However, the incidence of stroke, a component of the primary outcome, was significantly reduced. The standard gly- cemia subgroup did show significant benefit in ACCORD, and a meta-analysis of the only 2 trials (ACCORD and SPRINT) testing an SBP goal of <120 mm Hg showed significant reduc- tion in CVD events.S8.1.5-17 SPS-3 failed to demonstrate benefit for the primary endpoint of recurrent stoke (P=0.08) but found a significant reduction in a subgroup with hemorrhagic stroke. Pooling of the experience from 19 trials (excluding SPRINT) that randomly assigned participants to different BP treatment targets identified a significant reduction in CVD events, MI, and stroke in those assigned to a lower (average achieved SBP/DBP was 133/76 mm Hg) versus a higher BP treatment Similar patterns of benefit were reported in 3 other meta-analyses of trials in which participants were randomly Table 18. Oral Antihypertensive Drugs Class Drug Usual Dose, Range (mg/d)* Daily Frequency Comments Primary agents Thiazide or thiazide- type diuretics Chlorthalidone 12.5 25 1 Chlorthalidone is preferred on the basis of prolonged half-life and proven trial reduction of CVD. Monitor for hyponatremia and hypokalemia, uric acid and calcium levels. Use with caution in patients with history of acute gout unless patient is on uric acid lowering therapy. ACE inhibitors Benazepril 10 40 1 or 2 Do not use in combination with ARBs or direct renin inhibitor. There is an increased risk of hyperkalemia, especially in patients with CKD or in those on K+ supplements or K+ -sparing drugs. There is a risk of acute renal failure in patients with severe bilateral renal artery stenosis. Do not use if patient has history of angioedema with ACE inhibitors. Avoid in pregnancy. ARBs Azilsartan 40 80 1 Do not use in combination with ACE inhibitors or direct renin inhibitor. 