Login Register Cart 0
Generic placeholder image

Reviews on Recent Clinical Trials

Editor-in-Chief

ISSN (Print): 1574-8871
ISSN (Online): 1876-1038

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Meta-Analysis

A Systematic Review and Meta-Analysis of the Effects of Statin Therapy on Heart Transplantation

In Press, (this is not the final "Version of Record"). Available online 04 June, 2024
Author(s): Hossein Mardani-Nafchi, Seyed Mahmoud Reza Hashemi Rafsanjani, Saeid Heidari-Soureshjani, Saber Abbaszadeh, Babak Gholamine and Nasrollah Naghdi*
Published on: 04 June, 2024

DOI: 10.2174/0115748871301446240513093612

Price: $95

Abstract

Background: Most of the mortality after Heart Transplantation (HT) is attributed to severe cardiac allograft vasculopathy (CAV) and rejection.

Objectives: This meta-analysis aimed to investigate the effects of postoperative statin therapy on outcomes (mortality, rejection, and CAV in HT patients).

Methods: This systematic review and meta-analysis was performed on publications between 1980 and October 2023 in Web of Science, Scopus, PubMed, Cochrane, Science Direct, Google Scholar, and Embase databases. Heterogeneity was assessed using Chi-square, I2, and forest plots. Publication bias was evaluated using Begg's and Egger's tests. Analyses were performed in Stata 15 with significance at p < 0.05.

Results: This meta-analysis included 17 studies comprising 4,627 participants and conducted between 1995 to 2021. Compared to non-users, the odds of mortality were lower among statin users (OR= 0.49, 95% CI: 0.32–0.75, p < 0.001). The odds of CAV were also reduced with statin use (OR= 0.71, 95% CI: 0.53–0.96, p = 0.027). The odds of rejection were not significantly different (OR= 0.69, 95% CI: 0.41–1.15, p = 0.152). However, rejection odds were lower with statins in RCTs (OR= 0.42, 95% CI: 0.21–0.82, p = 0.012) but not in case-control studies (OR= 0.87, 95% CI: 0.49-1.52, p = 0.615). No publication bias was observed with Begg's test, but Egger's test showed possible bias.

Conclusion: This meta-analysis found postoperative statin use associated with lower mortality and CAV, but not overall rejection, though RCT subgroup analysis showed decreased rejection with statins. Statin therapy may improve prognosis in HT patients.

