Statin side-effects would appear to affect only an estimated 9.1% of patients in an analysis of studies with over 4 million patients
The overall prevalence of statin-related side-effects is less than 10% according to the results of a large analysis of both randomised and observational studies by researchers from the Department of Public Health and Clinical Medicine, Umeå University, Sweden.
Hydroxymethyl glutaryl coenzyme A reductase inhibitors, or statins, have revolutionised the management of patients with coronary heart disease. In a 2016 systematic review it was found that among adults who were at an increased risk of cardiovascular disease, statin therapy was associated with reduced risk of all-cause and cardiovascular mortality and cardiovascular disease events. Whilst the evidence for effectiveness of statins is clear, other data has revealed that between 40 and 75% of patients discontinue their statin within one year after initiation. Reported statin side-effects have included myalgia, myopathy, rhabdomyolysis and diabetes with patients frequently discontinuing therapy without medical advice because of perceived side effects.
The precise extent to which adverse effects occur with statins is uncertain and has ranged from 7% in clinical trials to 30% in observational studies. Given this wide variation, for the present study, the Swedish team undertook a meta-analysis to try and provide an estimate of the overall prevalence of statin side-effects. They included both randomised trials and cohort studies which specifically reported on the incidence of adverse effects. The primary endpoint was set as the overall prevalence of adverse effects based on international diagnostic criteria. These criteria included the definition of an adverse effect as one affecting quality of life leading to treatment discontinuation, an inability to tolerate a dose of statin required to reduce an individual’s cardiovascular risk or in relation to adverse muscle-related pain and elevation of creatinine kinase levels.
Statin side-effects overall incidence
A total of 176 studies with 4,143,517 patients with a mean age of 60.5 years (40.9% female) and who were followed-up of 19 months were included in the analysis. The 176 studies comprised 112 randomised trials (195,575 patients) and the remainder cohort studies and White or Caucasian individuals accounted for the majority (81.1%) of participants.
The pooled estimate of statin side-effects was 9.1% (95% CI 8 – 10%) and this was similar for the different diagnostic criteria used. Interestingly, the prevalence of adverse effects was significantly lower in randomised trials compared to cohort studies (4.9% vs 17%). When comparing the different types of statins, the researchers found that for both lipophilic (e.g., atorvastatin, simvastatin, lovastatin) and hydrophilic (e.g., pravastatin, rosuvastatin) agents, the pooled prevalence was very similar (4% vs 5%, lipophilic vs hydrophilic).
Commenting on their findings, the authors suggested that the higher prevalence among cohort studies could have been over-estimated and that in randomised trials, there was a possibility for under-estimation especially because patients who were either older or with co-morbidities and who might therefore be more likely to experience adverse effects, would have been excluded from the trials.
They concluded that the prevalence of statin side-effects is low, highlighting the need for a careful assessment of patients who report adverse effects to reduce unnecessary discontinuation of therapy.
Bytyci I et al. Prevalence of statin intolerance: a meta-analysis Eur Heart J 20222