Long-Term Outcomes of Short-Term Statin Use in Healthy Adults: A Retrospective Cohort Study
- 372 Downloads
Data suggest that the beneficial cardiovascular effects of statins are maximized after the first year of statin use; yet, the timeline of statin-associated adverse events is not well delineated.
To examine the associations of short-term statin use (≤1 year) with short- and long-term adverse events and beneficial cardiovascular outcomes in a ‘healthy’ cohort.
Participants and Methods
A cohort study of a healthy Tricare population (fiscal year [FY] 2002 through FY 2011) who have no cardiovascular disease, major comorbidities requiring medications, or functional limitations. Statin users used statins for 90–365 days during FY 2005 as their only prescription medication. Nonusers had medical encounters but did not receive prescription medications during FY 2005, and did not receive any statins throughout the study period from FY 2002 to FY 2011. Outcomes were the occurrence of major acute cardiovascular events, diabetes mellitus and its complications, kidney diseases, musculoskeletal diseases, obesity, cataracts, malignancy, and death.
We matched 1525 statin users to 1525 nonusers. During the follow-up period (FY 2006 to FY 2011), statin users had significantly higher odds of developing diabetes and diabetic complications that persisted throughout follow-up (odds ratio [OR] 1.93, 95 % confidence interval [CI] 1.55–2.41 and OR 2.15, 95 % CI 1.20–3.86, respectively). Short-term statin use was not associated with decreased odds of major acute cardiovascular events (OR 1.17, 95 % CI 0.72–1.92). There were no differences in risks of kidney diseases, musculoskeletal diseases, or malignancy.
Short-term statin use for primary prevention in this healthy cohort was associated with an increased risk of long-term diabetes and diabetic complications without cardiovascular benefits. Further study using pragmatic studies and prospective observational studies appropriately equipped to eliminate unidentified confounders are urgently needed.
Compliance with Ethical Standards
Drs. Halm and Mortensen were supported in part by a grant from the Agency for Healthcare Research and Quality (R24 HS022418) for the University of Texas Southwestern Center for Patient-Centered Outcomes Research.
No funding was provided for the conduct of this study. This material is the result of work supported with resources and the use of facilities at the VA North Texas Health Care System and the University of Texas Southwestern.
Conflicts of interest
Ishak Mansi, Jenny English, Song Zhang, Eric Mortensen, and Ethan Halm declare that they have no conflicts of interest that are directly relevant to the content of this study.
The views expressed herein are those of the authors and do not reflect the official policy or position of the Department of the Army, Department of Defense, VA Healthcare administration, or the US Government. The authors are employees of the US Government. This work was prepared as part of their official duties and, as such, there is no copyright to be transferred.
- 8.Simes J, Furberg CD, Braunwald E, Davis BR, Ford I, Tonkin A, et al. Effects of pravastatin on mortality in patients with and without coronary heart disease across a broad range of cholesterol levels. The Prospective Pravastatin Pooling project. Eur Heart J. 2002;23(3):207–15.CrossRefPubMedGoogle Scholar
- 11.Moniz C. Outpatient workload (RVU) predictors: age, gender and beneficiary category. Graduate Management Project. Baltimore, MD: US Army Medical Department Center and School, Medicine JH; 2008 June 15, Report No.: Contract No.: 34-08.Google Scholar
- 13.George SZ, Childs JD, Teyhen DS, Wu SS, Wright AC, Dugan JL, et al. Brief psychosocial education, not core stabilization, reduced incidence of low back pain: results from the Prevention of Low Back Pain in the Military (POLM) cluster randomized trial. BMC Med. 2011;9(1):128.CrossRefPubMedPubMedCentralGoogle Scholar
- 17.Elixhauser A, Steiner C, Palmer L. Clinical Classifications Software (CCS) for ICD-9-CM. Databases and related tools from the healthcare cost and utilization project (HCUP) [Internet]. 2012 01/01/2012: [Appendix A p.]. http://www.hcup-us.ahrq.gov/toolssoftware/ccs/ccs.jsp. Accessed 16 Mar 2015.
- 29.Thoemmes F. An SPSS R menu for propensity score matching. 2011. http://www.arxiv.org. Accessed 21 May 2015.
- 30.Cohen J. Statistical power analysis for the behavioral sciences. 2nd ed. Hillsdale: Lawrence Erlbaum Associates Publishers; 1988.Google Scholar
- 31.Yang D, Dalton JE. A unified approach to measuring the effect size between two groups using SAS, SAS Global Forum 2012—Statistics and Data Analysis; Paper 335-2012. http://support.sas.com/resources/papers/proceedings12/335-2012.pdf.
- 32.Stone NJ, Robinson JG, Lichtenstein AH, Bairey Merz CN, Blum CB, Eckel RH, et al. 2013 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. Circulation. 2014;129(25 Suppl 2):S1–45.CrossRefPubMedGoogle Scholar
- 33.Army Regulation 40-501; Standards of Medical Fitness. Washington, DC: Headquarters, Medical Services, Department of the Army, 14 December 2007. 2007.Google Scholar
- 39.Tonkin A, Aylward P, Colquhoun D, Glasziou P, Harris P, MacMahon S, Magnus P, Newel D, Nestel P, Sharpe N, Hunt D. Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. N Engl J Med. 1998;339(19):1349–57.CrossRefGoogle Scholar
- 40.Enas EA, Kuruvila A, Khanna P, Pitchumoni CS, Mohan V. Benefits and risks of statin therapy for primary prevention of cardiovascular disease in Asian Indians—a population with the highest risk of premature coronary artery disease and diabetes. Indian J Med Res. 2013;138(4):461–91.PubMedPubMedCentralGoogle Scholar
- 54.Sukhija R, Prayaga S, Marashdeh M, Bursac Z, Kakar P, Bansal D, et al. Effect of statins on fasting plasma glucose in diabetic and nondiabetic patients. J Investig Med Off Publ Am Fed Clin Res. 2009;57(3):495–9.Google Scholar
- 55.Aguirre L, Hijona E, Macarulla MT, Gracia A, Larrechi I, Bujanda L, et al. Several statins increase body and liver fat accumulation in a model of metabolic syndrome. J Physiol Pharmacol Off J Pol Physiol Soc. 2013;64(3):281–8.Google Scholar
- 65.Allareddy V, Rampa S, Anamali S, Lee MK, Allareddy V, Nalliah RP. Obesity and its association with comorbidities and hospital charges among patients hospitalized for dental conditions. Journal of investigative and clinical dentistry. 2015. doi: 10.1111/jicd.12146] (Epub ahead of print).
- 66.Wier L, Encinosa W. Obesity in children: Hospitalizations from 2000 to 2009. HCUP Statistical Brief #138. July 2012. Agency for Healthcare Research and Quality, Rockville, MD. http://www.hcup-us.ahrq.gov/reports/statbriefs/sb138.pdf. Accessed 16 Mar 2015.
- 67.Weiss A, Elixhauser A. Obesity-related hospitalizations, 2004 versus 2009. HCUP Statistical Brief #137. July 2012. Agency for Healthcare Research and Quality. Rockville, MD. http://www.hcup-us.ahrq.gov/reports/statbriefs/sb137.pdf. Accessed 16 Mar 2015.
- 68.Elixhauser A, Steiner C. Obese patients in US Hospitals, 2004. HCUP Statistical Brief #20. December 2006. Agency for Healthcare Research and Quality, Rockville, MD. http://www.hcup-us.ahrq.gov/reports/statbriefs/sb20.pdf. Accessed 16 Mar 2015.