Cardiovascular Disease — 8

The good news is that there is a surge of new drugs for abnormal lipids, mostly biologic small-interfering RNA, targeting genes that were formerly not possible. This completely changes the landscape of both screening and treatment options for patients deemed high risk. We also have good alternatives for patients who cannot tolerate statins, such as bempedoic acid, and multiple PCSK9 blockers.

While managing abnormal lipids is a mainstay to prevent atherosclerosis, tight control of hypertension and diabetes, when present, is equally important. These risk factors are connected, and blood supply to all organs of the body relies on our cardiovascular health. Beyond that direct connection from the heart and blood vessels to all our organ systems, there is considerable overlap of the risk factors that affect each of them.

With the preponderance of evidence that inflammation is a key culprit underpinning atherosclerosis, and that high-sensitivity C-reactive protein (hs-CRP) is a blood biomarker for body-wide inflammation, the stage was set for clinical trials—to test the hypothesis that a potent anti-inflammatory agent could suppress heart disease. Published in 2017, the Canakinumab Anti-inflammatory Thrombosis Outcome Study (CANTOS) enrolled over ten thousand participants who had a prior heart attack, an elevated hs-CRP, and were randomly assigned to three different doses of the drug (canakinumab, a monoclonal antibody to interleukin -1β), given every three months by injection, or a matching placebo for nearly four years. The drug reduced hs-CRP by 40 percent at the higher doses, which also achieved, without any effect on lipid levels, a significant reduction of heart attack, stroke, and cardiovascular death. However, there was a small (affecting about twelve per ten thousand individuals treated) but significant increase in fatal infections or sepsis for the drug (0.3%) compared with placebo (0.18%), which reflects its immune suppression effect. Something else quite noteworthy about the outcomes of this trial: a significant reduction of fatal cancer and lung cancer. We can conclude that a potent anti-inflammatory drug suppressed both heart events and cancer, with a small absolute increased risk of fatal infection. The drug manufacturer, Novartis, decided not to pursue the indication for cardiovascular event reduction.