Document Type : Original Article
Authors
- Hamid Sanei 1
- Kiyan Heshmat-Ghahdarijani 2
- Ali Asadi 3
- Mohammad Kermani-Alghoraishi 4
- Ali Safaei 5
- masoumeh Sadeghi 1
1 Cardiac Rehabilitation Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran
2 Heart Failure Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran
3 Hypertension Research Center, Cardiovascular Research Institute; Isfahan University of Medical Sciences, Isfahan, Iran
4 Interventional Cardiology Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran
5 Isfahan Cardiovascular Research Center, Cardiovascular Research Institute; Isfahan University of Medical Sciences, Isfahan, Iran
Abstract
INTRODUCTION: The use of allopurinol has shown promising outcomes in reducing oxidative processes responsible for atherogenic-related cardiovascular events. The current study aims to assess the effects of high-dose allopurinol on the post-revascularization coronary blood flow and inflammatory biomarkers in patients with non-ST segment elevated myocardial infarction (NSTEMI).
METHOD: Eighty NSTEMI patients were randomly divided into two groups: the intervention group (n=40), medicated with a high loading dose of 600 mg allopurinol before the coronary angiography, and the control group (n=40), treated with a placebo. The highly sensitive C-reactive protein (hs-CRP) was measured at baseline and within 24 hours after the cardiac interventions and compared between the case and control groups. Post percutaneous coronary intervention (PCI) Thrombolysis in Myocardial Infarction (TIMI) flow grading was also evaluated as a revascularization endpoint.
RESULTS: The two groups of the study were similar in terms of demographic, clinical, laboratory, and angiographic characteristics (P-value>0.050). The assessed TIMI flow was similar between the cases and the controls both prior to (P-value=0.141) and after (P-value=0.395) the coronary angioplasty. The hs-CRP (P-value=0.016) was significantly higher in the control group. Post-angiographic assessment of hs-CRP revealed an insignificant difference between the groups (P-value=0.104).
CONCLUSION: In conclusion, premedication with a high dose of allopurinol in NSTEMI patients did not affect the inflammatory biomarker or the revascularization endpoint.
Keywords
2. Fuentes E, Moore-Carrasco R, de Andrade Paes AM, Trostchansky A. Role of platelet activation and oxidative stress in the evolution of myocardial infarction. J Cardiovasc Pharmacol Ther 2019; 24(6): 509-20.https://doi.org/10.1177/1074248419861437
3. Abbate A, Bussani R, Amin MS, Vetrovec GW, Baldi A. Acute myocardial infarction and heart failure: role of apoptosis. Int J Biochem Cell Biol 2006; 38(11): 1834-40. https://doi.org/10.1016/j.biocel.2006.04.010
4. Xiao J, She Q, Wang Y, Luo K, Yin Y, Hu R, et al. Effect of allopurinol on cardiomyocyte apoptosis in rats after myocardial infarction. Eur J Heart Fail 2009; 11(1): 20-7. https://doi.org/10.1093/eurjhf/hfn003
5. Trkulja V, Car S. On-admission serum uric acid predicts outcomes after acute myocardial infarction: systematic review and metaanalysis of prognostic studies. Croat Med J 2012; 53(2): 162-72. https://doi.org/10.3325/cmj.2012.53.162
6. Okafor ON, Farrington K, Gorog DA. Allopurinol as a therapeutic option in cardiovascular disease. Pharmacol Ther 2017; 172: 139-50. https://doi.org/10.1016/j.pharmthera.2016.12.004
7. Richette P, Perez-Ruiz F, Doherty M, Jansen TL, Nuki G, Pascual E, et al. Improving cardiovascular and renal outcomes in gout: what should we target? Nat Rev Rheumatol 2014; 10(11): 654-6. https://doi.org/10.1038/nrrheum.2014.124
8. Feig DI, Kang D-H, Johnson RJ. Uric acid and cardiovascular risk. N Engl J Med 2008; 359(17): 1811-2. https://doi.org/10.1056/NEJMra0800885
9. Grech ED, Jackson MJ, Ramsdale DR. Reperfusion injury after acute myocardial infarction. BMJ 1995.https://doi.org/10.1136/bmj.310.6978.477
10. Rentoukas E, Tsarouhas K, Tsitsimpikou C, Lazaros G, Deftereos S, Vavetsi S. The prognostic impact of allopurinol in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention. Int J Cardiol 2010; 145(2): 257-8. https://doi.org/10.1016/j.ijcard.2009.08.037
11. Miwa-Nishimura N, Kanaide H, Abe S, Nakamura M. Does allopurinol prevent myocardial injury as a result of hypoxia-re-oxygenation in rats?. Int J Exp Pathol 1990; 71(5): 727.
