Issue 154 Item 12 Calcium Channel Blocker Rivals Beta Blocker in Preventing Deat

New-onset diabetes lower with CCB A calcium channel blocker-based antihypertensive treatment strategy in patients with coronary artery disease is as effective as a -blocker-based strategy in preventing death, acute MI, and stroke—and significantly better at preventing new-onset diabetes, according to a landmark clinical trial.

The 13% reduction in relative risk of new-onset diabetes with a verapamil-based antihypertensive regimen was a surprising finding of the International Verapamil SR-Trandolapril (INVEST) trial and requires confirmation in a prospective study. If it holds up, the public health implications would be enormous in light of the emerging epidemic of type 2 diabetes, INVEST Principal Investigator Dr. Carl J. Pepine declared at the annual meeting of the American College of Cardiology.

INVEST involved 22,576 hypertensive patients with documented coronary artery disease randomized at 862 sites in 15 countries to a non-dihydropyridine calcium channel blocker-based antihypertensive strategy with verapamil SR as the first drug, or a -blocker-based one built upon atenolol.

The verapamil arm of the Abbott Laboratories-sponsored trial featured the angiotensin-converting enzyme inhibitor trandolapril as the second agent, or the use of the combined tablet containing both drugs, with the diuretic hydrochlorothiazide as the third drug if required. In the atenolol arm, hydrochlorothiazide was the second agent, in accord with long-established published treatment guidelines, with trandolapril reserved as the third drug when needed.

Two or more antihypertensive drugs were required by 83% of patients in each study arm. After a mean of 2.7 years or nearly 64,000 patient-years of follow-up, the primary combined study end point—death, acute MI, or stroke—had occurred in 9.6% of patients in the verapamil arm and 9.8% in the atenolol arm.

This achieved the study’s main goal: to prove whether a calcium channel blocker-based treatment strategy is an effective alternative to the long-established -blocker-based approach to managing hypertension in coronary disease patients. A calcium channel blocker had not previously been put to the test in a large trial with clinical end points, and some critics had questioned the drugs’ safety.

Given the poor job physicians are doing in controlling hypertension around the world today, effective alternative regimens are welcome, said Dr. Pepine, professor of medicine and chief of cardiovascular medicine at the University of Florida, Gainesville.

Roughly 1,200 cases of new-onset diabetes occurred during the massive INVEST trial. The incidence was 6.2% in the verapamil arm compared with 7.3% in the atenolol arm. The combined rate of another key secondary end point—death or new-onset diabetes—was 11.9% with the calcium channel blocker-based strategy, significantly less than the 13.4% incidence with the -blocker-based approach.

Preliminary modeling suggests the explanation for the reduced incidence of new-onset diabetes in the verapamil group lies not in the increased use of trandolapril in that study arm, nor with the use of the calcium channel blocker; rather, the key factor appeared to be the greater use of hydrochlorothiazide in the atenolol arm.

Among other noteworthy findings in INVEST; patients above age 70 had a primary event rate that was almost threefold higher than that of patients below that age, patients with a prior MI had an event rate nearly identical to that of patients without prior MI, and patients with prior heart failure had almost threefold greater mortality than those without heart failure.

Blood pressure control in INVEST was identical in both study arms and was “spectacular,” said Dr. Pepine.