Prevalence of statin intolerance: a meta-analysis

Ibadete Bytyçi; Peter E Penson; Dimitri P Mikhailidis; Nathan D Wong; Adrian V Hernandez; Amirhossein Sahebkar; Paul D Thompson; Mohsen Mazidi; Jacek Rysz; Daniel Pella; Željko Reiner; Peter P Toth; Maciej Banach

doi:10.1093/eurheartj/ehac015

Prevalence of statin intolerance: a meta-analysis

Eur Heart J. 2022 Sep 7;43(34):3213-3223. doi: 10.1093/eurheartj/ehac015.

Authors

Ibadete Bytyçi^{1

2}, Peter E Penson^{3

4}, Dimitri P Mikhailidis⁵, Nathan D Wong⁶, Adrian V Hernandez^{7

8}, Amirhossein Sahebkar^{9

10

11}, Paul D Thompson^{12

13}, Mohsen Mazidi^{14

15}, Jacek Rysz¹⁶, Daniel Pella¹⁷, Željko Reiner¹⁸, Peter P Toth^{19

20}, Maciej Banach^{21

22}

Affiliations

¹ Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.
² Clinic of Cardiology, University Clinical Centre of Kosovo, Prishtina, Kosovo.
³ School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, UK.
⁴ Liverpool Centre for Cardiovascular Science, Liverpool, UK.
⁵ Department of Clinical Biochemistry, Royal Free Hospital Campus, University College London Medical School, University College London (UCL), London, UK.
⁶ Heart Disease Prevention Program, Division of Cardiology, University of California, Irvine School of Medicine Predictive Health Diagnostics, Irvine, CA, USA.
⁷ Health Outcomes, Policy, and Evidence Synthesis (HOPES) Group, University of Connecticut School of Pharmacy, Storrs, CT, USA.
⁸ Vicerrectorado de Investigación, Universidad San Ignacio de Loyola (USIL), Lima, Peru.
⁹ Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
¹⁰ Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
¹¹ School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
¹² Division of Cardiology, Hartford Hospital, 80 Seymour Street, Hartford, CT, USA.
¹³ Department of Internal Medicine, University of Connecticut, Farmington, CT, USA.
¹⁴ Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.
¹⁵ Department of Nutritional Sciences, King's College London, London, UK.
¹⁶ Department of Hypertension, Nephrology and Family Medicine, Medical University of Lodz (MUL), Lodz, Poland.
¹⁷ 2nd Department of Cardiology, Faculty of Medicine, Pavol Jozef Safarik University and East Slovak Institute of Cardiovascular Diseases, Kosice, Slovakia.
¹⁸ Department of Internal Diseases, University Hospital Center Zagreb, School of Medicine, Zagreb University, Zagreb, Croatia.
¹⁹ CGH Medical Center, Sterling, IL, USA.
²⁰ Cicarrone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
²¹ Department of Preventive Cardiology and Lipidology, Medical University of Lodz (MUL), Rzgowska 281/289, 93-338 Lodz, Poland.
²² Cardiovascular Research Centre, University of Zielona Gora, Zielona Gora, Poland.

Abstract

Aims: Statin intolerance (SI) represents a significant public health problem for which precise estimates of prevalence are needed. Statin intolerance remains an important clinical challenge, and it is associated with an increased risk of cardiovascular events. This meta-analysis estimates the overall prevalence of SI, the prevalence according to different diagnostic criteria and in different disease settings, and identifies possible risk factors/conditions that might increase the risk of SI.

Methods and results: We searched several databases up to 31 May 2021, for studies that reported the prevalence of SI. The primary endpoint was overall prevalence and prevalence according to a range of diagnostic criteria [National Lipid Association (NLA), International Lipid Expert Panel (ILEP), and European Atherosclerosis Society (EAS)] and in different disease settings. The secondary endpoint was to identify possible risk factors for SI. A random-effects model was applied to estimate the overall pooled prevalence. A total of 176 studies [112 randomized controlled trials (RCTs); 64 cohort studies] with 4 143 517 patients were ultimately included in the analysis. The overall prevalence of SI was 9.1% (95% confidence interval 8.0-10%). The prevalence was similar when defined using NLA, ILEP, and EAS criteria [7.0% (6.0-8.0%), 6.7% (5.0-8.0%), 5.9% (4.0-7.0%), respectively]. The prevalence of SI in RCTs was significantly lower compared with cohort studies [4.9% (4.0-6.0%) vs. 17% (14-19%)]. The prevalence of SI in studies including both primary and secondary prevention patients was much higher than when primary or secondary prevention patients were analysed separately [18% (14-21%), 8.2% (6.0-10%), 9.1% (6.0-11%), respectively]. Statin lipid solubility did not affect the prevalence of SI [4.0% (2.0-5.0%) vs. 5.0% (4.0-6.0%)]. Age [odds ratio (OR) 1.33, P = 0.04], female gender (OR 1.47, P = 0.007), Asian and Black race (P < 0.05 for both), obesity (OR 1.30, P = 0.02), diabetes mellitus (OR 1.26, P = 0.02), hypothyroidism (OR 1.37, P = 0.01), chronic liver, and renal failure (P < 0.05 for both) were significantly associated with SI in the meta-regression model. Antiarrhythmic agents, calcium channel blockers, alcohol use, and increased statin dose were also associated with a higher risk of SI.

Conclusion: Based on the present analysis of >4 million patients, the prevalence of SI is low when diagnosed according to international definitions. These results support the concept that the prevalence of complete SI might often be overestimated and highlight the need for the careful assessment of patients with potential symptoms related to SI.

Keywords: Cardiovascular disease; Prevalence; Risk factors; Statin intolerance.

Publication types

Meta-Analysis
Research Support, Non-U.S. Gov't

MeSH terms

Atherosclerosis / drug therapy
Female
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors* / adverse effects
Lipids
Male
Prevalence
Randomized Controlled Trials as Topic
Risk Factors

Substances

Hydroxymethylglutaryl-CoA Reductase Inhibitors
Lipids