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Effects of pentoxifylline on inflammatory markers and blood pressure: a systematic review and meta-analysis of randomized controlled trials

Brie, Daniel; Sahebkar, Amirhossein; Penson, Peter E.; Dinca, Madalina; Ursoniu, Sorin; Serban, Maria-Corina; Zanchetti, Alberto; Howard, George; Ahmed, Ali; Aronow, Wilbert S.; Muntner, Paul; Lip, Gregory Y.H.; Wong, Nathan D.; Rysz, Jacek; Banach, MaciejLipid, Blood Pressure Meta-analysis Collaboration (LBPMC) Group

doi: 10.1097/HJH.0000000000001086
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Introduction: Pentoxifylline is a xanthine derivative with potential cardiovascular benefits.

Aim: To evaluate the impact of pentoxifylline on blood pressure (BP) and plasma TNF-α, C-reactive protein (CRP) and IL-6 through a systematic review and meta-analysis of randomized controlled trials.

Methods: The protocol was registered (PROSPERO: CRD42016035988). The search included PUBMED, ProQuest, Scopus and EMBASE until 1 September 2015 to identify trials reporting BP or inflammatory markers during pentoxifylline therapy. Quantitative data synthesis was performed using a random-effects model, with weighted mean difference (WDF) and 95% confidence intervals (CIs) as summary statistics.

Results: Fifteen studies (16 treatment arms) were found to be eligible for inclusion. Meta-analysis did not suggest any effect of pentoxifylline on either SBP or DBP. Pentoxifylline treatment was associated with a significant reduction in plasma concentrations of TNF-α (WDF: −1.03 pg/ml, 95% CI: −1.54, −0.51; P < 0.001, 11 treatment arms) and CRP (WDF: −1.39 mg/l, 95% CI: −2.68, −0.10; P = 0.034, five treatment arms). No alteration in plasma IL-6 concentration was observed. The impact of pentoxifylline on plasma TNF-α levels was found to be positively associated with treatment duration (slope: 0.031; 95% CI: 0.004, 0.057; P = 0.023) but independent of pentoxifylline dose (slope: −0.0003; 95% CI: −0.002, 0.001; P = 0.687).

Conclusion: Pentoxifylline did not alter BP or plasma IL-6 concentration, but significantly reduced circulating TNF-α and CRP concentrations.

aInstitute for Cardiovascular Medicine Timisoara, Cardiology Department, University of Medicine and Pharmacy ‘Victor Babes’, Timisoara, Romania

bBiotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

cMetabolic Research Centre, Royal Perth Hospital, School of Medicine and Pharmacology, University of Western Australia, Perth, Australia

dSchool of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, UK

eIndependent Pharmacist Researcher, Leuven, Belgium

fDepartment of Functional Sciences, Discipline of Public Health, ‘Victor Babes’ University of Medicine and Pharmacy, Timisoara, Romania

gDepartment of Epidemiology, University of Alabama at Birmingham, Birmingham, Alabama, USA

hDepartment of Functional Sciences, Discipline of Pathophysiology, ‘Victor Babes’ University of Medicine and Pharmacy, Timisoara, Romania

iIstituto Auxologico Italiano, University of Milan, Milan, Italy

jDepartment of Biostatistics, University of Alabama at Birmingham, Birmingham, Alabama, USA

kVeterans Affairs Medical Center, Washington, District of Columbia

lDepartment of Medicine, New York Medical College, Valhalla, New York, USA

mUniversity of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham, UK

nDivision of Cardiology, Heart Disease Prevention Program, University of California, Irvine, California, USA

oChair of Nephrology and Hypertension

pDepartment of Hypertension, Chair of Nephrology and Hypertension, Medical University of Łódź, Łódź, Poland

Correspondence to Prof Maciej Banach, MD, PhD, FNLA, FAHA, FESC, FASA, Head, Department of Hypertension, WAM University Hospital in Lodz, Medical University of Lodz, Zeromskiego 113, 90-549 Lodz, Poland. Tel: +48 42 639 37 71; fax: +48 42 639 37 71; e-mail: maciejbanach@aol.co.uk

Abbreviations: ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin II receptor blocker; BNP, brain natriuretic peptide; BP, blood pressure; cAMP, cyclic adenosine monophosphate; cGMP, cyclic GMP; CI, confidence interval; CMA, comprehensive meta-analysis; CRP, C-reactive protein; GFR, glomerular filtration rate; IL, interleukin; LVEF, left ventricle ejection fraction; NASH, nonalcoholic steatohepatitis; NR, not reported; NYHA, New York Heart Association; PAI-1, plasminogen activator inhibitor-1; RCT, randomized controlled trial; sTNFRI, soluble tumor necrosis factor receptor; TGF, tumor growth factor; TNF, tumor necrosis factor; WMD, weighted mean difference

* Drs Daniel Brie and Amirhossein Sahebkar contributed equally to the article.

Received 17 April, 2016

Accepted 22 July, 2016

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