Instructions:Using the supplied information, prepare a written summary (<2 minutes) of the assigned study and answer for a provider (based on the question). The major points and data for each summary are provided below. The goal is to be able to select the most important details and succinctly present them, simulating common experiences to expect during APPE rotations.Provider Query 2Question:In patients with myocardial infarction (MI) in the last 30 days, does colchicine reduce the risk of recurrent cardiovascular events versus placebo?Study:Tardif J, et al. "Efficacy and safety of low-dose colchicine after myocardial infarction". The New England Journal of Medicine. 2019. : epub doi 10.1056/NEJMoa1912388.Design:• Multicenter, double-blind, three-arm, randomized, controlled trial• N=4745• Colchicine 0.5MG daily (N=2366)• Placebo (N=2379)• Setting: 167 sites in 12 countries• Enrollment: December 2015 - August 2018• Median follow-up: 22.3 months• Analysis: Intention-to-treat• Primary Outcome: death from cardiovascular causes, resuscitated cardiac arrest, myocardial infarction, stroke, or urgent hospitalizationPopulation:Inclusion Criteria:• Age ≥ 18 years• Documented acute myocardial infarction within the last 30 days• Treatment according to national guidelines (including antiplatelet therapy, statin, renin-angiotensin-aldosterone inhibitor, beta-blocker, as indicated)• Completed any planned percutaneous revascularization for index MI• Female is either not of childbearing potential or is on durable contraception• Judged to be in good general health by the principal investigator• Willing and able to comply with the study protocolExclusion Criteria:• Poorly controlled medical condition (e.g., NYHA III-IV heart failure, LVEF ≤ 35%, stroke within last 3 months) in the setting of which participation would pose undue risk to the patient• Prior coronary artery bypass within the past 3 years, or planned• Cardiogenic shock or hemodynamic instability• History of cancer or lymphoproliferative disease within the past 3 years• Inflammatory bowel disease or chronic diarrhea• Pre-existent progressive neuromuscular disease or CPK level > 3x ULN (unless due to MI, which is allowed)• Significant anemia, lymphopenia, thrombocytopenia, transammonitis, bilirubin elevation, or kidney injury• Cirrhosis, chronic active hepatitis, or severe hepatic disease• Pregnant, breastfeeding, or planning to become pregnant• Clinically significant drug or alcohol abuse in the past year• Using or planning to use chronic systemic steroids• Currently taking colchicine for a chronic condition• History of allergy or sensitivity to colchicine• Considered by the investigator to be inappropriate for the study for any reasonBaseline Characteristics:From the placebo group.• Demographics: Age 60.5 years, female 18.4%, white 72.1%,• Comorbidities: BMI 28.4, smoking 29.8%, HTN 52.0%, DM 20.9%, prior MI 16.7%, prior PCI 17.1%, prior CABG 3.4%, heart failure 1.8%, stroke/TIA 2.8%• Index MI: time from event to randomization 13.5 days, index PCI 93.3%• Medications: aspirin 98.9%, other antiplatelet 98.2%, statin 99.1%, beta blocker 88.3%Interventions:• Patients randomized 1:1 to colchicine 0.5MG daily or placebo• Randomization occurred within 30 days of index acute myocardial infarction• Any planned revascularization for index MI must have been completed prior to enrollment• Clinical evaluations occurred at 1 month and 3 months after randomization and every 3 months thereafter• Potential trial endpoint events were adjudicated by an independent clinical endpoint committee composed of experienced cardiologists and neurologists blinded to study group assignmentsOutcomes:Comparisons are colchicine versus placeboPrimary OutcomeDeath from cardiovascular causes, resuscitated cardiac arrest, myocardial infarction, stroke, or urgent hospitalization for angina leading to revascularization131 (5.5%) vs 170 (7.1%); HR 0.77 (95% CI 0.61-0.96); p=0.02Adverse EventsAny related adverse event372 (16.0%) vs. 371 (15.8%); p=0.89GI adverse event408 (17.5%) vs. 414 (17.6%); p=0.90Diarrhea225 (9.7%) vs. 208 (8.9%); p=0.35Pneumonia21 (0.9%) vs. 9 (0.4%); p=0.03Criticisms:• Median follow-up of 23 months precludes the ability to draw firm conclusions regarding the long-term safety and efficacy of colchicine• Findings apply only to the acute post-MI period• Small numbers of individuals had inflammatory biomarker testing (e.g., CRP, WBC) at baseline and follow-up. As a result, confirmation of the proposed mechanism of benefit of colchicine (reduction in inflammatory mediators) was not achieved by this study• Since there was no correction for multiple testing, p-values were not reported for non-primary outcome events. As a result, these findings (e.g., marked reduction in stroke rates with colchicine) must be considered hypothesis-generating.
