Impact of Dual Antiplatelet Therapy on Outcomes Among Aspirin-Resistant Patients Following Coronary Artery Bypass Grafting

Abstract

Coronary artery bypass grafting is pivotal in the contemporary management of complex coronary artery disease. Interpatient variability to antiplatelet agents, however, harbors the potential to compromise the revascularization benefit by increasing the incidence of adverse events. This study was designed to define the impact of dual antiplatelet therapy (dAPT) on clinical outcomes among aspirin-resistant patients who underwent coronary artery surgery. We randomly assigned 219 aspirin-resistant patients according to multiple electrode aggregometry to receive clopidogrel (75 mg) plus aspirin (300 mg) or aspirin-monotherapy (300 mg). The primary end point was a composite outcome of all-cause death, nonfatal myocardial infarction, stroke, or cardiovascular hospitalization assessed at 6 months postoperatively. The primary end point occurred in 6% of patients assigned to dAPT and 10% of patients randomized to aspirin-monotherapy (relative risk 0.61, 95% confidence interval 0.25 to 1.51, p = 0.33). No significant treatment effect was noted in the occurrence of the safety end point. The total incidence of bleeding events was 25% and 19% in the dAPT and aspirin-monotherapy groups, respectively (relative risk 1.34, 95% confidence interval 0.80 to 2.23, p = 0.33). In the subgroup analysis, dAPT led to lower rates of adverse events in patients with a body mass index >30 kg/m(2) (0% vs 18%, p <0.01) and those <65 years (0% vs 10%, p = 0.02). In conclusion, the addition of clopidogrel in patients found to be aspirin resistant after coronary artery bypass grafting did not reduce the incidence of adverse events, nor did it increase the number of recorded bleeding events. dAPT did, however, lower the incidence of the primary end point in obese patients and those <65 years.

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.…”

“…A subgroup analysis revealed that dAPT led to lower rates of adverse events in patients with a body mass index >30 kg/m(2) (0% vs 18%, p <0.01) and those <65 years (0% vs 10%, p = 0.02) [8]. This was the first prospective randomized study to address the clinical impact of dual APT after CAS in patients with aggregometry-documented aspirin resistance [8]. We cannot reliably exclude the possibility that this study may have been underpowered and the addition of clopidogrel would result generally in better outcomes if we have had larger patient cohort recruited [8].…”

“…If aspirin resistance occurs after relatively high doses of aspirin being administered, addition of another, supplemental, antiplatelet agent is rational. Recently, our working group has evaluated the impact of clopidogrel addition on outcomes among aspirin resistant patients following CAS [8]. A subgroup analysis revealed that dAPT led to lower rates of adverse events in patients with a body mass index >30 kg/m(2) (0% vs 18%, p <0.01) and those <65 years (0% vs 10%, p = 0.02) [8].…”

“…Recently, our working group has evaluated the impact of clopidogrel addition on outcomes among aspirin resistant patients following CAS [8]. A subgroup analysis revealed that dAPT led to lower rates of adverse events in patients with a body mass index >30 kg/m(2) (0% vs 18%, p <0.01) and those <65 years (0% vs 10%, p = 0.02) [8]. This was the first prospective randomized study to address the clinical impact of dual APT after CAS in patients with aggregometry-documented aspirin resistance [8].…”

“…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.…”