title: Potential statin-drug interactions: prevalence and clinical significance.
abstract: BACKGROUND
  Statins are cholesterol-lowering drugs widely used for cardiovascular prevention. Although safe when used alone, in combination with other drugs the likelihood of adverse drug reactions increases significantly. The exposure of the Bulgarian population to coprescriptions leading to potential statin-drug interactions is currently unknown.
  
  
  OBJECTIVE
  The aim of this study was to investigate the incidence of coprescriptions involving statins and to compare the exposure of outpatients and inpatients to potential statin-drug interactions.
  
  
  METHODS
  A cardiology clinic of the teaching University hospital in Varna, Bulgaria.
  
  
  METHODS
  This observational retrospective study examined the medical records of hospitalized patients prescribed a statin in combination with potentially interacting drugs. Patients who entered the hospital with a statin coprescription (considered outpatients) were compared with those coprescribed a statin at discharge from hospital (considered inpatients). Potentially interacting drugs included inhibitors and inducers of cytochrome P450 (CYP) enzymes and drugs of narrow safety margin (coumarin anticoagulants, digitalis).
  
  
  METHODS
  The proportion of patients exposed to statin coprescriptions with potentially interacting drugs at hospital admission and discharge.
  
  
  METHODS
  laboratory evidence supporting possible statin-drug interactions.
  
  
  RESULTS
  Out of 1641 hospitalized patients examined, 572 were prescribed a statin, either at hospital admission or discharge. Simvastatin was most commonly prescribed and simvastatin-drug coprescription predominated, especially at discharge. The exposure to all potential statin-drug interactions was similar at hospital admission (26.1%) and discharge (24.4%), as was the exposure to statin combinations with CYP inhibitors, 6.4% and 4%, correspondingly. Overall, more coprescriptions were generated, than were eliminated by hospital physicians. Amiodarone was the CYP inhibitor most frequently coprescribed. Of all interacting drugs acenocoumarol was the most commonly found, the proportions of statin-acenocoumarol coprescriptions being roughly the same at hospital entry (11.5%) and discharge (12.4%). In 7 patients out of 69 exposed to the combination, INR was found to be higher than 3, indicating a risk of over-anticoagulation.
  
  
  CONCLUSIONS
  Potential statin-drug interactions are common. Although they do not differ between outpatient and inpatient settings, new hazardous coprescriptions are more frequently generated in hospital. Caution is required when acenocoumarol is coprescribed with statins, especially simvastatin.
authors.affiliation: Department of Preclinical and Clinical Pharmacology, Varna Medical University, 55 Marin Drinov Street, Varna, 9002 Bulgaria.
authors.forename: Maria
authors.initials: M
authors.lastname: Zhelyazkova-Savova
authors.affiliation: Department of Preclinical and Clinical Pharmacology, Varna Medical University, 55 Marin Drinov Street, Varna, 9002 Bulgaria.
authors.forename: Silvia
authors.initials: S
authors.lastname: Gancheva
authors.affiliation: University Hospital "St Marina", First Clinic of Cardiology, 1 Hristo Smirnenski Street, Varna, 9010 Bulgaria.
authors.forename: Vera
authors.initials: V
authors.lastname: Sirakova
keywords: Acenocoumarol-statin interactions; CYP inhibitors; Hospital admission; Hospital discharge; INR; Statin-drug interactions