Abstract
Background Although statins have great benefit on the prevention of cardiovascular diseases with limited adverse effects (AEs), little is known about patients’ contribution of AE reports in clinical practice. Objectives To explore patients’ experiences of statin AEs and related laboratory monitoring in clinical practice. Setting Outpatient clinics of two University hospitals in northeast Thailand. Methods Generic symptom checklist questionnaires for self-reporting AEs were distributed to patients prescribed simvastatin, atorvastatin, or rosuvastatin at outpatient clinics. Clinical information was obtained from medical records. Reported symptoms were assessed for causality considering previously known statin AEs, concomitant diseases and drugs. Main outcome measure Potential statin AEs reported by patients and monitoring of laboratory parameters related to musculoskeletal and liver disorders. Results Of the total 718 valid responses, 76.0 % of patients reported at least one symptom, most of which (69.0 %) were probable/possible statin AEs. Musculoskeletal and liver-related symptoms were reported by 283 (39.4 %) and 134 patients (18.7 %), respectively. Probable/possible AEs were categorized in 56.7 % of their musculoskeletal and gastrointestinal symptoms. Majority of patients had at least one laboratory test on initiation of (64.8 %) and during statin treatment (61.8 %). Patients taking atorvastatin or rosuvastatin, and patients with history of chronic renal diseases were more likely to have creatine kinase (CK) monitored on initiation of and during statin treatment. Additionally, taking drugs which could potentially increase muscle injury (OR 1.929, P < 0.01) and self-reporting of musculoskeletal symptoms (OR 1.805, P < 0.01) were associated with CK monitoring during statin treatment. Reporters of musculoskeletal symptoms also had significantly higher mean CK level than those not reporting any musculoskeletal symptoms (207.35 ± 155.40 vs. 143.95 ± 83.07 U/L, respectively; P = 0.037). Patient reporting of liver AEs was not related to alanine aminotransferase (ALT) level and monitoring, however, prior history of liver disorders was significantly associated with monitoring of ALT on initiation of and during statin treatment (OR 5.745 and OR 23.063, respectively; P < 0.01). Conclusion Many patients experienced at least one possible adverse effects on a statin. The findings suggest that laboratory monitoring is relatively selective in relation to risks and patient-reported adverse symptoms.
References
World Health Organization. The 10 leading causes of death, 2010 and 2011. http://www.who.int/gho/mortality_burden_disease/causes_death/mbd_013.jpg. Accessed 15 Dec 2014.
Stone NJ, Robinson J, Lichtenstein AH, Bairey Merz CN, Blum CB, Eckel RH, et al. ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013;63(25 Pt B):2889–934.
Expert Panel on Detection Evaluation and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Third Report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (adult treatment panel III) final report. Circulation. 106(25):3143–421.
Martin SS, Metkus TS, Horne A, Blaha MJ, Hasan R, Campbell CY, et al. Waiting for the National Cholesterol Education Program Adult Treatment Panel IV Guidelines, and in the meantime, some challenges and recommendations. Am J Cardiol. 2012;110(2):307–13.
Silva MA, Swanson AC, Gandhi PJ, Tataronis GR. Statin-related adverse events: a meta-analysis. Clin Ther. 2006;28(1):26–35.
Jones PH, Davidson MH, Stein EA, Bays HE, Mckenney JM, Miller E, et al. Comparison of the efficacy and safety of rosuvastatin versus atorvastatin, simvastatin, and pravastatin across doses (STELLAR*Trial). Am J Cardiol. 2003;93:152–60.
Consumers Union of United States, Inc. Consumer reports best buy drugs™. Evaluating statin drugs to treat: high cholesterol and heart disease-comparing effectiveness, safety, and price. http://www.consumerreports.org/health/resources/pdf/best-buy-drugs/StatinsUpdate-FINAL.pdf. Accessed 15 Dec 2014.
McKenney JM, Davidson MH, Jacobson TA, Guyton JR. Final conclusions and recommendations of the national lipid association statin safety assessment task force. Am J Cardiol. 2006;97(8A):89C–94C.
FDA Consumer Health Information, U.S. Food and Drug Administration. FDA expands advice on statin risks. http://www.fda.gov/downloads/ForConsumers/ConsumerUpdates/UCM293705.pdf. Accessed 15 Dec 2014.
Cohen DE, Anania FA, Chalasani N. An assessment of statin safety by hepatologists. Am J Cardiol. 2006;97(8A):77C–81C.
Thompson PD, Clarkson PM, Rosenson RS. An assessment of statin safety by muscle experts. Am J Cardiol. 2006;97(8A):69C–76C.
Ward JK, Armitage G. Can patients report patient safety incidents in a hospital setting? A systematic review. BMJ Qual Saf. 2012;21(8):685–99.
van Hunsel F, Harmark L, Pal S, Olsson S, van Grootheest K. Experiences with adverse drug reaction reporting by patients: an 11-country survey. Drug Saf. 2012;35(1):45–60.
Inch J, Watson MC, Anakwe-Umeh S. Patient versus healthcare professional spontaneous adverse drug reaction reporting: a systematic review. Drug Saf. 2012;35(10):807–18.
