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. Author manuscript; available in PMC: 2024 May 1.
Published in final edited form as: Am J Cardiol. 2023 Aug 1;204:26–28. doi: 10.1016/j.amjcard.2023.07.029

Major Adverse Cardiovascular Events After Colchicine Administration Before Percutaneous Coronary Intervention: Follow-Up of the Colchicine-PCI Trial

Binita Shah a,b,*, Nathaniel R Smilowitz a,b, Yuhe Xia c, Frederick Feit b, Stuart D Katz b, Judy Zhong c, Bruce Cronstein d, Jeffrey D Lorin a,b, Michael H Pillinger d,e
PMCID: PMC10947505  NIHMSID: NIHMS1972346  PMID: 37536200

Abstract

Periprocedural inflammation is associated with major adverse cardiovascular events in patients who undergo percutaneous coronary intervention (PCI). In the contemporary era, 5% to 10% of patients develop restenosis, and in the acute coronary syndrome cohort, there remains a 20% major adverse cardiovascular events rate at 3 years, half of which are culprit-lesion related. In patients at risk of restenosis, colchicine has been shown to reduce restenosis when started within 24 hours of PCI and continued for 6 months thereafter, compared with placebo. The Colchicine-PCI trial, which randomized patients to a 1-time loading dose of colchicine or placebo 1 to 2 hours before PCI, showed a dampening of the inflammatory response to PCI but no difference in postprocedural myocardial injury. On mean follow-up of 3.3 years, the incidence of major adverse cardiovascular events did not differ between colchicine and placebo groups (32.5% vs 34.9%; hazard ratio 0.95 [0.68 to 1.34]).

Keywords: colchicine, inflammation, percutaneous coronary intervention

Periprocedural inflammation is associated with major adverse cardiovascular events (MACEs) in patients who undergo percutaneous coronary intervention (PCI).1 Iatrogenic crush injury of the tunica media and denudation of the vascular endothelium during PCI causes an inflammatory response that promotes smooth muscle proliferation and restenosis. In animal models, neutrophils adhere to injured endothelium after balloon angioplasty, with maximal infiltration by 3 days.2 In humans, upregulation of neutrophil adhesion molecules early after coronary angioplasty is associated with restenosis.1,3 Despite optimization of periprocedural antithrombotic therapies, lipid-lowering therapies, lesion preparation, stent design, and deployment techniques, restenosis continues to occur in 5% to 10% of patients after PCI in the contemporary era, and periprocedural inflammation remains an independent predictor of target vessel revascularization (TVR).1 In the population with acute coronary syndrome, there remains a 20% MACE rate at 3 years, half of which are culprit-lesion related.4

Colchicine inhibits chemotaxis, adhesion, and activation of neutrophils, and in patients with diabetes mellitus who undergo PCI with a bare metal stent, a 6-month course of colchicine results in lower rates of restenosis.5 The Colchicine-PCI trial, which randomized patients to a loading dose (1.2 mg followed by 0.6 mg after 1 hour) of colchicine or placebo 1 to 2 hours before PCI, indicated a dampening of the inflammatory response to PCI but no difference in postprocedural myocardial injury.6 The impact of periprocedural colchicine on long-term clinical outcomes after PCI is not known.

In this study, we present prespecified long-term follow-up of the randomized, double-blind, placebo-controlled Colchicine-PCI trial, the methods of which were described previously.6 After randomization, participants were contacted by telephone, and their medical record was reviewed for ascertainment of MACE at 30 days, 6 months, and yearly thereafter (minimum of 2 years; maximum of 5). If an event occurred outside the site’s healthcare system, source documentation was obtained. Vital status was confirmed through the Veterans Affairs (VA) system, which is updated from the Veterans Benefits Administration Beneficiary Identification and Records Locator System. This system, in turn, receives mortality information from the veteran’s family, VA hospitals, VA National Cemetery Administration, and the Social Security Administration. Events were adjudicated by a clinical events committee comprising 3 cardiologists blinded to treatment allocation. MACE was defined as a composite of the earliest occurrence of all-cause mortality, nonfatal myocardial infarction (MI) (further categorized as type 4a PCI-related MI or spontaneous MI per the Third Universal Definition), or TVR. Kaplan–Meier time-to-event curves were generated for the intention-to-treat cohort (shown as hazard ratio, 95% confidence intervals) and compared by log-rank tests with a 2-sided significance level of 0.05. The trial was approved by the institutional review board and is registered at ClinicalTrials.gov (NCT02594111). All patients provided written informed consent before enrollment.

