PP  Vol.4 No.3 , June 2013
Discontinuation of Statin Treatment in Relation to Chronic Diseases and Laboratory Findings
Abstract: Purpose: The aim was to study discontinuation of statin treatment, especially with respect to clinical characteristics and adverse effect measured by clinical laboratory tests indicating muscle damage (plasma creatine kinase, CK) and liver AEs (plasma alanine aminotransferase, ALAT). Methods: The initial study population included 60,488 individuals who had purchased first time statin prescription in Helsinki-Uusimaa region between 01-01-2007 and 31-12-2009. The follow-up started when first statin prescription was purchased and ended 31-12-2009 or death, which ever occurred first. From this population 54,172 individuals were defined to eligible to study population of this study. Clinical laboratory measurements were obtained from Helsinki-Uusimaa University Hospital (HUSLAB) that which provides the laboratory tests for the Helsinki-Uusimaa region serving about a population of 1.5 million. Results: In this fairly large real-life study the occurrence of ALAT-AE and mild CK-elevations after initiation of first statin treatments were relatively low. Increasing age and the presence of co-morbidities increased the risk of these AEs. Further, the ALAT-AEs implied increased risk of discontinuation of treatment. Diabetic patients discontinued treatment more often than non-diabetics, whereas the presence of other chronic conditions implied higher persistence of statin treatment. Conclusions: It is essential that those who would benefit from statin therapy actually are treated and by far in most patients treatment seems to be safe and well tolerated. For those who cannot tolerate statins new therapeutic options are needed.
Cite this paper: L. Niskanen, J. Suvisaari, J. Suvisaari, A. But and J. Haukka, "Discontinuation of Statin Treatment in Relation to Chronic Diseases and Laboratory Findings," Pharmacology & Pharmacy, Vol. 4 No. 3, 2013, pp. 318-324. doi: 10.4236/pp.2013.43046.

[1]   C. Baigent, A. Keech, P. M. Kearney, L. Blackwell, G. Buck, C. Pollicino, et al., “Efficacy and Safety of Cholesterol-Lowering Treatment: Prospective Meta-Analysis of Data from 90,056 Participants in 14 Randomised Trials of Statins,” Lancet, Vol. 366, No. 9493, 2005, pp. 12671278. doi:10.1016/S0140-6736(05)67394-1

[2]   A. Kashani, C. O. Phillips, J. M. Foody, Y. Wang, S. Mangalmurti, D. T. Ko, et al., “Risks Associated with Statin Therapy a Systematic Overview of Randomized Clinical Trials,” Circulation, Vol. 114, No. 25, 2006, pp. 2788-2797. doi:10.1161/CIRCULATIONAHA.106.624890

[3]   “MRC/BHF Heart Protection Study of Cholesterol-Lowering with Simvastatin in 5963 People with Diabetes: A Randomised Placebo-Controlled Trial,” The Lancet, Vol. 361, No. 9374, 2003, pp. 2005-2016. doi:10.1016/S0140-6736(03)13636-7

[4]   P. M. Kearney, L. Blackwell, R. Collins, A. Keech, J. Simes, R. Peto, et al., “Efficacy of Cholesterol-Lowering Therapy in 18,686 People with Diabetes in 14 Randomised Trials of Statins: A Meta-Analysis,” Lancet, Vol. 371, No. 9607, 2008, pp. 117-125. doi:10.1016/S0140-6736(08)60104-X

[5]   J. Hippisley-Cox and C. Coupland, “Unintended Effects of Statins in Men and Women in England and Wales: Population Based Cohort Study Using the Qresearch Database,” BMJ, Vol. 340, No. 7759, 2010, p. c2197.

[6]   D. M. Cutler and W. Everett, “Thinking outside the Pillbox—Medication Adherence as a Priority for Health Care Reform,” New England Journal of Medicine, Vol. 362, No. 17, 2010, pp. 1553-1555. doi:10.1056/NEJMp1002305

[7]   S. J. Kamal-Bahl, T. Burke, D. Watson and C. Wentworth, “Discontinuation of Lipid Modifying Drugs among Commercially Insured United States Patients in Recent Clinical Practice,” The American Journal of Cardiology, Vol. 99, No. 4, 2007, pp. 530-534. doi:10.1016/j.amjcard.2006.08.063

[8]   A. Helin-Salmivaara, P. Lavikainen, M. J. Korhonen, H. Halava, S. Y. T. Junnila, R. Kettunen, et al., “Long-Term Persistence with Statin Therapy: A Nationwide Register Study in Finland,” Clinical Therapeutics, Vol. 30, 2008, pp. 2228-2240. doi:10.1016/j.clinthera.2008.12.003

[9]   C. A. Jackevicius, M. Mamdani and J. V. Tu, “Adherence with Statin Therapy in Elderly Patients with and without Acute Coronary Syndromes,” JAMA, Vol. 288, No. 4, 2002, pp. 462-467. doi:10.1001/jama.288.4.462

