Statin Alternatives

By Peter Galvin, MD

It is now generally recognized that the administration of statins (Lipitor, Crestor, etc.) is the cornerstone of contemporary therapy to reduce the risk of major cardiovascular disease (CVD) events (i.e., heart attack, stroke, etc.) in patients for whom primary or secondary prevention is indicated. Primary prevention prevents the onset of CVD in those at risk of developing it (like diabetics and people with hypertension) while secondary prevention prevents worsening of CVD in those who already have it. Research has shown that statins not only lower total cholesterol and LDL (“bad cholesterol”) but also reduce CVD risk due to their anti-inflammatory effects. But there is a sizeable number of patients, estimated between 15% and 30%, who cannot tolerate statins due to their side effects, especially myalgias (muscle aches). Incidentally, research has also shown that many individuals who report myalgia may be suffering from the nocebo effect, also known as the power of suggestion. For example, a patient who is given statins knows that myalgia is a common side effect and therefore expects to get it. Sudden withdrawal from statin therapy can potentially be dangerous because of the increased risk of adverse cardiovascular events. Thankfully, there are alternatives to statins for those who cannot take them.

The first alternative is ezetimibe (brand name Zetia). This works in the gut to bind cholesterol that was consumed and eliminate it. It is not absorbed into the body, so it has minimal side effects (mostly diarrhea) but also does not have any anti-inflammatory properties. Research has shown that ezetimibe may lower total cholesterol but does not affect CVD risk. Also, because it is not absorbed, ezetimibe is not very effective at lowering LDL because, in most people with high cholesterol and LDL, the high levels come from their body making too much cholesterol, not from ingesting it. It is usually prescribed with a statin and rarely by itself. Another alternative to statins is bempedoic acid (brand names Nexlizet and Nizlizol). Unlike ezetimibe, bempedoic acid is absorbed into the body and works in the liver to block cholesterol production. Bempedoic acid was originally intended to treat those with familial, or genetic, hypercholesteremia. After several studies showed that bempedoic acid reduced LDL levels by 17% to 28%, in 2020 the FDA approved it for this use.

Recently, the results of the CLEAR (Cholesterol Lowering by Bempedoic Acid [ECT1002], an ACL-inhibiting Regimen) Outcomes trial were published. In this large study, bempedoic acid was given to volunteers who were unable to tolerate statins. The study found that bempedoic acid reduced the incidence of adverse cardiovascular events by 13% as compared to the placebo group. It also found that levels of high-sensitivity CRP (C-reactive protein), a marker for inflammation, were significantly reduced as compared to placebo. And the side effect profile for bempedoic acid was similar to placebo, meaning that it did not cause the achiness often seen with statins. So, it seems that medical science may finally have found a safe and effective alternative for statins for those unable to take them. Of course, because bempedoic acid is so new, more studies are needed. But the future looks bright for those statin-intolerant individuals at risk for CVD.

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