Erectile dysfunction, phosphodiesterase-5 inhibitor use and risk of cardiovascular disease and mortality in people with diabetes: A systematic review and meta-analysis

Samuel Seidu; Ana Cebrián; Setor K Kunutsor; Kamlesh Khunti

doi:10.1016/j.pcd.2022.09.004

Erectile dysfunction, phosphodiesterase-5 inhibitor use and risk of cardiovascular disease and mortality in people with diabetes: A systematic review and meta-analysis

Samuel Seidu^*
, Ana Cebrián
, Setor K Kunutsor
, Kamlesh Khunti

^*Corresponding author for this work

Research output: Contribution to journal › Article (Academic Journal) › peer-review

18 Citations (Scopus)

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Abstract

Background
Phosphodiesterase-5 inhibitors (PDE5-Is), used in the management of erectile dysfunction (ED), have potential cardioprotective benefits. The impact of PDE5-Is on reducing adverse cardiovascular outcomes in patients with diabetes mellitus (DM) and ED is uncertain. Using a systematic review and meta-analysis of observational cohort studies and randomised controlled trials (RCTs), we evaluated if (i) the association of PDE5-Is in people with ED and DM and their risk of cardiovascular disease (CVD) and mortality and (ii) ED confers an excess risk of CVD and mortality in patients with DM compared with no DM.

Methods
Studies were identified from MEDLINE, Embase, the Cochrane Library, Web of Science citation search and search of bibliographies to April 2022. Study-specific risk ratios (RRs) with 95% confidence intervals (CIs) were pooled.

Results
Eighteen unique studies reported on the cardiovascular impact of ED in patients with and without DM. In the general population, the RRs (95% CIs) of ED for composite CVD/MACE, all-cause mortality, CHD and stroke were 1.43 (1.31–1.55), 1.47 (1.31–1.65), 1.59 (1.39–1.82), and 1.34 (1.15–1.56), respectively. The respective estimates were 1.68 (1.15–2.45), 1.40 (0.90–2.18), 1.41 (1.24–1.61) and 1.32 (1.09–1.60) in the diabetes population. Interaction analyses suggested similar risk in both populations. Six studies reported the cardiovascular effects of PDE5-Is in people with ED and DM. Limited RCT data showed no significant differences in the risk of major adverse cardiac event (MACE), coronary heart disease (CHD) and all-cause mortality comparing PDE5-I use with non-use: RRs (95% CIs) of 3.47 (0.17–69.19), 1.31 (0.10–16.54) and 0.35 (0.12–1.05), respectively.

Conclusions
ED confers no excess risk of CVD and mortality in patients with DM compared with no DM. Limited and inadequately powered data shows no significant differences in the risk of adverse cardiovascular outcomes comparing use of PDE5-Is with non-use in patients with ED and DM.

Original language	English
Pages (from-to)	601-613
Journal	Primary Care Diabetes
Volume	16
Issue number	5
Early online date	14 Sept 2022
DOIs	https://doi.org/10.1016/j.pcd.2022.09.004
Publication status	Published - 15 Oct 2022

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@article{fb741aae84b741c08a49b8a695a26665,

title = "Erectile dysfunction, phosphodiesterase-5 inhibitor use and risk of cardiovascular disease and mortality in people with diabetes: A systematic review and meta-analysis",

abstract = "Background Phosphodiesterase-5 inhibitors (PDE5-Is), used in the management of erectile dysfunction (ED), have potential cardioprotective benefits. The impact of PDE5-Is on reducing adverse cardiovascular outcomes in patients with diabetes mellitus (DM) and ED is uncertain. Using a systematic review and meta-analysis of observational cohort studies and randomised controlled trials (RCTs), we evaluated if (i) the association of PDE5-Is in people with ED and DM and their risk of cardiovascular disease (CVD) and mortality and (ii) ED confers an excess risk of CVD and mortality in patients with DM compared with no DM. Methods Studies were identified from MEDLINE, Embase, the Cochrane Library, Web of Science citation search and search of bibliographies to April 2022. Study-specific risk ratios (RRs) with 95\% confidence intervals (CIs) were pooled. Results Eighteen unique studies reported on the cardiovascular impact of ED in patients with and without DM. In the general population, the RRs (95\% CIs) of ED for composite CVD/MACE, all-cause mortality, CHD and stroke were 1.43 (1.31–1.55), 1.47 (1.31–1.65), 1.59 (1.39–1.82), and 1.34 (1.15–1.56), respectively. The respective estimates were 1.68 (1.15–2.45), 1.40 (0.90–2.18), 1.41 (1.24–1.61) and 1.32 (1.09–1.60) in the diabetes population. Interaction analyses suggested similar risk in both populations. Six studies reported the cardiovascular effects of PDE5-Is in people with ED and DM. Limited RCT data showed no significant differences in the risk of major adverse cardiac event (MACE), coronary heart disease (CHD) and all-cause mortality comparing PDE5-I use with non-use: RRs (95\% CIs) of 3.47 (0.17–69.19), 1.31 (0.10–16.54) and 0.35 (0.12–1.05), respectively. Conclusions ED confers no excess risk of CVD and mortality in patients with DM compared with no DM. Limited and inadequately powered data shows no significant differences in the risk of adverse cardiovascular outcomes comparing use of PDE5-Is with non-use in patients with ED and DM. ",

author = "Samuel Seidu and Ana Cebri{\'a}n and Kunutsor, \{Setor K\} and Kamlesh Khunti",

year = "2022",

month = oct,

day = "15",

doi = "10.1016/j.pcd.2022.09.004",

language = "English",

volume = "16",

pages = "601--613",

journal = "Primary Care Diabetes",

issn = "1751-9918",

publisher = "Elsevier Limited",

number = "5",

}

Erectile dysfunction, phosphodiesterase-5 inhibitor use and risk of cardiovascular disease and mortality in people with diabetes: A systematic review and meta-analysis. / Seidu, Samuel; Cebrián, Ana; Kunutsor, Setor K et al.
In: Primary Care Diabetes, Vol. 16, No. 5, 15.10.2022, p. 601-613.

