Antiplatelet agents and anticoagulants for hypertension

Two review authors independently extracted data for inclusion criteria, our prespecified outcomes, and sources of bias. They assessed the risks and benefits of antiplatelet agents and anticoagulants by calculating odds ratios (OR), accompanied by the 95% confidence intervals (CI). They assessed risks of bias and applied GRADE criteria. MAIN RESULTS: Six trials (61,015 patients) met the inclusion criteria and were included in this review. Four trials were primary prevention (41,695 patients; HOT, JPAD, JPPP, and TPT), and two secondary prevention (19,320 patients, CAPRIE and Huynh). Four trials (HOT, JPAD, JPPP, and TPT) were placebo-controlled and two studies (CAPRIE and Huynh) included active comparators. Four studies compared acetylsalicylic acid (ASA) versus placebo and found no evidence of a difference for all-cause mortality (OR 0.97, 95% CI 0.87 to 1.08; 3 studies, 35,794 participants; low-certainty evidence). We found no evidence of a difference for cardiovascular mortality (OR 0.98, 95% CI 0.82 to 1.17; 3 studies, 35,794 participants; low-certainty evidence). ASA reduced the risk of all non-fatal cardiovascular events (OR 0.63, 95% CI 0.45 to 0.87; 1 study (missing data in 3 studies), 2540 participants; low-certainty evidence) and the risk of all cardiovascular events (OR 0.86, 95% CI 0.77 to 0.96; 3 studies, 35,794 participants; low-certainty evidence). ASA increased the risk of major bleeding events (OR 1.77, 95% CI 1.34 to 2.32; 2 studies, 21,330 participants; high-certainty evidence). One study (CAPRIE; ASA versus clopidogrel) included patients diagnosed with hypertension (mean age 62.5 years, 72% males, 95% Caucasians, mean follow-up: 1.91 years). It showed no evidence of a difference for all-cause mortality (OR 1.02, 95% CI 0.91 to 1.15; 1 study, 19,143 participants; high-certainty evidence) and for cardiovascular mortality (OR 1.08, 95% CI 0.94 to 1.26; 1 study, 19,143 participants; high-certainty evidence). ASA probably reduced the risk of non-fatal cardiovascular events (OR 1.10, 95% CI 1.00 to 1.22; 1 study, 19,143 participants; high-certainty evidence) and the risk of all cardiovascular events (OR 1.08, 95% CI 1.00 to 1.17; 1 study, 19,143 participants; high-certainty evidence) when compared to clopidogrel. Clopidogrel increased the risk of major bleeding events when compared to ASA (OR 1.35, 95% CI 1.14 to 1.61; 1 study, 19,143 participants; high-certainty evidence). In one study (Huynh; ASA verus warfarin) patients with unstable angina or non-ST-segment elevation myocardial infarction, with prior coronary artery bypass grafting (CABG) were included (mean age 68 years, 79.8% males, mean follow-up: 1.1 year). There was no evidence of a difference for all-cause mortality (OR 0.98, 95% CI 0.06 to 16.12; 1 study, 91 participants; low-certainty evidence). Cardiovascular mortality, non-fatal cardiovascular events, and all cardiovascular events were not available. There was no evidence of a difference for major bleeding events (OR 0.13, 95% CI 0.01 to 2.60; 1 study, 91 participants; low-certainty evidence). AUTHORS' CONCLUSIONS: There is no evidence that antiplatelet therapy modifies mortality in patients with elevated BP for primary prevention. ASA reduced the risk of cardiovascular events and increased the risk of major bleeding events. Antiplatelet therapy with ASA probably reduces the risk of non-fatal and all cardiovascular events when compared to clopidogrel. Clopidogrel increases the risk of major bleeding events compared to ASA in patients with elevated BP for secondary prevention. There is no evidence that warfarin modifies mortality in patients with elevated BP for secondary prevention. The benefits and harms of the newer drugs glycoprotein IIb/IIIa inhibitors, clopidogrel, prasugrel, ticagrelor, and non-vitamin K antagonist oral anticoagulants for patients with high BP have not been studied in clinical trials. Further RCTs of antithrombotic therapy including newer agents and complete documentation of all benefits and harms are required in patients with elevated BP.