Associations between phosphodiesterase type 5 inhibitors and vascular function: a systematic review and meta-analysis on randomized-controlled trials

Q: What are the key findings of this study?

Phosphodiesterase type-5 inhibitors significantly decreased systolic blood pressure (MD -2.80 mmHg) and improved multiple vascular parameters compared to placebo.

Q: What is the clinical evidence from this study?

Study design: Meta-Analysis. Population: Subclinical cardiovascular diseases (n=3242). Intervention: Phosphodiesterase type-5 inhibitors (PDE5is) vs. Placebo. Primary outcome: Systolic blood pressure (SBP) (MD -2.80 mmHg, 95% CI -4.24, -1.37, p=<0.001).

Q: What does this research mean for the field?

PDE5 inhibitors were associated with improved vascular function parameters compared to placebo in randomized controlled trials. Novelty: ClaimNovelty.SYNTHESIS. Consensus alignment: ConsensusAlignment.NEUTRAL.

Q: What question did this study set out to answer?

To evaluate the impact of phosphodiesterase type 5 inhibitors compared to placebo on vascular parameters and subclinical cardiovascular markers.

Yucong Zhang; Hao Peng; Sheng Xin; Jiaquan Mao; Jun Zhang; Hao Li; Yang Luan; Xia Liu; Tao Wang; Jihong Liu; Hanlin Zhang; Wen Song

doi:10.1186/s13643-025-03042-4

December 30, 2025Systematic ReviewsOpen Access

Associations between phosphodiesterase type 5 inhibitors and vascular function: a systematic review and meta-analysis on randomized-controlled trials

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Key result

PDE5 inhibitors lower systolic blood pressure by ~3 mmHg vs. placebo while improving vascular parameters.

MD -2.80 mmHg
95% CI -4.24, -1.37
P<0.001
n=3,242

Figures

Why the study?

Do phosphodiesterase type-5 inhibitors improve vascular parameters associated with subclinical cardiovascular diseases compared to placebo?

Key Points

To evaluate the impact of phosphodiesterase type 5 inhibitors compared to placebo on vascular parameters and subclinical cardiovascular markers.
Systematic review and meta-analysis of 63 randomized controlled trials published between 1998 and 2022 (N=3242 participants) searched across PubMed, Scopus, and Web of Science.
Included cohorts comprising healthy individuals (n=14 trials), erectile dysfunction patients (n=18), and participants with conditions such as chronic heart failure (n=10) and hypertension (n=6).
Calculated pooled mean differences (MDs) with 95% confidence intervals (CIs) across hemodynamic indices, arterial stiffness markers, endothelial function tests, and circulating biomarkers.
PDE5 inhibitors significantly reduced systolic blood pressure (MD: -2.80 mmHg, 95% CI: -4.24, -1.37, P < 0.001), diastolic blood pressure (MD: -1.80 mmHg, 95% CI: -2.37, -1.22, P < 0.001), carotid intima-media thickness (MD: -0.01 mm, 95% CI: -0.02, -0.01, P < 0.001), and pulse wave velocity (MD: -0.75 cm/s, 95% CI: -1.01, -0.49, P < 0.001).
Compared to placebo, PDE5 inhibitors increased peak systolic velocity (MD: 3.70 cm/s, 95% CI: 3.52, 3.88, P < 0.001), flow-mediated dilation (MD: 2.47%, 95% CI: 1.24, 3.71, P < 0.001), endothelial progenitor cells (MD: 475.29 cells/mL, 95% CI: 51.38, 899.20, P = 0.03), and endothelial microparticles (MD: 4.86%, 95% CI: 0.65, 9.07, P = 0.02).
No statistically significant changes were observed for augmentation index (MD: 0.27%, 95% CI: -3.61, 4.15, P = 0.89), brachial artery diameter (MD: 0.02%, 95% CI: -0.05, 0.09, P = 0.57), or reactive hyperemia index (MD: 0.23%, 95% CI: -0.21, 0.68, P = 0.31).

Study Design

Type

Meta-Analysis (n=3,242)

Structured PICO

Do phosphodiesterase type-5 inhibitors improve vascular parameters associated with subclinical cardiovascular diseases compared to placebo?

P

Population

3,242 subjects from 63 randomized controlled trials, including healthy individuals and patients with erectile dysfunction, chronic heart failure, and other conditions, evaluating the effects of PDE5is on vascular parameters.

I

Intervention

Phosphodiesterase type-5 inhibitors (PDE5is) as a class (including sildenafil, vardenafil, tadalafil, lodenafil, udenafil, avanafil).

C

Comparator

Placebo.

O

Outcome

Vascular parameters including systolic blood pressure, diastolic blood pressure, mean arterial pressure, carotid intima-media thickness, pulse wave velocity, augmentation index, flow-mediated dilation, reactive hyperemia index, endothelial microparticles, endothelial progenitor cells, and peak systolic velocity.surrogate

Main Result

Mean Difference: -2.8 (95% CI -4.24–-1.37)

p-value: p=<0.001

PDE5 inhibitors significantly improve multiple vascular parameters, including blood pressure, arterial stiffness, and endothelial function, suggesting potential benefits in the prevention and treatment of subclinical cardiovascular diseases.

