Effects of blood pressure-lowering treatment on cardiovascular outcomes and mortality

Background and objectives: The five major classes of blood pressure (BP)-lowering drugs have all been shown to significantly reduce the risk of major cardiovascular events when compared with placebo, and when directly (head-to-head) compared, no significant differences in their overall effectiveness have been detected, except for minor differences in cause-specific events. It is unknown, however, whether age-related differences exist and if some classes of drugs are differently effective in older or younger individuals. This clinically relevant question has been the object of a systematic search and meta-analysis of all available data. Methods: Two databases we had previously identified [72 placebo-controlled BP-lowering randomized clinical trials (RCTs) in 260 210 individuals and 50 RCTs head-to-head comparing treatments with BP-lowering drugs of different classes in 247 006 individuals) were searched for separately reported data on patients older or younger than 65 years, and the data were further stratified according to the class of drug [diuretics, beta-blockers, calcium antagonists, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers] compared with placebo or with other drug classes. Seven fatal and nonfatal outcomes were considered for benefits. Adverse events were investigated as permanent treatment discontinuations for adverse events. Risk ratios and absolute risk changes were calculated by a random effects model. Effects at older and younger ages were compared by heterogeneity test. Results: We identified 20 placebo-controlled RCTs on 55 645 older individuals and 21 on 99 621 younger individuals, and 21 head-to-head drug comparison RCTs on 94 228 older individuals and 27 on 100 232 younger individuals (for a total of 349 726 individuals). When compared with placebo, all five classes of BP-lowering drugs significantly reduced the risk of major cardiovascular events or stroke, with no significant difference between older and younger patients. However, in head-to-head comparisons, no significant difference was found between older and younger patients in the effects of diuretics, calcium antagonists, ACE inhibitors and angiotensin receptor blockers on all cardiovascular outcomes, whereas beta-blockers revealed an age-dependent effectiveness, being equally effective as the other agents at an age below 65 years, but less effective at an older age. Conclusion: Most BP-lowering classes are equally effective in preventing risk of fatal and nonfatal cardiovascular events both in older and younger patients, whereas beta-blockers, though being equally effective as the other agents in patients younger than 65, loose some of their effectiveness at an older age.