Pentoxifylline is a xanthine derivative with potential cardiovascular benefits.
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.
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.
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).
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: firstname.lastname@example.org
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