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One-Month Ticagrelor Monotherapy After PCI in Acute Coronary Syndromes - IVUS-ACS/ULTIMATE-DAPT
Contribution To Literature:
Highlighted text has been updated as of April 8, 2024.
The IVUS-ACS trial showed that IVUS-guided PCI is superior to angiography-guided PCI for 1 year outcomes among patients undergoing PCI for an ACS presentation.
The ULTIMATE-DAPT trial showed that compared with standard 12-month DAPT with aspirin and ticagrelor, 1-month DAPT followed by de-escalation to ticagrelor monotherapy reduces bleeding without an increase in ischemic events at 1 year among patients undergoing PCI for ACS.
Description:
The goal of the trial was to compare the efficacy of intravascular ultrasound (IVUS)-guided vs. angiography-guided percutaneous coronary intervention (PCI) among patients undergoing acute coronary syndrome (ACS) PCI. Further, it sought to assess the safety and efficacy of ticagrelor monotherapy compared with dual antiplatelet therapy (DAPT) with aspirin and ticagrelor for 12 months following completion of 1-month DAPT for ACS PCI.
Study Design
Initially, patients were randomized to IVUS-guided (n = 1,753) or angiography-guided (n = 1,752) PCI for index ACS event. All patients received DAPT with ticagrelor and aspirin for 30 days. If they had no ischemic or bleeding events at the end of 30 days, they were randomized to continuing DAPT for 12 months total (n = 1,700), or stopping aspirin and switching to ticagrelor + placebo (n = 1,700). Ticagrelor dose was 90 mg bid; aspirin dose was 100 mg daily. During follow-up, a reduction in ticagrelor from 90 mg to 60 mg bid was required in 0.8% of patients.
- Total randomized participants: 3,400
- Median duration of follow-up: 1 year
- Median patient age: 63 years
- Percentage female: 26%
Inclusion criteria:
- ≥18 years of age
- Either 1) biomarker-positive non–ST-segment elevation myocardial infarction (NSTEMI) or STEMI, OR 2) biomarker-negative unstable angina (DS ≥90%, ruptured plaque, or thrombotic lesion)
- Had been randomized in the IVUS-ACS trial of IVUS-guided vs. angiography-guided PCI (for ULTIMATE-DAPT)
- Remained event free after PCI with contemporary drug-eluting stents (DES) for 1 month on ticagrelor (90 mg bid) plus aspirin (100 mg qd)
Exclusion criteria:
- Stroke within 3 months or any permanent neurologic deficit
- Previous coronary artery bypass grafting
- Any planned surgery within 12 months
- Estimated glomerular filtration rate <20 mL/min/1.73 m²
- Need for chronic oral anticoagulation
- Life expectancy <1 year
Other salient features/characteristics:
- Chinese race: 88%
- Chronic kidney disease: 7%
- Prior PCI: 10%
- Prior stroke: 9%
- Presentation: unstable angina: 40%, NSTEMI: 32%, STEMI: 28%
- Left ventricular ejection fraction: 63%
- Number of diseased vessels: one-vessel disease (70%), two-vessel disease (23%)
- Type of DES use: Firehawk (52%), Resolute (41%)
Principal Findings:
IVUS-ACS:
The primary endpoint of target vessel failure (cardiac death, target vessel MI, or clinically driven target vessel revascularization) for IVUS-guided vs. angiography-guided PCI, was: 4.0% vs. 7.3% (hazard ratio 0.55, 95% confidence interval 0.41-0.74, p = 0.0001).
- Cardiac death: 0.5% vs. 1.1%, p = 0.17
- Spontaneous MI: 0.6% vs. 1.5%, p = 0.0143
- Clinically driven target vessel revascularization: 1.4% vs. 3.2%, p = 0.001
Key secondary outcomes for IVUS-guided vs. angiography-guided PCI:
- Definite or probable stent thrombosis: 0.6% vs. 0.9%, p = 0.64
- Clinically driven target lesion revascularization: 1.3% vs. 2.5%, p = 0.014
ULTIMATE DAPT:
The primary effectiveness endpoint, Bleeding Academic Research Consortium (BARC) 2, 3, or 5 bleeding for ticagrelor + placebo vs. ticagrelor + aspirin, was: 2.1% vs. 4.6% (hazard ratio 0.45, 95% confidence interval 0.30-0.66, p < 0.0001).
