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TWILIGHT-ACS: Ticagrelor monotherapy beneficial in PCI for ACS
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PHILADELPHIA — Among patients with ACS who underwent PCI, ticagrelor monotherapy reduced bleeding risk compared with dual antiplatelet therapy, with no additional ischemic risk, according to new data from the TWILIGHT study presented at the American Heart Association Scientific Sessions.
As Healio previously reported, in the main results of TWILIGHT, switching to ticagrelor (Brilinta, AstraZeneca) monotherapy from DAPT 3 months after PCI lowered bleeding risk without raising ischemic risk.
A TWILIGHT-ACS substudy of 5,763 patients with non-ST-segment elevation ACS showed results consistent with the main study, Usman Baber, MD, MS, assistant professor of medicine at Icahn School of Medicine at Mount Sinai and Cardiology Today Next Gen Innovator, said during a press conference.
At 1 year after randomization, which occurred 3 months after PCI, the rate of BARC 2, 3 or 5 bleeding was 7.6% in those assigned DAPT with ticagrelor and aspirin compared with 3.6% in those assigned ticagrelor monotherapy (HR = 0.47; 95% CI, 0.36-0.61), Baber said.
The results were consistent regardless of how many risk factors patients had (P for interaction = .69), he said.
According to Baber, other prespecified bleeding endpoints also favored the ticagrelor monotherapy group at 1 year after randomization:
- BARC 3 or 5 bleeding: 0.8% vs. 2.1%; P < .0001;
- TIMI major bleeding: 0.5% vs. 1%; P = .08;
- GUSTO moderate or severe bleeding: 0.6% vs. 1.6%; P = .002; and
- ISTH major bleeding: 0.9% vs. 2.2%; P = .001.
The primary ischemic outcome of death, MI or stroke at 1 year was almost identical in both groups, Baber said (monotherapy, 4.3%; DAPT, 4.4%; HR = 0.97; 95% CI, 0.74-1.28). He noted these results were also consistent regardless of the number of risk factors (P for interaction = .18).
There were no significant differences in prespecified ischemic endpoints including:
- CV death, MI or ischemic stroke: monotherapy, 4%; DAPT, 4.2%; P = .77;
- All-cause death: monotherapy, 1%; DAPT, 1.5%; P = .14;
- Any MI: 3.1% in both groups; P = .99;
- Ischemic stroke: monotherapy, 0.5%; DAPT, 0.3%; P = .21; and
- Definite or probable stent thrombosis: monotherapy, 0.4%; DAPT, 0.5%; P = .38.
“We found that the effect of ticagrelor monotherapy was uniform across different levels of risk, and the results were consistent regardless if you presented with unstable angina or non-STEMI,” Baber said at the press conference. “In aggregate, these findings are concordant with the primary results.”
Independent predictors of the primary ischemic endpoint included elevated troponin level (HR = 1.77; 95% CI, 1.23-2.55), established vascular disease (HR = 2.77; 95% CI, 1.94-3.97), atherectomy use (HR = 2.46; 95% CI, 1.19-5.1) and BARC 3 or 5 bleeding (HR = 6.7; 95% CI, 3.1-14.6), Baber said.
The primary bleeding and ischemic endpoints were consistent regardless of whether patients had unstable angina or non-STEMI, he said, noting that “a common theme was no excess ischemic risk with ticagrelor monotherapy, irrespective of clinical presentation.”
In a discussant presentation, Michelle L. O’Donoghue, MD, MPH, senior investigator for the TIMI Study Group, associate professor of medicine at Harvard Medical School and cardiologist at Brigham and Women’s Hospital, said that in a pooled analysis of TWILIGHT, GLOBAL LEADERS, SMART-CHOICE and STOPDAPT-2, the primary bleeding endpoint was reduced by 40% in those who had short-term DAPT followed by P2Y12 inhibitor monotherapy compared with those who had longer-term DAPT (HR = 0.6; 95% CI, 0.42-0.84), with no elevated risk for MACE (HR = 0.91; 95% CI, 0.79-1.04).
When the analysis was restricted to patients with ACS, the results were similar, with the relative bleeding risk reduction increasing to 51% (HR for bleeding = 0.49; 95% CI, 0.4-0.61; HR for MACE = 0.89; 95% CI, 0.73-1.09), she said.
“The remaining questions include, for patients on monotherapy, which P2Y12 inhibitor is the best choice?” O’Donoghue said. “Should we require genotyping or platelet function testing for patients on clopidogrel monotherapy? Beyond month 12, should the P2Y12 inhibitor be continued indefinitely without aspirin?” – by Erik Swain
Reference:
Baber U, et al. Late Breaking Science IV: State of the Art Interventional Management for ACS Patients. Presented at: American Heart Association Scientific Sessions; Nov. 16-18, 2019; Philadelphia.
Disclosures: The study was funded by AstraZeneca. Baber reports he received research funding from AstraZeneca and received personal fees from or serves on an advisory board for Amgen, AstraZeneca and Boston Scientific.
Perspective
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Dharam J. Kumbhani, MD, SM
This is a very important subgroup analyses from this landmark trial, because there were earlier data showing if you use shorter duration of DAPT in patients with ACS, you may pay a penalty. One, SMART-DATE, showed a concerning MI signal when DAPT was stopped at 6 months compared with 12 months. Against that background, TWILIGHT-ACS is reassuring that the bleeding benefit seen in the main trial is also present in the ACS subset, which is about two-thirds of the entire population. It was not powered for ischemic endpoints, but at least we didn’t see any obvious penalty in hard endpoints or stent thrombosis.
One distinction between SMART-DATE and TWILIGHT is that patients were kept on ticagrelor monotherapy in TWILIGHT till 12 months; it was altogether stopped at 6 months in SMART-DATE and aspirin monotherapy was continued. Another important nuance is that patients with STEMI were not included in TWILIGHT. One can imagine that those patients would have the highest thrombotic risk. These results are reassuring in non-STEMI, but patients with STEMI need to be further studied.
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