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      Phosphodiesterase type-5 inhibitor use in type 2 diabetes is associated with a reduction in all-cause mortality

      Heart
      BMJ Publishing Group

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          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.

          Supplementary appendix
          10.1136/heartjnl-2015-309223.supp1

          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.

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          Most cited references41

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          Impotence and its medical and psychosocial correlates: results of the Massachusetts Male Aging Study.

          We provide current, normative data on the prevalence of impotence, and its physiological and psychosocial correlates in a general population using results from the Massachusetts Male Aging Study. The Massachusetts Male Aging Study was a community based, random sample observational survey of noninstitutionalized men 40 to 70 years old conducted from 1987 to 1989 in cities and towns near Boston, Massachusetts. Blood samples, physiological measures, socio-demographic variables, psychological indexes, and information on health status, medications, smoking and lifestyle were collected by trained interviewers in the subject's home. A self-administered sexual activity questionnaire was used to characterize erectile potency. The combined prevalence of minimal, moderate and complete impotence was 52%. The prevalence of complete impotence tripled from 5 to 15% between subject ages 40 and 70 years. Subject age was the variable most strongly associated with impotence. After adjustment for age, a higher probability of impotence was directly correlated with heart disease, hypertension, diabetes, associated medications, and indexes of anger and depression, and inversely correlated with serum dehydroepiandrosterone, high density lipoprotein cholesterol and an index of dominant personality. Cigarette smoking was associated with a greater probability of complete impotence in men with heart disease and hypertension. We conclude that impotence is a major health concern in light of the high prevalence, is strongly associated with age, has multiple determinants, including some risk factors for vascular disease, and may be due partly to modifiable para-aging phenomena.
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            Survival bias associated with time-to-treatment initiation in drug effectiveness evaluation: a comparison of methods.

            The authors compared five methods of studying survival bias associated with time-to-treatment initiation in a drug effectiveness study using medical administrative databases (1996-2002) from Quebec, Canada. The first two methods illustrated how survival bias could be introduced. Three additional methods were considered to control for this bias. Methods were compared in the context of evaluating statins for secondary prevention in elderly patients post-acute myocardial infarction who initiated statins within 90 days after discharge and those who did not. Method 1 that classified patients into users and nonusers at discharge resulted in an overestimation of the benefit (38% relative risk reduction at 1 year). In method 2, following users from the time of the first prescription and nonusers from a randomly selected time between 0 and 90 days attenuated the effect toward the null (10% relative risk reduction). Method 3 controlled for survival bias by following patients from the end of the 90-day time window; however, it suffered a major loss of statistical efficiency and precision. Method 4 matched prescription time distribution between users and nonusers at cohort entry. Method 5 used a time-dependent variable for treatment initiation. Methods 4 and 5 better controlled for survival bias and yielded similar results, suggesting a 20% risk reduction of recurrent myocardial infarction or death events.
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              The Princeton III Consensus recommendations for the management of erectile dysfunction and cardiovascular disease.

              The Princeton Consensus (Expert Panel) Conference is a multispecialty collaborative tradition dedicated to optimizing sexual function and preserving cardiovascular health. The third Princeton Consensus met November 8 to 10, 2010, and had 2 primary objectives. The first objective focused on the evaluation and management of cardiovascular risk in men with erectile dysfunction (ED) and no known cardiovascular disease (CVD), with particular emphasis on identification of men with ED who may require additional cardiologic work-up. The second objective focused on reevaluation and modification of previous recommendations for evaluation of cardiac risk associated with sexual activity in men with known CVD. The Panel's recommendations build on those developed during the first and second Princeton Consensus Conferences, first emphasizing the use of exercise ability and stress testing to ensure that each man's cardiovascular health is consistent with the physical demands of sexual activity before prescribing treatment for ED, and second highlighting the link between ED and CVD, which may be asymptomatic and may benefit from cardiovascular risk reduction. Copyright © 2012 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.
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                Author and article information

                Journal
                Heart
                Heart
                heartjnl
                heart
                Heart
                BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )
                1355-6037
                1468-201X
                1 November 2016
                01 August 2016
                : 102
                : 21
                : 1750-1756
                Affiliations
                [1 ]Institute of Cardiovascular Sciences, University of Manchester , Manchester, UK
                [2 ]The George Institute for Global Health, Oxford Martin School, University of Oxford , Oxford, UK
                [3 ]The George Institute for Global Health, University of Sydney , Australia
                [4 ]Manchester Diabetes Centre, Central Manchester University Hospitals NHS Foundation Trust , Manchester, UK
                [5 ]Centre for Endocrinology and Diabetes, Institute of Human Development, University of Manchester , Manchester, UK
                [6 ]The Centre for Research in Primary & Community Care, University of Hertfordshire , Hatfield, UK
                [7 ]Department of Urology, Good Hope Hospital , Sutton Coldfield, UK
                [8 ]School of Medicine, and Manchester Academic Health Sciences Centre, University of Manchester , Manchester, UK
                [9 ]Leighton Hospital , Crewe, UK
                Author notes
                [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@ 123456manchester.ac.uk

                SGA and DCH contributed equally to this study.

                Article
                heartjnl-2015-309223
                10.1136/heartjnl-2015-309223
                5099221
                27465053
                656fccf7-da06-4fb6-8e89-16c073a6c88e
                Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

                This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

                History
                : 22 December 2015
                : 20 April 2016
                : 23 May 2016
                Categories
                1506
                Cardiac Risk Factors and Prevention
                Original article
                Custom metadata
                unlocked

                Cardiovascular Medicine
                Cardiovascular Medicine

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