27th July 2026, A/Prof Chee L Khoo
We are used to keeping patients on dual anti-platelet therapy (DAPT) usually consisting of aspirin and clopidogrel for 12 months following percutaneous coronary intervention (PCI) to prevent stent thrombosis. 12 months can pass quickly and we are supposed to revert these patients back to either aspirin or clopidogrel monotherapy after the 12 months but we may forget and these patients are on DAPT longer than the recommended 12 months. Is there any harm? Or more importantly, are there any benefits beyond the 12 months of DAPT?
We used to reassure our patients that once they have a PCI or a coronary artery bypass graft (CABG), they have a new lease of life. They had revascularisation and all is well now? Of course, we don’t do that anymore, do we? In fact, in the PROSPECT trial, in patients who had a PCI, over the subsequent 3-years, the cumulative rate of major adverse cardiovascular events was 20.4% (1). Interestingly, 12.9% of the events came from the (original) culprit and 11.6% came from non-culprit lesions. Not unexpectedly, the PCI only address stenoses > 70% and there are usually other sub-obstructive stenoses which can rupture later. These patients are at very high risk of further events after having an event.
Thus, in addition to ischemic events originating from previously treated coronary lesions, thrombotic events often arise from untreated segments of the coronary tree (1-3). The DAPT is to prevent thrombosis of the stent as well as to prevent further ischaemic events. Thus, while the risk of stent thrombosis passes after 12 months, the risk of further ischaemic events continues. DAPT beyond the 12 months may have additional benefits. Of course, we have to consider the bleeding risk in patients on DAPT. Whether the potential benefits of further extending the duration of DAPT in these patients outweigh the risk of bleeding is uncertain (4-6).
In a large open-label randomised trial in 97 centres in China, 8250 patients aged 18-75 years old with multi-vessel coronary artery disease who have received DAPT for 12 months following a PCI were randomised to either receive a further 12 months of DAPT or 12 months of aspirin monotherapy (7). These patients had no major bleeding events while on the first 12 months of DAPT. The primary efficacy end point was a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The primary safety end point was clinically relevant or major bleeding.
The mean patient age was 61 years; 2497 patients (30.3%) were female, and 2323 (28.2%) had diabetes. 98.3% had presented with an acute coronary syndrome before the index PCI. 79.5% of patients had a single vessel PCI. The median follow up was 34 months and only 1.8% of participants were lost to follow up.
About half of the participants had 2-vessel disease while the other half have more than 2-vessel disease. In more than 90% of participants, the diseased vessels were in the left anterior descending coronary artery. Thus, these were patients at very high risk of further plaque rupture.
A primary efficacy end-point event occurred in 222 patients in the DAPT group and in 266 patients in the aspirin-monotherapy group (hazard ratio, 0.82; p = 0.03). Clinically relevant or major bleeding occurred in 51 patients in the DAPT group and in 57 patients in the aspirin-monotherapy group (hazard ratio, 0.89; p = 0.54). The reduction in the risk of myocardial infarction with extended DAPT that was observed in the trial was driven mainly by fewer events arising from non-target coronary segments rather than from stented target sites.
Previous trials of extended DAPT, ischemic benefits were consistently offset by increased rates of major bleeding (8-10). Those trials did not specifically exclude patients who may have bleeding problems on the initial DAPT. In this trial, only patients who did not have bleeding problems in the first 12 months were recruited.
This latest trial suggests that in patients with multivessel disease who underwent PCI for coronary artery stenosis, a standard 12-month duration of DAPT may be insufficient. Extended duration of DAPT was associated with lower event rates without major bleeding risks provided they did not have major bleeding in the first 12 months.
References:
- Stone GW, Maehara A, Lansky AJ, de Bruyne B, Cristea E, Mintz GS, Mehran R, McPherson J, Farhat N, Marso SP, Parise H, Templin B, White R, Zhang Z, Serruys PW; PROSPECT Investigators. A prospective natural-history study of coronary atherosclerosis. N Engl J Med. 2011 Jan 20;364(3):226-35.
- Erlinge D, Maehara A, Ben-Yehuda O, et al. Identification of vulnerable plaques and patients by intracoronary near-infrared spectroscopy and ultrasound (PROSPECT II): a prospective natural history study. Lancet 2021; 397: 985-95.
- Jiang S, Fang C, Xu X, et al. Identifica tion of high-risk coronary lesions by 3-ves sel optical coherence tomography. J Am Coll Cardiol 2023; 81: 1217-30.
- Bhatt DL, Fox KAA, Hacke W, et al. Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrom botic events. N Engl J Med 2006; 354: 1706 17.
- Mauri L, Kereiakes DJ, Yeh RW, et al. Twelve or 30 months of dual antiplatelet therapy after drug-eluting stents. N Engl J Med 2014; 371: 2155-66.
- Helft G, Steg PG, Le Feuvre C, et al. Stopping or continuing clopidogrel 12 months after drug-eluting stent place ment: the OPTIDUAL randomized trial. Eur Heart J 2016; 37: 365-74.
- Tian J, Wang Z, Wang Y, et al. DAPT-MVD Trial Investigators. Extended Dual Antiplatelet Therapy for Multivessel Coronary Artery Disease. N Engl J Med. 2026 Jul 16;395(3):233-242.
- Mauri L, Kereiakes DJ, Yeh RW, et al. Twelve or 30 months of dual antiplatelet therapy after drug-eluting stents. N Engl J Med 2014; 371: 2155-66.
- Bonaca MP, Bhatt DL, Cohen M, et al. Long-term use of ticagrelor in patients with prior myocardial infarction. N Engl J Med 2015; 372: 1791-800.
- Steg PG, Bhatt DL, Simon T, et al. Ticagrelor in patients with stable coro nary disease and diabetes. N Engl J Med 2019; 381: 1309-20.