Skip to main content
Log in

Does Sildenafil Cause Myocardial Infarction or Sudden Cardiac Death?

  • Current Opinion
  • Published:
American Journal of Cardiovascular Drugs Aims and scope Submit manuscript

Abstract

Sildenafil was the first oral compound to be approved for the treatment of erectile dysfunction. In this paper, we review the current knowledge of the effects of sildenafil on myocardial infarction and sudden cardiac death. The first factor we examine is the sexual activity itself. As several studies have shown, the relative risk for an acute coronary syndrome during intercourse is not very high. Several studies examining the effects of sildenafil on mortality have been published during recent years. The great majority of these studies found that sildenafil is not an extra risk factor for an acute coronary syndrome or sudden cardiac death. In 1997, the rate of myocardial infarction in men 55–64 years of age was 1542 per 1 000 000 in the US. According to this, the expected number of deaths as a result of myocardial infarction in patients 55–64 years of age receiving sildenafil, in the 24-hour period after use, from late March 1997 to mid November 1998, should have been 52. Instead, the number of reported deaths were only 15. One very optimistic finding was that sildenafil not only does not increase mortality, but in fact ‘preconditions’ the heart and has a cardioprotective effect. Besides, many studies have shown that sildenafil does not reduce the exercise tolerance in men with known coronary artery disease. As far as BP is concerned, the differences before and after the use of sildenafil are not clinically significant. The only contraindications for sildenafil are co-administration with α-adrenoceptor antagonists or with nitric oxide donors. According to the most recent studies, isoform 5 of phosphodiesterase has also been detected in the myocardium and controls the soluble pool of 3′, 5′-cyclic guanosine monophosphate (cGMP). Sildenafil is very specific for cGMP but it may increase cyclic adenosine monophosphate in the myocardium indirectly. This does not occur with small therapeutic doses of the drug. There is some dispute regarding the association of sildenafil with arrhythmias, where the available evidence is not clear. However, there are suspicions that sildenafil may cause sympathetic activation. The overall conclusion is that sildenafil is a safe drug and that its appropriate use does not seem to increase the risk for myocardial infarction or sudden cardiac death.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Naylor AM. Endogenous neurotransmitters mediated penile erection. Br J Urol 1998; 81: 424–31.

    Article  PubMed  CAS  Google Scholar 

  2. Wallis RM, Corbin JD, Francis SH, et al. Tissue distribution of phosphodiesterase families and the effects of sildenafil on tissue cyclic nucleotides, platelet function, and the contractile responses of trabeculae carneae and aortic rings in vitro. Am J Cardiol 1999; 83(5A): 29C–34C.

    Google Scholar 

  3. Wilkens H, Guth A, König G, et al. Effect of inhaled iloprost plus oral sildenafil in patients with primary pulmonary hypertension. Circulation 2001; 104(11): 1218–22.

    Article  PubMed  CAS  Google Scholar 

  4. Porter A, Mager A, Birnbaum Y, et al. Acute myocardial infarction following sildenafil citrate (Viagra) intake in a nitrate-free patient. Clin Cardiol 1999; 22(11): 762–3.

    Article  PubMed  CAS  Google Scholar 

  5. Kekilli M, Beyazit Y, Purnak T, et al. Acute myocardial infarction after sildenafil citrate ingestion. Ann Pharmacother 2005; 39(7–8): 1362–4.

    Article  PubMed  Google Scholar 

  6. Mittleman MA, Siscovick DS. Physical exertion as a trigger of myocardial infarction and sudden cardiac death. Cardiol Clin 1996; 14: 263–70.

    Article  PubMed  CAS  Google Scholar 

  7. Muller JE, Mittleman MA, Maclure M, et al. Triggering myocardial infarction by sexual activity: low absolute risk and prevention by regular exertion. JAMA 1996; 275: 1405–9.

    Article  PubMed  CAS  Google Scholar 

  8. Kloner RA, Zusman RM. Cardiovascular effects of sildenafil citrate and recommendations for its use. Am J Cardiol 1999; 84: 11N–7N.

    Article  PubMed  CAS  Google Scholar 

  9. Ebrahim S, May M, Ben Shlomo Y, et al. Sexual intercourse and risk of ischaemic stroke and coronary heart disease: the Caerphilly study. J Epidimiol Community Health 2002; 56(2): 99–102.

    Article  CAS  Google Scholar 

  10. Drory Y, Shapira I, Fisman EZ, et al. Myocardial ischemia during sexual activity in patients with coronary disease. Am J Cardiol 1995; 75(12): 835–7.

    Article  PubMed  CAS  Google Scholar 

  11. Feldman HA, Goldstein I, Hatzichristou DG, et al. Impotence and its medical and psychosocial correlates: results of the Massachusetts male aging study. J Urol 1994; 151: 54–61.

