Build trust, offer options when navigating statin intolerance for patients
Click Here to Manage Email Alerts
Key takeaways:
- The true incidence of statin intolerance is estimated to be between 5% and 10%.
- For most patients, clinicians can identify an acceptable statin treatment.
Editor's Note: This is part 1 of a three-part Healio Exclusive series on navigating statin intolerance.
Statin therapy is a first-line recommendation for all adults with established atherosclerotic vascular disease or at high ASCVD risk, yet studies and anecdotal reports show many patients cannot — or will not — take statins as prescribed.
Statin therapy is a cornerstone of CVD prevention and one of the most widely studied classes of medications. Data demonstrate substantial LDL lowering, particularly with high-intensity statins, by as much as 50% or more, thereby reducing risk for a CV event.
However, approximately 5% to 30% of people in the U.S. and globally are deemed statin intolerant, often due to patient-reported adverse effects such as muscle pain. Some patients express fear of initiating a statin regimen because of concerns about adverse effects. That hesitancy contributes to reduced statin adherence and persistence, as well as higher risk for adverse CV outcomes, according to the National Lipid Association.
“Statin intolerance is one of the most vexing problems that we face in cardiology, but also in family practice and internal medicine,” Healio | Cardiology Today Editorial Board Member Steven E. Nissen, MD, MACC, chief academic officer of the Sydell and Arnold Miller Family Heart, Vascular & Thoracic Institute and the Lewis and Patricia Dickey Chair in Cardiovascular Medicine at Cleveland Clinic, said in an interview. “Patients come to see us and have clear indications for treatment with a statin, and they say they cannot tolerate the drugs. We have needed an approach that will work.”
For most patients with statin intolerance, clinicians can identify an acceptable statin treatment which may require a different dose, statin or dosing schedule, Kevin C. Maki, PhD, CLS, FNLA, president and chief scientist of Midwest Biomedical Research, adjunct professor at Indiana University School of Public Health and immediate past president of the NLA, told Healio | Cardiology Today. For some patients, that requires a nuanced discussion that does not discount reported symptoms.
“There is a lot of psychology involved and a lot of education involved,” Maki said in an interview. “Part of that education is to say, ‘We are going to work together as a team and we are going to get to something that works. We are going to keep our eye on the prize, which is achieving a low level of LDL cholesterol that is commensurate with reducing your risk.’ Most people who have symptoms associated with their statin therapy can tolerate some statin regimen. Only a few cannot. If they cannot, then there are other options including other medications.”
Assessing prevalence of statin intolerance
The prevalence of statin intolerance remains a matter of debate and depends on how statin intolerance is defined and measured.
In a global meta-analysis from the Lipid and Blood Pressure Meta-Analysis Collaboration and the International Lipid Expert Panel (ILEP), the overall prevalence of statin intolerance was 9.1%. The prevalence according to societal diagnostic criteria was even lower: 7% using NLA criteria, 6.7% using ILEP criteria and 5.9% using European Atherosclerosis Society criteria.
The meta-analysis, which included more than 4 million patients, also showed that as many as 50% of patients prescribed statins take reduced or no doses due to perceived statin intolerance.
The researchers reported higher rates of statin intolerance in adults over age 65 years, women and those of Asian and African American races. Positive associations were noted in those with obesity or diabetes, hypothyroidism or chronic liver or renal disease. A higher dose of statin was associated with more reports of statin intolerance.
Other studies suggest adverse symptoms attributed to statins are no different than symptoms attributed to placebo. In the SAMSON trial, published in 2020 in The New England Journal of Medicine, who had previously discontinued a statin after developing symptoms within 2 weeks of initiation, reported similar side effects while on placebo and statin when they were re-treated, suggesting a large proportion of burden owed to the “nocebo” effect.
When this nocebo effect was revealed to participants who had initially discontinued statin therapy due to adverse effects, half were open to resuming treatment.
“A lot of times, people are willing to attribute daily aches and pains and things that the aging population experience to their statin, when it is this ‘nocebo’ effect,” Healio | Cardiology Today Editorial Board Member Erin D. Michos, MD, MHS, FACC, FAHA, FASE, FASPC, associate professor of medicine and director of women’s cardiovascular health research at Johns Hopkins Medicine, said in an interview. “When you think something is going to harm you, you are more likely to perceive any adverse symptoms. This can be challenging, because I do talk to patients about the nocebo effect, and I even bring up slides from the SAMSON trial. Regardless of whether it is a nocebo effect or not, it is very real for the patient.”
Updated guidance for clinicians
Professional societies have issued updated guidance for how best to treat patients with true or partial statin intolerance. In June 2022, the NLA published a scientific statement that defined statin intolerance as “one or more adverse effects associated with statin therapy which resolves or improves with dose reduction or discontinuation and can be classified as a complete inability to tolerate any dose of a statin, or partial intolerance with inability to tolerate the dose necessary to achieve the patient-specific therapeutic objective.”
The updated definition was created to reflect a continuum of “intolerance,” ranging from complete to partial intolerance, which prevents the patient and clinicians from reaching the therapeutic objective and requires a clinician-patient discussion, Maki said.
The updated definition also does not state that any side effects are necessarily due to pharmacodynamic effects of statins.
“One thing that is very clear is that many more people think they have muscle symptoms related to taking a statin than actually have muscle symptoms related to taking a statin,” Maki, a co-chair of the NLA scientific statement, said. “Muscle aches and pains are very common. Most likely, the true incidence of statin intolerance for patients above what you see with placebo is probably in the range of 2% to 4%. But when you look at how many people report what they think is statin intolerance, it is somewhere between 10% and 30%.”
The question of whether statin intolerance is real or a phenomenon attributed to a combination of misleading media reports and symptoms caused by other health issues is ultimately one that does not matter, according to Nissen.
“Some people prescribed statins have these vague neurological complaints; they may call it brain fog,” Nissen said. “I am not sure these symptoms are real, and a certain amount of muscle intolerance studies have shown these symptoms probably are not real. But it doesn't really matter. If a patient comes in my office, looks me in the eye, and says, ‘I have tried statins on multiple occasions, I cannot tolerate them and I will not take them,’ then, we have no alternative. They are not going to take a statin, and they are therefore statin intolerant.”
Editor’s Note: Part 2 of this Healio Exclusive series will explore why data show women are consistently underprescribed statins compared with men.
We want to hear from you:
Healio wants to hear from you: What are you hearing from your patients about their experiences with statin therapy? Share your thoughts with Healio by emailing the author at rschaffer@healio.com or tagging @CardiologyToday on X (Twitter). We will contact you if we wish to publish any part of your story.
References:
- Bytyci I, et al. Eur Heart J. 2022;doi:10.1093/eurheartj/ehac015.
- Chelley MK, et al. J Clin Lipidol. 2022;doi:10.1016/j.jacl.2022.05.068.
- Wood FA, et al. N Engl J Med. 2023;doi:10.1056/NEJMc2031173.
For more information:
Kevin C. Maki, PhD, CLD, FNLA, can be reached at kmaki@mbclinicalresearch.com.
Erin D. Michos, MD, MHS, FACC, FAHA, FASPC, can be reached at edonnell@jhmi.edu; X (Twitter): @erinmichos.
Steven E. Nissen, MD, MACC, can be reached at nissens@ccf.org.
Collapse
Healio Interviews
Click Here to Manage Email Alerts