Safety and Effectiveness of Statins for Prevention of Recurrent Myocardial Infarction in 12 156 Typical Older Patients: A Quasi-Experimental Study

Alessandro Ble, Peter M Hughes, Joao Delgado, Jane A Masoli, Kirsty Bowman, Jan Zirk-Sadowski, Ruben E Mujica Mota, William E Henley, David Melzer, Alessandro Ble, Peter M Hughes, Joao Delgado, Jane A Masoli, Kirsty Bowman, Jan Zirk-Sadowski, Ruben E Mujica Mota, William E Henley, David Melzer

Abstract

Background: There is limited evidence on statin risk and effectiveness for patients aged 80+. We estimated risk of recurrent myocardial infarction, muscle-related and other adverse events, and statin-related incremental costs in "real-world" older patients treated with statins versus no statins.

Methods: We used primary care electronic medical records from the UK Clinical Practice Research Datalink. Subhazard ratios (competing risk of death) for myocardial infarction recurrence (primary end point), falls, fractures, ischemic stroke, and dementia, and hazard ratios (Cox) for all-cause mortality were used to compare older (60+) statin users and 1:1 propensity-score-matched controls (n = 12,156). Participants were followed-up for 10 years.

Results: Mean age was 76.5±9.2 years; 45.5% were women. Statins were associated with near significant reduction in myocardial infarction recurrence (subhazard ratio = 0.84, 0.69-1.02, p = .073), with protective effect in the 60-79 age group (0.73, 0.57-0.94) but a nonsignificant result in the 80+ group (1.06, 0.78-1.44; age interaction p = .094). No significant associations were found for stroke or dementia. Data suggest an increased risk of falls (1.36, 1.17-1.60) and fractures (1.33, 1.04-1.69) in the first 2 years of treatment, particularly in the 80+ group. Treatment was associated with lower all-cause mortality. Statin use was associated with health care cost savings in the 60-79 group but higher costs in the 80+ group.

Conclusions: Estimates of statin effectiveness for the prevention of recurrent myocardial infarction in patients aged 60-79 years were similar to trial results, but more evidence is needed in the older group. There may be an excess of falls and fractures in very old patients, which deserves further investigation.

Keywords: Falls; Fractures; Myocardial infarction; Older; Statins.

© The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America.

Figures

Figure 1.
Figure 1.
Effectiveness of statins for prevention of recurrence of myocardial infarction in the whole sample (60+) and by age and disease burden group (competing risk of death, excluding first 2 years’ events).
Figure 2.
Figure 2.
Risk of disabling conditions of older age in the whole sample (60+, competing risk of death, excluding first 2 years’ events for ischemic stroke and dementia).

