DAPT increases bleeding without decreasing mortality in patients with coronary disease and diabetes
Background: The PARTHENON clinical development program has conducted several clinical trials to assess the effectiveness of ticagrelor in multiple cardiovascular diseases. A prior study revealed the addition of ticagrelor to aspirin in patients with history of MI showed a small benefit in cardiovascular outcomes but with increased bleeding risk. While this effect was seen in both patients with and without diabetes, the absolute benefit for those with diabetes was considered large because of their higher baseline risk. Given this, investigators wanted to know if addition of ticagrelor to aspirin could also be beneficial in diabetics with known coronary disease but without history of MI or stroke.
Dr. Elizabeth Breitbach
Study design: Randomized, double-blind trial, intention-to-treat analysis.
Setting: Multicenter, 950 centers across 35 countries.
Synopsis: In this AstraZeneca-funded trial, 19,000 patients with diabetes and coronary disease without prior MI or stroke received either aspirin or DAPT (aspirin + ticagrelor). The composite outcome including cardiovascular death, MI, stroke, or death from any cause at 36 months was reduced in the DAPT arm (6.9% vs. 7.6%; hazard ratio, 0.90; 95% confidence interval, 0.81-0.99; P = .04) with a number needed to treat of 138. This composite outcome was driven by MI and stroke without differences in cardiovascular death or death from any cause. However, the primary safety outcome of major bleeding was higher with DAPT (2.2% vs. 1.0%; HR, 2.32; 95% CI, 1.82-2.94; P less than .001) with a number needed to treat of 93. Intracranial bleeding was higher with DAPT. Incidence of irreversible harm measured by death, MI, stroke, fatal bleeding, or intracranial hemorrhage showed no difference.
Further studies into risk stratification based on prothrombotic versus bleeding risk could be beneficial in identifying specific groups that could benefit from DAPT. Conclusions from this study suggest the benefit of DAPT in diabetics does not outweigh its risk.
Bottom line: Addition of ticagrelor to aspirin in diabetic patients with stable coronary disease and no prior MI or stroke is not recommended.
Citation: Steg PG et al. Ticagrelor in patients with stable coronary disease and diabetes. N Eng J Med. 2019 Oct 3;381(14):1309-20.
Dr. Breitbach is assistant professor of medicine, hospital medicine, at the Rocky Mountain Veterans Affairs Regional Medical Center, Aurora, Colo.
