Editor's Note:
Statins are the cornerstone of primary and secondary prevention of atherosclerotic cardiovascular disease (ASCVD).
It is unshakable. However, in clinical practice, patients' adherence and adherence to statin therapy is less than ideal.
Many people think that intolerance is a major reason for the long-term use of statins, is this the case?
Recently, a meta-analysis of more than 4 million patients showed that as many as 50% of patients taking statins reduced their doses or discontinued without authorization after feeling intolerant, but the actual prevalence of statin intolerance was less than 10%.
The prevalence of statin intolerance is not surprising
This meta-analysis included 4 143 517 patients in 176 studies (112 randomized controlled studies, 64 cohort studies). The main results are as follows:
The overall prevalence of statin intolerance was 9.1% (95% CI: 8% to 10%). According to the diagnostic criteria of the National Lipid Association (NLA), the International Group of Experts (ILEP), and the European Atherosclerosis Association (EAS), the prevalence of statin intolerance was similar, 7% (95% CI: 6% to 8%), 6.7% (95% CI: 5% to 8%), and 5.9% (95% CI: 4% to 7%), respectively;
The prevalence of statin intolerance was higher in cohort studies than in randomized controlled studies (17% [95% CI: 14%-19%] vs. 4.9% [95% CI:4%-6%], P<0.001);
The prevalence of statin intolerance in studies where statins were used for both primary and secondary prophylaxis (18%, 95% CI: 14% to 21%) was higher than in studies where primary prophylaxis alone (8.2%, 95% CI: 6% to 10%) or only secondary prophylaxis (9.1%, 95% CI: 6% to 11%) was used.
Dr. Maciej Banach, Director of the Hypertension Centre at the Faculty of Medicine of the University of Lodz in Poland and Head of the Cardiovascular Research Center at the University of Tsironagra, said: "We are not surprised by these results! In fact, in most cases, the prevalence of statin intolerance is overestimated and overdiagnosed. This result suggests that approximately 93% of patients receiving statin therapy can obtain effective treatment and are well tolerated and safe. ”
Independent predictor of statin intolerance
Meta-regression analysis showed that independent predictors of statin intolerance included demographic characteristics, comorbid diseases, and drug effects.
Demographic characteristics: those aged ≥ 65 years were more intolerant of statins (OR=1.31; 95% CI: 1.22 to 1.45; P=0.04), women were more intolerant of statins (OR=1.47; 95% CI: 1.38 to 1.53; P=0.007), Asians and Africans were more intolerant of statins (both P<0.05).
Comorbidities: obesity (OR=1.3; P=0.02), diabetes mellitus (OR=1.26; P=0.02), hypothyroidism (OR=1.37; P=0.01), chronic liver disease (OR=1.24; P=0.03), and chronic renal failure (OR=1.25; P=0.03) all increase the risk of statin intolerance. However, depression was inversely associated with statin tolerance (OR=0.88; P=0.04), and hypertension was not associated with statin tolerance.
Drug effects: Calcium channel blockers (OR=1.31, P=0.03) and antiarrhythmic drugs (OR=1.35, P=0.03) increased the risk of statin intolerance; warfarin was not associated with statin tolerance (OR=1.04, P=0.15). In addition, the higher the dose of statins, the higher the risk of intolerance (OR=1.37, P=0.01).
Smoking was not associated with statin tolerance (OR=1.03, P=0.60), alcohol consumption increased the risk of statin intolerance (OR=1.22, P=0.03), and exercise increased the risk of statin intolerance (OR=1.23, P=0.03).
Figure 1. Independent predictor of statin intolerance
In clinical practice, statin intolerance should be treated with caution
In clinical practice, we should evaluate the patient's symptoms very carefully. First, determine whether these symptoms are caused by statins; second, assess whether patients perceive statins as unsafe, the so-called Nocebo effect, which can lead to more than 50% of symptoms. In particular, patients should not reduce or discontinue statins without consulting a doctor.
The most important significance of this study is to emphasize the importance of continuing to take statins as directed by a doctor, and to emphasize that when symptoms of suspected intolerance occur, you should discuss with your doctor in time to seek help, rather than stopping the drug without authorization. Of course, doctors should also recognize that statin intolerance is often overestimated in clinical practice, which affects the prevention of cardiovascular disease. Therefore, in patients who take statins for a long time, we should carefully evaluate the patient's medical history, symptom manifestations, when symptoms appear, other drugs taken at the same time, comorbidities, and other risk factors. As a result, we will find that statins can be safely used in most patients, which is essential for lowering cholesterol levels and preventing cardiovascular disease and death.
Expert commentary
Abha Khandelwal
Associate Professor of Cardiology, Stanford University
This is the first large-scale meta-analysis of more than 4 million patients reporting the global prevalence of statin intolerance. The researchers reported the prevalence of statin intolerance under different diagnostic criteria, and overall, the overall prevalence of statin intolerance was 9.1%. The results of the study showed that the prevalence of statin intolerance in randomized controlled studies was lower than in cohort studies, and there was no difference in the tolerance of lipophilic and hydrophilic statins.
In addition, the researchers' analysis found that statin intolerance rates in people over 65 years of age, women, Asians, and Africans were higher, obesity, diabetes, hypothyroidism or chronic liver and kidney disease increased the risk of statin intolerance, and high-dose application of statins also increased the risk of intolerance.
These findings are very consistent with what we have observed in clinical practice. We note that patients with statin intolerance are usually older, mostly female, and often have a combination of chronic diseases. Of course, high doses can also lead to statin intolerance. We have long found that the actual prevalence of statin intolerance is higher than reported in randomised controlled studies, possibly in part because randomized controlled studies generally exclude older, less physically ill individuals. In fact, the prevalence of statin intolerance at the Women's Heart Health Center where I worked was likely to exceed 9 percent, which may be related to the fact that the patients presented were all women.
In clinical practice, each decision should adequately assess the patient's risk-benefit ratio. By observing the patient's reactivity and intolerance, we can adjust the drug dosage and frequency in a timely manner, or switch to alternative drugs such as PCSK9 inhibitors. As more and more studies focus on patient-reported outcomes, we can also share more research progress related to quality of life with patients. Most importantly, when patients have doubts about taking medications, they should discuss with their doctors in a timely manner and give full play to their shared decision-making power.
This study is currently the largest study of the prevalence of statin intolerance, providing significant global data on statin intolerance. At present, cardiovascular disease remains the largest group of diseases in the world in terms of morbidity and mortality. Statins are the cornerstone of the prevention and treatment of cardiovascular disease, so we are very pleased to see these data. These data will influence clinical practice to some extent and improve cardiovascular outcomes.
Reference: Bytyçi I, et al. Eur Heart J. 2022;doi:10.1093/eurheartj/ehac015.
(Source: Editorial Board of Diabetes International)
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