[1]
Tsao CW, Aday AW, Almarzooq ZI, et al. Heart disease and stroke statistics—2022 update: A report from the American heart association. Circulation 2022; 145(8): e153-639.
[http://dx.doi.org/10.1161/CIR.0000000000001052] [PMID: 35078371]
[2]
Chatzinikolaou A, Tzikas S, Lavdaniti M. Assessment of quality of life in patients with cardiovascular disease using the SF-36, MacNew, and EQ-5D-5L questionnaires. Cureus 2021; 13(9): e17982.
[http://dx.doi.org/10.7759/cureus.17982] [PMID: 34667665]
[3]
Gheorghe A, Griffiths U, Murphy A, Quigley LH, Lamptey P, Perel P. The economic burden of cardiovascular disease and hypertension in low- and middle-income countries: A systematic review. BMC Public Health 2018; 18(1): 975.
[http://dx.doi.org/10.1186/s12889-018-5806-x] [PMID: 30081871]
[4]
Golbus JR, Adie S, Yosef M, Murthy VL, Aaronson KD, Konerman MC. Statin intensity and risk for cardiovascular events after heart transplantation. ESC Heart Fail 2020; 7(5): 2074-81.
[http://dx.doi.org/10.1002/ehf2.12784] [PMID: 32578953]
[5]
Masarone D, Kittleson MM, Falco L, et al. The ABC of heart transplantation—part 1: Indication, eligibility, donor selection, and surgical technique. J Clin Med 2023; 12(16): 5217.
[http://dx.doi.org/10.3390/jcm12165217] [PMID: 37629260]
[6]
Fuchs M, Schibilsky D, Zeh W, Herz BM, Beyersdorf F, Siepe M. Does the heart transplant have a future? Eur J Cardiothorac Surg 2019; 55(S1): i38-48.
[http://dx.doi.org/10.1093/ejcts/ezz107] [PMID: 31106338]
[7]
Asleh R, Alnsasra H, Villavicencio MA, Daly RC, Kushwaha SS. Cardiac transplantation: Physiology and natural history of the transplanted heart. Compr Physiol 2023; 13(3): 4719-65.
[http://dx.doi.org/10.1002/cphy.c220001] [PMID: 37358515]
[8]
McGwin G Jr, Xie A, Owsley C. The use of cholesterol-lowering medications and age-related macular degeneration. Ophthalmology 2005; 112(3): 488-94.
[http://dx.doi.org/10.1016/j.ophtha.2004.10.027] [PMID: 15745779]
[9]
Vavvas DG, Daniels AB, Kapsala ZG, et al. Regression of some high-risk features of age-related macular degeneration (AMD) in patients receiving intensive statin treatment. EBioMedicine 2016; 5: 198-203.
[http://dx.doi.org/10.1016/j.ebiom.2016.01.033] [PMID: 27077128]
[10]
Wenke K, Meiser B, Thiery J, Reichart B. Impact of simvastatin therapy after heart transplantation an 11-year prospective evaluation. Herz 2005; 30(5): 431-2.
[http://dx.doi.org/10.1007/s00059-005-2685-6] [PMID: 16132246]
[11]
Anbari K, Amiri MM, Heidari-Soureshjani S, Sherwin CMT, Kasiri K. A systematic review and meta-analysis on the role of statins in the prevention of mortality following pancreatic cancer. Anticancer Agents Med Chem 2023; 23(19): 2073-82.
[http://dx.doi.org/10.2174/1871520623666230824095226] [PMID: 37622694]
[12]
Memarzadeh E, Soureshjani HS. The relationship between statin and risk of age-related macular degeneration: A systematic review and meta-analysis. J Ophthalmol 2022; 2022: 1-9.
[http://dx.doi.org/10.1155/2022/8564818] [PMID: 35586594]
[13]
Hafshejani MA, Sherwin CMT, Soureshjani HS. Do statins play any role in reducing the incidence and mortality of ovarian cancer? A systematic review and meta-analysis. J Prev Med Hyg 2020; 61(3): E331-9.
[PMID: 33150223]
[14]
Kazi DS, Penko JM, Domingo BK. Statins for primary prevention of cardiovascular disease. Med Clin North Am 2017; 101(4): 689-99.
[http://dx.doi.org/10.1016/j.mcna.2017.03.001] [PMID: 28577620]
[15]
Darvishi M, Amiri MM, Soureshjani HS, Sherwin CM, Nafchi MH. The association between statins intake and risk of post stroke pneumonia: A systematic review and meta-analysis. Curr Rev Clin Exp Pharmacol 2023; 2023
