Tailored antiplatelet therapy to improve prognosis in patients exhibiting clopidogrel low-response prior to percutaneous coronary intervention for stable angina or non-ST elevation acute coronary syndrome

Abstract

Aim: To investigate whether an intensified antiplatelet regimen could improve prognosis in stable or non-ST elevation in acute coronary syndrome (ACS) patients exhibiting high on-treatment platelet reactivity (HTPR) on clopidogrel and treated with percutaneous coronary intervention (PCI). There is a wide variability in the platelet reactivity to clopidogrel and HTPR has been associated with a poor prognosis. Methods: In this observational study, 923 consecutive patients without ST-elevation myocardial infarction (STEMI) and adequately pre-treated with clopidogrel were screened for HTPR with multiple electrode aggregometry after assessment of the coronary anatomy. Patients were grouped based on their response to clopidogrel and the assigned antiplatelet strategy. The primary endpoint was a composite of cardiovascular death, myocardial infarction, stroke, or stent thrombosis. Results: HTPR was demonstrated in 237 patients (25.7%). Of these, 114 continued on conventional clopidogrel therapy, while the remaining 123 received intensified antiplatelet therapy with either double-dose clopidogrel (150 mg daily, n = 55) or the newer P₂Y₁₂-inhibitors, prasugrel or ticagrelor (n = 68) for at least 30 days after the index procedure. The median follow-up was 571 days (interquartile range, 373–746). Intensifying antiplatelet therapy reduced the rate of the composite endpoint (p < 0.001). After adjustment for potential confounders, HTPR in combination with conventional clopidogrel therapy remained independently associated with an increased risk of cardiovascular events (hazard ratio (HR), 2.92; 95% CI, 1.90–4.48), whereas intensified treatment reduced the risk to a level equivalent to that of patients exhibiting normal platelet reactivity (HR, 1.08; 95% CI, 0.59–1.99). Conclusion: Tailored antiplatelet therapy significantly reduced the event rate in patients exhibiting HTPR prior to PCI.

• Antiplatelet therapy
• clopidogrel
• ischemic heart disease
• prasugrel
• prognosis

Acknowledgements

The authors thank the staff nurses at the cardiac catheterization laboratory for their invaluable assistance as well as the skilled technicians at the Haemostatic Research Laboratory of Rigshospitalet, Denmark. They also thank the Jaascha Foundation, the Arvid Nilsson Foundation and the Danish Heart Association for financial support.

Declaration of interest

Dr T. Engstrøm is a member of the Eli Lilly National Advisory Board; Dr L. Holmvang and Prof. P. Clemmensen are members of the National Advisory Boards of Eli Lilly and Astra Zeneca. The remaining authors, including the main author, have no conflicts of interest to declare.