16 Current Drug Safety, 2012, 7, 16-20 Analgesic Drug Use Associated with Statin Prescription – A Cross- Sectional Study in Primary Care Settings D. Moßhammer*,1, J. Schwarz1, S. Meznaric1, R. Muche2, G. Lorenz1 and K. Mörike3 1Division of General Practice, University Hospital Tübingen, Germany 2Institute of Biometrics, University of Ulm, Germany 3University Hospital Tübingen, Institute of Experimental and Clinical Pharmacology and Toxicology, Department of Clinical Pharmacology, Germany Abstract: Background: To investigate whether features of muscular complaints (MC) differ between receivers of a statin prescription and non-receivers. To analyze the relationship between analgesics prescription, statin prescription and/or musculoskeletal disorders. Methods: Cross-sectional study. Consecutive patients in offices of family practitioners were interviewed using a standardized questionnaire. Target variables: Rates of features of MC in patients with or without a statin prescription and rates of analgesic drug prescription in patients with or without statin prescription and/or musculoskeletal disorders. Odds ratios (adjusted for age, sex, and socio-economic status) were calculated using logistic regression analysis. Results: 1135 patients in 26 general practitioners’ offices were asked to participate, and 1031 patients agreed. Features of MC did not differ between the two groups of patients. Analgesic prescription was found to be associated with statin prescription in patients without musculoskeletal disorders (OR 2.2, CI 1.1-4.7 without statin, OR 2.5, CI 0.9-6.9 with statin) and particularly in those with musculoskeletal disorders (OR 5.2, CI 2.9-9.3 without statin, OR 9.3, CI 4.5-19.1 with statin). Conclusions: Analgesic prescriptions are probably positively associated with statin prescription. Assuming that analgesics attenuate MC, an even stronger association between MC and statin use seems likely. The results generate the hypothesis that statin use contributes to analgesic use in primary care patients. Keywords: Lipid-lowering drugs, statins, musculoskeletal disorders, general practice, analgesics, primary health care. INTRODUCTION In a retrospective analysis of large community-practice data (N=32,225 patients), statin initiation was found to be Data on the features of muscular adverse side effects of associated with an approximate doubling of the risk for statins mainly derive from clinical trials and are sparse in myopathic events (myalgia, mild myositis) [6]. primary care. Newer data has revealed a ten percent rate of mild to moderate muscular complaints (MC) under high dose In our recent analysis of this cross-sectional study in statin therapy in unselected primary care patients [1]. Since primary care settings among 1031 patients ( 50 years), a in primary care MC might be due to a variety of underlying similar positive association (OR 1.5; 95%-CI 1.1-2.0) causes, it has been supposed that primary-care physicians between statin prescription and the reporting of MC was may easily miss statin-associated muscular side effects [2, found. In the complete patient cohort (n=1031), the rate of 3]. It is unknown whether the features of statin-associated reporting muscular complaints in the previous 4 weeks was MC differ from MC of other origin. Commonly, muscular 40% (n=411), and 23% (n=239) of patients were found to adverse effects of statins are collectively termed as have a prescription of a statin. Furthermore, the use of myopathy which includes muscular pain, tenderness, cramps, analgesic drugs was detected in the multivariate logistic heaviness, stiffness or weakness [4]. regression model to be positively associated with MC (odds ratio 1.8; 95% confidence interval 1.3-2.5) [7]. It is The U.S. National Health and Nutrition Examination Survey unknown, however, whether statin use is associated with (from 1999-2002), in a representative cross-sectional study analgesic drugs use. This is particularly important because among 3580 adults without arthritis (40 years), found an analgesics may attenuate MC. association between musculoskeletal pain and statin use (Odds Ratio [OR] 1.5; 95% confidence interval [95%-CI] 1.07-2.11). This report includes the analysis of (1.) the MC features Also, a significant association with lower back pain (OR 1.59; of patients with and without a statin prescription and (2.) the 95%-CI 1.04-2.44) and lower extremity pain (OR 1.50; 95%-CI relationships between analgesics prescription, statin 1.02-2.22), respectively, was observed [5]. prescription and/or musculoskeletal disorders. METHODS *Address correspondence to this author at the Division of General Practice, Eberhard Karls University of Tübingen, University Hospital Tübingen, The approach and methodology have been described in a Österbergstrasse 15, D-72074 Tübingen, Germany; previous report [7]. In brief, a cross-sectional study was Tel: +49 7071 29-80255; Fax: +49 7071 29-5896; performed in 26 general practitioners´ offices from March, E-mail: [email protected] 2006, to March, 2007. It was an exploratory approach. 