Author + information
- Loukianos S. Rallidis, MD∗ ( and )
- Maria Anastasiou-Nana, MD
- ↵∗Second Department of Cardiology, University General Hospital Attikon, 74 Thermopylon, Argyroupolis 16451 Athens, Greece
We read with great interest the American College of Cardiology/American Heart Association (ACC/AHA) new guidelines on the treatment of blood cholesterol (1). The guidelines are based on a thorough evaluation of randomized controlled trials (RCTs), systemic reviews, and meta-analyses of RCTs with atherosclerotic cardiovascular disease outcomes.
However, the issue of statin-related myopathy (SRM) has been greatly underestimated, and this contrasts with findings of observational studies that suggest that SRM is relatively common (2,3). The committee states that SRM is rare (∼0.01 excess case per 100 statin-treated individuals per year), and this notion is derived from data from RCTs that have systematically underestimated SRM for several reasons (4):
1. Application of strict criteria to define myopathy, such as creatine kinase (CK) elevation >10× upper limit normal (ULN) with or without muscle symptoms, which is a rare manifestation of myopathy. Therefore, the reported incidence of myopathy in most trials was <0.3%, for example, in the HPS (Heart Protection Study) study, it was 0.11% (5); in the 4S (Scandinavian Simvastatin Survival Study) study, 0.27% (6); and so on. Furthermore, in some trials, myopathy was defined as a persistent increase in CK >10× ULN on 2 consecutive measurements, which reduced even more the incidence of myopathy. This is the case with the TNT (Treating to New Targets) trial (7) in which none of the participants, even on a high statin dose, fulfilled the criteria for myopathy.
2. Failure to systematically report myalgias: in many trials, patients were not interviewed for mild muscle complaints, the commonest manifestation of myopathy, or for fatigue, another form of myopathy.
3. Exclusion of patients most likely to suffer from myopathy, such as patients with renal or liver insufficiency, patients taking drugs with possible interaction with statins, older patients, and so on.
4. Exclusion of patients experiencing muscle symptoms during the open-label run-in phase of the trials. In some of them, up to 30% of the eligible patients were excluded in pre-randomization phases because they did not meet randomization criteria or had adverse events (7).
Observational studies report an incidence of SRM ranging between 5% and 10% (2,3), and this is consistent with our daily clinical practice. It is therefore essential to emphasize that SRM is not uncommon, and when it appears, does not always necessitates statin discontinuation. In most cases, myalgias are mild, and after careful clinical evaluation, discussion with the patient, and weighing the benefits and risk, it is likely that the patient will remain on statin therapy, probably at lower dose, and have all the clinical benefits associated with statin treatment.
- Stone N.J.,
- Robinson J.,
- Lichtenstein A.H.,
- et al.