized comparing the magnitude of difference between groups, given that the enormous size of the database could allow for statistical but inconsequential differences among b-blockers. Obvious limitations to this study are the lack of randomization and the use of data collected from medical records, although the authors stated that the data were very complete. Also, b-blockers prescribed in the hospital may have been changed after discharge, and these data were not collected.

OUTCOMES MEASURED: Outcomes included 1- and 2-year mortality adjusted for age, race, sex, length of hospital stay, severity of illness, type of AMI, cardiovascular interventions (ie, angioplasty, bypass surgery, thrombolytics), various comorbidities (ie, diabetes, congestive heart failure, chronic obstructive pulmonary disease, asthma), and medication use (ie, angiotensin-converting enzyme inhibitors, calcium channel blockers).

RESULTS: Sixty-five percent (n=44,865) of the CCP patients were given metoprolol; 25% (n=17,411) received atenolol; and 6% (n=4236) were given propranolol in the CCP. No other b-blocker was prescribed for more than 1% of the patients. Adjusted 1-year mortality was similar among the patient groups (8.3% for metoprolol, 8.2% for atenolol, 9.6% for propranolol, and 9.2% for other b-blockers). In comparison, adjusted 2-year mortality was similar for the cardioselective b-blockers, metoprolol and atenolol (13.52% vs 13.41%, respectively). Patients discharged while taking propranolol had a slightly increased mortality rate (15.91%), which may have been related to undetected differences in severity of illness at baseline in this group. Compared with metoprolol, patients discharged while taking propranolol had a 15% increased mortality rate at 1 year and an 18% increased mortality rate at 2 years. Overall, survival with all b-blockers was superior to the 23.2% 2-year mortality rate documented in patients not receiving therapy (number needed to treat = 10-14 over 2 years).

RECOMMENDATIONS FOR CLINICAL PRACTICE

Overall, b-blocker therapy in patients following a myocardial infarction produces a substantial decrease in mortality over the following 2 years (13%-15% vs 23%). There is little difference between atenolol and metoprolol in reducing mortality after AMI, despite their different pharmacologic characteristics. Propranolol may be slightly less effective, but all agents resulted in improved survival when compared with patients not receiving b-blockers. Atenolol and metoprolol are both once-daily b-blockers. As atenolol is now available generically, it is considerably less expensive than metoprolol (<$10/month vs $25-$45/month).

BACKGROUND: The impact of b-blockers on survival after AMI has been well demonstrated in multiple randomized controlled trials. However, differences among specific b-blockers have not been evaluated. Because b-blockers differ in b-receptor selectivity and lipophilicity, researchers and clinicians have postulated variations in efficacy due to these properties. Also, clinicians are often hesitant to use b-blockers in certain patient populations with comorbid conditions, despite the known benefit after AMI. This study was designed to compare the effectiveness of 3 b-blockers (atenolol, metoprolol, and propranolol) on survival after AMI. Atenolol and metoprolol are cardioselective b-blockers; metoprolol and propranolol are lipophilic agents.

POPULATION STUDIED: Data were obtained from the Cooperative Cardiovascular Project (CCP), a database of acute care hospital claims for Medicare patients with AMI from 1994 to 1995 (n=201,752). Of this group, 69,338 patients (34%) were prescribed b-blockers, and they comprise the population for this study. Patients were elderly (mean age = approximately 73 years), 45% men, primarily white, and had comorbidities, including illness (ie, diabetes mellitus and chronic obstructive pulmonary disease) for which b-blocker use is often considered a relative contraindication. The mean systolic blood pressure was 146 mm Hg; heart rate was 81 to 83 beats per minute; and ejection fraction was 46% to 48%.

STUDY DESIGN AND VALIDITY: This study was a retrospective chart review of hospital claims data submitted to Medicare. Survival data were based on Social Security records and were reported to be 99% accurate at 60 days. Outcomes of patients prescribed different b-blockers were compared on the basis of demographic and clinical variables. The investigators emphasized comparing the magnitude of difference between groups, given that the enormous size of the database could allow for statistical but inconsequential differences among b-blockers. Obvious limitations to this study are the lack of randomization and the use of data collected from medical records, although the authors stated that the data were very complete. Also, b-blockers prescribed in the hospital may have been changed after discharge, and these data were not collected.

OUTCOMES MEASURED: Outcomes included 1- and 2-year mortality adjusted for age, race, sex, length of hospital stay, severity of illness, type of AMI, cardiovascular interventions (ie, angioplasty, bypass surgery, thrombolytics), various comorbidities (ie, diabetes, congestive heart failure, chronic obstructive pulmonary disease, asthma), and medication use (ie, angiotensin-converting enzyme inhibitors, calcium channel blockers).

