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Arthritis Research & Therapy
Published in: Arthritis Research & Therapy 1/2016

Open Access 01-12-2016 | Research article

Allopurinol reduces the risk of myocardial infarction (MI) in the elderly: a study of Medicare claims

Authors: Jasvinder A. Singh, Shaohua Yu

Published in: Arthritis Research & Therapy | Issue 1/2016

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Abstract

Background

Previous observational studies that have examined the association of allopurinol with myocardial infarction (MI) have provided contradictory results. One study showed that allopurinol reduced the risk, while another study showed an increased risk with allopurinol. Therefore, our objective was to assess whether allopurinol use is associated with a reduction in the risk of MI in the elderly.

Method

We used the 2006–2012 5 % random sample of Medicare beneficiaries to study the association of new allopurinol initiation and the risk of incident MI in a cohort study. Multivariable-adjusted Cox regression models adjusted for age, gender, race, and Charlson index, in addition to various cardio-protective medications (beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, diuretics, statins). We calculated hazard ratios (HRs) with 95 % confidence intervals (CIs). Sensitivity analyses adjusted for coronary artery disease (CAD) risk factors, including hypertension, hyperlipidemia, diabetes, and smoking.

Results

Of the 29,298 episodes of incident allopurinol use, 1544 were associated with incident MI (5.3 % episodes). Allopurinol use was associated with reduced hazards of MI, with a HR of 0.85 (95 % CI, 0.77 to 0.95). Compared to no allopurinol use, longer durations of allopurinol use were associated with a lower HR of MI: 1–180 days, 0.98 (95 % CI, 0.84 to 1.14); 181 days to 2 years, 0.83 (95 % CI, 0.72 to 0.95); and >2 years, 0.70 (95 % CI, 0.56 to 0.88). Other factors associated with a higher hazard of MI were: age 75 to <85 years and ≥85 years, male gender, higher Charlson index score, and the use of an ACE inhibitor. Adjustment for CAD risk factors confirmed these findings.

