Statin-induced muscle toxicity and susceptibility to malignant hyperthermia and other muscle diseases: a population-based case-control study including 1st and 2nd degree relatives.

Abstract

Case reports have suggested an association between susceptibility to malignant hyperthermia (MH) and other muscle diseases in subjects with statin-induced muscle toxicity. The aim of the study was to further scrutinize this association in a population-based case-control study including 1st and 2nd degree relatives. Spontaneously reported cases with muscle disorders associated with statin therapy until September 2006 were identified in the Swedish Adverse Drug Reaction Registry at the Medical Products Agency. For each case, ten population-based controls, matched on year of birth and gender, were randomly selected from the National Registry of Swedish Citizens. First and 2nd degree relatives to cases and controls were identified in the Swedish Multi-Generation Registry. ICD codes that could be associated with susceptibility to MH or other muscle diseases were chosen, and subjects were followed until December 2007 with regard to occurrence of selected ICD codes in the Swedish Registries for Cause of Death and Hospital Discharge Diagnoses, respectively. The chosen ICD codes were significantly overrepresented in case families compared with control families (RR 1.56; 95 % CI 1.15-2.10). The strongest associations were identified for a diagnosis of drug-induced or specified or unspecified myopathy (RR 52; 95 % CI 22-123) or a diagnosis of unspecified hyperthermia in combination with drug-induced or specified or unspecified myopathy (RR 30; 95 % CI 6-148). In contrast, a diagnosis of unspecified hyperthermia in the absence of drug-induced or specified or unspecified myopathy was significantly underrepresented among case families (RR 0.42; 95 % CI 0.23-0.76). In a case-control study including 1st and 2nd degree relatives, statin-induced muscle toxicity was significantly associated with a diagnosis of drug-induced or specified or unspecified myopathy and with a diagnosis of unspecified hyperthermia in combination with a diagnosis of drug-induced or specified or unspecified myopathy.