Safety and effectiveness of atorvastatin and rosuvastatin monotherapy and with fibrate combination among patients receiving protease inhibitors
DOI:
https://doi.org/10.14456/dcj.2014.15Keywords:
protease inhibitors (boosted Pls), statin, atorvastatin, rosuvastatin, fibrate, gemfibrozil, fenofibrate, Adverse events, LDL-C reduction, LDL-C goal achievementAbstract
This study aimed to determine the safety and the effectiveness of atorvastatin and rosuvastatin using alone compared with atorvastatin and rosuvastatin using with fibrate (gemfibrozil or fenofibrate) in reducing low-density lipoprotein cholesterol (LDL-C), and achieving LDL-C goal according to NCEP ATPIII guideline among HIV-infected patients who were recieving boosted-Pls or Pls. A retrospective cohort study was conducted by using medical records among patients who came for follow up during January 1, 2010 through June 30, 2012 at Bamrasnaradura Infectious Disease Institute. The participants must age >18 years at statin-starting date, had LDL-C records at least 2 times: within 3 months before the first statin was used with boosted Pls (or PI) and after being used concomitantly for at least 3 months and had never used any statin 3 months before boosted-Pls starting. Lipid profiles and related data at least for 1 year before and after statins/boosted Pls using were determined and collected. Outcomes were the rates of adverse events (AEs) and the effectiveness of atorvastatin and rosuvastatin: mean % LDL-C reduction and LDL-C goal achievement according to NCEP ATP III. Of 116 patients, 82 were men and 34 were women: mean of age was 45 years; 53 used atorvastatin: 14 with gemfibrozil and 14 with fenofibrate; 63 used rosuvastatin: 14 with gemfibrozil and 15 with fenofibrate. AEs were found 4 (3.596), 2 with myalgia and discontinued statins and another 2 with CPK- increasing >2 times of ULN but they could continue both statins and fibrates. Of 4 AEs cases, 3 used LPV/r regimen and 1 used LPV/ATV/r, all used rosuvastatin 10 mg daily with fibrates: 3 with gemfibrozil and 1 with fenofibrate. Of total, rosuvastatin was more effective than atorvastatin, both mean % LDL-C reduction (33.096 vs 24.196, p = 0.015) and LDL-C goal achievement (68.396 vs 49.196; OR = 2.23, p = 0.036). This study revealed that statin-monotherapy comparing with statin- fibrate combination didn’t affect the effectiveness of both rosuvastatin and atorvastatin in reducing LDL-C levels (p = 0.395 and 0.619, respectively) and in achieving the goal of LDL-C (p = 0.314 and 0.185 respectively). Of 59 cases who used statins alone, rosuvastatin was more effective than atorvastatin in reducing LDL-C (34.996 vs 22.996, p = 0.025) and achieving LDL-C goal (OR = 4.27, p = 0.008). Of 57 cases who used statins with gemfibrozil or fenofibrate, the mean 96 LDL-C reduction in rosuvastatin group and atorvastatin group did not significantly differ (p = 0.778 and 0.235, respectively), as well as achieving the goal did not significantly differ too (OR = 2.75, p = 0.225 and OR = 0.64, p = 0.550, respectively). In summary, if it's necessary to use atorvastatin or rosuvastatin with gemfibrozil or fenofibrate, atorvastatin is preferable to rosuvastatin for more safety and no difference in effectiveness.
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2. Stein JH, Hadigan CM, Brown TT, Chadwick Ellen, Feinberg Judith, M0ler NF, et al. Prevention strategies for cardiovascular disease in HIV-infected patients. Circulation 2 008; 118: e54-e60.
3. Triant V, Lee H, Hadigan C, Grinspoon S. Increased acute myocardial infarction rates and cardiovascular risk factors among patients with human immunodeficiency virus disease. J Clin Endocr Metab 2007;92:2506-12.
4. Obel N, Thomsen H, Kronborg G, Larsen C, Hildebrandt P, SorensenH, et al. Ischemic heart disease in HIV-infected and HIV-uninfected individuals: a population-based cohort study. Clin Infect Dis 2007;44:1625-31.
