Polypill and Colchicine for Risk Reduction in Atherosclerotic Cardiovascular Disease

Официальное название

Evaluation of a POlypill and Colchicine for Risk Reduction in Patients With Established Atherosclerotic Cardiovascular Disease: The EPOCA Randomized Clinical Trial

Обзор

The EPOCA study (Evaluation of a POlypill and Colchicine for risk reduction in patients with established Atherosclerotic cardiovascular disease) will be a randomized, superiority, parallel, 2x2 factorial, multicenter clinical trial which will include at least 7713 and up to a maximum of 10797 participants with established atherosclerotic cardiovascular disease.

Подробное описание

Cardiovascular disease is the leading cause of morbidity and mortality worldwide and in Brazil. Additionally, cardiovascular risk factors are highly prevalent conditions which are, frequently, present in association. Despite the last therapeutic advances, rates of adequate control of these conditions are still low. One proposed strategy to increase such control and decrease cardiovascular risk is the use of fixed-dose combinations of different pharmacological classes, to be taken on single daily dose - a polypill. This strategy has already been studied in other parts of the world, especially in patients with established or at risk for coronary heart disease (CHD).

Furthermore, there has been a need to explore other therapeutic targets beyond traditional risk factors that could impact the process of atherosclerosis. Among the various options evaluated, colchicine has emerged as a viable alternative, given its clinical use experience, mechanism of action, and the results showing a reduction in inflammatory biomarkers as well as clinical outcomes in individuals with different manifestations of coronary artery disease. However, it is important to highlight some key points regarding the available studies evaluating both the treatment strategy based on a polypill and the use of colchicine in the context of atherosclerotic cardiovascular disease (ASCVD).

The studies supporting both approaches were primarily conducted with participants with coronary artery disease from centers in Europe, the U.S., Iran, Oceania, and India, and there is a lack of robust evidence regarding these therapeutic strategies in other countries with a diverse population like Brazil, as well as in individuals with other manifestations of ASCVD (including peripheral arterial disease and cerebrovascular disease).

Given high prevalence of atherosclerotic cardiovascular disease and its traditional risk factors, low control rates, high levels of poor adherence and therapeutic inertia, and the specific realities of the population and healthcare system, evaluating the efficacy of a polypill strategy (fixed-dose an antihypertensive, aspirin, and high-potency statin) with a single daily dose, along with colchicine, in preventing cardiovascular events could contribute to improving cardiovascular care.

Вмешательства

• Препарат Cardiovascular Polypill (Valsartan, Atorvastatin, Aspirin)
  Cardiovascular Polypill contains Valsartan, Atorvastatin, Aspirin 1. Valsartan 160 mg + Atorvastatin 40 mg + Aspirin 100 mg or 2. Valsartan 160 mg + Atorvastatin 80 mg + Aspirin 100 mg or 3. Valsartan 320 mg + Atorvastatin 40 mg + Aspirin 100 mg or 4. Valsartan 320 mg + Atorvastatin 80 mg + Aspirin100 mg or 5. Valsartan 80 mg + Atorvastatin 40 mg + Aspirin 100 mg or 6. Valsartan 80 mg + Atorvastatin 80 mg + Aspirin 100 mg or 7. Valsartan 80 mg + Atorvastatin 20 mg + Aspi
• Препарат Colchicine 0.5 mg
  Colchicine 0.5 mg once daily
• Препарат Usual Care Group
  Patients allocated to the usual care arm will receive standard of care therapies for secondary prevention according to the guidelines. Drugs and doses will be left at the discretion of the treating physicians.
• Препарат Colchicine-placebo 0.5 mg
  Matching Colchicine-placebo 0.5 mg once daily

Первичные конечные точки

• Primary efficacy endpoint: Major adverse cardiovascular and limb events (MACLE) [Срок оценки: Through study completion, an estimated average of 3 years]

Вторичные конечные точки (4)

• Key secondary endpoint: Major adverse cardiovascular events (MACE) [Срок оценки: Through study completion, an estimated average of 3 years]
• Cardiovascular death [Срок оценки: Through study completion, an estimated average of 3 years]
• Non-fatal type 1 myocardial infarction [Срок оценки: Through study completion, an estimated average of 3 years]
• Non-fatal ischemic stroke [Срок оценки: Through study completion, an estimated average of 3 years]

Критерии участия

Критерии включения

• Individuals aged ≥ 45 years AND
• Signature of the Informed Consent Form (ICF) AND at least one of the following criteria:
• Previous atherothrombotic cardiovascular event (acute coronary syndrome, ischemic stroke, high-risk transient ischemic stroke, acute limb ischemia/arterial occlusion, or non-traumatic limb amputation) AND/OR
• Previous arterial revascularization (percutaneous, surgical, and/or hybrid) OR
• Diagnosis of significant atherosclerotic disease with ≥ 50% obstruction in any arterial territory (coronary, cerebrovascular, or peripheral), in the absence of a prior cardiovascular event or arterial revascularization.

