Dual antiplatelet therapy (DAPT) consisting of aspirin plus P2Y12 Inhibitors have become the standard of care for preventing thrombotic events in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI).
A new pilot study demonstrated that aspirin could be discontinued the day after PCI, and colchicine, an anti-inflammatory agent, could be added to reduce the risk of ischemic events in these patients, while reducing the increased risk of bleeding associated with aspirin.
We conducted a pilot trial in ACS patients treated with drug-eluting stents (DES) who received low-dose colchicine the day after PCI, along with P2Y.12 inhibitor (ticagrelor or prasugrel) maintenance therapy. Aspirin use was discontinued.
At 3 months, only 1% of patients had stent thrombosis, and only 1 patient showed high platelet reactivity. In addition, at 1 month, high-sensitivity C-reactive protein (hs-CRP) and platelet reactivity both decreased, indicating reduced inflammation.
“In ACS patients undergoing PCI, it is reasonable to discontinue aspirin therapy and give low-dose colchicine the day after PCI in addition to ticagrelor or prasugrel P2Y.12 inhibitors,” wrote Seung-Yul Lee, MD, CHA Bundang Medical Center, CHA University, Seongnam, Korea, and colleagues. “This approach is associated with good platelet function and inflammatory profiles.”
The study was published online on August 16 JACC: Cardiovascular Intervention.
Safety Without Compromising 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 of myocardial infarction, stroke, coronary revascularization, and cardiovascular death in adult patients with established atherosclerosis. . disease or multiple risk factors for cardiovascular disease. It targets residual inflammation as the underlying cause of cardiovascular events.
Patients after PCI are generally treated using DAPT, but given the increased risk of 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 studies have yielded mixed results regarding discontinuation of aspirin therapy after 1 to 3 months and maintenance of P2Y.12 inhibitory 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, the investigators tested “a strategy that replaces aspirin with colchicine during the acute phase to maximize the effect of treatment in reducing ischemia and recurrent bleeding,” they wrote. Mono Antiplatelet and Colchicine Therapy (MACT) a one-arm, open-label proof-of-concept study was designed to investigate this approach.
Researchers studied 200 patients with non-ST-segment elevation ACS and ST-segment elevation myocardial infarction (STEMI) undergoing PCI with DES (mean [SD] age, 61.4 [10.7] many years; 90% male; 100% of Asian ethnicity), who received ticagrelor or prasugrel plus a dose of aspirin.
On the day after PCI, aspirin was discontinued, and low-dose colchicine (0.6 mg once daily) was given in addition to P2Y.12 inhibitor. In case of staged PCI, it is carried out under maintenance of colchicine and ticagrelor or prasugrel.
No other antiplatelet or anticoagulant agents are permitted.
The patient underwent platelet function testing using VerifyNow P2Y12 test before disposal. hs-CRP levels 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 3 months.
The primary outcome was stent thrombosis within 3 months of follow-up. Secondary outcomes included all cause death, MI, revascularization, major hemorrhage, combined cardiac death, target vessel MI, or target lesion revascularization, P2Y12 reaction unit (PRU), and changes in hs-CRP levels between 24 h post-PCI and 1-month follow-up.
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 did not adhere to taking antiplatelet medication.
“Although bleeding occurred in 36 patients, major bleeding occurred in only 1 patient,” report the authors.
The level of platelet reactivity on release was 27 ± 42 PRU. Most of the patients (91%) met the criteria for low platelet reactivity, whereas only 0.5% met the criteria for high platelet reactivity. Platelet reactivity was similar, regardless of which P2Y12 inhibitor (ticagrelor or prasugrel) the patient is taking.
In all patients, the level of inflammation “reduced significantly” over time: after 1 month, the hs-CRP level decreased from 6.1 mg/L (interquartile range to [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 < 0.001).
The prevalence of high inflammatory 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 < 0.001).
Major bleeding is rare, they reported, with a 3-month incidence of 0.5%.
“Inflammation plays a fundamental role in the development and progression of the atherothrombotic process,” explain the authors. A series of factors also trigger an “intense inflammatory response” in the acute phase of MI, which can lead to detrimental myocardial remodeling. In this study, the level of inflammation reduced rapidly.
They note some limitations. For example, all enrolled patients were Asian and had relatively low bleeding and ischemic risks. “Although ticagrelor or prasugrel are effective regardless of ethnicity, clinical data supporting these de-escalation strategies is limited,” they said. In addition, there is no control group for comparison.
These findings warrant further investigation, they concluded.
Promising but Preliminary
Comment for theheart.org | Medscape Cardiology, Francesco Costa, MD, PhD, interventional cardiologist and assistant professor, University of Messina, Sicily, Italy, says he thinks it is “too early for a broad clinical translation of these findings.”
In contrast, larger and more extensive randomized trials “are on the way to provide more precise estimates of the risks and benefits of early aspirin discontinuation in ACS.”
However, added Costa, who was not involved with the current study, “in this setting, adding colchicine early looks very promising for reducing potential thrombotic risk without increasing bleeding risk.”
Meanwhile, the study “provides new insights into early aspirin withdrawal and P2Y12 monotherapy in unselected populations, incl [those with] STEMI,” said Costa, also a co-author of the editorial. The findings “could be of particular concern to patients at very high bleeding risk or who are genuinely aspirin intolerant, 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 Center for Cardiovascular Research, Seoul, Korea. Lee reports no relevant financial relationships. Disclosures of other authors listed in the original paper. Costa has served on the advisory board for AstraZeneca And own receive speaker fees from Chiesi Farmaceutici. The co-authors reported no relevant financial relationships.
Batya Swift Yasgur MA, LSW, is a freelance writer with a counseling practice in Teaneck, New Jersey. He is a regular contributor to various medical publications, including Medscape and WebMD, and is the author of several consumer-oriented health books and Behind the Burqa: Our Life in Afghanistan and How We Flee to Freedom (memories of two brave Afghan sisters telling their stories).
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