CLINICAL QUESTION: Is there a difference in efficacy between older and newer antihypertensive medications in preventing cardiovascular morbidity and mortality?
BACKGROUND: It is well known that b-blockers and diuretics decrease cardiovascular morbidity and mortality.1 However, the efficacy of newer classes of antihypertensive drugs, such as angiotensin-converting enzyme (ACE) inhibitors and calcium antagonists, has not been established.
POPULATION STUDIED: Subjects included 6628 hypertensive men and women aged 70 to 84 years from 312 health centers in Sweden. Hypertension was defined as a reading of >179 mm Hg systolic, >104 mm Hg diastolic, or both.
STUDY DESIGN AND VALIDITY: This was a prospective randomized trial. Patients were assigned treatment to 1 of 3 categories of medications: conventional antihypertensive drugs, ACE inhibitors, or calcium antagonists. Conventional drugs used were oral atenolol 50 mg, metoprolol 100 mg, pindolol 5 mg, or fixed-ratio hydrochlorothiazide 25 mg plus amiloride 2.5 mg, all given once daily. The ACE inhibitors were enalapril 10 mg or lisinopril 10 mg given once daily, and the calcium antagonists were felodipine 2.5 mg or isradipine 2.5 mg given once daily. If the target blood pressure of 160/95 mm Hg had not been reached by 2 months, combination therapy was instituted. Patients on b-blockers or ACE inhibitors were given a diuretic, while those on diuretics or calcium antagonists were given a b-blocker. After the initial dose-titration periods, patients were seen twice each year. At each visit heart rate and blood pressure were measured. Adverse events were evaluated from the patient’s history. Laboratory tests and electrocardiograms were done annually and on an as-needed basis.
OUTCOMES MEASURED: The primary end point was the rate of cardiovascular mortality. Secondary outcomes included the rates of fatal and nonfatal stroke, fatal and nonfatal myocardial infarction, atrial fibrillation, congestive heart failure, diabetes mellitus, and all-cause mortality. Subgroup analysis was performed on people with diabetes.
RESULTS: Most patients in this study had Stage 3 hypertension > 180 mm Hg systolic or 110 mm Hg diastolic). The rates of the primary and secondary end points were similar among the 3 treatment arms. The only difference was fewer fatal and nonfatal myocardial infarctions and less congestive heart failure among patients taking ACE inhibitors than those taking calcium antagonists. Although 46% of patients required more than one drug to control their hypertension, 61% to 66% of the patients in each group were on their original regimen at the end of the trial. Adverse events were common in all 3 groups: 25.5% of patients taking calcium antagonists had ankle edema, 30% on an ACE inhibitor had cough, and 25% to 28% in each group had dizziness.
The risk of cardiovascular morbidity and mortality was similar in all groups of elderly patients taking either conventional hypertensives, ACE inhibitors, or calcium antagonists. It is reassuring that there was no increase in stroke using ACE inhibitors as suggested in the Captopril Prevention Project study.2 Side effects were very common in all groups. Diuretics and b-blockers should still be recommended as first-line treatment on the basis of cost and efficacy. In general, ACE inihibitors are preferred to calcium antagonists because the former are more effective at preventing myocardial infarction and congestive heart failure.