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).
A new pilot study suggests that aspirin can be discontinued on the day after the PCI, and colchicine, an anti-inflammatory agent, could be added to reduce the risk for ischemic events 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, Korea, and colleagues. “This approach is associated with favorable platelet function and inflammatory profiles.”
The study was published online August 16 in JACC: Cardiovascular Interventions.
Safety Without Compromised Efficacy
The US 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 to 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.
The Role of Inflammation
Of the original 200 patients, 190 completed the full protocol and were available for follow-up.
The primary outcome occurred in only two patients. It turned out that one of the patients had not been adherent with antiplatelet medications.
“Although bleeding occurred in 36 patients, major bleeding occurred in only 1 patient,” the authors report.
The level of platelet reactivity at discharge was 27 ± 42 PRUs. Most patients (91%) met the criteria for low platelet reactivity, while only 0.5% met the criteria for high platelet reactivity. Platelet reactivity was similar, regardless of which P2Y12 inhibitor (ticagrelor or prasugrel) the patients were taking.
In all patients, the level of inflammation was “reduced considerably” over time: after 1 month, the hs-CRP level decreased from 6.1 mg/L (interquartile range [IQR], 2.6 – 15.9 mg/L) at 24 hours after PCI to 0.6 mg/L (IQR, 0.4 – 1.2 mg/L; P < .001).
The prevalence of high-inflammation criteria, defined as hs-CRP ≥ 2 mg/L, decreased significantly, from 81.8% at 24 hours after PCI to 11.8% at 1 month (P < .001).
Major bleeding was rare, they report, with a 3-month incidence of 0.5%.
“Inflammation plays a fundamental role in the development and progression of the atherothrombotic process,” the authors explain. A series of factors also trigger “an intense inflammatory response” in the acute phase of MI, which may lead to adverse myocardial remodeling. In the present study, inflammatory levels were rapidly reduced.
They noted several limitations. For example, all enrolled patients were Asian and were at relatively low bleeding and ischemic risk. “Although ticagrelor or prasugrel is effective regardless of ethnicity, clinical data supporting this de-escalation strategy are limited,” they state. Additionally, there was no control group for comparison.
The findings warrant further investigation, they conclude.
Promising but Preliminary
Commenting for theheart.org | Medscape Cardiology, Francesco Costa, MD, PhD, interventional cardiologist and assistant professor, University of Messina, Sicily, Italy, said he thinks it’s “too early for extensive clinical translation of these findings.”
Rather, larger, and more extensive randomized trials are “on their way to give more precise estimates regarding the risks and benefits of early aspirin withdrawal in ACS.”
However, added Costa, who was not involved with the current research, “in this setting, adding colchicine early looks very promising to mitigate potential thrombotic risk without increasing bleeding risk.”
In the meantime, the study “provides novel insights on early aspirin withdrawal and P2Y12 monotherapy in an unselected population, including [those with] STEMI,” said Costa, also the coauthor of an accompanying editorial. The findings “could be of particular interest for those patients at extremely high bleeding risk or who are truly intolerant to aspirin, a scenario in which options are limited.”
J Am Coll Cardiol Interv. Published online August 16, 2023. Abstract, Editorial
This study was supported by the Cardiovascular Research Center, Seoul, Korea. Lee reports no relevant financial relationships. The other authors’ disclosures are listed on the original paper. Costa has served on an advisory board for AstraZeneca and has received speaker fees from Chiesi Farmaceutici. His coauthor reports no relevant financial relationships.
Batya Swift Yasgur MA, LSW, is a freelance writer with a counseling practice in Teaneck, New Jersey. She is a regular contributor to numerous medical publications, including Medscape and WebMD, and is the author of several consumer-oriented health books as well as Behind the Burqa: Our Lives in Afghanistan and How We Escaped to Freedom (the memoir of two brave Afghan sisters who told her their story).
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