Statin intolerance can be managed through various pathways for different patients, according to a presentation at the Cardiometabolic Health Congress.

Patients at high risk who are on high-efficacy statins sometimes are unhappy with the side effects of the treatment, although guidelines recommend that they should be on this type of treatment, including the 2016 expert consensus decision from the American College of Cardiology. In those guidelines, it discussed that statin intolerance is common and that patients may experience unacceptable adverse events, including muscle-related symptoms, Christie M. Ballantyne, MD, professor of medicine, chief of the sections of cardiology and cardiovascular research and director of the Center for Cardiometabolic Disease Prevention at Baylor College of Medicine, said during the presentation.

The National Lipid Association defined statin-associated muscle symptoms in 2015 as myopathy, myalgia, myositis, clinical rhabdomyolysis and myonecrosis.

“It’s a very important thing in terms of encouraging our patients that these symptoms are manageable, and one way to manage it is you stop the medication,” Ballantyne said. In contrast to statins with side effects that can be managed, other commonly used drugs, such as aspirin may have adverse effects that are difficult to manage. For example, if someone taking aspirin wakes up with a terrible headache and they can’t move their arm and has a cerebral hemorrhage, that is not easy to manage.”

Several studies have shown that patients who have stopped taking or reduced the dose of statin therapy had an increased risk for recurrent MI and CHD.

The ACC developed an app to approach statin intolerance in a systematic way, which involves evaluation, follow-up and drug comparisons.

The 2016 ACC consensus decision also defined statin intolerance as unacceptable muscle-related symptoms that leads to discontinuation of at least two statins and occurs with at least one low-dose statin.

It is important to determine whether the muscle-related symptoms are related to the statin therapy or to an activity like exercise or another activity. Other items to be evaluated include the type of muscle symptoms, demographics and current statin and potential drug interactions, according to the presentation.

In the 1990s, numerous trials focused on the effects of statins, but studies have now shifted toward nonstatin therapy, including IMPROVE-IT, FOURIER, SPIRE 1, SPIRE 2 and REVEAL. These studies combined have included more than 100,000 patients.

The ACC published a focused update in 2017 that included data from FOURIER, SPIRE 1, SPIRE 2 and a recent analysis of IMPROVE-IT. It detailed when to continue monitoring adherence to medications and lifestyle changes and when to consider nonstatin medications such as ezetimibe or adding or replacing with a PCSK9 inhibitor for multiple patient populations such as those with stable clinical atherosclerotic CVD with and without comorbidities and diabetes.  

Various studies are in the pipeline, including the ORION-1 trial, on the effects of inclisiran (The Medicines Company) on small-interfering RNA and another trial on bempedoic acid.

An earlier study on bempedoic acid showed a greater change in LDL compared with placebo. Adding bempedoic acid to ezetimibe can lead to an estimated LDL reduction of 45%, according to the presentation. Data from the CLEAR program, a phase 3 trial, should be released in 2018.

“The good news is that most patients are able to tolerate some dose of statins,” Ballantyne said. “That’s been looked at by multiple observational studies. The majority can tolerate something. The other good news is that we now have data that nonstatin therapies are beneficial for these individuals.” – by Darlene Dobkowski

Reference:

Ballantyne CM. Treatment for statin-intolerant patients with hypercholesterolemia — today and tomorrow. Presented at: Cardiometabolic Health Conference; Oct. 4-7, 2017; Boston.