Nonetheless, a systematic review and meta-analysis (n = 247,006) [39] of head-to-head trials of various classes of antihypertensive agents found that the effects of all classes of antihypertensive agents (thiazide diuretics, calcium channel blockers, ACE inhibitors, and ARBs) were not significantly different on all evaluated outcomes, including the risks of stroke, cardiovascular disease, heart failure, cardiovascular death, and all-cause death, when their achieved blood pressure was equivalent. This evidence concerns the gene ACE and cardiovascular disorder.