[16]
Vallakati A, Reddy S, Dunlap ME, Taylor DO. Impact of statin use after heart transplantation. Circ Heart Fail 2016; 9(10): e003265.
[http://dx.doi.org/10.1161/CIRCHEARTFAILURE.116.003265] [PMID: 27729391]
[17]
Szyguła-Jurkiewicz B, Szczurek W, Zembala M. Heart and lung failure, transplantology the role of statins in patients after heart transplantation. Kardiochir Torakochirurgia Pol 2015; 1(1): 42-7.
[http://dx.doi.org/10.5114/kitp.2015.50567] [PMID: 26336477]
[18]
Ellimuttil TM, Harrison K, Rollins AT, et al. Effect of statin intensity on the progression of cardiac allograft vasculopathy. Card Fail Rev 2021; 7: e15.
[http://dx.doi.org/10.15420/cfr.2021.07] [PMID: 34950505]
[19]
Peterson J, Welch V, Losos M, Tugwell P. The Newcastle-Ottawa scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Ottawa: Ottawa Hospital Research Institute 2011; pp. 1-12.
[20]
Kjaergard LL, Villumsen J, Gluud C. Reported methodologic quality and discrepancies between large and small randomized trials in meta-analyses. Ann Intern Med 2001; 135(11): 982-9.
[http://dx.doi.org/10.7326/0003-4819-135-11-200112040-00010] [PMID: 11730399]
[21]
Jadad AR, Moore RA, Carroll D, et al. Assessing the quality of reports of randomized clinical trials: Is blinding necessary? Control Clin Trials 1996; 17(1): 1-12.
[http://dx.doi.org/10.1016/0197-2456(95)00134-4] [PMID: 8721797]
[22]
Magnani G, Carinci V, Magelli C, Potena L, Reggiani LB, Branzi A. Role of statins in the management of dyslipidemia after cardiac transplant: Randomized controlled trial comparing the efficacy and the safety of atorvastatin with pravastatin. J Heart Lung Transplant 2000; 19(7): 710-5.
[http://dx.doi.org/10.1016/S1053-2498(00)00128-5] [PMID: 10930822]
[23]
Moro J, Almenar L, Dolz ML, et al. Ezetimibe in heart transplantation: Initial experience. Transplant Proc 2007; 39(7): 2389-92.
[http://dx.doi.org/10.1016/j.transproceed.2007.06.043] [PMID: 17889199]
[24]
Fildes JE, Shaw SM, Mitsidou A, et al. HMG-CoA reductase inhibitors deplete circulating classical and non-classical monocytes following human heart transplantation. Transpl Immunol 2008; 19(2): 152-7.
[http://dx.doi.org/10.1016/j.trim.2008.02.002] [PMID: 18503891]
[25]
Rodríguez JA, Leiro CMG, Paniagua MJ, et al. Rhabdomyolysis in heart transplant patients on HMG-CoA reductase inhibitors and cyclosporine. Transplant Proc 1999; 31(6): 2522-3.
[http://dx.doi.org/10.1016/S0041-1345(99)00445-5] [PMID: 10500698]
[26]
Bae SS, Oganesian B, Golub I, Schoeman CC. Statin use in patients with NON-HMGCR idiopathic inflammatory myopathies: A retrospective study. Clin Cardiol 2020; 43(7): 732-42.
[http://dx.doi.org/10.1002/clc.23375] [PMID: 32432360]
[27]
Samman A, Imai C, Straatman L, Frolich J, Humphries K, Ignaszewski A. Safety and efficacy of rosuvastatin therapy for the prevention of hyperlipidemia in adult cardiac transplant recipients. J Heart Lung Transplant 2005; 24(8): 1008-13.
[http://dx.doi.org/10.1016/j.healun.2004.07.016] [PMID: 16102434]
[28]
Tremblay-Gravel M, Racine N, de Denus S, et al. Changes in outcomes of cardiac allograft vasculopathy over 30 years following heart transplantation. JACC Heart Fail 2017; 5(12): 891-901.
[http://dx.doi.org/10.1016/j.jchf.2017.09.014] [PMID: 29191295]
[29]
Heeney SA, Tjugum SL, Corkish ME, Hollis IB. Safety and tolerability of high-intensity statin therapy in heart transplant patients receiving immunosuppression with tacrolimus. Clin Transplant 2019; 33(1): e13454.
[http://dx.doi.org/10.1111/ctr.13454] [PMID: 30485535]
[30]
