Most Hypertension Drugs, Except ARBs, Better Than No Treatment for CHD Risk Reduction

May 07, 2009

May 7, 2009 (San Francisco, California) — Two large analyses estimating the cardiovascular and stroke benefit with initial drug treatment for hypertension showed that only angiotensin receptor blockers (ARBs) were not significantly better than placebo for the prevention of coronary events, while all antihypertensive drugs were better than placebo for the prevention of stroke.

Dr William Elliott

Regarding the lack of cardiovascular protection with ARBs, investigators suggest that this is the result of a limited number of studies and cardiovascular outcomes in these trials compared with the other drug classes.

"People should feel very comfortable that when their doctor is giving them a certain medication they don't have to worry," said lead investigator Dr William Elliott (Rush Medical College, Chicago, IL). "The concern we have with the ARBs is probably because we simply don't have enough data at this time. . . . There really aren't enough data with ARBs to make a really strong statement."

The two meta-analyses were presented here this week at the American Society of Hypertension (ASH) 2009 Scientific Meeting.

Meta-Analysis Includes Recent Hypertension Trials

During a press conference with assembled media, Elliott said that the last meta-analysis estimating outcomes with initial hypertensive therapy was performed in 2003, before the publication of Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7). In that analysis, researchers concluded there was a reduction in stroke with any hypertensive drug but that low-dose diuretics were the most effective first-line agents for preventing cardiovascular disease.

However, with the publication of the Avoiding Cardiovascular Events in Combination Therapy in Patients Living with Systolic Hypertension (ACCOMPLISH), a study showing the ACE inhibitor benazepril plus the calcium-channel blocker amlodipine was more effective than treatment with the ACE inhibitor and diuretic in reducing major fatal and nonfatal cardiovascular events, there is some uncertainty if this is still true, said Elliott.

In the two new meta-analyses, investigators included all published outcomes-based clinical trials with minimum follow-up of one year. All subjects included in the analysis were required to have hypertension, thereby excluding studies such as HOPE, PROGRESS, EUROPA, PEACE, and ONTARGET, among others, and the drug used must have been prescribed as initial antihypertensive therapy. The reference drug in the two analyses was diuretic therapy.

In an analysis estimating the reduction in stroke risk with the hypertensive medications, which included nearly 270 000 hypertensive patients in 60 clinical trials, all medications were significantly better than placebo for reducing the risk of stroke. Diuretics and calcium-channel blockers were slightly more protective than ARBs but were significantly better than ACE inhibitors and beta blockers.

Network Meta-Analysis: Risk of Stroke

Treatment Odds ratio (95% CI)
Placebo 1.56 (1.44–1.77)
Beta blockers 1.22 (1.11–1.35)
ACE inhibitor 1.17 (1.07–1.29)
Angiotensin receptor blocker 1.10 (0.96–1.26)
Calcium-channel blocker 1.00 (0.92–1.10)
Diuretic Reference

Investigators noted that the results were identical whether the reference diuretic was chlorthalidone or hydrochlorothiazide and that the overall network findings were confirmed by Bayesian analysis. Moreover, the data are robust to numerous changes in the data set, which included the addition of ACCOMPLISH to the analysis as well as different studies that included add-on drug therapy for the treatment of hypertension and studies that didn't include patients with high blood pressure.

"The fact is that it doesn't really matter when you add in these other studies, you get the same answer," said Elliott.

Cardiovascular Risk Reduction With Antihypertensive Drugs

In the second meta-analysis examining coronary heart disease risk reduction with the different antihypertensive drugs, the researchers used the same entry criteria and included 57 clinical trials involving 276 000 patients. In that analysis, all drugs, except ARBs, were significantly better than placebo or no treatment for reducing the risk of coronary events.

"The good news is that all of the generically available medicines are significantly better than placebo, and the take-home message for patients and doctors is that you can be sure whatever generic medicine you're taking does protect you better than placebo or no treatment for heart attack and sudden cardiac death," said Elliott.

The findings also showed that ACE inhibitors were significantly better than ARBs and beta blockers for coronary heart disease risk reduction, which echoes previous reports suggesting ACE inhibitors have pleiotropic effects independent from blood-pressure lowering that protect patients from cardiovascular events.

Like the stroke findings, the results were similar when different studies were added to the analysis and when the different diuretics were used as the reference drugs.

Speaking with the media, Elliott noted that the results have been heralded as a "tempest in a teapot" because most patients with hypertension are treated with multiple antihypertensive drugs, whereas this analysis was concerned primarily with looking at risk reduction with initial hypertension therapy. However, since treatment in the US follows "road maps," and patients are typically started with one drug, it is important to know the differences with the different pathways that lead to getting blood pressure down, he said.

Elliott reports serving as a consultant to Novartis Pharmaceuticals and is on the speakers' bureau for Novartis, Pfizer, a Bristol Myers-Squibb/Sanofi-Synthelabo partnership, and Sanofi-Aventis.

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