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).
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).