Dual antiplatelet therapy in patients with aspirin resistance following coronary artery bypass grafting: study protocol for a randomized controlled trial [NCT01159639]

Abstract

BackgroundCoronary artery disease remains the dominant cause of mortality in developed countries. While platelets have been recognized to play a pivotal role in atherothrombosis, the ideal antiplatelet regime after coronary artery surgery remains elusive.The evolution of CABG has presently moved beyond technical improvements to involve modulation of pharmacologic management designed to improve patient outcomes. The aim of this trial will be to test the hypothesis that the addition of clopidogrel to patients with documented postoperative aspirin resistance will reduce the incidence of major cardiovascular events.MethodsPatients scheduled for isolated coronary artery surgery will be eligible for the study. Patients in whom postoperative multiple electrode aggregometry documents aspirin resistance will be randomized into two groups. The control group will receive 300 mg of aspirin. The dual antiplatelet group will receive 75 mg of clopidogrel in addition to 300 mg of aspirin. Patients will be followed for 6 months. Major adverse cardiac and cerebrovascular events (death from any cause, myocardial infarction, stroke, hospitalization due to cardiovascular pathology) as well as bleeding events will be recorded.DiscussionThis will be the first trial that will specifically address the issue of dual antiplatelet therapy in patients undergoing coronary artery surgery who have been found to be aspirin resistant. In the event that the addition of clopidogrel proves to be beneficial in this subset of surgical patients, this study could significantly impact their future antiplatelet management.This randomized controlled trial has been registered at the ClinicalTrials.gov website (Identifier NCT01159639).

Development of a concept for a personalized approach in the perioperative antiplatelet therapy administration/discontinuation management based on multiple electrode aggregometry in patients undergoing coronary artery surgery

“…In addition to this, we have evaluated the perioperative dynamics of platelet reactivity and have found that patients have hyperactive platelets in early postoperative phase resulting in a significant increase in prevalence of aspirin resistance in the early postoperative phase [10] . Furthermore, we evaluated the clinical relevance of aspirin resistance [11] as well as the treatment modalities to overcome aspirin resistance [2,7,8]. Although some studies performed by our working group were actually underpowered to reliably evaluate association between on treatment platelet reactivity and relatively infrequent adverse outcomes, the findings that we gained through our research help us to establish the platform for the "therapeutic window" concept.…”

“…Based upon our own clinical and research experience using multiple electrode aggregometry (MEA) (Multiplate® ; Roche Diagnostics, Mannheim, Germany) in this particular field [2][3][4][5][6][7][8][9][10][11][12][13], we sought to define pre-and post CAS therapeutic window for the most commonly administered APT such as aspirin and adenosine di-phosphate receptor blockers.…”

Impact of aspirin resistance on outcomes among patients following coronary artery bypass grafting: exploratory analysis from randomized controlled trial (NCT01159639)

“…We adhered to ethical standards in line with the Declaration of Helsinki. Study design details and eligibility criteria have previously been published 17 . In brief, 2034 patients were initially assessed for eligibility and 439 patients underwent platelet function testing on the fourth postoperative day (POD 4).…”

“…In brief, 2034 patients were initially assessed for eligibility and 439 patients underwent platelet function testing on the fourth postoperative day (POD 4). 224 out of 439 patients were found to be aspirin resistant at POD 4 and were randomly assigned to receive clopidogrel (75mg) plus aspirin (300mg) -interventional arm or aspirin-monotherapy (300mg) -non-interventional (control) arm 17 .…”

“…More in detail data regarding primary and secondary outcomes have been already published 17,19 . Put briefly, the primary efficacy end point was the incidence of major adverse cardiac and cerebrovascular events (MACCEs) after 6 months follow up 19 .…”