The overall goal of treatment should be reduction in BP, in the context of underlying CVD risk. Five drug classes have been shown, in high-quality RCTs, to prevent CVD as compared with placebo (diuretics, ACE inhibitors, ARBs, CCBs, and beta blockers).S8.1.6-11,S8.1.6-12 In head-to-head comparisons of first-step therapy, different drug classes have been reported to provide somewhat divergent capac- ity to prevent specific CVD events. Interpretation of meta- analyses comparing agents from different drug classes is challenging because the relevant RCTs were conducted in different time periods, during which concurrent antihyper- tensive therapy was less or more common, and the efficacy of agents from certain drug classes may have changed. In recognition of this, someS8.1.6-2 but not allS8.1.6-11,S8.1.6-12 meta- analyses, as well as the largest individual RCT that com- pared first-step agents,S8.1.6-3 have suggested that diuretics, especially the long-acting thiazide-type agent chlortha- lidone, may provide an optimal choice for first-step drug therapy of hypertension. In contrast, some meta-analyses have suggested that beta blockers may be less effective, especially for stroke prevention in older adults, but inter- pretation is hampered by inclusion of RCTs that used beta blockers that are now considered to be inferior for preven- tion of CVD.S8.1.6-13,S8.1.6-14 In a systematic review and net- work meta-analysis conducted for the present guideline, beta blockers were significantly less effective than diuretics Whelton et al 2017 High Blood Pressure Clinical Practice Guideline e47 for prevention of stroke and cardiovascular events.S8.1.6-1 Diuretics were also significantly better than CCBs for pre- vention of HF. There were some other nonsignificant differ- ences between diuretics,ACE inhibitors,ARBs, and CCBs, but the general pattern was for similarity in effect. As in- dicated in Section 8.1.6.1, most adults with hypertension require >1 drug to control their BP. 