    PubMed  CAS  Google Scholar 

  12. Cooke JP. Does ADMA cause endothelial dysfunction? Arterioscler Thromb Vasc Biol 2000; 20: 2032–7.

    Article  PubMed  CAS  Google Scholar 

  13. Billups KL. Erectile dysfunction as an early sign of cardiovascular disease. Int J Inpot Res 2005: 17 Suppl. 1: S19–24.

    Article  Google Scholar 

  14. Shakir SA, Wilton LV, Boshier A, et al. Cardiovascular events in users of sildenafil: results from the first phase of prescription event monitoring in England. BMJ 2001; 322(7287): 651–2.

    Article  PubMed  CAS  Google Scholar 

  15. Wysowski DK, Farinas E, Swartz L. Comparison of reported and expected deaths in sildenafil (Viagra) users. Am J Cardiol 2002; 89(11): 1331–4.

    Article  PubMed  CAS  Google Scholar 

  16. Mittleman MA, Maclure M, Glasser DB. Evaluation of acute risk of myocardial infarction in men treated with sildenafil citrate. Am J Cardiol 2005; 96(3): 443–6.

    Article  PubMed  CAS  Google Scholar 

  17. Mittleman MA, Glasser DB, Orazem J. Clinical trials of sildenafil citrate (Viagra) demonstrate no increase in risk of myocardial infarction and cardiovascular death compared with placebo. Int J Pract 2003; 57(7): 597–600.

    CAS  Google Scholar 

  18. Ishikura F, Beppu S, Hamada T, et al. Effects of sildenafil citrate (Viagra) combined with nitrate on heart. Circulation 2000; 14: 2516–21.

    Article  Google Scholar 

  19. Castro LR, Verde I, Cooper DM, et al. Cyclic guanosine monophosphate compartmentation in rat cardiac myocytes. Circulation 2006; 113(18): 2221–8.

    Article  PubMed  CAS  Google Scholar 

  20. Takimoto E, Champion HC, Belardi D, et al. cGMP catabolism by phosphodiesterase 5A regulates cardiac adrenergic stimulation by NOS3-dependent mechanism. Circ Res 2005; 96(1): 100–9.

    Article  PubMed  CAS  Google Scholar 

  21. Senzaki H, Smith C, Juang G, et al. Cardiac phosphodiesterase 5 (cGMP-specific) modulates beta-adrenergic signaling in vivo and is down-regulated in heart failure. FASEB J 2001; 15: 1718–26.

    Article  PubMed  CAS  Google Scholar 

  22. Ballard SA, Gingell CJ, Tang K, et al. Effect of sildenafil on the relaxation of human corpus cavernosum tissue in vitro and on the activities of cyclic nucleotide phosphodiesterase isozymes. J Urol 1998; 159(6): 2164–71.

    Article  PubMed  CAS  Google Scholar 

  23. Sildenafil [prescribing information]. New York: Pfizer, 2004.

  24. Stief CJ, Uckert S, Becker AJ, et al. Effects of sildenafil on cAMP and cGMP in isolated human cavernous and cardiac tissue. Urology 2000; 55: 146–50.

    Article  PubMed  CAS  Google Scholar 

  25. du Toit EF, Rossouw E, Salie R, et al. Effect of sildenafil on reperfusion function, infarct size, and cyclic nucleotide levels in the isolated rat heart model. Cardiovasc Drugs Ther 2005; 19(1): 23–31.

    Article  PubMed  Google Scholar 

  26. Ochaili R, Salloum F, Hawkins J, et al. Sildenafil (Viagra) induces powerful cardioprotective effect via opening of mitochondrial K(ATP) channels in rabbits. Am J Physiol Heart Circ Physiol 2002; 283(3): H1263–9.

    Google Scholar 

  27. Salloum F, Yin C, Xi L, et al. Sildenafil induces delayed preconditioning through inducible nitric oxide synthase-dependent pathway in mouse heart. Circ Res 2003; 92(6): 595–7.

    Article  PubMed  CAS  Google Scholar 

  28. Phillips BG, Kato M, Pesek CA, et al. Sympathetic activation by sildenafil. Circulation 2000; 102(25): 3068–73.

    Article  PubMed  CAS  Google Scholar 

  29. Jackson G, Benjamin N, Jackson N, et al. Effects of sildenafil citrate on human hemodynamics. Am J Cardiol 1999; 83(5A): 13C–20C.

    Article  PubMed  CAS  Google Scholar 

  30. Herrmann HC, Chang G, Klugherz BD, et al. Hemodynamic effects of sildenafil in men with severe coronary artery disease. N Engl J Med 2000; 343(13): 967–8.

    Article  Google Scholar 

  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; 83(5A): 21C–8C.

    Article  PubMed  CAS  Google Scholar 

  32. Kloner RA, Zusman RM. Cardiovascular effects of sildenafil citrate and recommendations for its use. Am J Cardiol 1999; 84: 11N–7N.

    Article  PubMed  CAS  Google Scholar 

  33. Webb DJ, Muirhead GJ. Wulff 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(1): 25–31.

    Article  PubMed  CAS  Google Scholar 

  34. Kloner RA. Cardiovascular effects of the 3 phosphodiesterase-5 inhibitors approved for the treatment of erectile dysfunction. Circulation 2004; 110: 3149–55.

