期刊论文详细信息
BMC Medicine
Is chronic inhibition of phosphodiesterase type 5 cardioprotective and safe? A meta-analysis of randomized controlled trials
Andrea M Isidori2  Andrea Lenzi2  Federica Barbagallo2  Roberto Badagliacca3  Valentina Dall’Armi1  Riccardo Pofi2  Daniele Gianfrilli2  Tiziana Feola2  Elisa Giannetta2 
[1] Unit of Clinical and Molecular Epidemiology, IRCCS San Raffaele Pisana of Rome, Via della Pisana 235, Rome 00163, Italy;Department of Experimental Medicine, Sapienza University of Rome, Viale del Policlinico 155, Rome 00161, Italy;Department of Cardiovascular and Respiratory Science, Sapienza University of Rome, Piazzale Aldo Moro 5, Rome 00185, Italy
关键词: Pulmonary hypertension;    Sildenafil;    Erectile dysfunction;    Cardiac hypertrophy;    Cardiac remodeling;    Endothelial function;    Hypertension;    Heart failure;    Phosphodiesterase-5;   
Others  :  1121392
DOI  :  10.1186/s12916-014-0185-3
 received in 2014-07-11, accepted in 2014-09-17,  发布年份 2014
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【 摘 要 】

Background

The myocardial effects of phosphodiesterase type 5 inhibitors (PDE5i) have recently received consideration in several preclinical studies. The risk/benefit ratio in humans remains unclear.

Methods

We performed a meta-analysis of randomized, placebo-controlled trials (RCTs) to evaluate the efficacy and safety of PDE5i on cardiac morphology and function. From March 2012 to December 2013 (update: May 2014), we searched English-language studies from MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and SCOPUS-selecting RCTs of continuous PDE5i administration that reported cardiovascular outcomes: cardiac geometry and performance, afterload, endothelial function and safety. The pooled estimate of a weighted mean difference between treatment and placebo was obtained for all outcomes using a random effects model. A test for heterogeneity was performed and the I2 statistic calculated.

Results

Overall, 1,622 subjects were treated, with 954 randomized to PDE5i and 772 to placebo in 24 RCTs. According to our analysis, sustained PDE5 inhibition produced: (1) an anti-remodeling effect by reducing cardiac mass (−12.21 g/m2, 95% confidence interval (CI): −18.85; −5.57) in subjects with left ventricular hypertrophy (LVH) and by increasing end-diastolic volume (5.00 mL/m2; 95% CI: 3.29; 6.71) in non-LVH patients; (2) an improvement in cardiac performance by increasing cardiac index (0.30 L/min/m2, 95% CI: 0.202; 0.406) and ejection fraction (3.56%, 95% CI: 1.79; 5.33). These effects are parallel to a decline of N-terminal-pro brain natriuretic peptide (NT-proBNP) in subjects with severe LVH (−486.7 pg/ml, 95% CI: −712; -261). PDE5i administration also produced: (3) no changes in afterload parameters and (4) an improvement in flow-mediated vasodilation (3.31%, 95% CI: 0.53; 6.08). Flushing, headache, epistaxis and gastric symptoms were the commonest side effects.

Conclusions

This meta-analysis suggests for the first time that PDE5i have anti-remodeling properties and improve cardiac inotropism, independently of afterload changes, with a good safety profile. Given the reproducibility of the findings and tolerability across different populations, PDE5i could be reasonably offered to men with cardiac hypertrophy and early stage heart failure. Given the limited gender data, a larger trial on the sex-specific response to long-term PDE5i treatment is required.

【 授权许可】

   
2014 Giannetta et al.; licensee BioMed Central Ltd.

【 预 览 】
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