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Original article
Phosphodiesterase type-5 inhibitor use in type 2 diabetes is associated with a reduction in all-cause mortality
  1. Simon G Anderson1,2,
  2. David C Hutchings1,
  3. Mark Woodward2,3,
  4. Kazem Rahimi2,
  5. Martin K Rutter4,5,
  6. Mike Kirby6,
  7. Geoff Hackett7,
  8. Andrew W Trafford1,
  9. Adrian H Heald8,9
  1. 1Institute of Cardiovascular Sciences, University of Manchester, Manchester, UK
  2. 2The George Institute for Global Health, Oxford Martin School, University of Oxford, Oxford, UK
  3. 3The George Institute for Global Health, University of Sydney, Australia
  4. 4Manchester Diabetes Centre, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK
  5. 5Centre for Endocrinology and Diabetes, Institute of Human Development, University of Manchester, Manchester, UK
  6. 6The Centre for Research in Primary & Community Care, University of Hertfordshire, Hatfield, UK
  7. 7Department of Urology, Good Hope Hospital, Sutton Coldfield, UK
  8. 8School of Medicine, and Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK
  9. 9Leighton Hospital, Crewe, UK
  1. Correspondence to Dr Simon G Anderson, Institute of Cardiovascular Sciences, University of Manchester, 3.24 Core Technology Facility, 46 Grafton Street, Manchester M13 9NT, UK; simon.anderson{at}manchester.ac.uk

Abstract

Objective Experimental evidence has shown potential cardioprotective actions of phosphodiesterase type-5 inhibitors (PDE5is). We investigated whether PDE5i use in patients with type 2 diabetes, with high-attendant cardiovascular risk, was associated with altered mortality in a retrospective cohort study.

Research design and methods Between January 2007 and May 2015, 5956 men aged 40–89 years diagnosed with type 2 diabetes before 2007 were identified from anonymised electronic health records of 42 general practices in Cheshire, UK, and were followed for 7.5 years. HRs from multivariable survival (accelerated failure time, Weibull) models were used to describe the association between on-demand PDE5i use and all-cause mortality.

Results Compared with non-users, men who are prescribed PDE5is (n=1359) experienced lower percentage of deaths during follow-up (19.1% vs 23.8%) and lower risk of all-cause mortality (unadjusted HR=0.69 (95% CI: 0.64 to 0.79); p<0.001)). The reduction in risk of mortality (HR=0.54 (0.36 to 0.80); p=0.002) remained after adjusting for age, estimated glomerular filtration rate, smoking status, prior cerebrovascular accident (CVA) hypertension, prior myocardial infarction (MI), systolic blood pressure, use of statin, metformin, aspirin and β-blocker medication. PDE5i users had lower rates of incident MI (incidence rate ratio (0.62 (0.49 to 0.80), p<0.0001) with lower mortality (25.7% vs 40.1% deaths; age-adjusted HR=0.60 (0.54 to 0.69); p=0.001) compared with non-users within this subgroup.

Conclusion In a population of men with type 2 diabetes, use of PDE5is was associated with lower risk of overall mortality and mortality in those with a history of acute MI.

This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/

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Footnotes

  • SGA and DCH contributed equally to this study.

  • Correction notice Since this paper was first published online two updates have been made. In the abstract methods section the follow up period has been updated to 7.5 years. In the paragraph entitled ‘All-cause mortality’ the follow up period has also been updated to 7.5 years.

  • Contributors SGA and AHH had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: SGA, DCH and AHH. Acquisition of data; AHH. Analysis and interpretation of data: All authors. Drafting of manuscript: SGA, DCH and AHH. Critical revision of the manuscript for important intellectual content: All authors. Statistical analysis: SGA. Advisor on statistical analysis: MW. Study guarantors: SGA and AHH.

  • Funding SGA is an Academic Clinical Lecturer in Cardiology and is funded by the National Institute of Health Research (NIHR). DCH is a British Heart Foundation Clinical Research Training Fellow (FS/15/28/31476). AWT is a British Heart Foundation Senior Research Fellow (FS/12/57/29717). MW is supported by a Principal Research Fellowship from the Australian Health and Medical Research Council and is a consultant for Amgen and Novartis. KR is supported by the NIHR Oxford Biomedical Research Centre and an NIHR Career Development Fellowship. The work of George Institute is supported by the Oxford Martin School.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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