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

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Staessen JA, Wang JG, Thijs L. Cardiovascular protection and blood pressure reduction: a meta-analysis. Lancet 2001; 358:1305-15.



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.


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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