Aspirin Use for Primary Prevention Associated With Lower Risk of Cardiovascular Events and an Increased Risk of Major Bleeding A Systematic Review and Meta-analysis

An original investigation by Zheng et al. published in JAMA showed that the use of aspirin in individuals without cardiovascular disease was associated with a lower risk of cardiovascular events and an increased risk of major bleeding.  This may assist in discussions with patients about aspirin for the primary prevention of cardiovascular events and bleeding.

Zheng et al. conducted the study as a systematic review of 13 trials that had 164 228 participants without cardiovascular disease. It was analyzed in individuals with low and high cardiovascular risk, people with diabetes and in cancer-based on ARRIVE(Aspirin to Reduce Risk of Initial Vascular Events), ASCEND(A Study of Cardiovascular Events in Diabetes) and ASPREE(Aspirin in Reducing Events in the Elderly) trials respectively. The primary cardiovascular outcome was a composite of cardiovascular mortality, non-fatal myocardial infarction, and non-fatal stroke. Secondary cardiovascular outcomes included all-cause mortality, cardiovascular-related mortality, myocardial infarction, total stroke (ischemic, hemorrhagic, and unknown), and ischemic stroke. The primary bleeding outcome
was major bleeding and was individually defined by studies. Secondary bleeding outcomes included intracranial bleeding
(intracerebral, subarachnoid, and subdural) and major gastrointestinal bleeding.

The investigators reported that the use of aspirin was associated with reductions in the composite cardiovascular outcome (HR, 0.89 [95% CrI, 0.84-0.95]; number needed to treat [NNT], 265 ; myocardial infarction (HR, 0.85 [95% CrI, 0.73-0.99];  NNT, 361) and ischemic stroke (HR, 0.81 [95% CrI, 0.76-0.87]; NNT, 540) , as compared with no aspirin. Moreover, aspirin use was found to have an increased rate of major bleeding(HR, 1.43 [95% CrI, 1.30-1.56]; number needed to harm [NNH], 210) ; an intracranial hemorrhage (HR, 1.34 [95% CrI, 1.14-1.57]; NNH, 927) and major gastrointestinal bleeding(HR, 1.56 [95% CrI, 1.38-1.78]; NNH, 334) as compared to no aspirin. 

The authors addressed certain limitations in their study that comprised of poorly reported outcomes of the study in different trials and differing aspirin doses. Also, the adoption of additional primary prevention strategies, such as risk factor modification and development of public health initiatives, limited the applicability of earlier studies to current practice. The study mainly included the 3 studies ARRIVE, ASPREE and ASCEND. In the ARRIVE trial, the findings reflected that aspirin had an absolute risk decrease of 0.51% but an absolute increase of 0.64% for major bleeding. In addition, the ASPREE trial showed that there was an increased risk of cancer-related mortality and it did not decrease the same. In the ASCEND trial, there was no harm or benefit from the use of aspirin. The investigators also noted that the absolute risk reduction for cardiovascular events and absolute risk increase for major bleeding associated with aspirin use were of similar magnitude. Aspirin use was not associated with a reduction in cardiovascular mortality, and deaths due to bleeding were rare. While widespread use of aspirin for primary prevention in the middle-aged and elderly needs to be avoided, the decision can be aided by weighing the risk of serious GI bleed (e.g., >75 years, the previous history) and intracranial hemorrhage (e.g., hypertension) on an individual basis.