Limitations

Significant heterogeneity was observed in the meta-analysis due to differences in specific PDE5is, dosages, treatment durations, patient populations, and measurement methods.
The impact of confounding factors and specific interventions could not be fully evaluated as most studies did not report confounder-adjusted results.
Constrained by the scope of original studies, preventing assessment of physiological state's effect on vascular response, drug-drug interactions, or pre- to post-intervention changes.
Significant heterogeneity due to differences in specific PDE5is, dosages, treatment durations, patient populations, and vascular parameter measurement methods.
Did not conduct meta-regression to explore heterogeneity further.
Subgroup stratification by disease status failed to fully mitigate heterogeneity.
Robust subgroup analyses were hindered by limited study numbers and inconsistent treatment regimens.
The impact of confounding factors and specific interventions could not be fully evaluated.

Implication

PDE5 inhibitors may be considered for vascular health; confirms surrogate benefits across RCTs.

Abstract

BACKGROUND: Phosphodiesterase type-5 inhibitors (PDE5is) are used for the treatment of erectile dysfunction (ED) and have potential cardioprotective effects. The impacts of PDE5is on cardiovascular parameters, which may be associated with the occurrence and progression of subclinical cardiovascular diseases, remain uncertain. In this study, we evaluated the effects of PDE5is on vascular parameters. METHODS: Randomized controlled trials (RCTs) that compared the effects of PDE5is and placebo on vascular parameters and were published from 1998 to 2022 were identified from PubMed, Scopus and Web of Science. Mean differences (MDs) with 95% confidence intervals (CIs) were pooled. A sensitivity analysis was conducted to confirm the robustness of the pooled results. The keywords that were searched in the databases are as follows: ((systolic blood pressure) OR (SBP) OR (diastolic blood pressure) OR (DBP) OR (mean arterial pressure) OR (MAP) OR (Pulse Wave Velocity) OR (PWV) OR (intima-media thickness) OR (cIMT) OR (augmentation Index) OR (AI) OR (FMD) OR (flow-mediated dilation) OR (reactive hyperemia index) OR (RHI) OR (Endothelial microparticles) OR (EMP) OR (EPCs) OR (Endothelial Progenitor Cells) OR (PSV) OR (peak systolic velocity)) AND ((PDE5 Inhibitors) OR (PDE5i) OR (Sildenafil) OR (Vardenafil) OR (Tadalafil) OR (Lodenafil) OR (Udenafil) OR (Avanafil)). RESULTS: Sixty-three studies involving 3242 subjects were included. Overall, PDE5is decreased systolic blood pressure (MD: -2.80 mmHg, 95% CI: -4.24, -1.37, P < 0.001), diastolic blood pressure (MD: -1.80 mmHg, 95% CI: -2.37, -1.22, P < 0.001), carotid intima‒media thickness (MD: -0.01 mm, 95% CI: -0.02, -0.01, P < 0.001), and pulse wave velocity (MD: -0.75 cm/s, 95% CI: -1.01, -0.49, P < 0.001). In addition, PDE5is increased the peak systolic velocity (MD: 3.70 cm/s, 95% CI: 3.52, 3.88, P < 0.001), flow-mediated dilation (MD: 2.47%, 95% CI: 1.24, 3.71, P < 0.001), concentration of endothelial progenitor cells (MD: 475.29 cells/mL, 95% CI: 51.38, 899.20, P = 0.03), and concentration of endothelial microparticles (MD: 4.86%, 95% CI: 0.65, 9.07, P = 0.02). However, the effects of PDE5is on the augmentation index, brachial artery diameter and reactive hyperemia index were not statistically significant. CONCLUSION: Compared with the placebo, PDE5is improved vascular parameters, indicating the potential of PDE5is for treating subclinical cardiovascular diseases. Further research is needed to confirm the role of the improvement on vascular parameters by PDE5isin preventing and treating cardiovascular diseases. SYSTEMATIC REVIEW REGISTRATION: The present study protocol was reviewed and approved by PROSPERO. The title is "Associations between PDE5is and vascular parameters: A systematic review and meta-analysis" ( https://www.crd.york.ac.uk/PROSPERO/ ) (Reg. No. CRD42023387924).

Discussion

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Cite This Study

Zhang et al. (2025) conducted a meta-analysis in Subclinical cardiovascular diseases (n=3,242). Phosphodiesterase type-5 inhibitors (PDE5is) vs. Placebo was evaluated on Systolic blood pressure (SBP) (MD -2.80 mmHg, 95% CI -4.24, -1.37, p=<0.001). Phosphodiesterase type-5 inhibitors significantly decreased systolic blood pressure (MD -2.80 mmHg) and improved multiple vascular parameters compared to placebo.

synapsesocial.com/papers/6963220c91e05aa366cb87cc https://doi.org/10.1186/s13643-025-03042-4

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Associations between phosphodiesterase type 5 inhibitors and vascular function: a systematic review and meta-analysis on randomized-controlled trials

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

Associations between phosphodiesterase type 5 inhibitors and vascular function: a systematic review and meta-analysis on randomized-controlled trials

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

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