Aspirin and dual antiplatelet therapy (DAPT) yielded similar outcomes in patients with diabetes who underwent coronary artery bypass grafting (CABG), according to a post hoc secondary analysis of the FREEDOM trial (Future Revascularization Evaluation in Patients With Diabetes Mellitus: Optimal Management of Multivessel Disease; ClinicalTrials.gov identifier: NCT00086450).
The analysis, published in the Journal of the American College of Cardiology, compared patients who received DAPT (aspirin plus thienopyridine) with patients who received aspirin monotherapy at 30 days post-CABG.
The primary outcome was the FREEDOM trial primary end point, defined as 5-year all-cause mortality, nonfatal myocardial infarction (MI), or stroke. Secondary outcomes included the individual components of the composite outcomes: vascular death, MI, and cardiovascular hospitalization. Major bleeding, blood transfusion, and hospitalization for bleeding were defined as the safety outcomes.
As the researchers noted, diabetes is independently associated with an increased risk of perioperative and long-term mortality in patients who receive CABG and may also be a risk factor for vein graft failure.
Of the 947 patients from FREEDOM who were randomly assigned to undergo CABG, 795 were included in the analysis. There were no significant differences between groups in the 5-year primary composite outcome (12.5% vs 16.0%; adjusted hazard ratio [HR]: 0.83; 95% CI, 0.54-1.27; P =.39) or in the secondary outcomes.
In addition, the researchers observed no major differences between DAPT-only and aspirin-only treated patients in the safety outcomes of major bleeding (5.6% vs 5.7%; HR: 1.00; 95% CI, 0.50-1.99; P =.99), blood transfusions (4.8% vs 4.5%; HR: 1.09; 95% CI, 0.50-2.34; P =.82), and hospitalizations for bleeding (2.6% vs 3.3%; HR: 0.80; 95% CI, 0.31-2.04; P =.64).
Outcomes were also similar by surgical indication (acute coronary syndrome or stable angina), SYNTAX scores, DAPT duration, completeness of revascularization, and by on-pump or off-pump CABG.
“The lack of an observed difference in major bleeding by treatment assignment in this analysis was an unexpected finding,” the authors wrote. “Prior meta-analyses have reported point estimates for bleeding were nonsignificantly higher in DAPT CABG patients. We hypothesize this finding may be due to inadequate power because of a small number of events or differential treatment strategies.”
Based on their findings, the researchers concluded that routine DAPT may not be warranted in these patients, but more adequately powered randomized trials are needed to confirm the most optimal course of therapy.
- Outcomes were taken from prescription rates at 30 days after CABG, meaning that clinical and bleeding outcomes associated with early postoperative use cannot be inferred.
- This analysis was conducted prior to the approval of P2Y12 inhibitors (ticagrelor and prasugrel); therefore, the results cannot be extrapolated to these drugs.
- A small number of patients in whom DAPT post-CABG is recommended had off-pump CABG.
- DAPT dosing information was unavailable in case report form.
- The results should be considered hypothesis generating because the analysis was nonrandomized and may not have been adequately powered.
Disclosures: Dr van Diepen reports receiving honoraria and/or grant support from AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Pfizer, Merck, Novartis, Amgen, Sorin, Abbott, and Janssen. Dr Goodman reports receiving research grant support and speaker/consulting honoraria from AstraZeneca, Bayer, Bristol-Myers Squibb, Daiichi-Sankyo, Eli Lilly, and Sanofi-Aventis.
van Diepen S, Fuster V, Verma S, et al. Dual antiplatelet therapy vs aspirin monotherapy in diabetics with multivessel disease undergoing CABG. FREEDOM insights. J Am Coll Cardiol. 2017;69(2):119-127. doi.10.1016/j.jacc.2016.10.043