A new patient tells you that he read in a men’s health magazine that people with hypertension should take daily aspirin. He asks if you agree.
Should we prescribe antiplatelet agents or anticoagulants for all patients with hypertension?
Antiplatelet agents should not be used in patients with hypertension and no previous history of heart attack or stroke. However, these agents are recommended for use in hypertensive patients who already have vascular disease. Anticoagulants should not be used for prevention of vascular events, alone or in combination with acetylsalicylic acid (ASA), in patients with elevated blood pressure. Currently, there is not enough evidence to recommend the use of glycoprotein IIb/IIIa inhibitors, ticlopidine, or clopidogrel for primary prevention of vascular events.
Background. Elevated systemic blood pressure results in high intravascular pressure. The main complications, coronary heart disease, ischemic strokes, and peripheral vascular disease, are related to thrombosis rather than hemorrhage. Some complications related to elevated blood pressure, heart failure, and atrial fibrillation are associated with stroke and thromboembolism. It seems plausible that antithrombotic therapy may be particularly useful in preventing thrombosis-related complications of elevated blood pressure.
Objectives. To conduct a systematic review of the role of antiplatelet therapy a
nd anticoagulation in patients with hypertension, including those with elevations in systolic and diastolic blood pressure and those with isolated elevations of systolic or diastolic blood pressure. The following hypotheses were addressed: (1) antiplatelet agents reduce total deaths and major thrombotic events compared with other active treatment or placebo; and (2) oral anticoagulants reduce total deaths and major thromboembolic events compared with other active treatment or placebo.
Search Strategy. The authors1 studied reference lists of articles found by searching electronic databases (MEDLINE, EMBASE, DARE) and abstracts from national and international cardiovascular meetings. Relevant authors of these studies were contacted to obtain further data.
Selection Criteria. Randomized controlled trials (RCTs) in patients with elevated blood pressure were included if they were of at least three months’ duration and compared antithrombotic therapy with other active treatment or placebo.
Data Collection and Analysis. Data were independently collected and verified by two reviewers. Data from different trials were pooled when appropriate.
Primary Results. The Antiplatelet Trialists’ Collaboration meta-analysis of antiplatelet therapy for secondary prevention in patients with elevated blood pressure reported a 4.1 percent absolute reduction in vascular events compared with placebo. Data on the patients with elevated blood pressure from the 29 individual trials were requested but could not be obtained. Three additional trials met the inclusion criteria and were included. Acetylsalicylic acid (ASA) did not reduce stroke or “all cardiovascular events” compared with placebo in primary prevention patients with elevated blood pressure and no prior cardiovascular disease. In one large trial (the Hypertension Optimal Treatment trial), ASA taken for five years reduced rates of myocardial infarction (MI) (absolute risk reduction, 0.5 percent; number needed to treat [NNT], 200 for five years), increased rates of major hemorrhage (absolute risk increase, 0.7 percent; NNT, 154), and did not reduce all-cause mortality or cardiovascular mortality. In the Clopidogrel vs. Aspirin in Patients at Risk of Ischemic Events trial, there was no significant difference between ASA and clopidogrel for the composite end point of stroke, MI, or vascular death. In two small trials, warfarin alone or in combination with ASA did not reduce rates of stroke or coronary events.
Reviewers’ Conclusions. Antiplatelet therapy with ASA cannot be recommended for primary prevention of vascular events in patients with elevated blood pressure, because the magnitude of benefit—a reduction in rates of MI—is negated by a harm of similar magnitude, an increase in rates of major hemorrhage. Antiplatelet therapy is recommended for secondary prevention in patients with elevated blood pressure because the magnitude of the absolute benefit is many times greater.2 Warfarin therapy alone or in combination with aspirin in patients with elevated blood pressure cannot be recommended because of lack of demonstrated benefit. Glycoprotein IIb/IIIa inhibitors, as well as ticlopidine and clopidogrel, have not been evaluated sufficiently in patients with elevated blood pressure. Further trials of antithrombotic therapy with complete documentation of all benefits and harms are needed in patients with elevated blood pressure.
These summaries have been derived from Cochrane reviews published in the Cochrane Database of Systematic Reviews in the Cochrane Library. Their content has, as far as possible, been checked with the authors of the originalreviews, but the summaries should not be regarded as an official product of the Cochrane Collaboration; minorediting changes have been made to the text (http://www.cochrane.org).
This review shows that aspirin should be used for prophylaxis only in patients with hypertension and a history of stroke, transient ischemic attack, myocardial infarction (MI), angina, or peripheral vascular disease. An appropriate choice and dosage of antiplatelet agent for secondary prevention would be 75 or 81 mg of enteric-coated ASA daily.2
The primary analysis of the review is based on four large, high-quality trials. Some additional analysis is based on a previous meta-analysis of prolonged antiplatelet therapy compared with placebo. The four trials were analyzed and discussed individually. Results were consistent among studies and were measured with reasonable precision.
The authors were careful to assess benefit and harm for each intervention. This is why prescribing an antiplatelet agent or anticoagulant is not recommended for primary prevention of adverse vascular events in patients with hypertension. In the case of antiplatelet agents, the benefit (reduction in rates of MI) was balanced by a harm (increase in major hemorrhagic events), resulting in no overall decrease in all-cause or cardiovascular mortality. No benefit was observed for anticoagulants. There is not enough evidence to recommend for or against the use of ticlopidine, clopidogrel, and glycoprotein IIb/IIIa inhibitors. However, they should not be used for primary prevention of vascular events in hypertensive patients because they are expensive and provide no significant benefit.
There is evidence from the Antiplatelet Trialists’ Collaboration meta-analysis3 that ASA in patients with a history of vascular disease for secondary prevention of major adverse events provides a benefit that outweighs the risk of harm and the cost of the medication. However, no subgroup analysis was done to assess the benefit and harm from prolonged low-dosage ASA in hypertensive patients with a history of gastrointestinal bleeding.4 Therefore, there is insufficient evidence to recommend prolonged low-dosage ASA for secondary prevention in such patients. In patients for whom ASA would provide benefit but is contraindicated, clopidogrel would serve equally well for secondary prevention of adverse vascular events. It should not be used as first-line therapy because it is expensive and no more effective than ASA.
A search of the National Guideline Clearinghouse in October 2004 found no guidelines that discussed the use of antiplatelet agents or anticoagulants in the management of hypertension. The Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure5 does not address the use of antiplatelets or anticoagulants. This Cochrane review is the best and most up-to-date information available on this topic at this time. Clinical Evidence6 outlines several other effective measures for the secondary prevention of adverse vascular events. The ones that are of interest to family physicians include beta blockers, angiotensin-converting enzyme inhibitors, cholesterol reduction, smoking cessation, the Mediterranean diet, eating more fish, managing stress, and getting regular exercise.