Global meta-analysis: Prevalence of statin intolerance less than 10%
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As many as 50% of patients prescribed statins take reduced or no doses due to perceived statin intolerance, but the actual prevalence of statin intolerance is less than 10%, according to a meta-analysis of more than 4 million patients.
According to the 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% (95% CI, 8-10), and the prevalence according to societal diagnostic criteria was even lower: 7% (95% CI, 6-8) using National Lipid Association criteria, 6.7% (95% CI, 5-8) using ILEP criteria and 5.9% (95% CI, 4-7) using European Atherosclerosis Society criteria.
‘Not a surprise’
“These results were not a surprise to me, but they were for many other experts,” Maciej Banach, MD, PhD, FNLA, FAHA, FESC, professor of cardiology and head of the department of hypertension at the Medical University of Lodz and head of the Cardiovascular Research Centre at the University of Zielona Góra, Poland, said in a press release. “They show that in most cases statin intolerance is overestimated and overdiagnosed, and they mean that around 93% of patients on statin therapy can be treated effectively, with very good tolerability and without any safety issues.”
Banach and colleagues analyzed 4,143,517 patients from 176 randomized trials or cohort studies.
According to the researchers, the prevalence of statin intolerance was higher in those from cohort studies (17%; 95% CI, 14-19) than in those from randomized trials (4.9%; 95% CI, 4-6).
Statin intolerance was observed more frequently in studies that analyzed statin use for both primary and secondary prevention (18%; 95% CI, 14-21) than in those that analyzed it for primary prevention only (8.2%; 95% CI, 6-10) or for secondary prevention only (9.1%; 95% CI, 6-11), according to the researchers.
Independent predictors
Independent predictors of statin intolerance were age (OR = 1.33; 95% CI, 1.25-1.41; P = .04), female sex (OR = 1.47; 95% CI, 1.38-1.53; P = .007), Asian and Black race (P for both < .05), obesity (OR = 1.3; P = .02), diabetes (OR = 1.26; P = .02), hypothyroidism (OR = 1.37; P = .01), chronic liver disease (OR = 1.24; P = .03) and chronic renal failure (OR = 1.25; P = .03), the researchers wrote.
Depression had an inverse association with statin intolerance (OR = 0.88; P = .04) and arterial hypertension had no association, according to the researchers.
Other factors associated with statin intolerance were use of antiarrhythmic drugs, use of calcium channel blockers, alcohol use and increased statin dose, the researchers wrote.
“Our findings mean that we should evaluate patients’ symptoms very carefully, firstly to see whether symptoms are indeed caused by statins, and secondly, to evaluate whether it might be patients’ perceptions that statins are harmful — so-called nocebo or drucebo effect — which could be responsible for more than 50% of all symptoms, rather than the drug itself,” Banach said in the release.
Discontinuation of statins without consulting with a clinician should be discouraged, Banach said in the release.
“The most important message to patients as a result of this study is that they should keep on taking statins according to the prescribed dose, and discuss any side effects with their doctor, rather than discontinuing the medication,” he said. “The same clear message can be addressed to physicians treating patients with high cholesterol levels. Most cases of statin intolerance observed in clinical practice are associated with effects caused by patients’ misconceptions about the side effects of statins or may be due to other reasons. Therefore, we should carefully evaluate symptoms, assessing in detail patients’ medical histories, when the symptoms appeared, specific details of pain, other medications the patients are taking, and other conditions and risk factors. Then we will see that statins can be used safely in most patients, which is critically important for reducing their cholesterol levels and preventing heart and blood vessel diseases and death.”
Reference:
- Statin intolerance is “over-estimated and over-diagnosed”. https://www.escardio.org/The-ESC/Press-Office/Press-releases/Statin-intolerance-is-over-estimated-and-over-diagnosed. Published Feb. 15, 2022. Accessed Feb. 16, 2022.
Perspective
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Abha Khandelwal, MD, FACC
This is the first large-scale meta-analysis looking at 4 million patients to report prevalence of statin intolerance. The researchers also report this looking at different definitions from the various societies. They report a pooled prevalence of 9.1% irrespective of the definition applied. They noted lower rates in randomized controlled trials vs. cohort studies and no difference between lipophilic vs. hydrophilic statins. They noted higher rates of statin intolerance in patients over the age of 65, women and those of Asian and African American races. Positive associates were noted in those who were obese or had diabetes, hypothyroid or chronic liver or renal disease. They also noted a higher dose of statin was more associated with statin intolerance.
The findings are in concordance with what we see in clinical practice. We often note those who have more statin intolerance are older, female and have some of the comorbidities listed above. We have noted that higher doses tend to result in this as well. We have long seen higher rates of statin intolerance than reported in randomized controlled trial literature, partially because of the exclusion of some of our older, more frail individuals from study designs. In clinical practice in our women's heart health center, we tend to see it more frequently than the 9% reported, but this is likely related to the population that visits our clinic.
In clinical practice, every decision is a risk-benefit assessment from the patient. We look at the indication for the patient and the severity of the intolerance. Based on this, we can adjust drug and dose frequency or investigate alternatives such as PCSK9 inhibitors. It is important to give the data to the patients, and as studies look at more patient-reported outcomes we will have more patient-relevant and quality-of-life reporting metrics to share with them. The most important thing to convey to the patient is if they have hesitation about their medications, it is important to talk about this with their health care professional so there can be shared decision-making in their cardiac care.
The study presents a global view of statin intolerance, which is important, as CVD is still globally the largest cause of morbidity and mortality. Statins are a cornerstone for our treatment against CVD and it is nice to see these data be reported. The trial has limitations of a meta-analysis (and heterogeneity) but is the largest pooled reporting of statin intolerance to my knowledge. It is important to note the nocebo/drucebo effect was not examined in these studies and could impact findings.
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