Prior Medications and the Cardiovascular Benefits From Combination Angiotensin‐Converting Enzyme Inhibition Plus Calcium Channel Blockade Among High‐Risk Hypertensive Patients

BACKGROUND: The ACCOMPLISH (Avoiding Cardiovascular Events Through Combination Therapy in Patients Living with Systolic Hypertension) trial demonstrated that combination therapy using amlodipine, rather than hydrochlorothiazide, in conjunction with benazepril provided greater cardiovascular risk reduction among high‐risk hypertensive patients. Few trials have evaluated the effect of prior antihypertensive therapy used among participants on the study outcomes. METHODS AND RESULTS: In a post hoc observational analysis, we examined the characteristics of the drug regimens taken before trial enrollment in the context of the primary composite outcome (death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, hospitalization for angina, resuscitation after sudden cardiac death, and coronary revascularization). In the “primary subgroup” (n=4475), patients previously taking any renin‐angiotensin system blockade plus either a diuretic or a calcium channel blocker alone or as part of their antihypertensive regimen, there were 206 of 2193 (9.4%) versus 281 of 2282 (12.3%) primary composite events among those randomized to combination therapy involving amlodipine versus hydrochlorothiazide, respectively (adjusted Cox proportional hazard ratio, 0.74; 95% confidence interval, 0.62–0.89; P=0.0015). All other participants (n=6975) previously taking any antihypertensive regimen not included in the primary subgroup also benefited from randomization to amlodipine plus benazepril (adjusted hazard ratio, 0.84; 95% confidence interval, 0.72–0.98; P=0.024). Outcomes among most other subgroups, including patients previously taking lipid‐lowering medications or dichotomized by prior blood pressure control status, showed similar results. CONCLUSIONS: When combined with an angiotensin‐converting enzyme inhibitor, amlodipine provides cardiovascular risk reduction superior to hydrochlorothiazide, largely regardless of prior medication use. These findings add further support for the initial use of this combination regimen among high‐risk hypertensive patients.