Критерии исключения

• Pregnant or lactating women;
• Women of childbearing age who do not use any form of contraception;
• Known history of chronic kidney disease, stage ≥ 4 (estimated glomerular filtration rate ≤ 30 mL/min, if available);
• Known history of cirrhosis or severe liver disease (e.g., transaminase levels > 3 times the upper limit of normal, if available);
• Known history of inflammatory muscle disease (e.g., dermatomyositis or polymyositis) or creatine phosphokinase (CPK) levels > 3 times the upper limit of normal, if available);
• Known history of moderate or severe valvular heart disease with anticipated need for valvular intervention within the next 12 months;
• Planned arterial revascularization (inclusion is possible 30 days after completion of all planned procedures);
• Left ventricular ejection fraction ≤40% (with the exception of patients with documented intolerance to ACE inhibitors and/or sacubitril/valsartan, who remain eligible for study enrollment);
• Heart failure with functional class ≥ III according to the New York Heart Association (NYHA), regardless of left ventricular ejection fraction;
• Blood pressure < 120/80 mmHg in the absence of antihypertensive therapy;
• Life expectancy ≤ 12 months;
• Acute arterial event (acute coronary syndrome, non-cardioembolic ischemic stroke, acute limb ischemia) in the past 30 days;
• Substance abuse/alcoholism;
• Psychiatric and/or neurodegenerative disorder limiting self-care capacity;
• Concurrent participation in another randomized clinical trial;
• Contraindication to any component of the polypill;
• Current or planned use of oral anticoagulant therapy within the next 12 months (except rivaroxaban 2.5 mg twice daily for patients with peripheral artery disease);
• High risk of bleeding (e.g., but not limited to: blood dyscrasias, hemophilia, previous gastrointestinal or central nervous system bleeding);
• Contraindication to colchicine;
• Current use of colchicine.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Факторный дизайн

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Бразилия · 13 центров

• Centro de Pesquisas Clínicas Dr. Marco Mota — Maceió
• Secretária da Saúde do Estado do Ceará - Hospital de Messejana Dr. Carlos Alberto Studart — Messejana
• Empresa Brasileira de Serviços Hospitalares - EBSERCH - Hospital de Ensino Dr. Washington — Petrolina
• Centro de Pesquisa Cardiolima — Teresina
• Fundação Técnico Educacional Souza Marques — Rio de Janeiro
• Fundação Universitária de Cardiologia - ICFUC — Porto Alegre
• Instituto de Pesquisa e Ensino em Saúde - IPES — Porto Velho
• CMEP - Centro Multidisciplinar de Ensino especializado e Pesquisa — Joinville
• … и ещё 5 центров

Публикации

• Tramujas L, Nogueira A, Felix N, Maia I, de Barros E Silva PGM, Cavalcanti AB, Abizaid A. Trends in colchicine use across the spectrum of coronary artery disease. Vascul Pharmacol. 2025 Jun;159:107502. doi: 10.1016/j.vph.2025.107502. Epub 2025 May 13. No abstract available. PMID 40373935
• de Barros E Silva PGM, do Nascimento CT, Pedrosa RP, Nakazone MA, do Nascimento MU, de Araujo Melo L, Junior OLS, Zimmermann SL, de Melo RMV, Bergo RR, Precoma DB, Tramujas L, Lima EG, Dantas JMM, do Amaral Baruzzi AC, Flumignan RLG, de Oliveira Paiva MSM, Gowdak LHW, de Carvalho PN, de Figueiredo Neto JA, Silvestre OM, Fioranelli A, Vieira RD', Horak ACP, Miyada DHK, Kojima FCS, de Oliveira JS, d PMID 38378735
• de Abreu-Silva EO, Siepmann M, Siepmann T. Polypills in the Management of Cardiovascular Risk-A Perspective. J Clin Med. 2024 Sep 16;13(18):5487. doi: 10.3390/jcm13185487. PMID 39336974
• Tramujas L, Nogueira A, Felix N, de Barros E Silva PGM, Abizaid A, Cavalcanti AB. Association of colchicine use with cardiovascular and limb events in peripheral artery disease: Insights from a retrospective cohort study. Atherosclerosis. 2024 Nov;398:118563. doi: 10.1016/j.atherosclerosis.2024.118563. Epub 2024 Aug 9. PMID 39299823

Идентификаторы

NCT: NCT06930885 · EPOCA TRIAL

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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