Clinical Question

Does antiplatelet therapy prevent myocardial infarction in patients with chronic kidney disease (CKD)?

Evidence-Based Answer

Antiplatelet therapy reduces the risk of myocardial infarction by 0.8% compared with placebo (95% CI, 0.1% to 1.5%; number needed to treat [NNT] = 125) in patients with CKD but is associated with an increased risk of major bleeding (number needed to harm [NNH] = 100).¹ (Strength of Recommendation: C, disease-oriented evidence.)

Practice Pointers

Conditions that increase the risk of CKD, including hypertension, obesity, and diabetes mellitus, are increasing worldwide with a commensurate increase in the global health care expense related to these conditions. Myocardial infarction is three times more likely in patients with CKD compared with those who have normal kidney function. In general, cardiovascular disease is the leading cause of morbidity and mortality in patients with CKD.^2,3 Excessive platelet activation in CKD is postulated to create a prothrombotic state and antiplatelet agents have been extensively used in these patients.⁴ The authors of this analysis sought to discern the effectiveness of antiplatelet agents in preventing myocardial infarction.

The 2021 Cochrane review is an update of the 2013 review and included 118 studies (randomized and quasi-randomized), enrolling 51,959 participants. The population included patients 18 years and older with CKD, defined as a glomerular filtration rate of less than 60 mL per minute per 1.73 m²; those receiving kidney replacement therapy; those with a functioning kidney transplant; or patients with proteinuria (Kidney Disease Outcomes Quality Initiative stages 1 to 5) or elevated creatinine levels (i.e., serum creatinine level higher than 120 μmol per L [1.36 mg per dL]). There were 90 studies (40,597 participants) that compared an antiplatelet agent with placebo or no treatment, and 29 studies (11,805 CKD participants) that compared one antiplatelet agent with another. The studies were conducted across North and South America, Europe, Asia, Australia, and New Zealand; they were single or multicentric trials and were performed in one or multiple countries.

The antiplatelet agents that were studied included, but were not limited to, acetylsalicylic acid (i.e., aspirin); adenosine diphosphate receptor inhibitors (e.g., ticlopidine, clopidogrel); adenosine reuptake inhibitors (e.g., dipyridamole); glycoprotein IIb/IIIa inhibitors (e.g., abciximab, eptifibatide, tirofiban [Aggrastat], defibrotide [Defitelio]); phosphodiesterase 3 inhibitors (e.g., cilostazol); P2Y₁₂ antagonists (e.g., prasugrel [Effient], ticagrelor [Brilinta], cangrelor [Kengreal]); and sulfinpyrazone (Anturane). Agents were administered at different doses and via different routes.

Use of an antiplatelet agent compared with placebo probably reduced the risk of fatal or nonfatal myocardial infarction in people with CKD during a median follow-up of 12 months (moderate-certainty evidence; absolute risk reduction = 0.8% [95% CI, 0.1% to 1.5%]; NNT = 125 [95% CI, 66 to 1,000]; n = 15,289). There was no statistically significant effect on all-cause mortality.

Major bleeding as a risk of antiplatelet therapy was defined as retroperitoneal; intra-articular; intraocular, intracranial, or intracerebral hemorrhage; or gastrointestinal bleeding. It also included bleeding that was fatal, life-threatening, disabling, required transfusion, or needed corrective surgery or hospitalization, with or without a fall in hemoglobin or melena. Antiplatelet use compared with placebo probably increased major bleeding in people with CKD over a median follow-up of six months (moderate certainty of evidence; NNH = 100; 95% CI, 53 to 333; n = 16,194).

A meta-analysis of 50 studies of patients with CKD (27,773 participants) showed a reduction in the risk of myocardial infarction (NNT = 62; 95% CI, 25 to 166; n = 18,382) and an increased risk of major bleeding (NNH = 111; 95% CI, 62 to 333).⁵ The Kidney Disease Improving Global Outcomes guideline supports aspirin use for adults with CKD and balancing the increased bleeding risk.⁶ The decision to use antiplatelet therapy should be individualized according to the treatment goals of each patient.

The practice recommendations in this activity are available at https://www.cochrane.org/CD008834.

Editor's Note: The absolute risk reduction, CIs, NNHs, and NNTs reported in this Cochrane for Clinicians were calculated by the authors based on raw data provided in the original Cochrane review.