Reporting the CONVINCE results, Dr. Black said, "We always believed that the size and scope of this study would result in confirmation of the hypothesis that all treatment regimens would provide a similar positive impact in preventing cardiovascular events. The standard of care arm has been shown in previous trials to provide benefit in reduction of cardiovascular events. CONVINCE confirmed that extended-release verapamil did as well."
The primary objective of CONVINCE was to examine whether a controlled-onset extended-release calcium channel blocker, COVERA-HS, could provide equivalent effects on the rate of heart attack, stroke and death as compared with standard of care therapy (the beta blocker atenolol or the diuretic hydrochlorothiazide).
The study enrolled 16,602 hypertensive patients with a second risk factor for cardiovascular disease (i.e., history of heart attack, stroke or smoking; type II diabetes; left ventricular hypertrophy; low HDL cholesterol; history of transient ischemic attack (TIA); body weight greater than 20% above ideal; atherosclerotic vascular disease; or presence of vascular bruit).
Patients were randomized to receive one of two study medications: either 180 mg/day of COVERA-HS or the physician directed choice of 12.5 mg/day of HCTZ or 50 mg/day of atenolol. Thereafter, therapy was doubled if blood pressure goals were not met (<140 mmHg systolic and <90 mmHg diastolic). Other medications could be added if blood pressure control was not achieved after the doubling of the dose. At the time when the study ended, patients had been followed for an average of three years post-enrollment. More than 660 clinical sites in 15 countries participated in the CONVINCE trial.
At randomization, only 20% of patients had controlled blood pressure. At the end of medication titration, 84.8% of subjects had achieved control of both systolic and diastolic pressures (less than 140/90 mmHg). As the study progressed, the proportion of patients with controlled blood pressure readings decreased, but by the end of follow-up (36 months), the majority of patients had achieved blood pressure goals: 2 out of 3 patients had blood pressure readings lower than 140 mmHg/90mmHg with 91.8% of patients with controlled systolic blood pressure and 67.8% with controlled diastolic blood pressure - a new record for any hypertension clinical study. CONVINCE provided clear evidence that blood pressure goals can be reached but that single drug is rarely enough.
The trial was limited by the sponsor, Pharmacia Corporation, to a three-year versus the original five-year period over which patients were to be monitored for progression to cardiovascular events. Overall there was no statistical difference between the two treatment arms in the prevention of the composite endpoint of stroke, heart attack or cardiovascular death. In part because of the smaller than expected number of events, the statistical criteria for equivalence was not met by less than 2%.
Added Dr. Black, "Overall, adding the results of CONVINCE to the rest of the world's literature about calcium channel blockers shows that these drugs are safe and likely to be as effective as diuretics and beta blockers."