Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Drug Safety
Published in: Drug Safety 6/2016

01-06-2016 | Original Research Article

Long-Term Outcomes of Short-Term Statin Use in Healthy Adults: A Retrospective Cohort Study

Authors: Ishak A. Mansi, Jenny English, Song Zhang, Eric M. Mortensen, Ethan A. Halm

Published in: Drug Safety | Issue 6/2016

Login to get access

Abstract

Introduction

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.

Objective

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.

Results

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.

Conclusions

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.
Appendix
Available only for authorised users
Literature
1.
Sattar N, Preiss D, Murray HM, Welsh P, Buckley BM, de Craen AJ, et al. Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials. Lancet. 2010;375(9716):735–42.CrossRefPubMed
2.
Mansi I, Frei CR, Wang CP, Mortensen EM. Statins and new-onset diabetes mellitus and diabetic complications: a retrospective cohort study of US healthy adults. J Gen Intern Med. 2015;30(11):1599–610.CrossRefPubMed
3.
Sugiyama T, Tsugawa Y, Tseng CH, Kobayashi Y, Shapiro MF. Different time trends of caloric and fat intake between statin users and nonusers among US adults: gluttony in the time of statins? JAMA Intern Med. 2014;174(7):1038–45.CrossRefPubMedPubMedCentral
4.
Hippisley-Cox J, Coupland C. Unintended effects of statins in men and women in England and Wales: population based cohort study using the QResearch database. BMJ. 2010;340:c2197.CrossRefPubMedPubMedCentral
5.
Lee DS, Markwardt S, Goeres L, Lee CG, Eckstrom E, Williams C, et al. Statins and physical activity in older men: the osteoporotic fractures in men study. JAMA Intern Med. 2014;174(8):1263–70.CrossRefPubMedPubMedCentral
6.
DeFilippis AP, Young R, Carrubba CJ, McEvoy JW, Budoff MJ, Blumenthal RS, et al. An analysis of calibration and discrimination among multiple cardiovascular risk scores in a modern multiethnic cohort. Ann Intern Med. 2015;162(4):266–75.CrossRefPubMedPubMedCentral
7.
Ridker PM, Cook NR. Comparing cardiovascular risk prediction scores. Ann Intern Med. 2015;162(4):313–4.CrossRefPubMed
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.CrossRefPubMed
9.
Baigent C, Keech A, Kearney PM, Blackwell L, Buck G, Pollicino C, 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. 2005;366(9493):1267–78.CrossRefPubMed
10.
Mansi I. Statin adverse events in primary prevention: between randomized trials and observational studies. Am J Med Sci. 2015;350(4):330–7.CrossRefPubMed
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.
12.
Gantt CJ, Neely JA, Villafana IA, Chun CS, Gharabaghli SM. Analysis of weight and associated health consequences of the active duty staff at a major Naval medical center. Mil Med. 2008;173(5):434–40.CrossRefPubMed
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.CrossRefPubMedPubMedCentral
14.
Lilly SM, Mortensen EM, Frei CR, Pugh MJ, Mansi IA. Comparison of the risk of psychological and cognitive disorders between persistent and nonpersistent statin users. Am J Cardiol. 2014;114(7):1035–9.CrossRefPubMed
15.
Mann DM, Woodward M, Muntner P, Falzon L, Kronish I. Predictors of nonadherence to statins: a systematic review and meta-analysis. Ann Pharmacother. 2010;44(9):1410–21.CrossRefPubMedPubMedCentral
16.
Li DQ, Kim R, McArthur E, Fleet JL, Bailey DG, Juurlink D, et al. Risk of adverse events among older adults following co-prescription of clarithromycin and statins not metabolized by cytochrome P450 3A4. CMAJ Can Med Assoc J J de l’Association Med Can. 2015;187(3):174–80.CrossRef
17.
18.
Deyo RA, Cherkin DC, Ciol MA. Adapting a clinical comorbidity index for use with ICD-9-CM administrative databases. J Clin Epidemiol. 1992;45(6):613–9.CrossRefPubMed
19.
Miller DR, Safford MM, Pogach LM. Who has diabetes? Best estimates of diabetes prevalence in the Department of Veterans Affairs based on computerized patient data. Diabetes Care. 2004;27(Suppl 2):B10–21.CrossRefPubMed
20.
Kim SY, Servi A, Polinski JM, Mogun H, Weinblatt ME, Katz JN, et al. Validation of rheumatoid arthritis diagnoses in health care utilization data. Arthritis Res Ther. 2011;13(1):R32.CrossRefPubMedPubMedCentral
21.
