Patients who received platelet function monitoring and dose adjustments after stent implantation fared no better than those given standard care, according to a study published online Nov. 4 in the New England Journal of Medicine. The findings were simultaneously presented at the American Heart Association (AHA) scientific sessions in Los Angeles.
Noting that up to one-third of patients have inadequate platelet inhibition, which may lead to an increased risk of cardiac events, Jean-Phillippe Collet, MD, and colleagues from the Insititut de Cardiologie Hôpital Pitié-Salpêtrière and Université Pierre et Marie Curie in Paris conducted a randomized, open-label study of patients electing to undergo drug-eluting stent implantation at 38 centers in France.
The Assessment by Double Randomization of a Conventional Anti-Platelet Strategy for Drug-Eluting Stent Implantation and of Treatment Interruption vs. Continuation One Year After Stenting (ARCTIC) study identified patients with inadequate platelet-inhibitory responses and made adjustments to those patients' antiplatelet therapy. The researchers postulated that tailored antiplatelet therapy in patients demonstrating inadequate response to aspirin and/or clopidogrel might result in a 33 percent reduction in risk for the primary endpoint, a composite of death, MI, stroke or transient ischemic attack, urgent coronary revascularization and stent thrombosis.
Researchers established several exclusion criteria:
- Primary PCI for MI with ST-segment elevation;
- Planned use of glycoprotein IIb/IIIa inhibitors;
- Long-term anticoagulant therapy; and
- Bleeding diathesis.
The study enrolled 2,440 patients who were randomly assigned to either the monitoring group or the control group. Randomization took place after coronary angiography and before the intervention procedure. The groups were well-matched as to age, gender, body weight and diabetes. Twenty-seven percent of the patients presented with an acute coronary syndrome without ST-segment elevation (327 patients in the conventional treatment group and 330 patients in the monitoring group).
The 1,213 patients in the conventional treatment group received standard antiplatelet treatment without measurement of their individual platelet reactivity. The 1,227 patients in the monitoring group were subject to platelet reactivity monitoring and adjustment of antiplatelet drugs and dosages, if indicated. In both groups the researchers recommended a loading dose of P2Y12 inhibitors at least six hours before stent implantation.
Before the intervention, researchers took platelet function measurements for both aspirin and P2Y12 inhibitors in the monitoring group with the VerifyNow assay (Accumetrics). If the patient was highly reactive to aspirin, aspirin was administered intravenously. If the patient was highly reactive to clopidogrel, the patient received glycoprotein IIb/IIIA inhibitors and an additional loading dose of clopidogrel (dose greater than or equal to 600mg) or a loading dose of prasugrel (60 mg) before the procedure, followed by a daily maintenance dose of 150 mg clopidogrel or 10 mg prasugrel. Those patients who demonstrated adequate platelet inhibition received standard antiplatelet therapy. Between 14 and 30 days after the procedure, the researchers again tested the monitoring group patients for platelet reactivity and adjusted the medications, if indicated.
At one-year follow-up, 34.6 percent of patients in the monitoring group and 31.1 percent of patients in the conventional treatment group reached the primary endpoint. The primary endpoint was driven mainly by MI. Bleeding events occurred in less than 5 percent of the patients, and there was no statistically significant difference in the frequency of bleeding events between the two groups of patients. Results were similar for minor bleeding events.
The authors discussed several possible reasons for the trial's failure to demonstrate the benefit of tailored antiplatelet therapy:
- They enrolled high-risk patients in the study and one-year mortality was higher than would be expected among the general population who undergo elective stenting;
- The percentage of patients who responded poorly to clopidogrel is similar to the percentage identified in the GRAVITAS study, and they suggested that developing a different cutoff value for these patients might have elicited different results;
- The trial was a strategy trial, so the methods of treating patients with inadequate platelet response were "heterogeneous";
- Platelet reactivity during treatment may not be a valuable marker of risk;
- Platelet function testing and treatment adjustment cannot affect other factors such as treatment compliance, comorbidities or procedure-related technical problems;
- The poor predictive value of the VerifyNow assay; and
- The researchers did not use genetic profiling, a bedside resource that is now available.
The authors listed other studies that may provide more insights and concluded, “[O]ur data do not support the routine use of platelet-function testing in patients undergoing coronary stenting.”