Debra L. Beck and Eugene Braunwald, MD
Date Published: 18 Oct 2019
Balancing ischemic risk and bleeding risk after percutaneous coronary intervention (PCI) is an important dilemma for clinicians. Reducing the duration of aspirin after PCI may allow for more prolonged use of potent P1Y12 inhibitors while avoiding aspirin-related bleeding risk. Monotherapy with a P2Y12 inhibitor after a minimum period of dual antiplatelet therapy (DAPT) is an emerging approach. In the TWILIGHT trial, Mehran et al studied the effect of ticagrelor alone as compared to ticagrelor plus aspirin in patients undergoing PCI who are at high risk for ischemic or hemorrhagic complications and who have completed a 3-month course of DAPT with ticagrelor plus aspirin.
In this double-blind trial, 7119 patients (mean age 65 years, 24% female) who had not had a major bleeding event or an ischemic event after the index PCI were randomized after three months of DAPT with ticagrelor (90 mg daily) plus aspirin (81 to 100 mg daily) to receive either ticagrelor alone or continued DAPT. Participants had to have at least one clinical and one angiographic feature associated with increased risk of ischemic or bleeding events.
The majority of participants presented with acute coronary syndrome (65%) and had multivessel coronary artery disease (63%). The trial was conducted at 187 sites in 11 countries in North American, Europe, and Asia.
For the primary endpoint of Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding, the incidence was 4.0% in the ticagrelor alone arm and 7.1% in the ticagrelor plus aspirin arm (hazard ratio HR], 0.56; p<0.001). The treatment effect for the primary endpoint was consistent across predefined subgroups.
BARC type 3 or 5 bleeding was seen in 1.0% of the ticagrelor monotherapy arm and in 2.0% of the DAPT arm (HR, 0.49; 95% confidence intervals, 0.33 – 0.74).
The key secondary endpoint, the composite of death from any cause, nonfatal myocardial infarction, or nonfatal stroke from 0 to 12 months after randomization, was evaluated with the use of a prespecified noninferiority hypothesis with an absolute margin of 1.6 percentage points. Incidence rates were 3.9% for both groups (HR, 0.99; p<0.001 for noninferiority).
The researchers concluded that, in high-risk patients who underwent PCI and were free from ischemic or bleeding events after 3 months of DAPT, 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 over a period of 1 year.
These results may not be generalizable to all patients undergoing PCI, given the requirements in this trial for both high-risk (clinical and angiographic) features and freedom from major adverse events after three months of DAPT. Also, the trial was underpowered to detect difference in important yet rare clinical events, such as stent thrombosis and stroke.
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