Platelet reactivity among patients with acute coronary syndromes and multivessel coronary artery disease

Background Patients with multivessel or complex coronary artery disease (CAD) are at increased risk of atherothrombotic events. It has been suggested that these patients may derive an incremental benefit with more intense antiplatelet strategies, according to prior subgroup analyses from randomized clinical trials. However, whether there is any association between the presence and extension of multivessel CAD and platelet aggregability (PA) in patients with acute coronary syndromes (ACS) is unknown. Purpose To analyze the independent association between PA and presence of multivessel CAD in patients with ACS. Methods Patients with ACS on dual antiplatelet therapy (aspirin plus clopidogrel) were included in this study. Multivessel CAD was defined as the presence of significant ≥50% stenosis at two or more major epicardic vessels. Platelet aggregability was assessed by VerifyNow P2Y12 assay expressed in P2Y12 Reactivity Units (PRU) on the day of discharge from the coronary care unit. High On-treatment platelet reactivity (HPR) was defined as PRU ≥208. Stepwise linear and logistic regression models were applied to adjust for confounders. Models were adjusted for: age, sex, race, diabetes, hypertension, smoking, dyslipidemia, prior MI, prior PCI, prior CABG, prior HF, prior stroke and ACS phenotype (STEMI vs. Non-ST-segment elevation ACS). Results A total of 237 patients were included, among whom 143 (60.3%) had multivessel CAD at the coronary angiogram and 175 (73.8%) were submitted to PCI during index hospitalization. Patients with multivessel disease were older (mean age 64.8±12.1 vs. 58.9±11.2 years; p<0.001) and more likely to have a history of diabetes (47.6% vs. 29.8%; p=0.006) and non-ST-segment elevation ACS as the index event (55.2% vs. 28.7%; p<0.001), compared to patients without multivessel CAD. After adjustments, presence of multivessel CAD was associated with higher PA (mean 161.4±74 PRU in patients with versus 140.3±70.9 PRU in patients without multivessel CAD; adjusted mean difference 23.7 PRU; 95% CI 4.8 to 42.5; p=0.014). Additionally, there was an incremental of 12.5 PRU (95% CI 2.8 to 22.3; adj p=0.012) for each diseased vessel and of 4.67 PRU (95% CI 0.11 to 9.22; adj p=0.045) for each diseased coronary segment. Compared to patients with single-vessel disease, patients with three-vessel disease had higher rates of HPR. (Figure). Conclusion In patients with ACS, the presence and extension of multivessel CAD were associated with higher levels of platelet aggregability and higher rates of high on-treatment platelet reactivity with clopidogrel. This finding may explain the incremental benefit with more intense antiplatelet therapies seen in this particular subgroup in prior clinical trials. Prevalence of HPR and extension of CAD Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Sao Paulo Research Foundation (FAPESP)