Further hypothesis-driven trials are warranted, however, to test differences in efficacy of individual agents in specific subgroups of patients. BP control can be achieved in most patients, but most patients require therapy with 2 drugs.242,243 In 1 open-label trial conducted in Japan, among patients taking a calcium channel blocker who had not yet achieved a target BP, the addition of a thiazide diuretic significantly reduced the risk of stroke compared with the addition of either a -blocker (P=0.0109) or an ARB (P=0.0770).244 The advantage of the combination of a calcium channel blocker and thiazide was not seen, however, for other cardiovascular end points. Meta-analyses support that more intensive control of BP (SBP <130 mmHg) reduces risk of stroke more than less intensive control (SBP, 130 139 mmHg), although the effects on other outcomes and in all subgroups of patients remain unclear. Among 11 trials with 42572 participants, the RR of stroke for those whose SBP was <130 mmHg was 0.80 (95% CI, 0.70 0.92). The effect was greater among those with car- diovascular risk factors but without established CVD.245 This benefit of intensive BP lowering may be more specific to stroke than to other cardiovascular outcomes, at least among certain subgroups of patients. Among patients with diabetes mellitus at high cardiovascular risk enrolled in the ACCORD Blood Pressure Trial, more intensive BP control (SBP <120 mmHg) compared with standard control (<140 mmHg) led to a significant reduction in risk of stroke, a prespecified sec- However, there was no effect on either the primary composite outcome or overall mortality. This absence of benefit on nonstroke out- comes was not attributable to obesity because effects were simi- lar across levels of obesity. 