Among the 400 trial participants who underwent PCI (97% with second-generation drug-eluting stent, 49.5% with acute coronary syndrome), 206 were assigned to receive colchicine, and 194 were assigned to placebo. The mean follow-up was 1,207 ± 511 days (median follow-up 1,107 days); all participants achieved 30-day follow-up, and 93.5% (n = 374) were reached at 2 years. The incidence of MACE did not differ between colchicine and placebo groups (32.5% vs 34.9%). Type 4a MI (11.2% vs 12.1%), spontaneous MI (8.7% vs 9.8%), TVR (7.8% vs 7.2%), and all-cause mortality (12.6% vs 14.9%) also did not differ between the colchicine and placebo groups (Figure 1).

Figure 1.

Figure 1.

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Time-to-first-event curves for A) Major Adverse Clinical Events (MACE), B) Myocardial Infarction (MI), C) Target Vessel Revascularization (TVR), and D) All-Cause Mortality. HR = hazard ratio.

In conclusion, a 1-time load of colchicine administered 1 to 2 hours before PCI did not reduce the long-term incidence of MACE. Colchicine may need to be continued daily after PCI to show longer-term benefit as observed in previous studies.7,8 However, given that the benefit in the inflammatory response to vascular injury in the Colchicine-PCI trial was observed 24 hours after PCI, it remains uncertain whether earlier colchicine administration before PCI may confer greater benefit. The COPE-PCI (COlchicine to Prevent PeriprocEdural Myocardial Injury in Percutaneous Coronary Intervention) pilot trial randomized 75 patients who underwent PCI to a preprocedural load of colchicine or placebo 6 to 24 hours before procedure, earlier than in Colchicine-PCI, and revealed reductions in minor and major periprocedural myocardial injury.9 Thus, we await long-term follow-up of the COPE-PCI trial to provide additional insights into the role of periprocedural colchicine in preventing MACE after PCI.

Acknowledgment

The authors dedicate this manuscript to the memory of Steven Sedlis, MD, Professor of Medicine, consummate mentor, and dedicated physician who devoted his career to improving patient outcomes, educating the next generation of physicians, and advancing science. Sedlis played a pivotal role with his contributions to both the design and conduct of this trial.

The authors acknowledge the contributions of Leandro Maranan, MD, Ephram Weiss, MD, and Arman Qamar, MD in data collection and adjudication for this manuscript.

Footnotes

The study was partially funded by the American Heart Association (Chicago, Illinois) Clinical Research Program, 13CRP14520000 and the Veterans Affairs (Washington, DC) Office of Research and Development, iK2CX001074. Data analysis and statistical support were provided by New York University School of Medicine (New York, New York) Cardiovascular Outcomes Group. The drug was initially supplied by Takeda Pharmaceuticals (Tokyo, Japan) and then by the Veterans Affairs New York Harbor Health-care System (New York, New York), Manhattan Campus Research Pharmacy.

Declaration of Competing Interest

Dr. Shah receives grant funding from the Veterans Affairs Office of Research and Development and National Institutes of Health/National Heart Lung Blood Institute; serves on the advisory board for Philips Volcano and Horizon Therapeutics; and serves as a consultant for Terumo Medical. Dr. Smilowitz serves on the advisory board for Abbott. Dr. Feit is a shareholder of Boston Scientific, Medtronic, and Johnson and Johnson. Dr. Katz has research grant funding from Pfizer, Luitpold, AMAG Pharmaceuticals, Biocardia, and Array BioPharma and serves on a data safety monitoring board for Salubris Bio. Dr. Cronstein is a consultant to marvel Biosciences, has research grant funding from Regensoine, and is a founder of Regenosine, Inc. Dr. Pillinger serves as a consultant for Horizon, Sobi, and Fortress Biotech, and is the recipient of investigator-initiated grant support from Hikma and Horizon. The remaining authors have no competing interests to declare.

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