Drug Safety

, Volume 26, Issue 7, pp 453–460 | Cite as

Cardiovascular Safety of Sildenafil

Review Article

Abstract

Initial reports of myocardial infarction and sudden death in men with erectile dysfunction who had taken sildenafil (sometimes in conjunction with nitrates) raised concerns that sildenafil may increase the risk of cardiovascular events in men with erectile dysfunction and vascular disease. A significant body of evidence now indicates that sildenafil generally has a good safety profile in men with erectile dysfunction and cardiovascular disease.

Sildenafil therapy does not appear to be associated with ischaemic events either at the time of introduction of therapy or during longer-term use. Rates of discontinuation from sildenafil therapy due to adverse events are similar to placebo in men with cardiovascular disease. Sildenafil does not interact in a potentially hazardous way with antihypertensive or antianginal therapy, with the exception of nitrates. Nitrates should not be administered within 24 hours of sildenafil therapy, and care should be taken to determine whether sildenafil may have been used before nitrates are administered to patients.

Sildenafil appears to be generally well tolerated in most patients with chronic, stable cardiovascular disease.

Notes

Acknowledgements

No funding or support was provided for this review. Professor Howes has participated in several advisory boards for Pfizer products, none of which involved sildenafil. Dr Tran participates in numerous advisory boards for a number of pharmaceutical companies, all of which pay a small honoraria.

