Ticagrelor or Clopidogrel as Antiplatelet Agents in Patients with Chronic Kidney Disease and Cardiovascular Disease: A Meta-analysis

Introduction

The worldwide prevalence of chronic kidney disease (CKD) has significantly increased in the past decades. Scientific reports have shown CKD to be an enhancing risk factor for the development of cardiovascular disease (CVD), which is the leading cause of premature death in patients with CKD. Clinical practice guidelines are ambiguous in view of the use of antiplatelet drugs in patients with CKD because patients with moderate-to-severe CKD were often excluded from clinical trials evaluating the efficacy and safety of anticoagulants and antiplatelet agents. In this analysis, we aimed to systematically assess the adverse cardiovascular and bleeding outcomes that were observed with ticagrelor versus clopidogrel use in patients with CKD and cardiovascular disease.

Methods

Electronic databases including Web of Science, Google Scholar, http://www.ClinicalTrials.gov, Cochrane database, EMBASE, and MEDLINE were carefully searched for English-based articles comparing ticagrelor with clopidogrel in patients with CKD. Adverse cardiovascular outcomes and bleeding events were the endpoints in this study. The latest version of the RevMan software (version 5.4) was used to analyze the data. Risk ratios (RR) with 95% confidence intervals (CI) were used to represent the data post analysis.

Results

A total of 15,664 participants were included in this analysis, whereby 2456 CKD participants were assigned to ticagrelor and 13,208 CKD participants were assigned to clopidogrel. Our current analysis showed that major adverse cardiac events (MACEs) (RR: 0.85, 95% CI: 0.71–1.03; P = 0.09), all-cause mortality (RR: 0.82, 95% CI: 0.57– 1.18; P = 0.29), cardiovascular death (RR: 0.83, 95% CI: 0.56–1.23; P = 0.35), myocardial infarction (RR: 0.87, 95% CI: 0.70–1.07; P = 0.19), ischemic stroke (RR: 0.80, 95% CI: 0.58–1.11; P = 0.18), and hemorrhagic stroke (RR: 1.06, 95% CI: 0.38–2.99; P = 0.91) were not significantly different in CKD patients who were treated with ticagrelor versus clopidogrel. Thrombolysis in myocardial infarction (TIMI)-defined minor (RR: 0.89, 95% CI: 0.52–1.53; P = 0.68) and TIMI major bleeding (RR: 1.10, 95% CI: 0.69–1.76; P = 0.67) were also not significantly different. However, bleeding defined according to the academic research consortium (BARC) bleeding type 1 or 2 (RR: 1.95, 95% CI: 1.13–3.37; P = 0.02) and BARC bleeding type 3 or 5 (RR: 1.70, 95% CI: 1.17–2.48; P = 0.006) were significantly higher with ticagrelor.

Conclusions

When compared with clopidogrel, even though ticagrelor was not associated with higher risk of adverse cardiovascular outcomes in these patients with CKD, it was associated with significantly higher BARC bleeding. Therefore, the safety outcomes of ticagrelor still require further evaluation in patients with CKD. Nevertheless, this hypothesis should only be confirmed with more powerful results that could usually only be achieved using large-scale randomized trials.