Diuretics: Still first-line therapy for hypertension

A revolution in the pharmacologic treatment of hypertension is under way, according to experts reporting at a conference called "The State of the Hypertension Nation," held recently in New York City. Here are some highlights from the conference:

"Soon you may say good-bye to traditional 'one drug at a time' therapy that starts with an established diuretic or beta-blocker and then adds on other classes of drugs," said Kenneth Jamerson, M.D., professor of internal medicine, from the University of Michigan Cardiovascular Center, Ann Arbor. "The new emphasis is on drug combinations using newer agents from the start."

It no longer makes sense in clinical trials to compare one single drug with another-as is the custom-Jamerson continued. "We now know that a patient needs on average three or four drugs to control blood pressure. The focus of clinical trials should be developing optimum combinations of antihypertensive agents."

Jamerson currently heads a major global trial called ACCOMPLISH (Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension). It involves 12,000 high-risk patients randomized to one of two fixed-dose combination drug regimens as initial therapy.

The researchers are trying to answer the following question: Does the combination of an ACE inhibitor and a calcium-channel blocker (CCB)-Lotrel (amlodipine/benazepril HCl, Novartis)-more effectively reduce morbidity and mortality from cardiovascular events in a high-risk hypertensive population than an ACE inhibitor/diuretic combination-benazepril HCl/hydrochlorothiazide (Lotensin HCT, Novartis)?

ACE inhibitors are included on both sides of the study because of their proven benefits in such patients, Jamerson noted. The five-year ACCOMPLISH trial, now in its second year, may produce "some very exciting results relating to the newer drugs," he predicted.

Michael A. Weber, M.D., professor of medicine from the SUNY Downstate Medical Center, Brooklyn, and a past president of the American Society of Hypertension, strongly agreed. "ACCOMPLISH promises to revolutionize the way we treat hypertension," he said. "Now we know that one-drug treatment is by and large only modestly effective, although it can save lives on occasion." He suggested synergy may be involved in the better outcomes achieved using multiple drugs.

Data from six large earlier trials showed that it took at least three drugs on average for each patient to reduce blood pressure to below 140/90 mmHg, the point cited by most experts recently as where hypertension actually begins, Weber emphasized. "The future of blood pressure treatment starts with using two or more drugs at the same time," he reiterated.

Jamerson added: "A doctor isn't practicing standard of care unless he's using combination therapy."

Richard Devereaux, M.D., professor of medicine, Weill Medical College of Cornell University, New York City, analyzed another new trial that was recently completed, which he called "the first to really challenge the whole traditional antihypertensive approach."

This mega-study of 20,000 patients called ASCOT-BPLA (Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure-Lowering Arm) aimed to learn whether heart attacks and strokes were more effectively prevented with the combination of amlodipine plus perindopril (Aceon, Solvay Pharmaceuticals) or with atenolol plus bendroflumethiazide (Naturetin-5, Apothecon).

But the randomized controlled trial was stopped prematurely after five and a half years' median follow-up when it was found that fewer patients on the amlodipine-based regimen had experienced either a nonfatal heart attack or stroke or fatal coronary heart disease.

As the European researchers themselves summed up in the Sept. 10 issue of the Lancet, "The amlodipine-based regimen prevented more major cardiovascular events and induced less diabetes than the atenolol-based regimen.... While these effects may not be entirely explained by better blood pressure control, the results have implications with respect to optimum combinations of antihypertensive agents."