References

    1. Stone NJ, Robinson JG, Lichtenstein AH, et al. ; American College of Cardiology/American Heart Association Task Force on Practice Guidelines 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. J Am Coll Cardiol. 2014;63(25 Pt B):2889–2934. doi:10.1016/j.jacc.2013.11.002
    1. Fleg JL, Forman DE, Berra K, et al. ; American Heart Association Committees on Older Populations and Exercise Cardiac Rehabilitation and Prevention of the Council on Clinical Cardiology, Council on Cardiovascular and Stroke Nursing, Council on Lifestyle and Cardiometabolic Health Secondary prevention of atherosclerotic cardiovascular disease in older adults: a scientific statement from the American Heart Association. Circulation. 2013;128:2422–2446. doi:10.1161/01.cir.0000436752.99896.22
    1. Chokshi NP, Messerli FH, Sutin D, Supariwala AA, Shah NR. Appropriateness of statins in patients aged >/=80 years and comparison to other age groups. Am J Cardiol. 2012;110:1477–1481. doi:10.1016/j.amjcard.2012.06.058
    1. NICE. Lipid Modification: Cardiovascular Risk Assessment and the Modification of Blood Lipids for the Primary and Secondary Prevention of Cardiovascular Disease. NICE Guidelines [CG181]; 2014. . Accessed December 2, 2015.
    1. Baigent C, Keech A, Kearney PM, et al. ; Cholesterol Treatment Trialists’ (CTT) Collaborators Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet. 2005;366:1267–1278. doi:10.1016/S0140-6736(05)67394-1
    1. Mihaylova B, Emberson J, Blackwell L, et al. ; Cholesterol Treatment Trialists’ (CTT) Collaborators The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials. Lancet. 2012;380:581–590. doi:10.1016/S0140-6736(12)60367-5
    1. Taylor F, Ward K, Moore TH, et al. Statins for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2011;1:CD004816 doi:10.1002/14651858.CD004816.pub4
    1. Savarese G, Gotto AM, Jr, Paolillo S, et al. Benefits of statins in elderly subjects without established cardiovascular disease: a meta-analysis. J Am Coll Cardiol. 2013;62:2090–2099. doi:10.1016/j.jacc.2013.07.069
    1. Aronow WS, Ahn C. Incidence of new coronary events in older persons with prior myocardial infarction and serum low-density lipoprotein cholesterol > or = 125mg/dl treated with statins versus no lipid-lowering drug. Am J Cardiol. 2002;89:67–69.
    1. Herrett E, Gallagher AM, Bhaskaran K, et al. Data resource profile: Clinical Practice Research Datalink (CPRD). Int J Epidemiol. 2015;44:827–836. doi:10.1093/ije/dyv098
    1. Harris AD, McGregor JC, Perencevich EN, et al. The use and interpretation of quasi-experimental studies in medical informatics. J Am Med Inform Assoc. 2006;13:16–23. doi:10.1197/jamia.M1749
    1. Ah-See KW. British National Formulary. 65th ed. London, UK: London BMJ Group and Pharmaceutical Press; 2013.
    1. Weiner MG, Xie D, Tannen RL. Replication of the Scandinavian Simvastatin Survival Study using a primary care medical record database prompted exploration of a new method to address unmeasured confounding. Pharmacoepidemiol Drug Saf. 2008;17:661–670. doi:10.1002/pds.1585
    1. Tunstall-Pedoe H, Morrison C. Coronary heart disease in women. Women may be more ill when they reach hospital. BMJ. 1994;309:1303.
    1. Bhattarai N, Charlton J, Rudisill C, Gulliford MC. Coding, recording and incidence of different forms of coronary heart disease in primary care. PLoS One. 2012;7:e29776 doi:10.1371/journal.pone.0029776
    1. Smeeth L, Douglas I, Hall AJ, Hubbard R, Evans S. Effect of statins on a wide range of health outcomes: a cohort study validated by comparison with randomized trials. Br J Clin Pharmacol. 2009;67:99–109. doi:10.1111/j.1365-2125.2008.03308.x
    1. HSCIC. HSCIC prescription cost analysis 2014 Accessed December 2, 2015.
    1. Curtis L. PSSRU unit costs of health and social care 2014: University of Kent, 2014 Accessed December 2, 2015.
    1. Health Do. NHS reference costs 2015 Accessed December 2, 2015.
    1. Berry SD, Ngo L, Samelson EJ, Kiel DP. Competing risk of death: an important consideration in studies of older adults. J Am Geriatr Soc. 2010;58:783–787. doi:10.1111/j.1532-5415.2010.02767.x
    1. Fine JP, Gray RJ. A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc. 1999;94:496–509.
    1. Khan NF, Perera R, Harper S, Rose PW. Adaptation and validation of the Charlson Index for Read/OXMIS coded databases. BMC Fam Pract. 2010;11:1 doi:10.1186/1471-2296-11-1
    1. Stang A, Poole C, Bender R. Common problems related to the use of number needed to treat. J Clin Epidemiol. 2010;63:820–825. doi:10.1016/j.jclinepi.2009.08.006
    1. Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002;360:7–22. doi:10.1016/S0140-6736(02)09327-3
    1. Lloyd SM, Stott DJ, de Craen AJ, et al. Long-term effects of statin treatment in elderly people: extended follow-up of the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER). PLoS One. 2013;8:e72642 doi:10.1371/journal.pone.0072642
    1. Roberts CG, Guallar E, Rodriguez A. Efficacy and safety of statin monotherapy in older adults: a meta-analysis. J Gerontol A Biol Sci Med Sci. 2007;62:879–887.
    1. Strandberg TE, Kolehmainen L, Vuorio A. Evaluation and treatment of older patients with hypercholesterolemia: a clinical review. JAMA. 2014;312:1136–1144. doi:10.1001/jama.2014.10924
    1. Lewington S, Whitlock G, Clarke R, et al. ; Prospective Studies Collaboration Blood cholesterol and vascular mortality by age, sex, and blood pressure: a meta-analysis of individual data from 61 prospective studies with 55,000 vascular deaths. Lancet. 2007;370:1829–1839. doi:10.1016/S0140-6736(07)61778-4
    1. McGuinness B, Craig D, Bullock R, Passmore P. Statins for the prevention of dementia. Cochrane Database Syst Rev. 2009;2:CD003160 doi:10.1002/14651858.CD003160.pub2
    1. Abd TT, Jacobson TA. Statin-induced myopathy: a review and update. Expert Opin Drug Saf. 2011;10:373–387. doi:10.1517/14740338.2011.540568
    1. 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;172:1180–1182. doi:10.1001/archinternmed.2012.2171
    1. Scott D, Blizzard L, Fell J, Jones G. Statin therapy, muscle function and falls risk in community-dwelling older adults. QJM. 2009;102:625–633. doi:10.1093/qjmed/hcp093
    1. Swiger KJ, Martin SS, Tang F, et al. Cognitive and physical function by statin exposure in elderly individuals following acute myocardial infarction. Clin Cardiol. 2015;38:455–461. doi:10.1002/clc.22423
    1. Riechman SE, Andrews RD, Maclean DA, Sheather S. Statins and dietary and serum cholesterol are associated with increased lean mass following resistance training. J Gerontol A Biol Sci Med Sci. 2007;62:1164–1171.
    1. Cai H, Zhang G, Wang Z, Luo Z, Zhou X. Relationship between the use of statins and patient survival in colorectal cancer: a systematic review and meta-analysis. PLoS One. 2015;10:e0126944 doi:10.1371/journal.pone.0126944
    1. Ward S, Lloyd Jones M, Pandor A, et al. A systematic review and economic evaluation of statins for the prevention of coronary events. Health Technol Assess. 2007;11:1–160, iii.

Source: PubMed

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