References

  1. 1.
    Feldman HA, Goldstein I, Hatzichrisou DG, et al. Impotence and its medical and psychosocial correlates: results of the Massachusetts Male Aging Study. J Urol 1994; 151: 54–61PubMedGoogle Scholar
  2. 2.
    Olsson AM, Speakman MJ, Dinsmore WW, et al. Sildenafil citrate (Viagra) is effective and well-tolerated for treating erectile dysfunction of psychogenic or mixed aetiology. Int J Clin Pract 2000; 59(9): 561–6Google Scholar
  3. 3.
    Sadovsky R, Miller T, Moskowitz M, et al. Three-year update of sildenafil citrate (VIAGRA®) efficacy and safety: review. Int J Clin Pract 2001; 55(2): 115–28PubMedGoogle Scholar
  4. 4.
    Boyace EG, Umland EM. Sildenafil citrate: a therapeutic update. Clin Ther 2001; 23(1): 2–23CrossRefGoogle Scholar
  5. 5.
    Conti RC, Pepine CJ, Sweeney M. Efficacy and safety of sildenafil citrate in the treatment of erectile dysfunction in patients with ischaemic heart disease. Am J Cardiol 1999; 83: 29C–34CPubMedCrossRefGoogle Scholar
  6. 6.
    Zusman RM, Prisant LM, Brown MJ, et al. Effect of sildenafil citrate on blood pressure and heart rate in men with erectile dysfunction taking concomitant antihypertensive medication. J Hypertens 2001; 18(12): 1865–9CrossRefGoogle Scholar
  7. 7.
    Kloner RA, Brown M, Prisant ML, et al. Effect of sildenafil in patients with erectile dysfunction taking antihypertensive therapy. Am J Hypertens 2001; 14(1): 70–3PubMedCrossRefGoogle Scholar
  8. 8.
    Olsson AM, Persson CA. Efficacy and safety of Viagra (sildenafil citrate) in men with cardiovascular disease and erectile dysfunction [abstract]. J Am Coll Cardiol 2000; 35Suppl. A: 329Google Scholar
  9. 9.
    Rendell MS, Rajfer J, Wicker PA, et al. Sildenafil for treatment of erectile dysfunction in men with diabetes: a randomized controlled trial. JAMA 1999; 281: 421–6PubMedCrossRefGoogle Scholar
  10. 10.
    Price DE, Boolell M, Gepi-Atee S, et al. Sildenafil: study of a novel oral treatment for erectile dysfunction in diabetic men. Diabet Med 1998; 15: 821–5PubMedCrossRefGoogle Scholar
  11. 11.
    Hong EK, Lepor H, McCullough AR. Time dependent patient satisfaction with sildenafil for erectile dysfunction (ED) after nerve-sparing radical retropubic prostatectomy (RRP). Int J Impot Res 1999; 11Suppl. 1: S15–22PubMedCrossRefGoogle Scholar
  12. 12.
    Weber DC, Bieri S, Kurtz JM, et al. Prospective pilot study of sildenafil for treatment of post radiotherapy erectile dysfunction in patients with prostate cancer. J Clin Oncol 1999; 17: 3444–9PubMedGoogle Scholar
  13. 13.
    Zesiwicz TA, Helal M, Hauser RA. Sildenafil citrate (Viagra) for the treatment of erectile dysfunction in men with Parkinson’s disease. Mov Disord 2000; 15: 305–8CrossRefGoogle Scholar
  14. 14.
    Maytom MC, Derry FA, Dinsmore WW, et al. A two-part pilot study of sildenafil (Viagra) in men with erectile dysfunction caused by spinal cord injury. Spinal Cord 1999; 37: 110–6PubMedCrossRefGoogle Scholar
  15. 15.
    Morales A, Ginell C, Collins M, et al. Clinical safety of oral sildenafil citrate (Viagra™) in the treatment of erectile dysfunction. Int J Impot Res 1998; 10: 69–74PubMedCrossRefGoogle Scholar
  16. 16.
    Hermann HC, Chang G, Klugherz B, et al. Hemodynamic effects of sildenafil in men with severe coronary artery disease. N Engl J Med 2000; 342: 1622–6CrossRefGoogle Scholar
  17. 17.
    Cuellar D, Hamilton JP, Sklar GN. Sildenafil citrate in the transplant recipient with erectile dysfunction. J Urol 2000; 163Suppl. 4: 200Google Scholar
  18. 18.
    Kassim AA, Fabry ME, Nagel RL. Acute priapism associated with the use of sildenafil in a patient with sickle cell trait [letter]. Blood 2000; 95: 1878–9PubMedGoogle Scholar
  19. 19.
    Azarbal B, Mirocha J, Shah PK, et al. Adverse cardiovascular events associated with the use of VIAGRA [abstract]. J Am Coll Cardiol 2000; 35Suppl. A: 553AGoogle Scholar
  20. 20.
    Mittleman MA, Glasser DB, Orazem J, et al. Incidence of myocardial infarction and death in 53 clinical trials of Viagra (sildenafil citrate) [abstract]. J Am Coll Cardiol 2000; 35Suppl. A: 302Google Scholar
  21. 21.
    Shakir SAW, Wilton LV, Boshier A, et al. Cardiovascular events in users of sildenafil: results from first phase of prescription event monitoring in England. BMJ 2001; 322: 51–2CrossRefGoogle Scholar
  22. 22.
    Herrmann HC, Chang G, Klugherz B, et al. Haemodynamic effects of sildenafil in men with severe coronary artery disease. N Engl J Med 2000; 342: 1622–6PubMedCrossRefGoogle Scholar
  23. 23.
    Vardi Y, Bulus M, Reisner S, et al. Ergometric studies for evaluating sildenafil effect in cardiac patients. J Urol 2000; 163Suppl. 4: 200Google Scholar
  24. 24.
    Traverse JH, Du R, Chen YJ, et al. Sildenafil (Viagra) improves coronary blood flow distal to coronary stenosis during exercise[abstract 1000]. 72nd Scientific Sessions of the American Heart Association; 1999 Nov 7-10; Atlanta (GA)Google Scholar
  25. 25.
    Fox KM, Ma PTS, Nash SD, et al. Time to onset of limiting angina during treadmill exercise in men with erectile dysfunction and stable chronic angina: effect of sildenafil citrate [abstract 100019]. 74th Scientific Sessions of the American Heart Association; 2001 Nov 11-14; Anaheim (CA)Google Scholar
  26. 26.
    Patrizi R, Leonardo F, Pelliccia F, et al. Effect of sildenafil citrate upon myocardial ischaemia in patients with chronic stable angina in therapy with beta-blockers. Ital Heart J 2001; 2(11): 841–4PubMedGoogle Scholar
  27. 27.
    DeBusk RF. Evaluating the cardiovascular tolerance for sex. Am J Cardiol 2000; 86Suppl.: 51F–6FPubMedCrossRefGoogle Scholar
  28. 28.
    Boceli EA, Guimarcies G, Mocelin A, et al. Sildenafil effects on exercise, neurohumoral activation and erectile dysfunction in congestive heart failure: a double blind, placebo controlled, randomized study followed by a prospective treatment for erectile dysfunction. Am Heart J 2002; 106: 1097–103Google Scholar
  29. 29.
    Prisant LM, Carr AA, Bottini PB, et al. Sexual dysfunction with antihypertensive drugs. Arch Intern Med 1994; 154: 730–6PubMedCrossRefGoogle Scholar
  30. 30.
    Kloner RA. Cardiovascular risk and sildenafil. Am J Cardiol 2000; 86Suppl.: 57F–61FPubMedCrossRefGoogle Scholar
  31. 31.
    Webb DJ, Freestone S, Allen MJ, et al. Sildenafil citrate and blood pressure lowering drugs: results of drug interaction studies with an organic nitrate and a calcium antagonist. Am J Cardiol 1999; 83Suppl. 5A: 21C–8CPubMedCrossRefGoogle Scholar
  32. 32.
    Kloner RA, Brown M, Prisant LM, et al. Effect of sildenafil in patients with erectile dysfunction taking antihypertensive therapy. Am J Hypertens 2001; 14: 70–3PubMedCrossRefGoogle Scholar
  33. 33.
    Boyace EG, Umland EM. Sildenafil citrate: a therapeutic update. Clin Ther 2001; 23(1): 2–3CrossRefGoogle Scholar
  34. 34.
    Webb DJ, Muirhead GJ, Wulss M, et al. Sildenafil citrate potentiates the hypotensive effects of nitric oxide donor drugs in male patients with stable angina. J Am Coll Cardiol 2000; 36: 25–31PubMedCrossRefGoogle Scholar
  35. 35.
    Khoury V, Kritharides L. Diltiazem-mediated inhibition of sildenafil metabolism may promote nitrate-induced hypotension: case report. Aust N Z J Med 2000; 30: 641–62PubMedCrossRefGoogle Scholar
  36. 36.
    Dressa GK, Spence JD, Bailey DF. Pharmacokinetic pharmacodynamic consequences and clinical relevance of cytochronic P450 3A4 inhibition. Clin Pharmacokinet 2000; 38: 41–57CrossRefGoogle Scholar
  37. 37.
    Reed DB, Gough JE, Ho JD, et al. Prehospital consideration of sildenafil-nitrate interactions. Prehosp Emerg Care 1999; 3: 306–9PubMedCrossRefGoogle Scholar
  38. 38.
    DeBusk R, Drory Y, Goldstein I, et al. Management of sexual dysfunction in patients with cardiovascular disease: recommendations of the Princeton Consensus Panel. Am J Cardiol 2000; 86: 175–81PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2003

Authors and Affiliations

  1. 1.Department of Clinical Pharmacology, St George HospitalUniversity of New South WalesKogarahAustralia

Personalised recommendations