[10]   B. McGinnis, K. L. Olson, D. Magid, E. Bayliss, E. J. Korner, D. W. Brand, et al., “Factors Related to Adherence to Statin Therapy,” The Annals of Pharmacotherapy, Vol. 41, No. 11, 2007, pp. 1805-1811. doi:10.1345/aph.1K209

[11]   M. Jasińska-Stroschein, J. Owczarek, I. Wejman and D. Orszulak-Michalak, “Novel Mechanistic and Clinical Implications Concerning the Safety of Statin Discontinuation,” Pharmacological Reports, Vol. 63, No. 4, 2011, pp. 867-879.

[12]   M. Endres and U. Laufs, “Discontinuation of Statin Treatment in Stroke Patients,” Stroke, Vol. 37, No. 10, 2006, pp. 2640-2643. doi:10.1161/01.STR.0000240690.69406.28

[13]   C. Heeschen, C. W. Hamm, U. Laufs, S. Snapinn, M. Böhm and H. D. White, “Withdrawal of Statins Increases Event Rates in Patients with Acute Coronary Syndromes,” Circulation, Vol. 105, No. 12, 2002, pp. 14461452. doi:10.1161/01.CIR.0000012530.68333.C8

[14]   S. S. Daskalopoulou, J. A. C. Delaney, K. B. Filion, J. M. Brophy, N. E. Mayo and S. Suissa, “Discontinuation of Statin Therapy Following an Acute Myocardial Infarction: A Population-Based Study,” European Heart Journal, Vol. 29, No. 17, 2008, pp. 2083-2091. doi:10.1093/eurheartj/ehn346

[15]   “WHO Collaborating Centre for Drug Statistics Methodology,” 2008.

[16]   R. Lahti and A. Penttilä, “The Validity of Death Certificates: Routine Validation of Death Certification and Its Effects on Mortality Statistics,” Forensic Science International, Vol. 115, No. 1-2, 2001, pp. 15-32. doi:10.1016/S0379-0738(00)00300-5

[17]   R. M. Calderon, L. X. Cubeddu, R. B. Goldberg and E. R. Schiff, “Statins in the Treatment of Dyslipidemia in the Presence of Elevated Liver Aminotransferase Levels: A Therapeutic Dilemma,” Mayo Clinic Proceedings, Vol. 85, No. 4, 2010, pp. 349-356. doi:10.4065/mcp.2009.0365

[18]   “Overview of Benefit Programmes 2007,” Social Insurance Institution, Finland, 2007.

[19]   S. R. Cole and M. A. Hernan, “Constructing Inverse Probability Weights for Marginal Structural Models,” American Journal of Epidemiology, Vol. 168, No. 6, 2008, pp. 656-664. doi:10.1093/aje/kwn164

[20]   R Development Core Team, “R: A Language and Environment for Statistical Computing,” 2011.

[21]   B. A. Golomb and M. A. Evans, “Statin Adverse Effects: A Review of the Literature and Evidence for a Mitochondrial Mechanism,” American Journal of Cardiovascular Drugs, Vol. 8, No. 6, 2008, pp. 373-418. doi:10.2165/0129784-200808060-00004

[22]   D. L. McClure, R. J. Valuck, M. Glanz and J. E. Hokanson, “Systematic Review and Meta-Analysis of Clinically Relevant Adverse Events from HMG CoA Reductase Inhibitor Trials Worldwide from 1982 to Present,” Pharmacoepidemiology and Drug Safety, Vol. 16, No. 2, 2007, pp. 132-143. doi:10.1002/pds.1341

[23]   P. S. Phillips, R. H. Haas, S. Bannykh, S. Hathaway, N. L. Gray, B. J. Kimura, et al., “Statin-Associated Myopathy with Normal Creatine Kinase Levels,” Annals of Internal Medicine, Vol. 137, No. 7, 2002, pp. 581-585. doi:10.7326/0003-4819-137-7-200210010-00009

[24]   S. M. Haffner, S. Lehto, T. Rönnemaa, K. Pyörälä and M. Laak, “Mortality from Coronary Heart Disease in Subjects with Type 2 Diabetes and in Nondiabetic Subjects with and without Prior Myocardial Infarction,” New England Journal of Medicine, Vol. 339, No. 4, 1998, pp. 229234. doi:10.1056/NEJM199807233390404

[25]   A. L. Catapano, Z. Reiner, G. De Backer, I. Graham, M.R. Taskinen, O. Wiklund, et al., The Task Force for the Management of Dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS), “ESC/EAS Guidelines for the Management of Dyslipidaemias,” Atherosclerosis, Vol. 217, No. 1, 2011, pp. 3-46. doi:10.1016/j.atherosclerosis.2011.06.028