Meta-Analyses Spot Best HT Therapies for Stroke Prevention


SAN FRANCISCO — Initial therapy with any antihypertensive medication is significantly better than placebo at preventing stroke, and any antihypertensive except an angiotensin receptor blocker is better than placebo for preventing heart disease, results of new meta-analyses show.

“Don't let patients tell you, 'I just read someplace that this drug is not good at preventing stroke,'” Dr. William J. Elliott said at the annual meeting of the American Society of Hypertension. “All the drugs, in fact, are superior to placebo” in preventing stroke, he said.

For heart disease prevention, angiotensin receptor blockers (ARBs) may have fallen short of superiority to placebo in patients with hypertension for reasons related to statistical power, he hypothesized. “ARBs have not been around as long as some of our more tried-and-true drugs” and thus have had fewer trials as initial hypertensive agents, and fewer people in those trials develop coronary heart disease, said Dr. Elliott, professor of preventive medicine at Rush Medical College, Chicago.

The last major meta-analysis in 2003 of cardiovascular outcomes in hypertension treatment provided the basis for recommendations of low-dose diuretics as first-line antihypertensives to prevent cardiovascular disease in the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7).

Since then, at least 25 more trials have been published, with stroke data on 269,180 more subjects and heart disease data on 276,396 more subjects who were included in the current meta-analyses.

Dr. Elliott and his associates conducted two types of meta-analyses on data from all published outcome-based clinical trials with a minimum 1-year follow-up in which all subjects had hypertension and in which a drug was the initial antihypertensive therapy. Results of both the “network” and “Bayesian” meta-analyses were strikingly consistent, he said

For stroke prevention, initial treatment for hypertension with a diuretic was no better than was a calcium channel blocker (CCB) or ARB. All three were slightly but significantly better than a beta-blocker or ACE inhibitor in preventing stroke, Dr. Elliott said. The risk for stroke was 56% higher on placebo than on a diuretic or a CCB. There were 9,351 strokes among subjects in 144 randomized arms in the trials.

Initial treatment with an ACE inhibitor was about 8% more effective than was a diuretic in reducing coronary heart disease events, though the difference was not statistically significant.

The finding is consistent with other suggestions in the literature that ACE inhibitors are better than diuretics at preventing heart disease, Dr. Elliott said.

Calcium channel blockers appeared to be as effective as diuretics for preventing heart disease, and beta-blockers were just behind. Both ARBs and placebos were statistically inferior to ACE inhibitors, diuretics, CCBs, and beta-blockers for preventing heart disease. The risk for coronary heart disease was 26%–28% higher on placebo than on an ACE inhibitor. There were 11,122 coronary heart disease events among subjects in 136 arms in the trials.

Dr. Elliott has been a consultant or speaker for Novartis Pharmaceuticals, Pfizer, Bristol-Myers Squibb/Sanofi-Synthelabo Partnership, and Sanofi-Aventis, some of which market antihypertensive drugs. He also has received royalties from Elsevier, which owns this news organization.

Antihypertensives are superior to placebo in stroke prevention, but ARBs fall short for heart disease prevention. DR. ELLIOTT

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