5. Saves M, Chene G, Ducimetiere P, Leport C, Moal G, Amouyel P, et al. Risk factors for coronary heart disease in patients treated for human immunodeficiency virus infection compared with the general population. Clin Infect Dis 2003; 37:292-8.
6. Hiransuthikul N, Hiransuthikul P, Kanasook Y. Lipid profiles of Thai adult HIV-infected patients receiving protease inhibitors. Southeast Asian J Trop Med Public Health 2007;38:69- 77.
7. Calza L, Manfredi R, Farneti B, Chiodo F. Incidence of hyperlipidaemia in a cohort of 212 HIV-infected patients receiving a protease inhibitor-based antiretroviral therapy. International Journal of Antimicrobial Agents 2003;22:54- 9.
8. Malvestutto CD, Aberg JA. Management of dyslipidemia in HIV-infected patient. J Clin Lipidol 2011;6:447-62.
9. Feeney ER, Mallon PW. HIV and HA ART- associated dyslipidemia. open Cardiovasc Med J 2011;5:49-63.
10. Expert panel on detection, evaluation, and treatment of high blood cholesterol in adults. Third report of the National Cholesterol Education Pro-gram (NCEP). Final report. Maryland: National Institutes of Health; 2002.
11. Fichtenbaum C, Gerber J, Rosenkranz S, Segal Y, Aberg J, Blaschke T, et al. Pharmacokinetic interactions between protease inhibitors and statins in HIV seronegative volunteers: ACTG study A5047. AIDS 2002;16:569-77.
12. The HHS panel on Antiretroviral guidelines for adults and adolescents - a working group of the Office of AIDS Research Advisory Council. Guidelines for the use of Antiretroviral agents in HIV-1-Infected adults and adolescents [Internet], [cited 2014 May 1]. Available from: http://aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescent-arv-guidelines/284/pi-drug-interactions
13. FDA Drug Safety Communication. Interactions between certain HIV or hepatitis c drugs and cholesterol-lowering statin drugs can increase the risk of muscle injury [Internet], [cited 2014 Apr 20]. Available from: http://www.fda.gov/Drugs/DrugSafety/ucm293877.htm
14. FDA Drug Safety Communication. Important safety label changes to cholesterol-lowering statin drugs [Internet], [cited 2014 Apr 20]. Available from: http://www.fda.gov/Drugs/DrugSafety/ucm293101.htm
15. Singh S, Willig JH, Mugavero MJ, Crane PK, Harrington RD, Knopp RH, et al. Comparative effectiveness and toxicity of statins among HIV- Infected patients. Clin Infect Dis 2011;52:387- 95.
16. Calderon RM, Cubeddu LX, Goldberg RB, Schiff ER. Statins in the treatment of dyslipidemia in the presence of elevated Liver Aminotransferase levels: A therapeuticdilemma. Mayo Clin Proc [Internet]. 2010;85:349-56. [cited 2014 Apr 21] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2848423/
17. ศูนย์ข้อมูลข่าวสารด้านเวชภัณฑ์ กระทรวงสาธารณสุข. ราคาอ้างอิง [อินเทอร์เน็ต]. [สืบค้นเมื่อ 4 พ.ค. 2557]. แหล่งข้อมูล: http://dmsic.moph.go.th/ price.htm
18. U.S. Department of Health and Human Services. Guidelines for the use of Antiretroviral agents in HIV-Infected adults and adolescents [Internet], [cited 2014 Jun 20]. Available from: http:// aidsinfo.nih.gov/guidelineson6/l1/2014
19. Calza L, Manfredi R, Colangeli V, Pocaterra D, Pavoni M, Chiodo F. Rosuvastatin, pravastatin, and atorvastatin for the treatment of hypercholesterolemia in HIV-infected patients receiving protease inhibitors. Curr HIV Res 2008;6:572- 78.
20. James M. McKenney, Peter H. Jones, M. AngeliAdamczyk, Valerie A. Cain, Brian S. Bryzinski, James W. Comparison of the efficacy of rosuvastatin versus atorvastatin, simvastatin, and pravastatin in achieving lipid goals: results from the STELLAR trial. Curr Med Res Opin 2003;19:689-98.
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