Quan H, Li B, Saunders LD, Parsons GA, Nilsson CI, Alibhai A, et al. Assessing validity of ICD-9-CM and ICD-10 administrative data in recording clinical conditions in a unique dually coded database. Health Serv Res. 2008;43(4):1424–41.CrossRefPubMedPubMedCentral
22.
Goff SL, Pekow PS, Markenson G, Knee A, Chasan-Taber L, Lindenauer PK. Validity of using ICD-9-CM codes to identify selected categories of obstetric complications, procedures and co-morbidities. Paediatr Perinat Epidemiol. 2012;26(5):421–9.CrossRefPubMed
23.
Mansi I, Mortensen E. The controversy of a wider statin utilization: why? Expert Opin Drug saf. 2013;12(3):327–37.CrossRefPubMed
24.
Dormuth CR, Patrick AR, Shrank WH, Wright JM, Glynn RJ, Sutherland J, et al. Statin adherence and risk of accidents: a cautionary tale. Circulation. 2009;119(15):2051–7.CrossRefPubMedPubMedCentral
25.
Ho D, Imai K, King G, Stuart E. Matching as nonparametric preprocessing for reducing model dependence in parametric causal inference. Polit Anal. 2007;15:199–236.CrossRef
26.
Ho D, Imai K, King G, Stuart E. MatchIt: nonparametric preprocessing for parametric causal inference. J Stat Softw. 2011;42(8):1–28.CrossRef
27.
Hansen BB. Full matching in an observational study of coaching for the SAT. J Am Stat Assoc. 2004;99(467):609–18.CrossRef
28.
Hansen BB, Bowers J. Covariate balance in simple, stratified and clustered comparative studies. Stat Sci. 2008;23(2):219–36.CrossRef
29.
30.
Cohen J. Statistical power analysis for the behavioral sciences. 2nd ed. Hillsdale: Lawrence Erlbaum Associates Publishers; 1988.
31.
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.CrossRefPubMed
33.
Army Regulation 40-501; Standards of Medical Fitness. Washington, DC: Headquarters, Medical Services, Department of the Army, 14 December 2007. 2007.
34.
Mark DB, Hlatky MA, Harrell FE Jr, Lee KL, Califf RM, Pryor DB. Exercise treadmill score for predicting prognosis in coronary artery disease. Ann Intern Med. 1987;106(6):793–800.CrossRefPubMed
35.
Weiner DA, Ryan TJ, McCabe CH, Chaitman BR, Sheffield LT, Ferguson JC, et al. Prognostic importance of a clinical profile and exercise test in medically treated patients with coronary artery disease. J Am Coll Cardiol. 1984;3(3):772–9.CrossRefPubMed
36.
Taylor F, Huffman MD, Macedo AF, Moore TH, Burke M, Davey Smith G, et al. Statins for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2013;1:CD004816.PubMed
37.
Strandberg TE, Pyorala K, Cook TJ, Wilhelmsen L, Faergeman O, Thorgeirsson G, et al. Mortality and incidence of cancer during 10-year follow-up of the Scandinavian Simvastatin Survival Study (4S). Lancet. 2004;364(9436):771–7.CrossRefPubMed
38.
Ford I, Murray H, Packard CJ, Shepherd J, Macfarlane PW, Cobbe SM, et al. Long-term follow-up of the West of Scotland Coronary Prevention Study. N Engl J Med. 2007;357(15):1477–86.CrossRefPubMed
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.CrossRef
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.PubMedPubMedCentral
41.
Porta M, Curletto G, Cipullo D, Rigault de la Longrais R, Trento M, Passera P, et al. Estimating the delay between onset and diagnosis of type 2 diabetes from the time course of retinopathy prevalence. Diabetes Care. 2014;37(6):1668–74.CrossRefPubMed
42.
Ridker PM, Danielson E, Fonseca FA, Genest J, Gotto AM Jr, Kastelein JJ, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008;359(21):2195–207.CrossRefPubMed
43.
Culver AL, Ockene IS, Balasubramanian R, Olendzki BC, Sepavich DM, Wactawski-Wende J, et al. Statin use and risk of diabetes mellitus in postmenopausal women in the Women’s Health Initiative. Arch Intern Med. 2012;172(2):144–52.CrossRefPubMed
44.
Park ZH, Juska A, Dyakov D, Patel RV. Statin-associated incident diabetes: a literature review. Consult Pharm. 2014;29(5):317–34.CrossRefPubMed
45.
Yada T, Nakata M, Shiraishi T, Kakei M. Inhibition by simvastatin, but not pravastatin, of glucose-induced cytosolic Ca2+ signalling and insulin secretion due to blockade of L-type Ca2+ channels in rat islet beta-cells. Br J Pharmacol. 1999;126(5):1205–13.CrossRefPubMedPubMedCentral
46.
47.
Nakata M, Nagasaka S, Kusaka I, Matsuoka H, Ishibashi S, Yada T. Effects of statins on the adipocyte maturation and expression of glucose transporter 4 (SLC2A4): implications in glycaemic control. Diabetologia. 2006;49(8):1881–92.CrossRefPubMed
