Erectile dysfunction, cardiovascular disease and PDE5 inhibitors

Kloner RA, Burnett AL, Miner M, et al. Princeton IV consensus guidelines: PDE5 inhibitors and cardiac health. J Sex Med. Published online December 26, 2023. https://doi.org/10.1093/jsxmed/qdad163
 

Sildenafil and other phosphodiesterase 5 (PDE5) inhibitors are inextricably linked to cardiovascular disease. The serendipitous discovery that sildenafil (at the time a candidate for angina management) facilitates penile erection not only revolutionised the management of male sexual dysfunction, it also helped to focus attention on erectile dysfunction (ED) as a symptom and risk marker of cardiovascular disease.

Shortly after sildenafil became available in the late 1990s, concerns were raised about the safety of the drug (or, rather, the consequent increased sexual activity) in men with and without known pre-existing cardiovascular disease. The first Princeton consensus conference was convened in 1999 to examine available data at the time and develop guidelines for the management of sexual dysfunction in men with cardiovascular disease.

The recent Princeton IV consensus guidelines include updates to ED assessment and treatment algorithms based on recent evidence, and include discussion of emerging issues and evidence related to PDE5 inhibitors, erectile dysfunction and cardiovascular disease. Here’s what health practitioners need to know.

PDE5 inhibitors and nitrates

PDE5 inhibitors are contraindicated in people who use nitrates because of synergistic effects on blood pressure and the risk of serious hypotension. However, available evidence from the USA, Denmark and Sweden shows that co-prescription of nitrates and PDE5 inhibitors does occur and appears to be increasing. An increase in adverse cardiovascular events has not been observed in the US and Denmark, but evidence from the Swedish study (published after the Princeton IV consensus guidelines) shows increased risk of death (from cardiovascular and non-cardiovascular causes) and other adverse cardiac outcomes for men prescribed nitrates and PDE5 inhibitors. The Princeton IV guidelines suggest a well-designed randomised trial is needed to understand the effects of co-prescription before making changes to clinical practice.

Potential cardiovascular benefits of PDE5 inhibitors

The Princeton IV consensus guidelines highlight multiple studies that show benefit of PDE5 inhibitors for prevention of adverse cardiovascular events and mortality in men with type 2 diabetes, coronary artery disease, previous myocardial infarction, lower urinary tract symptoms and rheumatoid arthritis. To date, the protective effect of PDE5 inhibitors has been observed in only retrospective studies without the ability to prove causation. However, the Princeton IV consensus guidelines state that “PDE5 inhibitors may have cardioprotective effects and might play a role in preventative cardiology in the future”.

Emerging therapies for erectile dysfunction

So-called ‘regenerative therapies’– including stem cells, platelet-rich plasma and shock wave therapy – are beginning to be offered for treatment of erectile dysfunction but the Princeton IV consensus is that their safety and efficacy remain to be established. This is consistent with guidelines published by the Urological Society of Australia and New Zealand, the Australian Chapter of Sexual Health Medicine for the Royal Australian College of Physicians.

This brief summary contains only the parts of the Princeton IV conference guidelines that relate to PDE5 inhibitor use and cardiovascular disease in men. The full article includes discussion about rare adverse events, regulatory issues, second-line treatments for erectile dysfunction and the use of PDE5 inhibitors in females, and is available to read and download here.