    Article  PubMed  Google Scholar 

  35. Fox KM, Thadani U, Ma PT, et al. Sildenafil citrate does not reduce exercise tolerance in men with erectile dysfunction and chronic stable angina. Eur Heart J 2003; 24: 2206–12.

    Article  PubMed  CAS  Google Scholar 

  36. Arruda-Olson AM, Mahoney DW, Nehra A, et al. Cardiovascular effects of sildenafil during exercise in men with known or probable coronary artery disease: a randomized crossover trial. JAMA 2002; 287(6): 719–25.

    Article  PubMed  CAS  Google Scholar 

  37. Traverse JH, Chen YJ, Du R, et al. Cyclic nucleotide phosphodiesterase type 5 activity limits blood flow to hypoperfused myocardium during exercise. Circulation 2000; 102(24): 2997–3002.

    Article  PubMed  CAS  Google Scholar 

  38. Geelen P, Drolet B, Rail J, et al. Sildenafil (Viagra) prolongs cardiac repolarization by blocking the rapid component of the delayed rectifier potassium current. Circulation 2000; 102(3): 275–7.

    Article  PubMed  CAS  Google Scholar 

  39. Nagy O, Hajnal A, Parratt JR, et al. Sildenafil (Viagra) reduces arrhythmia severity during ischaemia 24h after oral administration in dogs. J Cardiovasc Pharmacol 2003: 41(5): 734–43.

    Article  Google Scholar 

  40. Reffelmann T, Kloner RA. Effects of sildenafil on myocardial infarct size, microvascular function, and acute ischemic left ventricular dilation. Cardiovasc Res 2003; 59(2): 441–9.

    Article  PubMed  CAS  Google Scholar 

  41. Swissa M, Ohara T, Lee MH, et al. Sildenafil-nitric oxide donor combination promotes ventricular tachyarrhythmias in the swine right ventricle. Am J Physiol Heart Circ Physiol 2002; 282(5): H1787–92.

    PubMed  CAS  Google Scholar 

  42. Cremers B, Scheler M, Maack C, et al. Effects of sildenafil (Viagra) on human myocardial contractility, in vitro arrhythmias, and tension of internal mammaria arteries and saphenous veins. J Cardiovasc Pharmacol 2003; 41(5): 734–43.

    Article  PubMed  CAS  Google Scholar 

  43. Pomara G, Morelli G, Pomara S, et al. Cardiovascular parameter changes in patients with erectile dysfunction using PDE-5 inhibitors: a study with sildenafil and vardenafil. J Androl 2004; 25(4): 625–9.

    PubMed  CAS  Google Scholar 

  44. Kloner RA, Mitchell M, Emmick JT. Cardiovascular effects of tadalafil. Am J Cardiol 2003; 92(9A): 37M–46M.

    Article  PubMed  CAS  Google Scholar 

  45. Product monograph for levitra (vardenafil HCL). Bayer Health Care, Glaxo SmithKline, 2003.

  46. Kloner RA, Hutter AM, Emmick JT, et al. Time course of the interaction between tadalafil and nitrates. J Am Coll Cardiol 2003; 42(10): 1855–60.

    Article  PubMed  CAS  Google Scholar 

  47. Giuliano F, Kaplan SA, Cabanis MJ, et al. Hemodynamic interaction study between the alpha 1-blocker alfuzosin and the phosphodiesterase-5 inhibitor tadalafil in middle-aged healthy male subjects. Urology 2006; 67(6): 1199–204.

    Article  PubMed  Google Scholar 

  48. Kloner RA, Jackson G, Emmick JT, et al. Interaction between the phosphodiesterase 5 inhibitor, tadalafil and 2 alpha-blockers, doxazosin and tamsulosin in healthy normotensive men. J Urol 2004; 172 (5 Pt 1): 1935–40.

    Article  PubMed  Google Scholar 

  49. Auerbach SM, Gittelman M, Mazzu A, et al. Simultaneous administration of vardenafil and tamsulosin does not induce clinically significant hypotension in patients with benign prostatic hyperplasia. Urology 2004; 64(5): 998–1003.

    Article  PubMed  Google Scholar 

  50. Beasley Jr CM, Mitchell MI, Dmitrienko AA, et al. The combined use of ibutilide as an active control with intensive electrocardiographic sampling and signal averaging as a sensitive method to assess the effects of tadalafil on the human QT interval. J Am Coll Cardiol 2005; 46(4): 678–87.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

No sources of funding were used in the preparation of this review. The authors have no conflicts of interest that are directly relevant to the content of this review.

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kontaras, K., Varnavas, V. & Kyriakides, Z.S. Does Sildenafil Cause Myocardial Infarction or Sudden Cardiac Death?. Am J Cardiovasc Drugs 8, 1–7 (2008). https://doi.org/10.2165/00129784-200808010-00001

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00129784-200808010-00001

Keywords

Navigation