Alyaydin E, Pogoda C, Dell’Aquila A, et al. Cardiac allograft vasculopathy in a long-term follow-up after heart transplantation: Role of remnant cholesterol in residual inflammation. Cardiol J 2022; 29(5): 782-90.
[http://dx.doi.org/10.5603/CJ.a2022.0013] [PMID: 35373329]
[31]
Nykänen AI, Holmström EJ, Tuuminen R, et al. Donor simvastatin treatment in heart transplantation: A randomized and blinded clinical trial. Circulation 2019; 140(8): 627-40.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.119.039932] [PMID: 31352795]
[32]
Syrjala SO, Holmstrom E, Dhaygude K, Lommi J, Nykanen A, Lemstrom K. (1083) donor simvastatin treatment in heart transplantation: 5-Year results of a randomized clinical trial. J Heart Lung Transplant 2023; 42(S4): S467.
[http://dx.doi.org/10.1016/j.healun.2023.02.1294]
[33]
Baba DF, Suciu H, Avram C, et al. The role of preoperative chronic statin therapy in heart transplant receipts—A retrospective single-center cohort study. Int J Environ Res Public Health 2023; 20(4): 3471.
[http://dx.doi.org/10.3390/ijerph20043471] [PMID: 36834166]
[34]
Peled Y, Klempfner R, Kassif Y, et al. Preoperative statin therapy and heart transplantation outcomes. Ann Thorac Surg 2020; 110(4): 1280-5.
[http://dx.doi.org/10.1016/j.athoracsur.2020.02.005] [PMID: 32156588]
[35]
Hirsch E, Nnani D, Patel S, et al. (450) tolerability and effectiveness of intensified statin after heart transplantation. J Heart Lung Transplant 2023; 42(4): S208.
[http://dx.doi.org/10.1016/j.healun.2023.02.465]
[36]
Townsend ML, Khoury M, Koehl D, et al. (188) Statin use may not benefit pediatric heart transplant recipients: A PHTS analysis. J Heart Lung Transplant 2023; 42(4): S93.
[http://dx.doi.org/10.1016/j.healun.2023.02.204]
[37]
Goehring K, Kuan W, Sieg A, Dawson KL, Kolodziej AR. Effect of statin intensity in the prevention of cardiac allograft vasculopathy. J Heart Lung Transplant 2020; 39(S4): S212-3.
[http://dx.doi.org/10.1016/j.healun.2020.01.839]
[38]
Golbus JR, Adie S, Hanigan S, et al. Higher intensity statin therapy reduces clinical endpoints after heart transplantation independent of lipid levels. J Heart Lung Transplant 2019; 38(S4): S76.
[http://dx.doi.org/10.1016/j.healun.2019.01.172]
[39]
Keogh A, Macdonald P, Kaan A, Aboyoun C, Spratt P, Mundy J. Efficacy and safety of pravastatin vs simvastatin after cardiac transplantation. J Heart Lung Transplant 2000; 19(6): 529-37.
[http://dx.doi.org/10.1016/S1053-2498(00)00077-2] [PMID: 10867332]
[40]
Mehra MR, Uber PA, Vivekananthan K, et al. Comparative beneficial effects of simvastatin and pravastatin on cardiac allograft rejection and survival. J Am Coll Cardiol 2002; 40(9): 1609-14.
[http://dx.doi.org/10.1016/S0735-1097(02)02340-9] [PMID: 12427413]
[41]
Kobashigawa JA, Katznelson S, Laks H, et al. Effect of pravastatin on outcomes after cardiac transplantation. N Engl J Med 1995; 333(10): 621-7.
[http://dx.doi.org/10.1056/NEJM199509073331003] [PMID: 7637722]
[42]
See VY Jr, DeNofrio D, Goldberg L, et al. Effect of atorvastatin on postcardiac transplant increase in low-density lipoprotein cholesterol reduces development of intimal hyperplasia and progression of endothelial dysfunction. Am J Cardiol 2003; 92(1): 11-5.
[http://dx.doi.org/10.1016/S0002-9149(03)00456-9] [PMID: 12842237]
[43]
Kobashigawa JA, Moriguchi JD, Laks H, et al. Ten-year follow-up of a randomized trial of pravastatin in heart transplant patients. J Heart Lung Transplant 2005; 24(11): 1736-40.
[http://dx.doi.org/10.1016/j.healun.2005.02.009] [PMID: 16297773]
[44]
Mahle WT, Vincent RN, Berg AM, Kanter KR. Pravastatin therapy is associated with reduction in coronary allograft vasculopathy in pediatric heart transplantation. J Heart Lung Transplant 2005; 24(1): 63-6.
