Hearts on Fire

Should we all take an ancient anti-inflammatory medication to prevent a heart attack?

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The medical community has known for a long time that there is a powerful link between inflammation and heart disease. People with chronic inflammatory conditions have higher rates of heart attack and stroke. But patients can have high levels of inflammation without knowing it. So for decades, doctors have been measuring blood levels of “high sensitivity C-reactive protein”, which is a marker of levels of inflammation, and a proven predictor of cardiac risk. Research studies have been designed and performed to specifically target this marker, to see if lowering inflammation would be of benefit and reduce the risk for heart attack.

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Recently, an announcement generated a lot of headlines: an ancient anti-inflammatory medication had been approved by the FDA to lower the risk of heart attack. In June 2023, AGEPHA Pharma introduced a medication called LODOCO® (which stands for “Low-Dose Colchicine”) and announced that it had been approved as the first anti-inflammatory drug for reducing risk of major adverse cardiovascular events among patients with pre-existing heart disease. Other anti-inflammatory drugs have not consistently proven that they can reduce the risk of heart attack, so this seems to be a big step in the right direction. Colchicine is a compound that comes from the autumn crocus (Colchicum autumnale), a toxic flowering plant also known as “naked ladies”. It has been used since 1500 BC in Egypt and Greece to treat joint swelling, and was first approved for medical use in the United States in 1961. Since then, it has been used to treat many conditions, including gout. In the cardiology world, it has mostly been used in the last decade to treat pericarditis, an inflammatory condition where the “bag” that holds the heart is inflamed and irritated. 

So what is this all based on? LoDoCo2 was a large, randomized “double-blind” trial designed to assess the effectiveness of this drug in reducing risk of major cardiac events. In this trial, 5522 well-treated patients with evidence of coronary disease by heart catheterization or a Calcium Score > 400 were randomized to receive either 0.5 mg colchicine daily or placebo for the duration of the study. 

The results were published in the New England Journal of Medicine in November 2020, and the investigators reported a 31% reduction in risk of major cardiac events among the patients who were taking colchicine once a day. 

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This result was not that unbelievable: Another similar trial called the Colchicine Cardiovascular Outcomes Trial was published in 2019 discovered that major adverse cardiac events were lower among recent heart attack patients who received colchicine compared to those who received placebo.

So what do we learn from this? It is very clear that patients with high levels of chronic inflammation are at higher risk for a cardiac event. Research has clearly shown that statins are exceptionally effective in these patients. We now also have proof that drugs that target inflammation can reduce the risk of a cardiac event, and now we have a drug branded and marketed for that specific purpose. 

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But all of this begs the question: Are these medications effective in patients WITHOUT high levels of inflammation? In the past, some studies have suggested a blunted (or even absent) effect of statins in patients with low levels of inflammation. Would Colchicine be as effective in patients without active or chronic inflammation? Unfortunately, we don’t know. The researchers did not check C-reactive protein levels (or any other inflammation biomarkers) in the LoDoCo2 trial. So we don’t know if those tests would be useful in predicting which patients would benefit from colchicine treatment.

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So while the prospect of taking yet another medication (which is likely to be expensive now that there is a new trademark and patent on it) to reduce inflammation and the risk of cardiac event may be promising to some, the team at Wisconsin Cardiology Associates still recommends the most effective and natural way of reducing inflammation: eating a healthy whole food, plant-based diet, exercising regularly and getting a good night’s sleep. And we don’t even get to patent that…

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Nidorf et al. N Engl J Med 2020; 383:1838-1847

Tardiff et al. N Engl J Med 2019; 381:2497-2505

Photo by Marek Piwnicki on Unsplash