1574-8863/12 $58.00+.00 © 2012 Bentham Science Publishers Analgesic Drug Use Associated with Statin Prescription Current Drug Safety, 2012, Vol. 7, No. 1 17 The ethical committee of the Medical Faculty of the Features of Musculoskeletal Symptoms Eberhard Karls University of Tübingen approved the study Table 2 shows the results of the univariate analysis of protocol. muscular symptoms in patients with and without statin Patients: Patients at the age of 50 years entering the offices prescription. Among MC patients (n=411), those with a statin were asked for participation after informed consent. Upon prescription reported amelioration of MC while recumbent (OR completion of an interview, the investigator asked the next 2.1, CI 1.2-3.5, adjusted OR 1.9, CI 1.1-3.3) (26%, n=28), as patient entering the office for participation. compared with statin non-prescription (15%, n=45). No Materials: A questionnaire was developed along established significant associations were found in other items, i.e., questionnaires for musculoskeletal complaints and pain [8, 9] localization, character, physical activity, and frequency. and covered information on the severity, frequency, time course, location, amelioration, deterioration, and character of muscular Analgesic Drug Prescription Associated with Statin Use complaints. To minimize recall bias in this cross-sectional and/or Musculoskeletal Disorders study, a period of 4 weeks preceding the interview was Recipients of analgesic prescriptions among MC patients considered to be appropriate for the reporting of MC. increased from those without underlying musculoskeletal With a standardized procedure, the interviewers (J.S. and disorder (OR 2.2, CI 1.1-4.7 without statin, OR 2.5, CI 0.9-6.9 S.M.) used this pseudonymized questionnaire to collect the with statin) to those with musculoskeletal disorder (OR 5.2, CI information from the patient during a personal interview and, 2.9-9.3 without statin, OR 9.3, CI 4.5-19.1 with statin). The subsequently, office documentation database (office files). From reference group were 251 patients without muscular symptoms the office files, the interviewers extracted information on and without preexisting musculoskeletal disorders (see Table 3). medication prescription and diseases of organ systems as th categorized by the International Classification of Diseases, 10 DISCUSSION revision (ICD 10). Prescriptions were grouped into drug classes and analyzed on a yes/no basis. The interviewers checked the Main Findings of this Study quality and completeness of the data at the end of the interview. Basically, no differences of MC between users and non- Data analysis: Data of patients with muscular symptoms users of statins were found. The only exception is that more (n=411, i.e. 40% of 1031 participating patients) were extracted users than non users of statins report amelioration of MC by from the complete data set of 1031 patients. To analyse for any recumbency. Buettner et al., however, in their large U.S. associations between features of muscular symptoms of patients National Health and Nutrition Examination Survey, observed (such as character, frequency, intensity, duration, amelioration, even further characteristics and localization of musculoskeletal deterioration) and statin prescription, odds ratios with 95%- pain in users as compared to non-users of statins. The most confidence intervals were calculated and chi-square tests were likely explanation is that our study did not exclude patients with performed. Univariate analysis was used to screen for factors arthritis. An underestimation of the true association may result. potentially associated with MC in statin users and non-users. An To strengthen these possible associations, the effects of alpha error of 0.05 was considered to be significant. If, in this termination or discontinuation of statin therapy on MC and univariate analysis, variables were found to be significant they creatine kinase serum activities should be included in the were included into a multivariate logistic regression analysis analysis in subsequent prospective studies. adjusting for age, sex, and socio-economic status (Wald-Odds Our second observation was that rates of analgesic ratios with 95%-confidence intervals). prescription receivers tended to increase among patients with To describe the relationships between analgesics statin prescription taking musculoskeletal disorders into account. prescription, statin prescription, and muscular