[http://dx.doi.org/10.1016/j.healun.2003.10.013] [PMID: 15653381]
[45]
Stojanovic I, Vrtovec B, Radovancevic B, et al. Survival, graft atherosclerosis, and rejection incidence in heart transplant recipients treated with statins: 5-year follow-up. J Heart Lung Transplant 2005; 24(9): 1235-8.
[http://dx.doi.org/10.1016/j.healun.2004.08.014] [PMID: 16143239]
[46]
Wu AH, Ballantyne CM, Short BC, et al. Statin use and risks of death or fatal rejection in the Heart Transplant Lipid Registry. Am J Cardiol 2005; 95(3): 367-72.
[http://dx.doi.org/10.1016/j.amjcard.2004.09.035] [PMID: 15670546]
[47]
Krishnan B, Vakil KP, Sankar A, Duprez D, Benditt DG. Impact of pre-operative statin use on risk of mortality and early atrial fibrillation after heart transplantation. Clin Transplant 2016; 30(5): 628-32.
[http://dx.doi.org/10.1111/ctr.12729] [PMID: 26928633]
[48]
Asleh R, Briasoulis A, Pereira NL, et al. Timing of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor initiation and allograft vasculopathy progression and outcomes in heart transplant recipients. ESC Heart Fail 2018; 5(6): 1118-29.
[http://dx.doi.org/10.1002/ehf2.12329] [PMID: 30019530]
[49]
Greenway SC, Butts R, Naftel DC, et al. Statin therapy is not associated with improved outcomes after heart transplantation in children and adolescents. J Heart Lung Transplant 2016; 35(4): 457-65.
[http://dx.doi.org/10.1016/j.healun.2015.10.040] [PMID: 26746989]
[50]
O’Rourke B, Barbir M, Mitchell AG, Yacoub MH, Banner NR. Efficacy and safety of fluvastatin therapy for hypercholesterolemia after heart transplantation. Int J Cardiol 2004; 94(2-3): 235-40.
[http://dx.doi.org/10.1016/j.ijcard.2003.04.009] [PMID: 15093987]
[51]
Wenke K, Meiser B, Thiery J, et al. Simvastatin initiated early after heart transplantation: 8-year prospective experience. Circulation 2003; 107(1): 93-7.
[http://dx.doi.org/10.1161/01.CIR.0000043241.32523.EE] [PMID: 12515749]
[52]
Fröhlich GM, Rufibach K, Enseleit F, et al. Statins and the risk of cancer after heart transplantation. Circulation 2012; 126(4): 440-7.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.111.081059] [PMID: 22761452]
[53]
Grigioni F, Carigi S, Potena L, et al. Long-term safety and effectiveness of statins for heart transplant recipients in routine clinical practice. Transplant Proc 2006; 38(5): 1507-10.
[http://dx.doi.org/10.1016/j.transproceed.2006.02.071] [PMID: 16797344]
[54]
Luo CM, Chou NK, Chi NH, et al. The effect of statins on cardiac allograft survival. Transplant Proc 2014; 46(3): 920-4.
[http://dx.doi.org/10.1016/j.transproceed.2013.11.016] [PMID: 24767381]
[55]
Mehra MR, Raval NY. Metaanalysis of statins and survival in de novo cardiac transplantation. Transplant Proc 2004; 36(5): 1539-41.
[http://dx.doi.org/10.1016/j.transproceed.2004.05.036] [PMID: 15251380]
[56]
Becchetti C, Dirchwolf M, Schropp J, et al. Use of statins after liver transplantation is associated with improved survival: Results of a nationwide study. Aliment Pharmacol Ther 2022; 56(7): 1194-204.
[http://dx.doi.org/10.1111/apt.17192] [PMID: 35979872]
[57]
Brugts JJ, Yetgin T, Hoeks SE, et al. The benefits of statins in people without established cardiovascular disease but with cardiovascular risk factors: Meta-analysis of randomised controlled trials. BMJ 2009; 338(jun30 1): b2376.
[http://dx.doi.org/10.1136/bmj.b2376] [PMID: 19567909]
[58]
Ramkumar S, Raghunath A, Raghunath S. Statin therapy: Review of safety and potential side effects. CMR Cardiac MRI SGRE 2016; 32(6): 631-9.
[PMID: 27899849]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy