Dual antiplatelet therapy (DAPT) consisting of aspirin plus a P2Y12 inhibitor has been the standard of care to prevent thrombotic events in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI).
in these patients, while mitigating the increased bleeding risk associated with aspirin.
Investigators conducted a pilot trial in ACS patients treated with drug-eluting stents (DES) who received low-dose colchicine the day after PCI, together with P2Y12 inhibitor (ticagrelor or prasugrel) maintenance therapy. Aspirin use was discontinued.
At 3 months, only 1% of the patients experienced stent thrombosis, and only 1 patient showed high platelet reactivity. Moreover, at 1 month, high-sensitivity C-reactive protein (hs-CRP) and platelet reactivity both decreased, pointing to reduced inflammation.
“In ACS patients undergoing PCI, it is feasible to discontinue aspirin therapy and administer low-dose colchicine on the day after PCI in addition to ticagrelor or prasugrel P2Y12 inhibitors,” write Seung-Yul Lee, MD, CHA Bundang Medical Center, CHA University, Seongnam, South Korea, and colleagues. “This approach is associated with favorable platelet function and inflammatory profiles.”
The study was published online in JACC: Cardiovascular Interventions.
Safety without compromised efficacy
The U.S. Food and Drug Administration recently approved colchicine 0.5-mg tablets (Lodoco, Agepha Pharma) as the first anti-inflammatory drug shown to reduce the risk for myocardial infarction, stroke, coronary revascularization, and cardiovascular death in adult patients with either established atherosclerotic disease or multiple risk factors for cardiovascular disease. It targets residual inflammation as an underlying cause of cardiovascular events.
Patients after PCI are generally treated using DAPT, but given the risk for increased bleeding associated with aspirin – especially when used long-term – there is a “need to identify strategies associated with a more favorable safety profile without compromising efficacy,” the authors write.
Previous research has yielded mixed results in terms of the discontinuation of aspirin therapy after 1-3 months and maintenance on P2Y12 inhibitor monotherapy. But one trial found colchicine to be effective in reducing recurrent ischemia, and its benefits may be more beneficial with early initiation in the hospital.
In this new study, researchers tested a “strategy that substitutes aspirin with colchicine during the acute phase to maximize the treatment effect of reducing recurrent ischemia and bleeding,” they write. The Mono Antiplatelet and Colchicine Therapy (MACT) single-arm, open-label proof-of-concept study was designed to investigate this approach.
The researchers studied 200 patients with non–ST-segment elevation ACS and ST-segment elevation myocardial infarction (STEMI) who underwent PCI with DES (mean [SD] age, 61.4 [10.7] years; 90% male; 100% of Asian ethnicity), who were receiving either ticagrelor or prasugrel plus a loading dose of aspirin.
On the day after PCI, aspirin was discontinued, and low-dose colchicine (0.6 mg once daily) was administered in addition to the P2Y12 inhibitor. In the case of staged PCI, it was performed under the maintenance of colchicine and ticagrelor or prasugrel.
No other antiplatelet or anticoagulant agents were permitted.
Patients underwent platelet function testing using the VerifyNow P2Y12 assay before discharge. Levels of hs-CRP were measured at admission, at 24 and 48 hours after PCI, and at 1-month follow-up. Clinical follow-up was performed at 1 and at 3 months.
The primary outcome was stent thrombosis within 3 months of follow-up. Secondary outcomes included all-cause mortality, MI, revascularization, major bleeding, a composite of cardiac death, target vessel MI, or target lesion revascularization, P2Y12 reaction units (PRUs), and change in hs-CRP levels between 24 hours post-PCI and 1-month follow-up.