The ASCOT Trial Results: Calcium Channel Blockers & ACE Inhibitors vs. Beta Blockers & Thiazide Diuretics

Results from the ASCOT trial were recently published in the Lancet. The results apparently showed that a regimen of a calcium channel blocker and ACE inhibitor was associated with a decreased rate of cardiovascular events and diabetes than a regimen of a beta blocker and thiazide diuretic.

The study was stopped prematurely after 5·5 years median follow-up and accumulated in total 106,153 patient-years of observation. Though not significant, compared with the atenolol-based regimen, fewer individuals on the amlodipine-based regimen had a primary endpoint (429 vs 474; unadjusted HR 0·90, 95% CI 0·79–1·02, p=0·1052), fatal and non-fatal stroke (327 vs 422; 0·77, 0·66–0·89, p=0·0003), total cardiovascular events and procedures (1362 vs 1602; 0·84, 0·78–0·90, p<0·0001), p="0·025).">The amlodipine-based regimen prevented more major cardiovascular events and induced less diabetes than the atenolol-based regimen. On the basis of previous trial evidence, these effects might not be entirely explained by better control of blood pressure, and this issue is addressed in the accompanying article. Nevertheless, the results have implications with respect to optimum combinations of antihypertensive agents.

A major criticism of the study is that patients in the calcium channel blocker arm had a lower blood pressure than patients in the beta blocker arm. In a separate analysis, this accounted for a large percentage of the benefit, and the adjusted results were no longer statistically significant.

Multivariate adjustment accounted for about half of the differences in coronary events and for about 40% of the differences in stroke events between the treatment regimens tested in ASCOT-BPLA, but residual differences were no longer significant. These residual differences could indicate inadequate statistical adjustment, but it remains possible that differential effects of the two treatment regimens on other variables also contributed to the different rates noted, particularly for stroke.

Based on these results, it is uncertain whether current blood pressure guidelines should be changed to favor calcium channel blockers and ACE inhibitors over beta blockers and thiazide diuretics.

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