Reticulated platelets predict cardiovascular death and adverse events in coronary artery disease

Abstract

Abstract Background/Introduction The pro-thrombotic immature or reticulated platelets (RPs) are known to be elevated in high risk patients and in different pathological settings. Several studies have shown that RPs correlate with an insufficient antiplatelet response to antiplatelet agents. In addition, RPs are emerging novel biomarkers for the prediction of adverse cardiovascular events in cardiovascular disease. Purpose The current study, using the totality of existing evidence, evaluated the prognostic role of RPs in patients with coronary artery disease. Methods We performed a systematic review and meta-analysis including trials of acute and chronic coronary syndrome reporting clinical outcomes according to RPs levels in the peripheral blood. Patients with elevated RPs were defined as RPshigh according to the single study definitions and compared to patients without elevated RPs (RPslow). Odds ratios (ORs) and 95% CIs were used as metric of choice for treatment effects with random-effects models. The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE). Secondary endpoints were cardiovascular death, myocardial infarction, ischemic stroke, urgent coronary revascularization and any bleeding. Prospero Registration number: CRD42022381282. Results A total of 7 studies, including 2213 patients, were included. The risk for MACCE was significantly higher in RPshigh compared to RPslow patients (OR 2.67 [1.87; 3.81], I2=43.8%, Figure 1). RPshigh were significantly associated with cardiovascular death (OR 2.09 [1.36; 3.22], I2=40.4%). No significant associations for RPshigh were detected with the other singular components of MACCE: myocardial infarction (OR 1.73 [0.89; 3.38] I2=60.5%) and stroke (OR 1.72 [0.59; 4.96] I2=21%). Urgent revascularization was not significantly associated with elevated RPs (OR 2.09 [0.90; 4.86] I2=55.5%). The risk of bleeding did not significantly differ between groups(OR 0.58 [0.15; 2.22] I2=86.1%). Conclusion Elevated RPs are significantly associated with increased risk of cardiovascular events and cardiovascular death in patients with coronary artery disease and should be considered a useful prognostic biomarker in this setting.Figure 1