12. Godin D, Bhimji S, McNeill J. Effects of allopurinol pretreatment on myocardial ultrastructure and arrhythmias following coronary artery occlusion and reperfusion. Virchows Arch B Cell Pathol Incl Mol Pathol 1986; 52(1): 327-41. https://doi.org/10.1007/BF02889975
13. Chambers DE, Parks DA, Patterson G, Roy R, McCord JM, Yoshida S, et al. Xanthine oxidase as a source of free radical damage in myocardial ischemia. J Mol Cell Cardiol 1985; 17(2): 145-52. https://doi.org/10.1016/S0022-2828(85)80017-1
14. Mendis S, Thygesen K, Kuulasmaa K, Giampaoli S, Mähönen M, Ngu Blackett K, et al. World Health Organization definition of myocardial infarction: 2008-09 revision. Int J Epidemiol 2011; 40(1): 139-46.https://doi.org/10.1093/ije/dyq165
15. Alemzadeh-Ansari MJ, Hosseini SK, Talasaz AH, Mohammadi M, Tokaldani ML, Jalali A, et al. Effect of high-dose allopurinol pretreatment on cardiac biomarkers of patients undergoing elective percutaneous coronary intervention: a randomized clinical trial. Am J Ther 2017; 24(6): e723-e9. https://doi.org/10.1097/MJT.0000000000000411
16. Huang Y, Zhang C, Xu Z, Shen J, Zhang X, Du H, et al. Clinical study on efficacy of allopurinol in patients with acute coronary syndrome and its functional mechanism. Hellenic J Cardiol 2017; 58(5): 360-5.https://doi.org/10.1016/j.hjc.2017.01.004
17. Guan W, Osanai T, Kamada T, Hanada H, Ishizaka H, Onodera H, 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. https://doi.org/10.1097/00005344-200305000-00005
18. Ekeløf S, Jensen SE, Rosenberg J, Gögenur I. Reduced oxidative stress in STEMI patients treated by primary percutaneous coronary intervention and with antioxidant therapy: a systematic review. Cardiovasc Drugs Ther 2014; 28(2): 173-81. https://doi.org/10.1007/s10557-014-6511-3
19. Rekhraj S, Gandy SJ, Szwejkowski BR, Nadir MA, Noman A, Houston JG, et al. High-dose allopurinol reduces left ventricular mass in patients with ischemic heart disease. J Am Coll Cardiol 2013; 61(9): 926-32.https://doi.org/10.1016/j.jacc.2012.09.066
20. 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. https://doi.org/10.1016/S0140-6736(10)60391-1
21. 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. https://doi.org/10.1001/jama.300.8.924
22. Higgins P, Dawson J, Walters M. The potential for xanthine oxidase inhibition in the prevention and treatment of cardiovascular and cerebrovascular disease. Cardiovasc Psychiatry Neurol 2009; 2009.https://doi.org/10.1155/2009/282059
23. Guthikonda S, Woods K, Sinkey CA, Haynes WG. Role of xanthine oxidase in conduit artery endothelial dysfunction in cigarette smokers. Am J Cardiol 2004; 93(5): 664-8. https://doi.org/10.1016/j.amjcard.2003.11.046
24. Eisele H-J, Markart P, Schulz R. Obstructive sleep apnea, oxidative stress, and cardiovascular disease: evidence from human studies. Oxid Med Cell Longev 2015; 2015. https://doi.org/10.1155/2015/608438
25. Mackenzie IS, Ford I, Walker A, Hawkey C, Begg A, Avery A, et al. Multicentre, prospective, randomised, open-label, blinded end point trial of the efficacy of allopurinol therapy in improving cardiovascular outcomes in patients with ischaemic heart disease: protocol of the ALL-HEART study. BMJ Open 2016; 6(9): e013774. https://doi.org/10.1136/bmjopen-2016-013774
26. Maruhashi T, Hisatome I, Kihara Y, Higashi Y. Hyperuricemia and endothelial function: From molecular background to clinical perspectives. Atherosclerosis 2018; 278: 226-31. https://doi.org/10.1016/j.atherosclerosis.2018.10.007
27. Givertz MM, Anstrom KJ, Redfield MM, Deswal A, Haddad H, Butler J, et al. 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. https://doi.org/10.1161/CIRCULATIONAHA.114.014536
28. Kanbay M, Ozkara A, Selcoki Y, Isik B, Turgut F, Bavbek N, et al. Effect of treatment of hyperuricemia with allopurinol on blood pressure, creatinine clearence, and proteinuria in patients with normal renal functions. Int Urol Nephrol 2007; 39(4): 1227-33. https://doi.org/10.1007/s11255-007-9253-3
29. Yiginer O, Ozcelik F, Inanc T, Aparci M, Ozmen N, Cingozbay BY, et al. Allopurinol improves endothelial function and reduces oxidant-inflammatory enzyme of myeloperoxidase in metabolic syndrome. Clin Res Cardiol 2008; 97(5): 334-40. https://doi.org/10.1007/s00392-007-0636-3
30. Muir SW, Harrow C, Dawson J, Lees KR, Weir CJ, Sattar N, et al. Allopurinol use yields potentially beneficial effects on inflammatory indices in those with recent ischemic stroke: a randomized, double-blind, placebo-controlled trial. Stroke 2008; 39(12): 3303-7. https://doi.org/10.1161/STROKEAHA.108.519793
31. Separham A, Ghaffari S, Najafi H, Ghaffari R, Ziaee M, Babaei H. The impact of allopurinol on patients with acute ST elevation myocardial infarction undergoing thrombolytic therapy. J Cardiovasc Pharmacol 2016; 68(4): 265-8. https://doi.org/10.1097/FJC.0000000000000409
32. Grimaldi-Bensouda L, Alpérovitch A, Aubrun E, Danchin N, Rossignol M, Abenhaim L, et al. Impact of allopurinol on risk of myocardial infarction. Ann Rheum Dis 2015; 74(5): 836-42. https://doi.org/10.1136/annrheumdis-2012-202972
33. Doehner W, Anker S. Xanthine oxidase inhibition for chronic heart failure: is allopurinol the next therapeutic advance in heart failure?. Heart 2005; 91(6): 707-9.https://doi.org/10.1136/hrt.2004.057190
34. Stone PH. Allopurinol a new anti-ischemic role for an old drug. J Am Coll Cardiol 2011; 58(8): 829-30.https://doi.org/10.1016/j.jacc.2011.02.072
35. Lukin A, Novak K, Polić S, Puljak L. Prognostic value of low and moderately elevated C-reactive protein in acute coronary syndrome: a 2-year follow-up study. Med Sci Monit 2013; 19: 777. https://doi.org/10.12659/MSM.884014