A uniform unguided de-escalation strategy significantly reduced bleeding events after index percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI), according to findings from an open-label, assessor-masked randomized trial published in The Lancet.
In the current study, researchers enrolled patients in the Ticagrelor Versus Clopidogrel in Stabilized Patients With AMI (TALOS-AMI) trial (ClinicalTrials.gov Identifier: NCT02018055), conducted at 32 centers in South Korea between 2014 and 2018. Patients who underwent PCI for AMI and received ticagrelor plus aspirin were randomly assigned 1:1 a month after PCI to a de-escalation or active control group. The de-escalation group received treatment with 75 mg daily clopidogrel plus 100 mg aspirin; the active control group continued receiving 90 mg twice-daily ticagrelor plus 100 mg aspirin. Researchers assessed clinical outcomes through 12 months.
The primary endpoints were cardiovascular death, MI, stroke, and Bleeding Academic Research Consortium (BARC) events type 2, 3, or 5.
A total of 2697 patients were included in the multicenter study. The de-escalation (clopidogrel) and control (ticagrelor) cohorts included patients with a mean age of 60.1±11.3 years and 59.9±11.4 years; 16.1% and 17.6% were women; body mass index (BMI) was 24.6±3.1 and 24.5±3.1; and 54.4% and 53.5% had ST-segment elevation MI, respectively.
At 12 months, 4.6% of the de-escalation and 8.2% of the control group achieved the primary endpoint (hazard ratio [HR], 0.55; 95% CI, 0.40-0.76; P =.0001).
Risk for cardiovascular death, MI, or stroke did not differ between cohorts (HR, 0.69; 95% CI, 0.42-1.14; P =.15), but BARC events were significantly reduced among the de-escalation vs control cohort (HR, 0.52; 95% CI, 0.35-0.77; P =.0012).
Among patient subgroups, most groups were at decreased risk for the primary endpoint with the de-escalation therapy, specifically among patients with ST-elevated MI, non-ST-elevated MI, diabetes, left ventricular ejection fraction of at least 40%, estimated glomerular filtration rate of at least 60 mL/min/1.73 m2, stent length less than 40 mm, those without diabetes who underwent single-vessel treatment, those younger than 75 years, and among both men and women.
The study may have been biased by its open-label design and the lack of a placebo control. The regimen may also only be viable for uncomplicated, stabilized patients with AMI receiving PCI.
Overall, the study authors noted, “a uniform, unguided de-escalation [dual antiplatelet therapy] strategy switching from ticagrelor to clopidogrel in stabilized patients with [AMI] who had no major ischemic or bleeding events during the first month after an index PCI was superior to the ticagrelor-based continuing [dual antiplatelet therapy] strategy in terms of net clinical benefit, with a significant decrease in bleeding risk and no increase in ischemic risk.”
Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.
Kim CJ, Park M-W, Kim M C, et al. Unguided de-escalation from ticagrelor to clopidogrel in stabilised patients with acute myocardial infarction undergoing percutaneous coronary intervention (TALOS-AMI): an investigator-initiated, open-label, multicentre, non-inferiority, randomised trial. Lancet. 2021;398(10308):1305-1316. doi:10.1016/S0140-6736(21)01445-8