How to use statins, PCSK9 inhibitors in chronic CAD

A session offers tips on tweaking treatments and lipid goals.

To achieve the best possible outcomes in patients with chronic coronary artery disease (CAD), internists must emphasize optimal medical therapy and a lifestyle that does not counter what medicines might accomplish.

Stephen L. Kopecky, MD, offered tips on how to follow these patients and tweak lipid goals and medical treatments along the way during Wednesday's precourse “Cardiology for the Internist 2017: The Key Points.” Among other topics, he covered how to optimize statin therapy and when to use the newer class of PCSK9 inhibitors.

Dr. Kopecky, a professor of medicine in the department of cardiovascular diseases at Mayo Clinic in Rochester, Minn., said patients' lifestyles play a critical role in the effectiveness of statin therapy. A 2012 study in Circulation showed that patients on statins who adhered to the healthiest diet compared to the unhealthiest diet reduced their risk of cardiovascular death, myocardial infarction, stroke, or congestive heart failure by 24%, Dr. Kopecky said. “But 40% of patients in this 20,000-patient study did not benefit. So the point is, if you're not eating healthy, the benefits of a statin are greatly reduced,” he said.

The same concept applies to physical fitness. “I tell patients that being physically fit enhances the benefit of the statin, and the statin does not replace lifestyle,” Dr. Kopecky said.

As if getting patients to adhere to healthy lifestyle changes weren't challenging enough, statin intolerance remains a challenge for the substantial amount of patients who report myalgia with statin therapy. “There's no gold standard for [diagnosing] statin intolerance—that's the problem,” said Dr. Kopecky, who runs a statin intolerance clinic. In recent trials, he said, about 75% of patients are able to tolerate some statin therapy.

If a patient may be intolerant to statins, he recommends stopping the drug for a month before starting a different statin. If the patient is intolerant to three or more statins, she may be able to tolerate a less-than-daily statin, Dr. Kopecky said. Rosuvastatin (5 mg), available in generic form as of 2016, “can get a 25% reduction in their LDL, and most people can tolerate it once or twice a week,” he said.

Although several health organizations suggest lowering LDL to 70 mg/dL, current guidelines from the American Heart Association and the American College of Cardiology shy away from specific targets, instead calling for a 50% reduction in LDL cholesterol. But how low is too low? “You probably need an LDL of 25 [mg/dL] to do all your normal functions, but above 25 [mg/dL] is fine,” said Dr. Kopecky.

In terms of non-statin drugs, PCSK9 inhibitors (e.g., evolocumab) are the future of reducing atherosclerotic cardiovascular disease events, he said. “The ideal patient for this therapy has three qualities: familial hypercholesterolemia, statin intolerance/not at goal, and atherosclerotic cardiovascular disease, Dr. Kopecky said. “Many of these patients have been on every statin in the book,” he said.

Internists should think of familial hypercholesterolemia when LDL is greater than 190 mg/dL and when the patient has early CAD (before age 65 in women and 55 in men) or a family history of early CAD, said Dr. Kopecky. About 1 in 200 people in the U.S. have familial hypercholesterolemia and have a 50% chance of passing the disease to their children, he said.

Internists are undoubtedly seeing patients with familial hypercholesterolemia, but fewer than one in 10 cases have been identified in the U.S., Dr. Kopecky said. Fortunately, drugs to treat these patients are very effective, he said.

These patients are the ones who will be helped the most by the PCSK9 inhibitors, which were approved in 2015, Dr. Kopecky said. “They are more effective than statins [alone],” he said, noting that adding the drugs to statin therapy can help patients achieve their cholesterol goals.

It is important to note that the drugs should not replace statins, he said. “Make sure that every one of these patients is on a statin—even once a week, whatever they can take—because a statin will raise their LDL receptors, which is where the PCSK9 works,” said Dr. Kopecky.