48.
Brault M, Ray J, Gomez YH, Mantzoros CS, Daskalopoulou SS. Statin treatment and new-onset diabetes: a review of proposed mechanisms. Metab Clin Exp. 2014;63(6):735–45.CrossRefPubMed
49.
Sattar N, Taskinen MR. Statins are diabetogenic–myth or reality? Atheroscler Suppl. 2012;13(1):1–10.CrossRefPubMed
50.
51.
Swerdlow DI, Preiss D, Kuchenbaecker KB, Holmes MV, Engmann JE, Shah T, et al. HMG-coenzyme A reductase inhibition, type 2 diabetes, and bodyweight: evidence from genetic analysis and randomised trials. Lancet. 2015;385(9965):351–61.CrossRefPubMedPubMedCentral
52.
Frayling TM. Statins and type 2 diabetes: genetic studies on target. Lancet. 2015;385(9965):310–2.CrossRefPubMed
53.
Liew SM, Lee PY, Hanafi NS, Ng CJ, Wong SS, Chia YC, et al. Statins use is associated with poorer glycaemic control in a cohort of hypertensive patients with diabetes and without diabetes. Diabetol Metab Syndr. 2014;6:53.CrossRefPubMedPubMedCentral
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.
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.
56.
Golomb BA, Evans MA, Dimsdale JE, White HL. Effects of statins on energy and fatigue with exertion: results from a randomized controlled trial. Arch Intern Med. 2012;172(15):1180–2.CrossRefPubMedPubMedCentral
57.
Danaei G, Rodriguez LA, Cantero OF, Logan R, Hernan MA. Observational data for comparative effectiveness research: an emulation of randomised trials of statins and primary prevention of coronary heart disease. Stat Methods Med Res. 2013;22(1):70–96.CrossRefPubMedPubMedCentral
58.
Jee SH, Sull JW, Park J, Lee SY, Ohrr H, Guallar E, et al. Body-mass index and mortality in Korean men and women. N Engl J Med. 2006;355(8):779–87.CrossRefPubMed
59.
Allison DB, Faith MS, Heo M, Townsend-Butterworth D, Williamson DF. Meta-analysis of the effect of excluding early deaths on the estimated relationship between body mass index and mortality. Obes Res. 1999;7(4):342–54.CrossRefPubMed
60.
Grundy SM, Cleeman JI, Merz CN, Brewer HB Jr, Clark LT, Hunninghake DB, et al. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation. 2004;110(2):227–39.CrossRefPubMed
61.
Cook NR, Ridker PM. Further insight into the cardiovascular risk calculator: the roles of statins, revascularizations, and underascertainment in the Women’s Health Study. JAMA Intern Med. 2014;174(12):1964–71.CrossRefPubMedPubMedCentral
62.
Memtsoudis SG, Bombardieri AM, Ma Y, Walz JM, Chiu YL, Mazumdar M. Mortality of patients with respiratory insufficiency and adult respiratory distress syndrome after surgery: the obesity paradox. J Intensive Care Med. 2012;27(5):306–11.CrossRefPubMed
63.
Scott SK, Rabito FA, Price PD, Butler NN, Schwartzbaum JA, Jackson BM, et al. Comorbidity among the morbidly obese: a comparative study of 2002 US hospital patient discharges. Surg Obes Relat Dis Off J Am Soc Bariatr Surg. 2006;2(2):105–11.CrossRef
64.
Vila-Corcoles A, Ochoa-Gondar O, Llor C, Hospital I, Rodriguez T, Gomez A. Protective effect of pneumococcal vaccine against death by pneumonia in elderly subjects. Eur Respir J. 2005;26(6):1086–91.CrossRefPubMed
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.
67.
68.
69.
Metadata
Title
Long-Term Outcomes of Short-Term Statin Use in Healthy Adults: A Retrospective Cohort Study
Authors
Ishak A. Mansi
Jenny English
Song Zhang
Eric M. Mortensen
Ethan A. Halm
Publication date
01-06-2016
Publisher
Springer International Publishing
Published in
Drug Safety / Issue 6/2016
Print ISSN: 0114-5916
Electronic ISSN: 1179-1942
DOI
https://doi.org/10.1007/s40264-016-0412-2

Other articles of this Issue 6/2016

Drug Safety 6/2016 Go to the issue

Original Research Article

A Pharmacovigilance Signaling System Based on FDA Regulatory Action and Post-Marketing Adverse Event Reports

Review Article

Safety Considerations with Dual Bronchodilator Therapy in COPD: An Update

Special Article

Good Signal Detection Practices: Evidence from IMI PROTECT

Leading Article

Medication Errors: New EU Good Practice Guide on Risk Minimisation and Error Prevention

Systematic Review

The Safety of Prochlorperazine in Children: A Systematic Review and Meta-Analysis

Original Research Article

Universal Correction for QT/RR Hysteresis