Benefits and Risks of the Combination of Clopidogrel and Aspirin in Patients Undergoing Surgical Revascularization for Non–ST-Elevation Acute Coronary Syndrome

Abstract

Background-Antiplatelet therapy and antithrombin therapy have been demonstrated to reduce the risk of cardiac events in patients presenting with acute coronary syndrome, yet all effective therapies also increase the risk of bleeding. Methods and Results-In the Clopidogrel in Unstable angina to prevent Recurrent ischemic Events (CURE) trial, 12 562 patients were randomized to clopidogrel or placebo in addition to aspirin, and the primary outcome was cardiovascular (CV) death, myocardial infarction (MI), or stroke. The benefits were consistent among those undergoing percutaneous coronary intervention (PCI) [9.6% for clopidogrel, 13.2% for placebo; relative risk (RR), 0.72; 95% CI, 0.57 to 0.90], coronary artery bypass grafting (CABG) surgery (14.5% for clopidogrel 16.2% for placebo; RR, 0.89; 95% CI, 0.71 to 1.11), and medical therapy only (8.1% for clopidogrel, 10.0% for placebo; RR, 0.80; 95% CI, 0.69 to 0.92; test for interaction among strata, 0.53). For CABG during the initial hospitalization (530 for placebo, 485 for clopidogrel), the frequency of CV death, MI or stroke before CABG was 4.7% for placebo and 2.9% for clopidogrel (RR, 0.56; 95% CI, 0.29 to 1.08). For the entire study, there was a 1% excess of major bleeding but no significant excess of life-threatening bleeding. Among patients undergoing CABG, the rates of life-threatening bleeding were 5.6% for clopidogrel and 4.2% for placebo (RR, 1.30; 95% CI, 0.91 to 1.95; both nonsignificant). Conclusions-The benefits versus risks of early and long-term clopidogrel therapy (freedom from CV death, MI, stroke, or life-threatening bleeding) are similar in those undergoing revascularization (CABG or PCI) and in the study population as a whole. Overall, the benefits of starting clopidogrel on admission appear to outweigh the risks, even among those who proceed to CABG during the initial hospitalization.

Changes in short- and long-term cardiovascular risk of incident diabetes and incident myocardial infarction—a nationwide study

“…In 2003, percutaneous coronary intervention was applied as the gold standard for acute ST-elevation MI in Denmark [10] and the use of beta-blockers, statins and platelet inhibitors has markedly increased [11][12][13][14]. However, no decline of relative risk was demonstrated when comparing the incident MI patients from the two time periods.…”

Precatheterization Use of P2Y 12 Inhibitors in Non‐ST‐Elevation Myocardial Infarction Patients Undergoing Early Cardiac Catheterization and In‐Hospital Coronary Artery Bypass Grafting: Insights From the National Cardiovascular Data Registry ®

“…Interestingly, the delay to surgery seems longer for ticagrelor despite its having a shorter half‐life compared with clopidogrel. Importantly, the observed duration from catheterization to CABG is significantly shorter than that seen in the clinical trials studying this topic previously 12, 13. The reluctance of clinicians to wait the recommended period may be possibly explained by a bias toward earlier revascularization5, 14; only a small proportion of NSTEMI patients treated with precatheterization P2Y 12 inhibitors deferred CABG to another hospitalization after the index NSTEMI hospitalization.…”

“…In a subgroup analysis of CABG patients in the CURE trial,12 pretreatment with clopidogrel was found to have similar clinical benefits without incurring increased risk of bleeding when CABG was performed more than 5 days after drug cessation but was associated with increased life‐threatening bleeding when clopidogrel was discontinued less than 5 days before CABG. Our study again showed that bleeding and transfusion rates were higher when CABG occurred within 5 days of precatheterization P2Y 12 inhibitor exposure, compared with CABG that occurred >5 days afterwards.…”

Antithrombotic therapy in cardiac surgery

“…52 The benefits and risks of clopidogrel were analyzed recently in patients undergoing CABG for non-ST elevation acute coronary syndrome. 67 The benefits of clopidogrel (re-introduced after six to 25 days after surgery) overweighed the bleeding risk. However, data indicate that the use of clopidogrel within three to five days before surgery is associated with increased bleeding.…”

“…However, data indicate that the use of clopidogrel within three to five days before surgery is associated with increased bleeding. 67,68 Therefore, cessation of clopidogrel at least five days before surgery, when possible, is clearly recommended. When clopidogrel has not been stopped before surgery (for example, emergency procedure), the use of antifibrinolytics (aprotinin, epsilon-aminocaproic acid or tranexamic acid) could be proposed, since such treatments decrease postoperative blood loss and transfusion requirements, without increasing early graft closure.…”