A 66-year-old man with a history of hypertension and coronary artery disease presents for an annual follow-up appointment. Two years ago, he underwent revascularization of his left circumflex artery with a drug-eluting stent in the setting of an ST-segment elevation myocardial infarction. He has had normal left ventricular function since then. He works as an accountant. He can climb 2 flights of stairs without symptoms, and every other weekend he swims 2 miles without any limitations. He is concerned about his risk of future cardiovascular events, particularly the risk of having another myocardial infarction. He is 5 feet 2 inches tall and weighs 160 pounds. His blood pressure is 118/78 mmHg, and his heart rate is 74 bpm. His medications include aspirin 81 mg daily, metoprolol succinate 50 mg daily, losartan 50 mg daily, and atorvastatin 80 mg daily. His laboratory values are significant for hemoglobin A1c of 5.4, creatinine of 2.2 mg/dl (estimated glomerular filtration rate of 28 mL/min), C-reactive protein level of 1.7 mg/dl, and a normal complete blood count. His last low-density lipoprotein cholesterol level was 98 mg/dl.
Based on the LoDoCo2 (Low Dose Colchicine for Secondary Prevention of Cardiovascular Disease 2) trial, should low-dose daily colchicine therapy be prescribed to decrease the risk of an acute cardiovascular event?
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The correct answer is: B. No, because his glomerular filtration rate is 28 mL/min
In the LoDoCo2 trial, colchicine 0.5 mg daily significantly reduced the risk of cardiovascular events (including myocardial infarction and the need for ischemia-driven coronary intervention) in patients with chronic coronary artery disease who were already taking lipid-lowering and antithrombotic medications. However, it did not reduce all-cause mortality despite a non-significant trend toward lower cardiovascular mortality. The results of this trial suggest a beneficial role of colchicine as a secondary preventive measure in patients with stable ischemic heart disease.
It is important to note that the LoDoCo2 trial recruited patients without regard for clinical or laboratory markers of risk; therefore, the benefits of colchicine therapy can be reasonably expected in most patients with chronic coronary disease. The benefits of therapy were also independent of other therapies including statins, angiotensin-converting enzyme inhibitors, and antithrombotic therapy. However, colchicine is contraindicated in patients with advanced renal disease (creatinine clearance <30 ml/min), and such patients were excluded from the LoDoCo2 trial. In addition, colchicine should not be used in patients with hematologic conditions with neutropenia, and it should not be combined with clarithromycin or antifungal or anti-rejection medications. A limitation of the trial is the lack of baseline data collection on blood pressure, lipid levels, or inflammatory state that would have allowed for reporting of outcomes according to risk-factor control.
The incidence of non-cardiovascular death was low in the colchicine and placebo groups (0.7 vs. 0.5 events per 100 person years, respectively), and the difference was not statistically significant (hazard ratio 1.51; 95% confidence interval, 0.99-2.31). However, this trend toward hazard is of concern, and additional trials are indicated to better assess risk-to-benefit ratio with long-term colchicine use.
References
Nidorf SM, Fiolet AT, Mosterd A, et al. Colchicine in Patients with Chronic Coronary Disease. N Engl J Med 2020;Aug 31:[Epub ahead of print].
Nidorf SM, Fiolet AT, Eikelboom JW, et al. The effect of low-dose colchicine in patients with stable coronary artery disease: The LoDoCo2 trial rationale, design, and baseline characteristics. Am Heart J 2019;218:46-56.
Nidorf SM, Eikelboom JW, Budgeon CA, Thompson PL. Low-dose colchicine for secondary prevention of cardiovascular disease. J Am Coll Cardiol 2013;61:404-10.
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