Moderate Recommendation Grade B For this recommendation, only RCTs that compared one class of antihypertensive medication to another and assessed the effects on health outcomes were reviewed; placebo-controlled RCTs were not included. However, the evidence review was informed by major placebo-controlled hypertension trials, includ- ing 3 federally funded trials (VA Cooperative Trial, HDFP, and SHEP), that were pivotal in demonstrating that treatment of hypertension with antihypertensive medications reduces cardio- vascular or cerebrovascular events and/or mortality.3,13,18 These trials all used thiazide-type diuretics compared with placebo or usual care as the basis of therapy. Additional evidence that BP lowering reduces risk comes from trials of -blocker vs and CCB vs placebo.1 Each of the 4 drug classes recommended by the panel in rec- cardiovascular,cerebrovascular,andkidneyoutcomes,withoneex- ception: heart failure. Initial treatment with a thiazide-type di- uretic was more effective than a CCB or ACEI (question 3, evidence statements 14 and 15), and an ACEI was more effective than a CCB (question 3, evidence statement 1) in improving heart failure out- comes.Whilethepanelrecognizedthatimprovedheartfailureout- comeswasanimportantfindingthatshouldbeconsideredwhense- lecting a drug for initial therapy for hypertension, the panel did not conclude that it was compelling enough within the context of the overallbodyofevidencetoprecludetheuseoftheotherdrugclasses for initial therapy. The panel also acknowledged that the evidence supported BP control, rather than a specific agent used to achieve thatcontrol,asthemostrelevantconsiderationforthisrecommen- dation. 