Princeton IV consensus guidelines: PDE5 inhibitors and cardiac health

[madman]

Been waiting on this one.

Damn, that is deep!



Abstract

Background

In 1999, 1 year after the approval of the first oral phosphodiesterase type 5 (PDE5) inhibitor for the treatment of erectile dysfunction(ED), the first Princeton Consensus Conference was held to address the clinical management of men with ED who also had cardiovascular disease. These issues were readdressed in the second and third conferences. In the 13 years since the last Princeton Consensus Conference, the experience with PDE5 inhibitors is more robust, and recent new data have emerged regarding not only safety and drug-drug interactions but also the potential cardioprotective effect of these drugs.


Aim

In March 2023, an interdisciplinary group of scientists and practitioners met for the fourth Princeton Consensus Guidelines at the HuntingtonMedical Research Institutes in Pasadena, California, to readdress the cardiovascular workup of men presenting with ED as well as the approach treatment of ED in men with known cardiovascular disease.


Method

A series of lectures from experts in the field followed by Delphi-type discussions were developed to reach consensus.


Outcomes

Consensus was reached regarding a number of issues related to erectile dysfunction and the interaction with cardiovascular health and phosphodiesterase-5 inhibitors.


Results

An algorithm based on recent recommendations of the American College of Cardiology and American Heart Association, including the use of computed tomography coronary artery calcium scoring, was integrated into the evaluation of men presenting with ED. Additionally, the issue of nitrate use was further considered in an algorithm regarding the treatment of ED patients with coronary artery disease. Other topics included the psychological effect of ED and the benefits of treating it; the mechanism of action of the PDE5 inhibitors; drug–drug interactions; optimizing the use of PDE5 inhibitors; rare adverse events; potential cardiovascular benefits observed in recent retrospective studies; adulteration of dietary supplements with PDE5 inhibitors; the pros and cons of over-the-counter PDE5 inhibitors; non–PDE5 inhibitor therapy for ED including restorative therapies such as stem cells, platelet-rich plasma, and shock therapy; other non–PDE5 inhibitor therapies, including injection therapy and penile prostheses; the issue of safety and effectiveness of PDE5 inhibitors in women; and recommendations for future studies in the field of sexual dysfunction and PDE5 inhibitor use were discussed.


Clinical Implications

Algorithms and tables were developed to help guide the clinician in dealing with the interaction of ED and cardiovascular risk and disease.


Strengths and Limitations

Strengths include the expertise of the participants and consensus recommendations. Limitations included that participants were from the United States only for this particular meeting.


Conclusion

The issue of the intersection between cardiovascular health and sexual health remains an important topic with new studies suggesting the cardiovascular safety of PDE5 inhibitors.




Epidemiology and pathophysiology revisited

*Sexual activity and cardiac risk: can he climb 2 flights of stairs?

*Erectile dysfunction and CVD: is ED a harbinger of future events?

*Psychogenic factors: how distressed is the man or his partner?




Clinical management of ED: updated guidelines

*CV risk management in men who present with ED without overt cardiac symptoms or disease

*Role of ED as a risk marker and risk-enhancing factor
-ED as a risk marker in younger vs older men.

*What testing should be considered?

*The role of CAC scoring as a risk factor.

*ED management in men with overt CV symptoms and/or CVD
-Sexual inquiry
-Exercise ability and sexual activity risk stratification

*ED treatment (low-risk patient) or referral to a cardiologist (high-risk patient)

*ED management in patients taking nitrate-containing medications or substances

*Drug-drug interactions and CV safety of PDE5inhibitors

*Optimizing therapy with PDE5 inhibitors

*Interactions of PDE5 inhibitors with nitrates and other CV drugs
-Safety concerns related to the interactions between PDE5inhibitors and nitrates
-Interactions between PDE5 inhibitors and sacubitril/valsartan
-Interactions between PDE5 inhibitors and riociguat
-Interactions between PDE5 inhibitors and α-1 receptor blockers
-Interactions between PDE5 inhibitors and antihypertensive therapies

*Rare adverse events associated with PDE5 inhibitors

*Visual disturbances
-Perception of blue color
-Nonarteritic anterior ischemic optic neuropathy
-Serous retinal detachment

*Ototoxicity

*Melanoma

*Prostate cancer recurrence

*Potential CV benefits and low rates of CV events in recent
retrospective/observational studies

*Regulatory and public health perspectives

*Marketing of dietary supplements with PDE5inhibitor components

*Should PDE5 inhibitors be available without a prescription? Is it time for the FDA to consider this change in status, and the implications for consumers and health practitioners?

