Cardiovascular Disease — 9

Another pass at this question was with colchicine, undertaken a few years later. As opposed to the monoclonal antibody, this potent anti-inflammatory, discovered over three thousand years ago and isolated in the 1800s, is inexpensive and administered orally. Its main side effects are gastrointestinal, particularly diarrhea in about one in four people. A randomized trial in nearly five thousand patients within thirty days of a heart attack, followed for two years, showed the colchicine assigned group to have a significant reduction of cardiovascular events compared with placebo (absolute benefit in about two per one hundred individuals). Like the CANTOS trials, there was an issue with infections—namely, an increased incidence of pneumonia, seen more frequently with colchicine.

Then came another colchicine large randomized trial of over five thousand people with chronic contrary artery disease with a 30 percent reduction in cardiovascular events (nearly three per one hundred people benefit), but there was an excess of noncardiovascular deaths (about two per one thousand people). Collectively, the consistent results of these three trials make a strong case that an anti-inflammatory drug can reduce heart attacks, stroke, and cardiovascular deaths. In June 2023, the FDA approved a version of colchicine (0.5 mg), called Lodoco, as the first drug ever to treat cardiovascular inflammation. It has a retail price at least tenfold higher than the generic version (0.6 mg) that can be prescribed by doctors. But neither is used in routine medical practice, even though the aggregate data, as summarized in figure 5.6, based on a meta-analysis of five randomized trials, is quite supportive. When the trials were pooled, there was no significant risk of infection or pneumonia. In 2024, an additional sixth randomized trial in patients who’d had a stroke further confirmed these benefits for colchicine.

It turns out there’s another way to get at coronary artery inflammation. A CT scan coronary angiogram can detect the level of inflammation from the fat surrounding each of the three coronary arteries. When that was done in over forty thousand people, with follow-up in a subset to nearly eight years, more than 80 percent of individuals did not have obstructive coronary disease (no significant atherosclerotic narrowing). But there was a marked increased risk of major adverse outcomes in this group, accounting for more than 60 percent of the major adverse cardiovascular events. In the cohort with extended follow-up, there was a striking relationship of arterial inflammation and such major adverse events. For example, there was a thirtyfold risk of cardiovascular death for inflammation detected in all three arteries, and a thirteenfold risk for one artery inflamed, as compared to none, over the extended follow-up (fig. 5.7). These findings were distinct from and additive to the traditional clinical risk factor determination.