Research output: Contribution to journal › Article (Academic Journal) › peer-review

TY - JOUR

T1 - Erectile dysfunction, phosphodiesterase-5 inhibitor use and risk of cardiovascular disease and mortality in people with diabetes

T2 - A systematic review and meta-analysis

AU - Seidu, Samuel

AU - Cebrián, Ana

AU - Kunutsor, Setor K

AU - Khunti, Kamlesh

PY - 2022/10/15

Y1 - 2022/10/15

N2 - Background Phosphodiesterase-5 inhibitors (PDE5-Is), used in the management of erectile dysfunction (ED), have potential cardioprotective benefits. The impact of PDE5-Is on reducing adverse cardiovascular outcomes in patients with diabetes mellitus (DM) and ED is uncertain. Using a systematic review and meta-analysis of observational cohort studies and randomised controlled trials (RCTs), we evaluated if (i) the association of PDE5-Is in people with ED and DM and their risk of cardiovascular disease (CVD) and mortality and (ii) ED confers an excess risk of CVD and mortality in patients with DM compared with no DM. Methods Studies were identified from MEDLINE, Embase, the Cochrane Library, Web of Science citation search and search of bibliographies to April 2022. Study-specific risk ratios (RRs) with 95% confidence intervals (CIs) were pooled. Results Eighteen unique studies reported on the cardiovascular impact of ED in patients with and without DM. In the general population, the RRs (95% CIs) of ED for composite CVD/MACE, all-cause mortality, CHD and stroke were 1.43 (1.31–1.55), 1.47 (1.31–1.65), 1.59 (1.39–1.82), and 1.34 (1.15–1.56), respectively. The respective estimates were 1.68 (1.15–2.45), 1.40 (0.90–2.18), 1.41 (1.24–1.61) and 1.32 (1.09–1.60) in the diabetes population. Interaction analyses suggested similar risk in both populations. Six studies reported the cardiovascular effects of PDE5-Is in people with ED and DM. Limited RCT data showed no significant differences in the risk of major adverse cardiac event (MACE), coronary heart disease (CHD) and all-cause mortality comparing PDE5-I use with non-use: RRs (95% CIs) of 3.47 (0.17–69.19), 1.31 (0.10–16.54) and 0.35 (0.12–1.05), respectively. Conclusions ED confers no excess risk of CVD and mortality in patients with DM compared with no DM. Limited and inadequately powered data shows no significant differences in the risk of adverse cardiovascular outcomes comparing use of PDE5-Is with non-use in patients with ED and DM.

AB - Background Phosphodiesterase-5 inhibitors (PDE5-Is), used in the management of erectile dysfunction (ED), have potential cardioprotective benefits. The impact of PDE5-Is on reducing adverse cardiovascular outcomes in patients with diabetes mellitus (DM) and ED is uncertain. Using a systematic review and meta-analysis of observational cohort studies and randomised controlled trials (RCTs), we evaluated if (i) the association of PDE5-Is in people with ED and DM and their risk of cardiovascular disease (CVD) and mortality and (ii) ED confers an excess risk of CVD and mortality in patients with DM compared with no DM. Methods Studies were identified from MEDLINE, Embase, the Cochrane Library, Web of Science citation search and search of bibliographies to April 2022. Study-specific risk ratios (RRs) with 95% confidence intervals (CIs) were pooled. Results Eighteen unique studies reported on the cardiovascular impact of ED in patients with and without DM. In the general population, the RRs (95% CIs) of ED for composite CVD/MACE, all-cause mortality, CHD and stroke were 1.43 (1.31–1.55), 1.47 (1.31–1.65), 1.59 (1.39–1.82), and 1.34 (1.15–1.56), respectively. The respective estimates were 1.68 (1.15–2.45), 1.40 (0.90–2.18), 1.41 (1.24–1.61) and 1.32 (1.09–1.60) in the diabetes population. Interaction analyses suggested similar risk in both populations. Six studies reported the cardiovascular effects of PDE5-Is in people with ED and DM. Limited RCT data showed no significant differences in the risk of major adverse cardiac event (MACE), coronary heart disease (CHD) and all-cause mortality comparing PDE5-I use with non-use: RRs (95% CIs) of 3.47 (0.17–69.19), 1.31 (0.10–16.54) and 0.35 (0.12–1.05), respectively. Conclusions ED confers no excess risk of CVD and mortality in patients with DM compared with no DM. Limited and inadequately powered data shows no significant differences in the risk of adverse cardiovascular outcomes comparing use of PDE5-Is with non-use in patients with ED and DM.

U2 - 10.1016/j.pcd.2022.09.004

DO - 10.1016/j.pcd.2022.09.004

M3 - Article (Academic Journal)

C2 - 36114105

SN - 1751-9918

VL - 16

SP - 601

EP - 613

JO - Primary Care Diabetes

JF - Primary Care Diabetes

IS - 5

ER -

Erectile dysfunction, phosphodiesterase-5 inhibitor use and risk of cardiovascular disease and mortality in people with diabetes: A systematic review and meta-analysis

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