Although case reports of a possible association between statin therapy and tendon rupture have been published, no analytical studies exploring this relationship have been reported. We conducted a case-control study using the electronic medical records at Michigan State University from 2002 to 2007 to assess whether statin use is a risk factor for tendon rupture. We compared exposure to statins in 93 cases of tendon rupture with similar exposure in 279 sex- and age-matched controls. Exposure to statins was defined as documentation in the electronic medical record of statin use in the 12 months preceding tendon rupture. For controls, the exposure period was defined as 1 year preceding the last office visit. We used a multivariate logistic regression model, controlling for diabetes, renal disease, rheumatologic disease, and steroid use, to calculate the adjusted odds ratios (ORs). There was no significant difference between cases and controls in the rates of statin use, with either univariate [OR = 1.0, 95% confidence interval (CI) 0.54-1.84] or multivariate analyses (OR = 1.10, 95% CI 0.57-2.13). Based on predetermined subgroup analyses, statin exposure was found to be a significant risk factor for tendon rupture in women (adjusted OR = 3.76, 95% CI 1.11-12.75) but not in men (adjusted OR = 0.66, 95% CI 0.29-1.51). In conclusion, we found no overall association between statin use and tendon rupture, but subgroup analysis suggested that women with tendon rupture were more likely to be on statins.

Since the introduction of HMG-CoA reductase inhibitors (statins) for lowering lipids, a large amount of data has been published demonstrating their potential benefits in conditions as varied as cancer, osteoporosis, and Alzheimer's dementia. We reviewed the published literature on MEDLINE from articles between 1950 and 2008 on the non-atheroprotective effects of statins and noted consistent benefits of statin use in improving outcomes of ventricular arrhythmias, sudden cardiac death, cardiac transplant rejection, chronic obstructive pulmonary disease, and sepsis. However, for these conditions, the level of evidence was inadequate to recommend statin use. The evidence for improving outcomes in atrial fibrillation, mortality in heart failure, contrast-induced nephropathy, cataract, age-related macular degeneration, sub-arachnoid hemorrhage, osteoporosis, dementia, and cancer incidence was conflicting and inconclusive. Furthermore, we found that most of the literature consists of small observational studies and their conclusions are often not corroborated by results from larger or randomized studies. Pending large, well designed, randomized trials, we conclude that there is no definite evidence for the use of statins in any condition besides hyperlipidemia and atherosclerosis.

Previous case reports and small studies have suggested that 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors (HMG-CoA-Is) may increase the risk of tendon rupture. We conducted a population-based retrospective cohort evaluation to better assess this relationship. From approximately 800,000 enrollees of a private insurance database, those who were aged ≤64 years with at least 1 year of continuous enrollment were selected. Exposure was defined as initiation of HMG-CoA-I after the beginning of the study period. Each exposed person was matched with 2 controls of similar age and gender. Baseline characteristics, including known risk factors for tendon rupture, were compared between exposed and control cohorts with fidelity to the study's matched design. After adjusting for differences in follow-up and baseline characteristics, incidence rate ratios for tendon rupture was assessed in HMG-CoA-I users and nonusers. A total of 34,749 exposed patients were matched with 69,498 controls. There was no difference in the occurrence of tendon ruptures in HMG-CoA-I users versus nonusers. The results remained unchanged after adjustment for age and gender. In conclusion, this population-based retrospective cohort evaluation suggests that use of HMG-CoA-Is as a group are not associated with tendon rupture.

Sudden cardiac death is an important cause of cardiovascular mortality with the majority of cases occurring in low-risk groups. HMG-CoA reductase inhibitors (statins) have recently been shown to reduce the incidence of ventricular tachycardia (VT)/fibrillation (VF) and sudden cardiac death, and this has been attributed to their pleiotropic effects. However, it is unclear whether this occurs through an 'indirect' anti-ischemic or 'direct' antiarrhythmic effect. We systematically reviewed articles published on MEDLINE between January 1996 and December 2009 focusing on the reduction of VT/VF and sudden cardiac death by statins and the potential mechanisms. Studies reporting sudden cardiac death or VT/VF outcomes with statin use (n = 23) or the pathophysiology of sudden cardiac death reduction by statins (n = 19) were included. We found that statins have been shown to reduce VT/VF and sudden cardiac death only in subjects with underlying coronary artery disease or ischemic cardiomyopathy. No definite benefits were seen with statins in sudden cardiac death and VT/VF in patients with non-ischemic cardiomyopathy. There is insufficient evidence to point toward a benefit in populations at low risk for VT/VF. In conclusion, an anti-ischemic rather than a primary antiarrhythmic effect emerges as the likely mechanism of sudden cardiac death reduction with statins.