FDA Approves Low-Dose Colchicine as First Anti-inflammatory Therapy to Reduce Cardiovascular Events

The US Food and Drug Administration today approved a low-dose colchicine tablet as the first anti-inflammatory, atheroprotective therapy for cardiovascular disease (CVD), according to manufacturer Agepha Pharma.¹

The agency based the drug's broad cardiovascular indication on clinical trials in which Lodoco® (colchicine, 0.5 mg tablets) was associated with reductions in risk of myocardial infarction (MI), stroke, coronary revascularization, and cardiovascular death in adult patients with established atherosclerotic cardiovascular disease or with multiple risk factors for cardiovascular disease.¹

Once-daily colchicine 0.5 mg can be taken alone or in combination with statin therapy and has been shown to reduce the risk of cardiac events in adults with ASCVD by 31% when added to the standard-of-care treatment, according to the company. Agepha Pharma expects the drug to be available in the second half of 2023.¹

“Approval by the FDA of the first drug to target cardiovascular inflammation is an important step forward for the care of our patients,” said Paul Ridker, MD, MPH, professor of medicine, Harvard Medical School and director of the Center for Cardiovascular Disease Prevention, Brigham and Women’s Hospital, in a company statement.¹ Ridker, who has for many years led research demonstrating the central role of inflammation in CVD, added, “To treat coronary disease effectively, cardiologists must aggressively reduce inflammation and cholesterol. For appropriate patients already taking a statin, adding the anti-inflammatory drug colchicine at a dose of 0.5 mg daily has been proven to significantly lower risks of recurrent heart attack and stroke.”

The FDA's approval is based on evidence from several large clinical trials with data widely published across US and European journals. In the 2019 COLCOT trial,² when compared with placebo, colchicine reduced the risk for ischemic events in patients with recent MI with the benefit based largely on reduction in the incidence of stroke and urgent hospitalization for unstable angina leading to revascularizations.

In 2020, the LoDoCo2 trial,³ which included nearly 5000 patients with chronic coronary disease receiving guideline-directed medical therapy, found that colchicine 0.5 mg reduced the composite endpoint of CV death, nonprocedural MI, ischemic stroke, or ischemia-driven coronary revascularization.

In a recent meta-analysis⁴ presented at the American College of Cardiology/World Congress of Cardiology 2023 meeting, Ridker presented findings from a meta-analysis of landmark international trials showing that for patients with or at high risk for ASCVD and on lipid lowering treatment, inflammation, as assessed by high-sensitivity C-reactive protein was a stronger predictor of future CV events than cholesterol, assessed by LDL-C.⁴

Michael Blaha, MD, MPH, director of clinical research and professor of medicine at the Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease said, “For the first time, patients with residual inflammatory risk, as measured by hs-CRP, will have an FDA-approved treatment option demonstrated to reduce the risk of cardiovascular disease by targeting the inflammatory pathways that influence major cardiac events.¹

“The cardiovascular research community has demonstrated that focusing on unmet patient medical needs and addressing the long-standing challenge of reducing cardiac inflammation can translate into meaningful risk reduction in the incidence of cardiac events,” he added.¹

According to the Agepha company statement, Lodoco is contraindicated in patients with kidney failure or severe liver disease. Lodoco should be temporarily discontinued for patients prescribed antibiotics including azithromycin and azole antibiotics.¹

References

1. U.S. FDA approves first anti-inflammatory drug for cardiovascular diseease. News release. Agepha Pharma. June 20, 2023. Accessed June 20, 2023.
2. Tardif JC, Kous S, Waters DD, et al. Efficacy and safety of low-dose colchicine after myocardial infarction. N Engl J Med. 2019;381:2497-2505. doi: 10.1056/NEJMoa1912388
3. Nidorf SM, Fiolet ATL, Mosterd A, et al, for the LoDoCo2 trial investigators. Colchicine in patients with chronic coronary disease. N Engl J Med. 2020;383:1838-1847. doi:10.1056/NEJMoa2021372J
4. Ridker PM, Bhatt DL, Pradhan AD, et al. Inflammation and cholesterol as predictors of cardiovascular events among patients receiving statin therapy: a collaborative analysis of three randomised trials. Lancet. 2023;401:1293-1301. doi:10.1016/S0140-6736(23)00215-5