Krska J, Anderson C, Murphy E, Avery AJ. How patient reporters identify adverse drug reactions: a qualitative study of reporting via the UK yellow card scheme. Drug Saf. 2011;34(5):429–36.
Jarernsiripornkul N, Kakaew W, Loalukkana W, Krska J. Adverse drug reaction monitoring: comparing doctor and patient reporting for new drugs. Pharmacoepidemiol Drug Saf. 2009;18(3):240–5.
Jarernsiripornkul N, Chaisrisawadsuk S, Chaiyakum A, Krska J. Patient self-reporting of potential adverse drug reactions to non-steroidal anti-inflammatory drugs in Thailand. Pharm World Sci. 2009;31(5):559–64.
Jarernsiripornkul N, Senacom P, Uchaipichat V, Chaipichit N, Krska J. Patient reporting of suspected adverse drug reactions to antiepileptic drugs: factors affecting attribution accuracy. Epilepsy Behav. 2012;24(1):102–6.
Boonmuang P, Nathisuwan S, Chaiyakunapruk N, Suwankesawong W, Pokhagul P, Teerawattanapong N, Supsongserm P. Characterization of statin-associated myopathy case reports in thailand using the health product vigilance center database. Drug Saf. 2013;36(9):779–87.
Golomb BA, McGraw JJ, Evans MA, Dimsdale JE. Physician response to patient reports of adverse drug effects: implications for patient-targeted adverse effect surveillance. Drug Saf. 2007;30(8):669–75.
Jarernsiripornkul N, Krska J, Capps PA, Richards RM, Lee A. Patient reporting of potential adverse drug reactions: a methodological study. Br J Clin Pharmacol. 2002;53(3):318–25.
Lacy CF. American Pharmacists Association. Drug information handbook: a comprehensive resource for all clinicians and healthcare professionals. 20th edn. Lexi-Comp, Ohio 2011–2012. ISBN: 978-1-59195-292-3.
Harris LJ, Thapa R, Brown M, Pabbathi S, Childress RD, Heimberg M, Braden R, Elam MB. Clinical and laboratory phenotype of patients experiencing statin intolerance attributable to myalgia. J Clin Lipidol. 2011;5(4):299–307.
Navarro VJ, Senior JR. Drug-related hepatotoxicity. N Engl J Med. 2006;354(7):731–9.
Mashayekhi SO, Ghandforoush-Sattari M, Baghdadchi ME, Kheyri M. Patients’ report of statins use and side-effects in a sample of hospitalized cardiac patients in the Islamic Republic of Iran. East Mediterr Health J. 2011;17(5):460–4.
Bent S, Padula A, Avins AL. Brief communication: better ways to question patients about adverse medical events: a randomized, controlled trial. Ann Intern Med. 2006;144(4):257–61.
van Hunsel F, Passier A, van Grootheest K. Comparing patients’ and healthcare professionals’ ADR reports after media attention: the broadcast of a Dutch television programme about the benefits and risks of statins as an example. Br J Clin Pharmacol. 2009;67(5):558–64.
Law M, Rudnicka AR. Statin safety: a systematic review. Am J Cardiol. 2006;97(8, Suppl 1):S52–60.
Calderon RM, Cubeddu LX, Goldberg RB, Schiff ER. Statins in the treatment of dyslipidemia in the presence of elevated liver aminotransferase levels: a therapeutic dilemma. Mayo Clin Proc. 2010;85(4):349–56.
Lampela P, Hartikainen S, Sulkava R, Huupponen R. Adverse drug effects in elderly people—a disparity between clinical examination and adverse effects self-reported by the patient. Eur J Clin Pharmacol. 2007;63:509–15.
Gandhi TK, Burstin HR, Cook EF, Puopolo AL, Haas JS, Brennan TA, Bates DW. Drug complications in outpatients. J Gen Intern Med. 2000;15(3):149–54.
Cirillo M, Venturini M, Ciccarelli L, Coati F, Bortolami O, Verlato G. Clinician versus nurse symptom reporting using the National Cancer Institute-Common Terminology Criteria for Adverse Events during chemotherapy: results of a comparison based on patient’s self-reported questionnaire. Ann Oncol. 2009;20(12):1929–35.
Thomson J, Wang W, Browning C, Kendig H. Self-reported medication side effects in an older cohort living independently in the community—the Melbourne Longitudinal Study on Healthy Ageing (MELSHA): cross-sectional analysis of prevalence and risk factors. BMC Geriatr. 2010;10(1):37.
Bowling A. Mode of questionnaire administration can have serious effects on data quality. J Public Health. 2005;27(3):281–91.
Acknowledgments
Special thanks are expressed to all patients who completed the questionnaires and to all staffs who provided helps in data collection at Srinagarind hospital and Queen Sirikit Heart Center.
Funding
This study received financial support from the Royal Golden Jubilee Ph.D. Programme (Grant Number: PHD/0038/2553).
Conflicts of interest
All authors declare that they have no conflict of interest.
Author information
Authors and Affiliations
Corresponding author
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Chaipichit, N., Krska, J., Pratipanawatr, T. et al. Statin adverse effects: patients’ experiences and laboratory monitoring of muscle and liver injuries. Int J Clin Pharm 37, 355–364 (2015). https://doi.org/10.1007/s11096-015-0068-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11096-015-0068-5