*Risks of OTC availability of PDE5 inhibitors

*Therapies for ED beyond PDE5 inhibitors

*Restorative therapy for ED: stem cells, platelet-rich plasma, and shock waves
-Second-line therapy
-Intracavernosal injection therapy
-Intraurethral vasoactive agents
-Vacuum devices
-Penile implant surgery
-Topical therapy

*PDE5 inhibitors in women: treatment of FSDand other indications

*Diagnostic and treatment guidelines for FSD

*Efficacy of PDE5 inhibitors in women

*Safety of PDE5 inhibitors in women




Conclusion

A number of major themes emerged from P4 that are new and that expand the findings from P3. ED is a risk marker and risk enhancer for ASCVD, and men who present with ED, especially vasculogenic ED, should have an assessment of their atherosclerotic CV risk as outlined by the ACC/AHA algorithms. Those patients at the borderline to intermediate risk for CV events should undergo CAC scoring by computed tomography scanning. The CAC score will aid in determining therapy and the need to refer to a cardiologist, which is also a newer aspect of the guidelines since P3. In addition, even psychogenic ED may be a harbinger for CVD, and there should at least be an inquiry about CVD and its risk factors in men presenting with this type of ED.

 

[madman]

Table 1. ED as a harbinger for CVD: supportive epidemiologic findings.

 

[madman]

Table 2. Observational studies of ED and psychological distress: a bidirectional association.

 

[madman]

Table 3. CV workup and management

 

[madman]

Figure 1. CV risk assessment of ED patients with no overt disease or cardiac symptoms. Algorithm 1 is derived from previous key papers with modifications: Evaluation and management of cardiovascular risk in men with vasculogenic ED but no known CVD is recommended. This applies primarily to men 40 to 79 years of age. Symptomatic men are presumed to have CVD and are therefore at high risk for CVD events. A thorough CV history, physical examination (including BP history) and measures, smoking history, lipid history, and lipid measurements (total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol), diabetes history and measures (fasting plasma glucose, hemoglobin A1C, measures of visceral adiposity), assessment of ED severity and duration, serum creatinine (estimated glomerular filtration rate) and albumin/creatinine ratio, and presence or absence of the metabolic syndrome and obstructive sleep apnea may be used to further characterize cardiovascular risk. Thereafter, 10-yearACC/AHA ASCVD risk is calculated with therapeutic intervention based on score. The ACC/AHA risk score can be found online (ASCVD Risk Estimator +). Persons with complex or unclear clinical situations (eg, borderline results) may be referred to a urologist, cardiologist, or other subspecialists as indicated. Modified with permission from Miner et al,56 Shah et al,70 and Arnett et al.8

 

[madman]

Figure 2. ED management in men with overt CV symptoms and/or CVD. Algorithm 2. w/o=work up. The risk of cardiovascular events with sexual activity is stratified based on exercise ability for age and thereafter on the presence or absence of use of nitrates in the management of CAD. Sexual activity with a usual partner in a long-standing relationship is equivalent to walking 1 mile on the flat in 20 minutes or briskly climbing 2 flights of stairs in 10 seconds. More moderate or vigorous intensity sexual activity is equivalent to 4 minutes of the Bruce Protocol Treadmill Test (5-6 METS). If the patient is at low risk and has a prescription for nitrates, the healthcare provider may determine whether nitrates are really needed. In some cases, they may not be needed or other antianginal therapies can be considered. If nitrates are not needed, then PDE5 inhibitors may be considered. If nitrates are needed, then other therapies for ED besides PDE5 inhibitors are considered. Modified with permission from Nehra et al4 and Miner et al.72

 

[madman]

Table 4. Retrospective studies supporting CV safety/benefits of PDE5 inhibitors.

 

[madman]

Table 5. AEs associated with PDE5 inhibitor therapy in clinical trials in women.

 

[madman]

PDE-5 INHIBITORS AND CARDIAC HEALTH SYMPOSIUM 2023

https://www.eventdex.com/princeton4/index.php Burnett, Mulhall, Goldstein, Parish, and Kim!

www.excelmale.com

 

[madman]

*In the 13 years since the last Princeton Consensus Conference, the experience with PDE5 inhibitors is more robust, and recent new data have emerged regarding not only safety and drug-drug interactions but also the potential cardioprotective effect of these drugs.

 

[madman]

Sildenafil, 25 Years Later

Sildenafil: 25 Years Later – Summary Twenty-five years ago, the FDA’s approval of sildenafil (Viagra) radically reshaped the treatment of erectile dysfunction. Editor-in-Chief of Grand Rounds in Urology, E. David Crawford, MD, sits down to discuss the history and future of PDE5 inhibitors with...

www.excelmale.com

Reducing Major Adverse Cardiac Events (MACE) with PDE5 Inhibitors

E. David Crawford, MD, sits down with Robert A. Kloner, MD, Ph.D., and Raymond Rosen, MD, to discuss retrospective evidence of PDE5 inhibitors in preventing major adverse cardiac events (MACE) in men. Crawford, Kloner, and Rosen discuss a retrospective study examining occurrences of MACE in men...

www.excelmale.com

 

[DorianGray]

This is really good. But what is the current approach of most primary care doctors? Sadly, at least in the US, it's not about prevention and barely any awareness of what should done to be proactive. Pisses the hell out of me.