Conclusion

Incident allopurinol use was associated with a reduction in the risk of incident MI in the elderly. Longer durations of allopurinol use reduced the risk of incident MI incrementally. Future studies should assess the underlying mechanisms for MI prevention and assess the risk-benefit ratio for allopurinol use.
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Literature
1.
2.
Murray CJ, Vos T, Lozano R, Naghavi M, Flaxman AD, Michaud C, Ezzati M, Shibuya K, Salomon JA, Abdalla S, et al. Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012;380(9859):2197–223.CrossRefPubMed
3.
GBD 2013 Mortality and Causes of Death Collaborators. Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2015;385(9963):117–71.CrossRef
4.
Roger VL. Epidemiology of myocardial infarction. Med Clin North Am. 2007;91(4):537–52. ix.
5.
Singh JA, Lu X, Ibrahim S, Cram P. Trends in and disparities for acute myocardial infarction: an analysis of Medicare claims data from 1992 to 2010. BMC Med. 2014;12(1):190.CrossRefPubMedPubMedCentral
6.
Sarawate CA, Brewer KK, Yang W, Patel PA, Schumacher HR, Saag KG, Bakst AW. Gout medication treatment patterns and adherence to standards of care from a managed care perspective. Mayo Clin Proc. 2006;81(7):925–34.CrossRefPubMed
7.
Singh JA, Hodges JS, Asch SM. Opportunities for improving medication use and monitoring in gout. Ann Rheum Dis. 2009;68(8):1265–70.CrossRefPubMed
8.
Bayram D, Tugrul Sezer M, Inal S, Altuntas A, Kidir V, Orhan H. The effects of allopurinol on metabolic acidosis and endothelial functions in chronic kidney disease patients. Clin Exp Nephrol. 2015;19(3):443–9.CrossRefPubMed
9.
Butler R, Morris AD, Belch JJ, Hill A, Struthers AD. Allopurinol normalizes endothelial dysfunction in type 2 diabetics with mild hypertension. Hypertension. 2000;35(3):746–51.CrossRefPubMed
10.
Doehner W, Schoene N, Rauchhaus M, Leyva-Leon F, Pavitt DV, Reaveley DA, Schuler G, Coats AJ, Anker SD, Hambrecht R. Effects of xanthine oxidase inhibition with allopurinol on endothelial function and peripheral blood flow in hyperuricemic patients with chronic heart failure: results from 2 placebo-controlled studies. Circulation. 2002;105(22):2619–24.CrossRefPubMed
11.
Dogan A, Yarlioglues M, Kaya MG, Karadag Z, Dogan S, Ardic I, Dogdu O, Kilinc Y, Zencir C, Akpek M, et al. Effect of long-term and high-dose allopurinol therapy on endothelial function in normotensive diabetic patients. Blood Press. 2011;20(3):182–7.CrossRefPubMed
12.
El Solh AA, Saliba R, Bosinski T, Grant BJ, Berbary E, Miller N. Allopurinol improves endothelial function in sleep apnoea: a randomised controlled study. Eur Respir J. 2006;27(5):997–1002.PubMed
13.
Noman A, Ang DS, Ogston S, Lang CC, Struthers AD. Effect of high-dose allopurinol on exercise in patients with chronic stable angina: a randomised, placebo controlled crossover trial. Lancet. 2010;375(9732):2161–7.CrossRefPubMedPubMedCentral
14.
Szwejkowski BR, Gandy SJ, Rekhraj S, Houston JG, Lang CC, Morris AD, George J, Struthers AD. Allopurinol reduces left ventricular mass in patients with type 2 diabetes and left ventricular hypertrophy. J Am Coll Cardiol. 2013;62(24):2284–93.CrossRefPubMed
15.
Rekhraj S, Gandy SJ, Szwejkowski BR, Nadir MA, Noman A, Houston JG, Lang CC, George J, Struthers AD. High-dose allopurinol reduces left ventricular mass in patients with ischemic heart disease. J Am Coll Cardiol. 2013;61(9):926–32.CrossRefPubMed
16.
de Abajo FJ, Gil MJ, Rodriguez A, Garcia-Poza P, Alvarez A, Bryant V, Garcia-Rodriguez LA. Allopurinol use and risk of non-fatal acute myocardial infarction. Heart. 2015;101(9):679-85. doi:10.​1136/​heartjnl-2014-306670. PubMed PMID: 25561685.
17.
Kok VC, Horng JT, Chang WS, Hong YF, Chang TH. Allopurinol therapy in gout patients does not associate with beneficial cardiovascular outcomes: a population-based matched-cohort study. PLoS One. 2014;9(6):e99102.CrossRefPubMedPubMedCentral
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.
Lin DY, Wei LJ. The robust inference for the Cox proportional hazards model. J Am Stat Assoc 1989;84(1074–8):1074–78.CrossRef
20.
Dubreuil M, Zhu Y, Zhang Y, Seeger JD, Lu N, Rho YH, Choi HK. Allopurinol initiation and all-cause mortality in the general population. Ann Rheum Dis. 2015;74(7):1368–72.CrossRefPubMed
21.
22.
Wei L, Fahey T, Struthers AD, MacDonald TM. Association between allopurinol and mortality in heart failure patients: a long-term follow-up study. Int J Clin Pract. 2009;63(9):1327–33.CrossRefPubMed
