Placebo-controlled RCT: In high-risk patients who completed 3 mo of DAPT after PCI, adding aspirin to ticagrelor increased clinically relevant bleeding at 1 y.
Mehran R, Baber U, Sharma SK, et al. Ticagrelor with or without Aspirin in High-Risk Patients after PCI. N Engl J Med. 2019 Sep 26. doi: 10.1056/NEJMoa1908419.

BACKGROUND: Monotherapy with a P2Y12 inhibitor after a minimum period of dual antiplatelet therapy is an emerging approach to reduce the risk of bleeding after percutaneous coronary intervention (PCI).

METHODS: In a double-blind trial, we examined the effect of ticagrelor alone as compared with ticagrelor plus aspirin with regard to clinically relevant bleeding among patients who were at high risk for bleeding or an ischemic event and had undergone PCI. After 3 months of treatment with ticagrelor plus aspirin, patients who had not had a major bleeding event or ischemic event continued to take ticagrelor and were randomly assigned to receive aspirin or placebo for 1 year. The primary end point was Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding. We also evaluated the composite end point of death from any cause, nonfatal myocardial infarction, or nonfatal stroke, using a noninferiority hypothesis with an absolute margin of 1.6 percentage points.

RESULTS: We enrolled 9006 patients, and 7119 underwent randomization after 3 months. Between randomization and 1 year, the incidence of the primary end point was 4.0% among patients randomly assigned to receive ticagrelor plus placebo and 7.1% among patients assigned to receive ticagrelor plus aspirin (hazard ratio, 0.56; 95% confidence interval [CI], 0.45 to 0.68; P<0.001). The difference in risk between the groups was similar for BARC type 3 or 5 bleeding (incidence, 1.0% among patients receiving ticagrelor plus placebo and 2.0% among patients receiving ticagrelor plus aspirin; hazard ratio, 0.49; 95% CI, 0.33 to 0.74). The incidence of death from any cause, nonfatal myocardial infarction, or nonfatal stroke was 3.9% in both groups (difference, -0.06 percentage points; 95% CI, -0.97 to 0.84; hazard ratio, 0.99; 95% CI, 0.78 to 1.25; P<0.001 for noninferiority).

CONCLUSIONS: Among high-risk patients who underwent PCI and completed 3 months of dual antiplatelet therapy, ticagrelor monotherapy was associated with a lower incidence of clinically relevant bleeding than ticagrelor plus aspirin, with no higher risk of death, myocardial infarction, or stroke. (Funded by AstraZeneca; TWILIGHT ClinicalTrials.gov number, NCT02270242.).

Ratings
Specialty Area Score
Family Medicine (FM)/General Practice (GP)
General Internal Medicine-Primary Care(US)
Cardiology
Hemostasis and Thrombosis
Hospital Doctor/Hospitalists
Internal Medicine
Comments from MORE raters

Cardiology

Very important study that is potentially practice-changing in the field of Interventional Cardiology. In the high-risk population studied, ticagrelor monotherapy was superior to dual antiplatelet therapy in patients with high-risk PCI after 3 months of DAPT. The inclusion of clinical and angiographic factors defining high-risk populations was very appropriate.

Hemostasis and Thrombosis

Truly novel findings.

This well-executed study informs the length of dual anti-platelet therapy after PCI when ticagrelor is chosen as a component of the initial anti-platelet regimen.

Hospital Doctor/Hospitalists

On page 3 of the manuscript, the authors state that randomization occurred 3 months after hospital discharge, however, later it is noted to be 3 months post-PCI. Did hospital discharge occur right after PCI in all cases? Only those who were deemed "eligible" and had no bleeding were randomized; all-comers were not randomized. The "high-risk bleeding factors" can be argued, given a small percentage of patients with CKD, PAD, DM, and those on insulin. Also, racial distribution is not equal (most are white). Overall, great study with high relevance, but we don`t have enough evidence to conclude anything specific with regard to the ischemic events based on the Kaplan-Meier plot. All we see is that there is no statistical difference. Clinically, there might be a difference in the ischemic endpoints.

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