Implications of recently published trials of blood pressure-lowering drugs in hypertensive or high-risk patients.

We reviewed 6 recent outcome trials of blood pressure (BP)-lowering drugs in 74,524 randomized hypertensive or high-risk patients. Over interpretation of nonsignificant or marginal probability values in large trials with overlapping end points, exclusion of patients not tolerating or not adhering to experimental treatments, labeling nonsignificant treatment effects as modest, and insufficient information on the quality of the BP measurements or on the BP changes early after randomization raise concern. From a clinical viewpoint, results should not be extrapolated to patients with characteristics dissimilar from those randomized. The benefit beyond BP lowering in cardiovascular prevention is tiny. Dual inhibition of the renin system should only be used in patients at high risk, in whom all drug combinations have been tried and who cannot be controlled by a single renin system inhibitor. Current evidence does not support BP lowering in normotensive patients or the use of renin system inhibitors for prevention of stroke recurrence. Because angiotensin-receptor blockers might offer less protection against myocardial infarction than angiotensin-converting enzyme inhibitors, the latter should remain the preferred renin system inhibitor for cardiovascular prevention in angiotensin-converting enzyme inhibitor-tolerant patients. In 2 trials, in which new-onset diabetes was a predefined end point, 1000 patients had to be treated for 1 year with an angiotensin-receptor blocker instead of placebo to prevent just 2 cases. From a design viewpoint, the time has come to revise the concept of large simple trials and to pursue research questions that serve patient interests more than showing noninferiority or highlight the ancillary qualities of marketable antihypertensive drugs.