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ALLHAT/GENHAT: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial

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GenHAT is an ancillary study to ALLHAT, which included 39,114 high-risk hypertensive participants with at least one other CVD risk factor age 55+ who were ethnically diverse. GenHAT aimed to determine if variants in hypertension-related genes interacted with type of antihypertensive drug to modify risk of CHD. Participants were randomized to one of four treatment groups: chlorthalidone 12.5-25 mg, amlodipine 2.5-10 mg, lisinopril 10-40 mg and doxazosin 2-8 mg; mean follow-up was 4.9 years. The main outcome was fatal CHD and nonfatal MI with secondary outcomes of individual and combined CVD. Secondary outcomes were all-cause mortality, combined CHD (CHD, coronary revascularization, or hospitalized angina), stroke, combined CVD (combined CHD, stroke, treated but not hospitalized angina, heart failure, or peripheral arterial disease), and end-stage renal disease. GenHAT initially set out to genotype 6 candidate genes (more were typed later) including ACE I/D. For the ACE I/D, GenHAT did not identify elevated risk for the DD genotype compared with ID and II for primary and secondary outcomes. No evidence was found to support the hypothesis that the ACE I/D genotype might influence the reduction in BP achieved with an ACEI compared with other commonly used medications.

ALLHAT/GENHAT Publications