RESULTS: Sixty-five percent (n=44,865) of the CCP patients were given metoprolol; 25% (n=17,411) received atenolol; and 6% (n=4236) were given propranolol in the CCP. No other b-blocker was prescribed for more than 1% of the patients. Adjusted 1-year mortality was similar among the patient groups (8.3% for metoprolol, 8.2% for atenolol, 9.6% for propranolol, and 9.2% for other b-blockers). In comparison, adjusted 2-year mortality was similar for the cardioselective b-blockers, metoprolol and atenolol (13.52% vs 13.41%, respectively). Patients discharged while taking propranolol had a slightly increased mortality rate (15.91%), which may have been related to undetected differences in severity of illness at baseline in this group. Compared with metoprolol, patients discharged while taking propranolol had a 15% increased mortality rate at 1 year and an 18% increased mortality rate at 2 years. Overall, survival with all b-blockers was superior to the 23.2% 2-year mortality rate documented in patients not receiving therapy (number needed to treat = 10-14 over 2 years).

RECOMMENDATIONS FOR CLINICAL PRACTICE

Overall, b-blocker therapy in patients following a myocardial infarction produces a substantial decrease in mortality over the following 2 years (13%-15% vs 23%). There is little difference between atenolol and metoprolol in reducing mortality after AMI, despite their different pharmacologic characteristics. Propranolol may be slightly less effective, but all agents resulted in improved survival when compared with patients not receiving b-blockers. Atenolol and metoprolol are both once-daily b-blockers. As atenolol is now available generically, it is considerably less expensive than metoprolol (<$10/month vs $25-$45/month).

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Are there differences between vasodilating and nonvasodilating b-blockers in patients with heart failure? Do patients with ischemic heart disease benefit to the same degree?

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Are there differences between vasodilating and nonvasodilating b-blockers in patients with heart failure? Do patients with ischemic heart disease benefit to the same degree?

BACKGROUND: Previous meta-analyses have demonstrated that b-blockers reduce morbidity (symptoms, left ventricular function, and rate of hospitalization) and mortality (cardiovascular and total) in patients with congestive heart failure (CHF). The authors of this meta-analysis explored differences in effectiveness between vasodilating and nonvasodilating agents and defined differences in outcomes related to the underlying cause of CHF.

POPULATION STUDIED: A total of 5849 patients (79% men) were studied for a median duration of 6 months. Approximately 50% received b-blockers. Both vasodilating b-blockers (carvedilol and bucindolol) and nonvasodilating b-blockers (metoprolol, bisoprolol, and propranolol) were used for patients with primarily class II and III heart failure. Most patients also received angiotensin-converting enzyme inhibitors, diuretics, and digitalis.

STUDY DESIGN AND VALIDITY: The authors of this meta-analysis combined the results of 21 randomized controlled trials comparing the various b-blockers with placebo. All studies evaluated mortality on an intention-to-treat basis.

OUTCOMES MEASURED: The primary outcomes were total and cardiovascular mortality (including death due to CHF, sudden death, myocardial infarction, and other cardiovascular causes) and hospitalizations. Outcomes were evaluated on the basis of the use of vasodilating and nonvasodilating b-blockers and the underlying cause of CHF (ischemic heart disease vs nonischemic heart disease).

RESULTS: b-blockers as a group reduced total mortality in patients with CHF (10.6% vs 16.6%, relative risk [RR]=0.71; 95% confidence interval [CI], 0.63-0.80; number needed to treat [NNT]=17). A similar benefit was demonstrated in cardiovascular mortality (9.0% vs 13.7%, RR=0.71; 95% CI, 0.59-0.86; NNT=21). The reduction in cardiovascular mortality was mainly because of a significant reduction in death due to CHF and sudden death.

RECOMMENDATIONS FOR CLINICAL PRACTICE

b-blockers are effective in reducing total and cardiovascular mortality in patients with CHF. In this meta-analysis, vasodilating b-blockers (carvedilol and bucindolol) offered a greater reduction in total mortality, but all agents affected cardiovascular mortality similarly. Patients with CHF not due to ischemic heart disease lived longer when given vasodilating b-blockers. However, this meta-analysis did not include a recently published major trial, and no studies have directly compared one b-blocker with another. b-blockers are helpful for patients with heart failure, but more research is needed to differentiate effectiveness among the various agents.

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Lori M. Dickerson, PharmD, BCPS
Peter J. Carek, MD
Medical University of South Carolina, Charleston E-mail: macfarll@musc.edu

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Lori M. Dickerson, PharmD, BCPS
Peter J. Carek, MD
Medical University of South Carolina, Charleston E-mail: macfarll@musc.edu

Author and Disclosure Information

Lori M. Dickerson, PharmD, BCPS
Peter J. Carek, MD
Medical University of South Carolina, Charleston E-mail: macfarll@musc.edu

BACKGROUND: Previous meta-analyses have demonstrated that b-blockers reduce morbidity (symptoms, left ventricular function, and rate of hospitalization) and mortality (cardiovascular and total) in patients with congestive heart failure (CHF). The authors of this meta-analysis explored differences in effectiveness between vasodilating and nonvasodilating agents and defined differences in outcomes related to the underlying cause of CHF.

