Eduard Shantsila, Monika Kozieł-Siołkowska, Gregory Lip

Review question

We reviewed the evidence that examined whether antiplatelet agents reduced total deaths or major thrombotic events or both in patients with elevated blood pressure (BP) when compared to placebo or other active treatment. We also assessed whether oral anticoagulants reduced total deaths or major thrombotic events or both in these patients when compared to placebo or other active treatment.

Background

Although systemic (arterial) elevations in BP result in high intravascular pressure, the main complications of elevated BP, coronary heart disease events, ischaemic stroke, and peripheral vascular disease, are associated with thrombosis.

We wanted to discover whether the use of antithrombotic or antiplatelet therapy may be of particular benefit for primary prevention in reducing total deaths or major thrombotic events or both in patients with elevated BP. Moreover, we tried to determine whether antithrombotic or antiplatelet therapy may be beneficial for secondary prevention in reducing total deaths or major thrombotic events or both in patients with elevated BP.

Search date

This update of a previously published systematic review is current to January 2021.

Study characteristics

We included six trials with a combined total of 61,015 patients in this review. Four trials were primary prevention (41,695 patients; HOT, JPAD, JPPP, and TPT) and two were secondary prevention (19,320 patients; CAPRIE and Huynh). Four trials were placebo‐controlled (HOT, JPAD, JPPP, and TPT) and two trials included active comparators (CAPRIE and Huynh). CAPRIE 1996 included patients from 16 countries in Europe and USA with recent ischaemic stroke, recent myocardial infarction (MI) or symptomatic peripheral vascular disease (PVD). Mean patients' age was 62.5 years. 72% of the patients were males, and 95% of the patients were Caucasians. HOT 1998 included patients from 26 countries, aged 50 to 80 years (mean 61.5 years) with hypertension. In TPT 1998, men aged between 45 and 69 years (mean 57.5 years) at high risk of ischaemic heart disease were recruited from 108 practices in the UK. Huynh 2001 included patients from Canada with mean age of 67 and with unstable angina or non‐ST‐segment elevation MI, with prior coronary artery bypass grafting (CABG), and who were poor candidates for a revascularisation procedure. JPAD 2012 included patients from Japan with type 2 diabetes, mean age 65 years and 55% male. JPPP 2019 included Japanese patients with atherosclerotic risk factors (hypertension, diabetes mellitus, or dyslipidaemia). Median age was 70 years and 42% of patients were men.

Key results

Antiplatelet therapy with acetylsalicylic acid (ASA), also known as aspirin, for primary prevention in patients with elevated BP did not modify mortality and increased the risk of major bleedings.

Antiplatelet therapy with aspirin probably reduces the risk of non‐fatal and all cardiovascular events when compared to clopidogrel. Clopidogrel increases the risk of major bleeding events when compared to aspirin in patients with elevated BP for secondary prevention. 

There is no evidence that oral anticoagulation with warfarin modifies mortality in patients with elevated BP for secondary prevention. 

Ticlopidine, clopidogrel, and newer antiplatelet agents, such as prasugrel and ticagrelor have not been sufficiently evaluated in patients with elevated BP. Newer antithrombotic oral drugs (dabigatran, rivaroxaban, apixaban, and edoxaban) are yet to be tested in patients with high BP.

Certainty of the evidence

Most evidence in this review is associated with low‐certainty evidence. The high risk of bias seemed to be associated with incomplete outcome data and selective reporting in two studies (Huynh and JPPP).