Aspirin for the primary prevention of cardiovascular disease in individuals with chronic kidney disease: a systematic review and meta-analysis

Aims Cardiovascular disease (CVD) is the major cause of morbidity and mortality in individuals with chronic kidney disease (CKD). This study assessed the risks and benefits of aspirin in the primary prevention of CVD in individuals with CKD. Methods and results Ovid MEDLINE was searched from 2015 to 15th of September 2020 to include randomized controlled trials that assessed aspirin versus placebo in adults with non-end stage CKD without a previous diagnosis of CVD. A pre-specified protocol was registered with PROSPERO (identification number CRD42014008860). A random effects model was used to calculate a pooled hazard ratio (HR), pooled risk difference, and the number needed to treat or harm (NNT/NNH). The primary endpoint was CVD. Secondary endpoints included: all-cause mortality; coronary heart disease; stroke; and major and minor bleeding events. Five trials were identified (n = 7852 total, n = 3935 aspirin, n = 3917 placebo). Overall, 434 CVD events occurred. There was no statistically significant reduction in CVD events (HR 0.76, 95% confidence interval (CI) 0.54-1.08; P = 0.13, I-2 = 63%), all-cause mortality (HR 0.94, 95% CI 0.74-1.19; P = 0.60, I-2 = 21%), coronary heart disease events (HR 0.66, 95% CI 0.27-1.63; P = 0.37, I-2 = 64%) or stroke (HR 0.87, 95% CI 0.6-1.27; P = 0.48, I-2 = 24%) from aspirin therapy. The risk of major bleeding events were increased by approximately 50% (HR 1.53, 95% CI 1.13-2.05; P = 0.01, I-2 = 0%) and minor bleeding events were more than doubled (HR 2.64, 95% CI 1.64-4.23; P < 0.01, I-2 = 0%). Conclusions Aspirin cannot be routinely recommended for the primary prevention of CVD in individuals with CKD as there is no evidence for its benefit but there is an increased risk of bleeding.