POPULATION STUDIED: A total of 5849 patients (79% men) were studied for a median duration of 6 months. Approximately 50% received b-blockers. Both vasodilating b-blockers (carvedilol and bucindolol) and nonvasodilating b-blockers (metoprolol, bisoprolol, and propranolol) were used for patients with primarily class II and III heart failure. Most patients also received angiotensin-converting enzyme inhibitors, diuretics, and digitalis.

STUDY DESIGN AND VALIDITY: The authors of this meta-analysis combined the results of 21 randomized controlled trials comparing the various b-blockers with placebo. All studies evaluated mortality on an intention-to-treat basis.

OUTCOMES MEASURED: The primary outcomes were total and cardiovascular mortality (including death due to CHF, sudden death, myocardial infarction, and other cardiovascular causes) and hospitalizations. Outcomes were evaluated on the basis of the use of vasodilating and nonvasodilating b-blockers and the underlying cause of CHF (ischemic heart disease vs nonischemic heart disease).

RESULTS: b-blockers as a group reduced total mortality in patients with CHF (10.6% vs 16.6%, relative risk [RR]=0.71; 95% confidence interval [CI], 0.63-0.80; number needed to treat [NNT]=17). A similar benefit was demonstrated in cardiovascular mortality (9.0% vs 13.7%, RR=0.71; 95% CI, 0.59-0.86; NNT=21). The reduction in cardiovascular mortality was mainly because of a significant reduction in death due to CHF and sudden death.

RECOMMENDATIONS FOR CLINICAL PRACTICE

b-blockers are effective in reducing total and cardiovascular mortality in patients with CHF. In this meta-analysis, vasodilating b-blockers (carvedilol and bucindolol) offered a greater reduction in total mortality, but all agents affected cardiovascular mortality similarly. Patients with CHF not due to ischemic heart disease lived longer when given vasodilating b-blockers. However, this meta-analysis did not include a recently published major trial, and no studies have directly compared one b-blocker with another. b-blockers are helpful for patients with heart failure, but more research is needed to differentiate effectiveness among the various agents.

BACKGROUND: Previous meta-analyses have demonstrated that b-blockers reduce morbidity (symptoms, left ventricular function, and rate of hospitalization) and mortality (cardiovascular and total) in patients with congestive heart failure (CHF). The authors of this meta-analysis explored differences in effectiveness between vasodilating and nonvasodilating agents and defined differences in outcomes related to the underlying cause of CHF.

POPULATION STUDIED: A total of 5849 patients (79% men) were studied for a median duration of 6 months. Approximately 50% received b-blockers. Both vasodilating b-blockers (carvedilol and bucindolol) and nonvasodilating b-blockers (metoprolol, bisoprolol, and propranolol) were used for patients with primarily class II and III heart failure. Most patients also received angiotensin-converting enzyme inhibitors, diuretics, and digitalis.

STUDY DESIGN AND VALIDITY: The authors of this meta-analysis combined the results of 21 randomized controlled trials comparing the various b-blockers with placebo. All studies evaluated mortality on an intention-to-treat basis.

OUTCOMES MEASURED: The primary outcomes were total and cardiovascular mortality (including death due to CHF, sudden death, myocardial infarction, and other cardiovascular causes) and hospitalizations. Outcomes were evaluated on the basis of the use of vasodilating and nonvasodilating b-blockers and the underlying cause of CHF (ischemic heart disease vs nonischemic heart disease).

RESULTS: b-blockers as a group reduced total mortality in patients with CHF (10.6% vs 16.6%, relative risk [RR]=0.71; 95% confidence interval [CI], 0.63-0.80; number needed to treat [NNT]=17). A similar benefit was demonstrated in cardiovascular mortality (9.0% vs 13.7%, RR=0.71; 95% CI, 0.59-0.86; NNT=21). The reduction in cardiovascular mortality was mainly because of a significant reduction in death due to CHF and sudden death.

RECOMMENDATIONS FOR CLINICAL PRACTICE

b-blockers are effective in reducing total and cardiovascular mortality in patients with CHF. In this meta-analysis, vasodilating b-blockers (carvedilol and bucindolol) offered a greater reduction in total mortality, but all agents affected cardiovascular mortality similarly. Patients with CHF not due to ischemic heart disease lived longer when given vasodilating b-blockers. However, this meta-analysis did not include a recently published major trial, and no studies have directly compared one b-blocker with another. b-blockers are helpful for patients with heart failure, but more research is needed to differentiate effectiveness among the various agents.

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The Journal of Family Practice - 49(06)
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The Journal of Family Practice - 49(06)
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496,571
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Are there differences between vasodilating and nonvasodilating b-blockers in patients with heart failure? Do patients with ischemic heart disease benefit to the same degree?
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