Tadalafil-induced improvement in left ventricular diastolic function in resistant hypertension

Santos, Rodrigo Cardoso; Faria, Ana Paula; Barbaro, Natália R.; Modolo, Rodrigo; Ferreira-Melo, Sílvia Elaine; Matos‐Souza, José R.; Coelho, Otávio Rizzi; Fontana, Vanessa; Calhoun, David A.; Moreno, Heitor

doi:10.1007/s00228-013-1611-8

Cited by 14 publications

(9 citation statements)

References 35 publications

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“…Analyses on NT-proBNP level, an indicator of myocardial stretch [ 47 ], follow the trend observed for ventricular mass and diastolic function [ 48 , 49 ], with a significant improvement in the subgroup of hypertrophic patients.…”

Section: Discussionmentioning

confidence: 87%

Is chronic inhibition of phosphodiesterase type 5 cardioprotective and safe? A meta-analysis of randomized controlled trials

Giannetta

Feola

Gianfrilli

et al. 2014

BMC Med

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BackgroundThe myocardial effects of phosphodiesterase type 5 inhibitors (PDE5i) have recently received consideration in several preclinical studies. The risk/benefit ratio in humans remains unclear.MethodsWe 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.ResultsOverall, 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.ConclusionsThis 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-014-0185-3) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 87%

Is chronic inhibition of phosphodiesterase type 5 cardioprotective and safe? A meta-analysis of randomized controlled trials

Giannetta

Feola

Gianfrilli

et al. 2014

BMC Med

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“…As we previously demonstrated, the use of a PDE5 inhibitor increases levels of cGMP in patients with RH. In this perspective, this class of drugs arises as a beneficial strategy in supporting BP control, since most antihypertensive drugs have poor influence on the nitric oxide/cGMP pathway .…”

Section: Discussionmentioning

confidence: 53%

Acute Sildenafil Use Reduces 24‐Hour Blood Pressure Levels in Patients With Resistant Hypertension: A Placebo‐Controlled, Crossover Trial

Catharina

Modolo

Ritter

et al. 2016

J of Clinical Hypertension

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The authors previously demonstrated that acute administration of sildenafil—a phosphodiesterase 5 (PDE5) inhibitor—improves hemodynamic parameters in patients with resistant hypertensive (RH), but its effect on ambulatory blood pressure monitoring (ABPM) is unknown. This interventional, nonrandomized, single‐blinded, placebo‐controlled, crossover trial included 26 patients with RH. A dose of sildenafil (187.5mg) was given, and after a washout period of 14 days the patients received a single oral dose of placebo and the protocol was repeated. The patients underwent 24‐hour ABPM recordings the day before and immediately after the protocols. The reduction of systolic (−8.8±1.4 vs 1.3±1.2 mm Hg, P=.02), diastolic (−5.3±3.3 vs 1.8±1.1 mm Hg, P=.03), and mean (−7.9±3.6 vs 0.8±0.9 mm Hg, P=.01) 24‐hour BP were found after the use of sildenafil compared with placebo. Improvement in daytime BP levels was also observed (systolic −6.0±4.7 vs 4.4±1.5 mm Hg [P=.02] and mean −4.8±3.9 vs 3.5±1.4 mm Hg [P=.02] for sildenafil vs placebo, respectively). Considering its antihypertensive effect, sildenafil may represent a therapeutic option for RH treatment.

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“…In summary, this short-term study demonstrated clinical relevance with the use of tadalafil for 2 weeks on LVDD treatment and diastolic function-related biomarkers in RHTN subjects, and this effect was independent of BP reduction 12 .…”

Section: Introductionmentioning

confidence: 57%

“…Therefore, because of the high prevalence of LVDD (95%) observed in our Outpatient Clinic specialized in RHTN (Campinas, Brazil) 5 and the lack of standard treatment, which reduces mortality rates 10 , our group recently sought to investigate LVDD condition by echocardiography - a non-invasive diagnostic method frequently used - in association with IPDE-5 in acute (sildenafil) and short-term (tadalafil) administration. Thus, this clinical update report two recently published findings that evaluated the effects of PDE-5 inhibitors on diastolic function in the specific group of resistant hypertensive subjects 11 , 12 .…”

Section: Introductionmentioning

confidence: 96%

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Effects of PDE type 5 inhibitors on Left Ventricular Diastolic Dysfunction in Resistant Hypertension

Faria¹,

Modolo²,

Moreno³

et al. 2014

Arquivos Brasileiros De Cardiologia

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Resistant hypertension (RHTN) is a multifactorial disease characterized by blood pressure (BP) levels above goal (140/90 mmHg) in spite of the concurrent use of three or more antihypertensive drugs of different classes. Moreover, it is well known that RHTN subjects have high prevalence of left ventricular diastolic dysfunction (LVDD), which leads to increased risk of heart failure progression. This review gathers data from studies evaluating the effects of phosphodiesterase-5 (PDE-5) inhibitors (administration of acute sildenafil and short-term tadalafil) on diastolic function, biochemical and hemodynamic parameters in patients with RHTN. Acute study with sildenafil treatment found that inhibition of PDE-5 improved hemodynamic parameters and diastolic relaxation. In addition, short-term study with the use of tadalafil demonstrated improvement of LVDD, cGMP and BNP-32 levels, regardless of BP reduction. No endothelial function changes were observed in the studies. The findings of acute and short-term studies revealed potential therapeutic effects of IPDE-5 drugs on LVDD in RHTN patients.

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Tadalafil-induced improvement in left ventricular diastolic function in resistant hypertension

Abstract: The current findings suggest that tadalafil improves LV relaxation through direct effects PDE-5-mediated in the cardiomyocytes with potential benefit as an adjunct to treat symptomatic subjects with LVDD such as RHTN patients.

Cited by 14 publications

References 35 publications

Is chronic inhibition of phosphodiesterase type 5 cardioprotective and safe? A meta-analysis of randomized controlled trials

Is chronic inhibition of phosphodiesterase type 5 cardioprotective and safe? A meta-analysis of randomized controlled trials

Acute Sildenafil Use Reduces 24‐Hour Blood Pressure Levels in Patients With Resistant Hypertension: A Placebo‐Controlled, Crossover Trial

Effects of PDE type 5 inhibitors on Left Ventricular Diastolic Dysfunction in Resistant Hypertension

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