23.
Thanassoulis G, Brophy JM, Richard H, Pilote L. Gout, allopurinol use, and heart failure outcomes. Arch Intern Med. 2010;170(15):1358–64.CrossRefPubMed
24.
Goicoechea M, de Vinuesa SG, Verdalles U, Ruiz-Caro C, Ampuero J, Rincon A, Arroyo D, Luno J. Effect of allopurinol in chronic kidney disease progression and cardiovascular risk. Clin J Am Soc Nephrol. 2010;5(8):1388–93.CrossRefPubMedPubMedCentral
25.
Givertz MM, Anstrom KJ, Redfield MM, Deswal A, Haddad H, Butler J, Tang WHW, Dunlap ME, LeWinter MM, Mann DL, Felker GM, O'Connor CM, Goldsmith SR, Ofili EO, Saltzberg MT, Margulies KB, Cappola TP, Konstam MA, Semigran MJ, McNulty SE, Lee KL, Shah MR, Hernandez AF. Effects of Xanthine Oxidase Inhibition in Hyperuricemic Heart Failure Patients: The Xanthine Oxidase Inhibition for Hyperuricemic Heart Failure Patients (EXACT-HF) Study. Circulation 2015;131(20):1763–71.CrossRefPubMedPubMedCentral
26.
Mellin V, Isabelle M, Oudot A, Vergely-Vandriesse C, Monteil C, Di Meglio B, Henry JP, Dautreaux B, Rochette L, Thuillez C, et al. Transient reduction in myocardial free oxygen radical levels is involved in the improved cardiac function and structure after long-term allopurinol treatment initiated in established chronic heart failure. Eur Heart J. 2005;26(15):1544–50.CrossRefPubMed
27.
Guan W, Osanai T, Kamada T, Hanada H, Ishizaka H, Onodera H, Iwasa A, Fujita N, Kudo S, Ohkubo T, et al. Effect of allopurinol pretreatment on free radical generation after primary coronary angioplasty for acute myocardial infarction. J Cardiovasc Pharmacol. 2003;41(5):699–705.CrossRefPubMed
28.
Tarkka MR, Vuolle M, Kaukinen S, Holm P, Eloranta J, Kaukinen U, Sisto T, Kataja J. Effect of allopurinol on myocardial oxygen free radical production in coronary bypass surgery. Scand Cardiovasc J. 2000;34(6):593–6.CrossRefPubMed
29.
Vina J, Gimeno A, Sastre J, Desco C, Asensi M, Pallardo FV, Cuesta A, Ferrero JA, Terada LS, Repine JE. Mechanism of free radical production in exhaustive exercise in humans and rats; role of xanthine oxidase and protection by allopurinol. IUBMB Life. 2000;49(6):539–44.CrossRefPubMed
30.
Movahed A, Nair KG, Ashavaid TF, Kumar P. Free radical generation and the role of allopurinol as a cardioprotective agent during coronary artery bypass grafting surgery. Can J Cardiol. 1996;12(2):138–44.PubMed
31.
Bando K, Tago M, Teramoto S. Prevention of free radical-induced myocardial injury by allopurinol. Experimental study in cardiac preservation and transplantation. J Thorac Cardiovasc Surg. 1988;95(3):465–73.PubMed
32.
Das DK, Engelman RM, Clement R, Otani H, Prasad MR, Rao PS. Role of xanthine oxidase inhibitor as free radical scavenger: a novel mechanism of action of allopurinol and oxypurinol in myocardial salvage. Biochem Biophys Res Commun. 1987;148(1):314–9.CrossRefPubMed
33.
Stull LB, Leppo MK, Szweda L, Gao WD, Marban E. Chronic treatment with allopurinol boosts survival and cardiac contractility in murine postischemic cardiomyopathy. Circ Res. 2004;95(10):1005–11.CrossRefPubMed
34.
Farquharson CA, Butler R, Hill A, Belch JJ, Struthers AD. Allopurinol improves endothelial dysfunction in chronic heart failure. Circulation. 2002;106(2):221–6.CrossRefPubMed
35.
Flynn Jr WJ, Pilati D, Hoover EL. Effect of allopurinol on venous endothelial dysfunction after resuscitated hemorrhagic shock. Int J Surg Investig. 1999;1(1):11–8.PubMed
36.
George J, Carr E, Davies J, Belch JJ, Struthers A. High-dose allopurinol improves endothelial function by profoundly reducing vascular oxidative stress and not by lowering uric acid. Circulation. 2006;114(23):2508–16.CrossRefPubMed
37.
Higgins P, Walters MR, Murray HM, McArthur K, McConnachie A, Lees KR, Dawson J. Allopurinol reduces brachial and central blood pressure, and carotid intima-media thickness progression after ischaemic stroke and transient ischaemic attack: a randomised controlled trial. Heart. 2014;100(14):1085–92.CrossRefPubMed
38.
Kanbay M, Huddam B, Azak A, Solak Y, Kadioglu GK, Kirbas I, Duranay M, Covic A, Johnson RJ. A randomized study of allopurinol on endothelial function and estimated glomular filtration rate in asymptomatic hyperuricemic subjects with normal renal function. Clin J Am Soc Nephrol. 2011;6(8):1887–94.CrossRefPubMedPubMedCentral
39.
Kao MP, Ang DS, Gandy SJ, Nadir MA, Houston JG, Lang CC, Struthers AD. Allopurinol benefits left ventricular mass and endothelial dysfunction in chronic kidney disease. J Am Soc Nephrol. 2011;22(7):1382–9.CrossRefPubMedPubMedCentral
