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Medicine constantly changes as new information becomes available. Treatment recommendations often follow as a result. In just the last several weeks, two pivotal studies have shifted the landscape for patients with coronary artery disease (CAD), the first with a statin substitute and the second, a reconsideration of the role of endurance exercise.
Bempedoic Acid: A New Statin Substitute
Statins are the most widely used drug for treating elevated cholesterol. For patients who do not tolerate statins, usually because of leg pain, avoiding statin treatment despite elevated LDL (bad) cholesterol levels puts them at increased risk for CAD.
A new drug, bempedoic acid, has very little skeleton muscle impact in part because it requires metabolic conversion in the liver to become active. Like statins, bempedoic acid reduces LDL as well as high sensitivity C-reactive protein, a marker of inflammation, by ∼20-30 percent.
The CLEAR Outcomes trial was a double-blind, randomized, placebo-controlled trial involving 14,000 patients at risk for CAD who were unable or unwilling to take statins because of unacceptable adverse effects. Bempedoic acid reduced LDL cholesterol by 21 percent compared to placebo (from a mean LDL cholesterol level at baseline 139 mg per deciliter in both groups) and was associated with a lower risk of major adverse cardiovascular events (death from cardiovascular causes, nonfatal heart attack, nonfatal stroke, or coronary revascularization).
These results indicate that bempedoic acid lowers LDL cholesterol as well as inhibiting inflammation in a fashion almost identical to that observed with statins, making it quite likely that bempedoic acid will be of use for statin-intolerant patients in the near future.
Endurance Exercise
It is generally accepted that the most physically fit, such as lifelong marathon runners, live long lives and enjoy a high quality of life. Recent information may challenge that assumption with the demonstration that master athletes develop increased calcification in the coronary arteries. In fact, lifelong endurance athletes were more likely than controls to have one or more coronary artery plaques (calcified and noncalcified obstructions) often at the origin of a coronary artery segment. The authors concluded that “lifelong endurance sport participation is not associated with a more favorable coronary plaque composition compared to a healthy lifestyle.”
Before we decide that too much exercise is bad, we must recognize that the study was not controlled for confounders such as genetics and family history, stress, suboptimal diets and other unhealthy habits. Nevertheless, we can conclude that no amount of exercise creates an immunity to developing CAD. Without question, exercise is beneficial and reduces the risk of CAD. However, it is unknown whether extreme exercise is harmful. At present it is too premature to discourage patients from high-level endurance exercise but its potential risk needs to be established in the future.
Also on the CAD horizon are two other important topics: just how low can LDL levels go while still being effective and not harmful, and how important inflammation is compared to elevated LDL in causing CAD. These will be discussed in the next column.
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