Calcium antagonist has clinical advantage over beta-blocker as initial antihypertensive therapy

An antihypertensive therapeutic strategy that starts with the calcium antagonist amlodipine is superior to one starting with the beta-blocker atenolol in preventing coronary heart disease (CHD) events, Peter S. Sever, MD, reported at the ACC Annual Scientific Session 2005.

He presented the results of a clinical trial known as ASCOT (Anglo-Scandinavian Cardiac Outcomes Trial), which was stopped prematurely on the advice of the trial's Data Safety Monitoring Board because of the magnitude of difference in the incidence of clinical events between the 2 treatment regimens.

The findings that were presented represent 95% of the final data, and the conclusions are not expected to change at the final follow-up, said Dr Sever.

The trial was stopped after an average follow-up of 5.5 years, at which time the composite end point of nonfatal MI or fatal CHD occurred in 10% fewer patients randomized to amlodipine/perindopril compared with atenolol/ bendroflumethiazide; however, this result did not reach statistical significance (P=.12).

"If the trial had gone along to the planned number of events... that relative reduction might have become significant," said Dr Sever. The study was powered to achieve significance with 1,150 events but was terminated after only 869 events.

Amlodipine/perindopril was associated with significant relative reductions in all-cause mortality (14%, P<.001), stroke (23%, P<.001), cardiovascular death (24%, P<.001), cardiovascular events and procedures (16%, P<.001), and total coronary events (14%, P=.005).

The significant reduction in mortality was a surprise, Dr Sever said, given the small sample size. "It's certainly a finding we would not have predicted because the trial wasn't powered for all-cause mortality," he said.

As expected, the beta-blocker/diuretic regimen was associated with a 32% excess in the development of new diabetes. "Something about this drug combination induces diabetes, and this is not good news at all, given the worldwide epidemic of diabetes," Dr Sever said.

The differences in event rates between the 2 arms should not be attributed to the initial drugs, he said. "The trial was designed to look at a treatment strategy rather than an individual drug because we recognize that most people with high blood pressure require at least 2 drugs to achieve target pressures," he said. Only 14.3% of the patients started on amlodipine and 8.6% of those started on atenolol finished on monotherapy.

In agreement was Richard Devereux, MD, professor of medicine, Weill Medical College of Cornell University, New York, NY, who noted the high use of diuretics in the beta-blocker arm (67%) and perindopril in the amlodipine arm (63%) as evidence that the effects cannot "solely be attributed to the initial drug in either arm."