40.
Melendez-Ramirez G, Perez-Mendez O, Lopez-Osorio C, Kuri-Alfaro J, Espinola-Zavaleta N. Effect of the treatment with allopurinol on the endothelial function in patients with hyperuricemia. Endocr Res. 2012;37(1):1–6.CrossRefPubMed
41.
Ng KP, Stringer SJ, Jesky MD, Yadav P, Athwal R, Dutton M, Ferro CJ, Cockwell P. Allopurinol is an independent determinant of improved arterial stiffness in chronic kidney disease: a cross-sectional study. PLoS One. 2014;9(3):e91961.CrossRefPubMedPubMedCentral
42.
Yelken B, Caliskan Y, Gorgulu N, Altun I, Yilmaz A, Yazici H, Oflaz H, Yildiz A. Reduction of uric acid levels with allopurinol treatment improves endothelial function in patients with chronic kidney disease. Clin Nephrol. 2012;77(4):275–82.CrossRefPubMed
43.
Yiginer O, Ozcelik F, Inanc T, Aparci M, Ozmen N, Cingozbay BY, Kardesoglu E, Suleymanoglu S, Sener G, Cebeci BS. Allopurinol improves endothelial function and reduces oxidant-inflammatory enzyme of myeloperoxidase in metabolic syndrome. Clin Res Cardiol. 2008;97(5):334–40.CrossRefPubMed
44.
Kanbay M, Siriopol D, Nistor I, Elcioglu OC, Telci O, Takir M, Johnson RJ, Covic A. Effects of allopurinol on endothelial dysfunction: a meta-analysis. Am J Nephrol. 2014;39(4):348–56.CrossRefPubMed
45.
Rajagopalan S, Meng XP, Ramasamy S, Harrison DG, Galis ZS. Reactive oxygen species produced by macrophage-derived foam cells regulate the activity of vascular matrix metalloproteinases in vitro. Implications for atherosclerotic plaque stability. J Clin Invest. 1996;98(11):2572–9.CrossRefPubMedPubMedCentral
46.
Beattie CJ, Fulton RL, Higgins P, Padmanabhan S, McCallum L, Walters MR, Dominiczak AF, Touyz RM, Dawson J. Allopurinol initiation and change in blood pressure in older adults with hypertension. Hypertension. 2014;64(5):1102–7.CrossRefPubMed
47.
Feig DI, Soletsky B, Johnson RJ. Effect of allopurinol on blood pressure of adolescents with newly diagnosed essential hypertension: a randomized trial. JAMA. 2008;300(8):924–32.CrossRefPubMedPubMedCentral
48.
Martinon F, Petrilli V, Mayor A, Tardivel A, Tschopp J. Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature. 2006;440(7081):237–41.CrossRefPubMed
49.
Pope RM, Tschopp J. The role of interleukin-1 and the inflammasome in gout: implications for therapy. Arthritis Rheum. 2007;56(10):3183–8.CrossRefPubMed
50.
Crisan TO, Cleophas MC, Oosting M, Lemmers H, Toenhake-Dijkstra H, Netea MG, Jansen TL, Joosten LA. Soluble uric acid primes TLR-induced proinflammatory cytokine production by human primary cells via inhibition of IL-1Ra. Ann Rheum Dis. 2015.
51.
He J, Yang Y, Peng DQ. Monosodium urate (MSU) crystals increase gout associated coronary heart disease (CHD) risk through the activation of NLRP3 inflammasome. Int J Cardiol. 2012;160(1):72–3.CrossRefPubMed
52.
Goicoechea M, Garcia de Vinuesa S, Verdalles U, Verde E, Macias N, Santos A, Perez de Jose A, Cedeno S, Linares T, Luno J. Allopurinol and progression of CKD and cardiovascular events: long-term follow-up of a randomized clinical trial. Am J Kidney Dis. 2015;65(4):543–9.CrossRefPubMed
53.
Yan RT, Yan AT, Tan M, Chow CM, Fitchett DH, Ervin FL, Cha JY, Langer A, Goodman SG. Canadian Acute Coronary Syndromes Registry I. Age-related differences in the management and outcome of patients with acute coronary syndromes. Am Heart J. 2006;151(2):352–9.CrossRefPubMed
54.
Bradley EH, Herrin J, Wang Y, McNamara RL, Webster TR, Magid DJ, Blaney M, Peterson ED, Canto JG, Pollack Jr CV, et al. Racial and ethnic differences in time to acute reperfusion therapy for patients hospitalized with myocardial infarction. JAMA. 2004;292(13):1563–72.CrossRefPubMed
55.
Wunsch H, Guerra C, Barnato AE, Angus DC, Li G, Linde-Zwirble WT. Three-year outcomes for Medicare beneficiaries who survive intensive care. JAMA. 2010;303(9):849–56.CrossRefPubMed
56.
Tseng VL, Yu F, Lum F, Coleman AL. Risk of fractures following cataract surgery in Medicare beneficiaries. JAMA. 2012;308(5):493–501.CrossRefPubMed
57.
Singh JA. When gout goes to the heart: does gout equal a cardiovascular disease risk factor? Ann Rheum Dis. 2015;74(4):631–4.CrossRefPubMed
Metadata
Title
Allopurinol reduces the risk of myocardial infarction (MI) in the elderly: a study of Medicare claims
Authors
Jasvinder A. Singh
Shaohua Yu
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue 1/2016
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/s13075-016-1111-1

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