The Effect of High-dose Allopurinol Pretreatment on Inflammatory Biomarkers and Post-revascularization Coronary Blood Flow in Non-STEMI Patients: A Randomized Double Blind Clinical Trial

Overview

Journal ARYA Atheroscler

Date 2024 Jun 17

PMID 38881997

Authors

Hamid Sanei

Kiyan Heshmat-Ghahdarijani

Ali Asadi

Mohammad Kermani-Alghoraishi

Ali Safaei

Masoumeh Sadeghi

Affiliations

Soon will be listed here.

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.

References

Grimaldi-Bensouda L, Alperovitch A, Aubrun E, Danchin N, Rossignol M, Abenhaim L . Impact of allopurinol on risk of myocardial infarction. Ann Rheum Dis. 2014; 74(5):836-42. DOI: 10.1136/annrheumdis-2012-202972. View

Eisele H, Markart P, Schulz R . Obstructive Sleep Apnea, Oxidative Stress, and Cardiovascular Disease: Evidence from Human Studies. Oxid Med Cell Longev. 2015; 2015:608438. PMC: 4475750. DOI: 10.1155/2015/608438. View

Feig D, Kang D, Johnson R . Uric acid and cardiovascular risk. N Engl J Med. 2008; 359(17):1811-21. PMC: 2684330. DOI: 10.1056/NEJMra0800885. View

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(4):327-41. DOI: 10.1007/BF02889975. View

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; 2009:282059. PMC: 2790135. DOI: 10.1155/2009/282059. View

Richette P, Perez-Ruiz F, Doherty M, Jansen T, Nuki G, Pascual E . Improving cardiovascular and renal outcomes in gout: what should we target?. Nat Rev Rheumatol. 2014; 10(11):654-61. DOI: 10.1038/nrrheum.2014.124. View

Muir S, Harrow C, Dawson J, Lees K, Weir C, Sattar N . 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. DOI: 10.1161/STROKEAHA.108.519793. View

Givertz M, Anstrom K, Redfield M, Deswal A, Haddad H, Butler J . 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. PMC: 4438785. DOI: 10.1161/CIRCULATIONAHA.114.014536. View

Grech E, Jackson M, Ramsdale D . Reperfusion injury after acute myocardial infarction. BMJ. 1995; 310(6978):477-8. PMC: 2548866. DOI: 10.1136/bmj.310.6978.477. View

10.

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):265-268. DOI: 10.1097/FJC.0000000000000409. View

11.

Huang Y, Zhang C, Xu Z, Shen J, Zhang X, Du H . Clinical Study on efficacy of allopurinol in patients with acute coronary syndrome and its functional mechanism. Hellenic J Cardiol. 2017; 58(5):360-365. DOI: 10.1016/j.hjc.2017.01.004. View

12.

Alemzadeh-Ansari M, Hosseini S, Talasaz A, Mohammadi M, Tokaldani M, Jalali A . 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-e729. DOI: 10.1097/MJT.0000000000000411. View

13.

Trkulja V, Car S . On-admission serum uric acid predicts outcomes after acute myocardial infarction: systematic review and meta-analysis of prognostic studies. Croat Med J. 2012; 53(2):162-72. PMC: 3342647. DOI: 10.3325/cmj.2012.53.162. View

14.

Chambers D, Parks D, Patterson G, Roy R, McCord J, Yoshida S . Xanthine oxidase as a source of free radical damage in myocardial ischemia. J Mol Cell Cardiol. 1985; 17(2):145-52. DOI: 10.1016/s0022-2828(85)80017-1. View

15.

Yiginer O, Ozcelik F, Inanc T, Aparci M, Ozmen N, Cingozbay B . Allopurinol improves endothelial function and reduces oxidant-inflammatory enzyme of myeloperoxidase in metabolic syndrome. Clin Res Cardiol. 2008; 97(5):334-40. DOI: 10.1007/s00392-007-0636-3. View

16.

Xiao J, She Q, Wang Y, Luo K, Yin Y, Hu R . Effect of allopurinol on cardiomyocyte apoptosis in rats after myocardial infarction. Eur J Heart Fail. 2009; 11(1):20-7. DOI: 10.1093/eurjhf/hfn003. View

17.

Abbate A, Bussani R, Amin M, Vetrovec G, Baldi A . Acute myocardial infarction and heart failure: role of apoptosis. Int J Biochem Cell Biol. 2006; 38(11):1834-40. DOI: 10.1016/j.biocel.2006.04.010. View

18.

Guthikonda S, Woods K, Sinkey C, Haynes W . Role of xanthine oxidase in conduit artery endothelial dysfunction in cigarette smokers. Am J Cardiol. 2004; 93(5):664-8. DOI: 10.1016/j.amjcard.2003.11.046. View

19.

Mendis S, Thygesen K, Kuulasmaa K, Giampaoli S, Mahonen M, Blackett K . World Health Organization definition of myocardial infarction: 2008-09 revision. Int J Epidemiol. 2010; 40(1):139-46. DOI: 10.1093/ije/dyq165. View

20.

Noman A, Ang D, Ogston S, Lang C, Struthers A . 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. PMC: 2890860. DOI: 10.1016/S0140-6736(10)60391-1. View