- BARC 3 or 5: 0.7% vs. 1.7%, p = 0.009
- TIMI major or minor bleeding: 0.7% vs. 1.6%, p = 0.01
The primary safety endpoint, major adverse cardiovascular or cerebrovascular events (cardiac death, MI, ischemic stroke, definite stent thrombosis, clinically driven target vessel revascularization): 3.6% vs. 3.7%, p < 0.0001 for noninferiority, p = 0.89 for superiority
Key secondary outcomes for ticagrelor + placebo vs. ticagrelor + aspirin:
- All-cause mortality: 0.7% vs. 0.8%, p = 0.84
- Nonprocedure MI: 0.9% vs. 0.7%, p = 0.29
- Repeat revascularization: 2.4% vs. 2.4%, p = 0.95
- Stent thrombosis: 0.3% vs. 0.3%, p = 0.96
Interpretation:
The results of this trial show that IVUS-guided PCI is superior to angiography-guided PCI for 1- year outcomes among patients undergoing PCI for an ACS presentation. Further, 1-month DAPT followed by de-escalation to ticagrelor monotherapy reduces bleeding compared with 12-month DAPT without an increase in ischemic events at 1 year among these patients (including those presenting with STEMI).
The IVUS data are concordant with recent studies suggesting a benefit with IVUS-guided PCI compared with angiography alone guided PCI, especially for complex subsets. This trial provides evidence for the same among ACS patients.
There have been several recent trials (such as TWILIGHT and TICO) suggesting that de-escalation from DAPT to APT monotherapy, typically P2Y12 inhibitor monotherapy, after 3 months post-PCI for ACS is feasible and safe. In the STOPDAPT-2 ACS trial, de-escalating DAPT to clopidogrel monotherapy after 1 month did not meet prespecified noninferiority criteria compared with standard 12 months of DAPT for ACS-PCI. The current trial suggests that DAPT duration of 1 month followed by ticagrelor monotherapy may be sufficient among patients undergoing ACS-PCI. These are important findings and may influence clinical practice. One caveat is that patients in this trial were mostly Chinese; extrapolation to other ethnic/racial groups is unclear. In addition, other trials have suggested some harm with shorter durations among STEMI patients (SMART-DATE, STOPDAPT-2 STEMI subgroup).
In the current trial, although the p-value for interaction was negative, the ischemic event rates appeared somewhat increased with shorter duration of DAPT. This population needs careful study in future studies. Finally, with the advent of high-sensitivity troponin assays, the incidence of true “unstable angina” has diminished in the United States. In the current trial, 40% were enrolled with a diagnosis of unstable angina. It is unclear if some of these represented non-ACS patients.
References:
Li X, Ge Z, Kan J, et al., on behalf of the IVUS-ACS Investigators. Intravascular ultrasound-guided versus angiography-guided percutaneous coronary intervention in acute coronary syndromes (IVUS-ACS): a two-stage, multicenter, randomized trial. Lancet 2024;Apr 8:[Epub ahead of print].
Ge Z, Kan J, Gao X, et al., on behalf of the ULTIMATE-DAPT Investigators. Ticagrelor alone versus ticagrelor plus aspirin from month 1 to month 12 after percutaneous coronary intervention in patients with acute coronary syndromes (ULTIMATE-DAPT): a randomized, placebo-controlled, double-blind clinical trial. Lancet 2024;Apr 7:[Epub ahead of print].
Presented by Dr. Shaoliang Chen at the American College of Cardiology Annual Scientific Session (ACC.24), Atlanta, GA, April 8, 2024.
Presented by Dr. Gregg W. Stone at the American College of Cardiology Annual Scientific Session (ACC.24), Atlanta, GA, April 7, 2024.
Clinical Topics: Acute Coronary Syndromes, Invasive Cardiovascular Angiography and Intervention, Interventions and ACS
Keywords: ACC24, ACC Annual Scientific Session, Acute Coronary Syndrome, Percutaneous Coronary Intervention
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