Cardiometabolic Health Congress

Cardiometabolic Health Congress

October 14, 2019
4 min read

Statin intolerance can be fought with intermittent dosing

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Leslie Cho

CHICAGO —Intermittent statin dosing is a treatment option that may have tremendous potential for addressing patients with statin intolerance who are trying to reduce LDL, according to a speaker at the Cardiometabolic Health Congress.

“Everyone should try intermittent statin,” Leslie Cho, MD, FACC, FSCAI, FESC, professor of medicine at the Cleveland Clinic Lerner College of Medicine of Case Western Medical School and section head of preventive cardiology and rehabilitation, director of the Women’ s Cardiovascular Center and an interventional cardiologist at Cleveland Clinic, told Healio. “First of all, you should look for a cause because it’s really, really simple. Once you look for a cause and they really don’t have a cause, then you should go to a hydrophilic and you should also do intermittent dosing.”

During her presentation, Cho championed the use of intermittent statin dosing in those with statin intolerance based the results of a 2013 study conducted at Cleveland Clinic published in the American Heart Journal. As part of the study, Cho and colleagues evaluated changes in LDL among patients who were able to take rosuvastatin every day, those with statin intolerance who were able to take rosuvastatin intermittently or fewer than five times per week and those who could not take rosuvastatin at all. The results revealed that for those with statin intolerance, “even with intermittent dosing, you get a nice reduction of their LDL,” Cho said, while adding that intermittent dosing also appeared to yield survival benefits.

Identifying the problem

Before intermittent statin dosing can be utilized, however, physicians must be able to confirm that a patient is actually statin intolerant. This is not simple, even though the condition affects between 5% and 10% of the population, according to Cho.

“When we think about statin intolerance and we think of the people that are affected, it’s actually a very, very large number of the patient population,” Cho said during a presentation. “The problem with statin intolerance [is] nobody knows how to define true statin intolerance.”

Cho said there are different thresholds and definitions for statin intolerance across organizations like the American College of Cardiology, the National Lipid Association and the FDA, making it more difficult to effectively and accurately identify the condition. Although this difficulty exists, there are strategies physicians can employ to make things easier, beginning with communication with patients.

“You have to ask them about how and why they think they are. What kind of symptoms are you having? When did it start? What muscles are being affected? Things like that,” Cho told Healio. Among the considerations Cho highlighted were the presence of aches in large muscle groups after 2 weeks or more of statin use, which she calls a “reasonable definition.” Physicians should also keep in mind that exercise can make statin intolerance worse and that mild hyporeflexia can play a role as well.


Statin intolerance doesn’t just make it difficult to utilize the medication but can also have side effects that affect the brain, liver and kidney, although most of these are not especially common or do not have particularly strong data, according to Cho.

Physicians also can better verify the condition by understanding some of the causes and characteristics that are most associated with statin intolerance.

“This risk factors for statin intolerance are patient-related and also treatment-related,” Cho said during a presentation. Among the patient-specific causes, women, those of older age and those who have undergone a transplantation are all more likely to present with statin intolerance, according to Cho, but these are not the only factors to consider. Cho also noted that those on the extreme ends of the BMI spectrum may be at higher risk. In addition, genetics can be part of the puzzle.

“There is 100% genetic disposition to statin intolerance,” Cho said, noting that this is difficult to confirm because the SLCO1B1 gene on chromosome 12 is “the only gene that you can test in 2019,” and that isn’t relevant for any statin other than simvastatin.

Besides the individual characteristics of each patients, Cho also said what patients are ingesting can make an impact.

“The most important one is the drugs that we sometimes put patients on. Common drugs like diltiazem, verapamil, warfarin and antibiotics,” Cho told Healio. “The other one is alcohol. We rarely ask patients about alcohol and it’s really important because that’s one of the No. 1 causes of the statin intolerance.”

The type of statin in question is also something to consider, as Cho noted that muscle aches are more common when the statin is lipophilic rather than hydrophilic.

Additional treatment strategies

Once statin intolerance is confirmed, there are strategies physicians can undertake to address the issue and continue to provide LDL-lowering therapy; Cho recommended the use of intermittent dosing.

Outside of this strategy, there are additional treatment avenues, including changes in diet and the use of medications like ezetimibe, niacin and bempedoic acid (Esperion Therapeutics), although this last option is still being researched. Cho also recommended the use of PCSK9 inhibitors, as the GAUSS-3 trial revealed that evolocumab (Repatha, Amgen) did “extremely well” and led to a “beautiful LDL reduction.” – by Phil Neuffer


Cho L. Statin Intolerance: Incidence, Prevalence and Treatment. Presented at: Cardiometabolic Health Congress; Oct. 10-13, 2019; Chicago.

Mampuya WM, et al. Am Heart J. 2013;doi:10.1016/j.ahj.2013.06.004.

Nissen SE, et al. JAMA. 2016;doi:10.1001/jama.2016.3608.

Disclosure: Cho reports she has received research support from Amgen, AstraZeneca, Esperion, and Novartis and has served as a consultant for Amgen.