Managing Erectile Dysfunction: Considerations for men taking heart medications

Erectile dysfunction (ED) affects about half of men over 50 and has many possible causes, including stress and mental health, diabetes, smoking, heart disease and medications. ED and heart disease often go together because both can result from narrowed or stiff blood vessels. For many men with heart disease, ED can be treated safely, but some medication combinations are dangerous. Your genes and your other medications also affect how your body handles both ED drugs and heart medications.

Can erectile dysfunction be a sign of heart disease?

Yes. The small arteries of the penis can show the effects of narrowed blood vessels before the larger arteries of the heart do. In a meta-analysis of studies including more than 92,000 men, men with ED had a 44% higher risk of heart attack, stroke and other cardiovascular events than men without ED. Expert consensus recommends that men with ED, especially younger men, have their cardiovascular risk assessed. If you have ED, talk to your health care provider about your heart health as well as your sexual health.

Which heart medications can affect erectile function?

Several heart and blood pressure medications have been linked to ED, including thiazide diuretics, spironolactone and digoxin. Beta-blockers are often blamed, but a review of randomized trials with more than 35,000 people found only a small increase in reported sexual problems, about 1 extra report for every 199 people treated each year. Other medications, such as some antidepressants, can also contribute.

Statins, on the other hand, may help. A meta-analysis of randomized trials found that statins modestly improved erectile function, and in one trial adding atorvastatin modestly improved the response to sildenafil in men with high cholesterol who had not responded to sildenafil alone.

Do not stop a heart medication on your own. If you think a medication is affecting your erections, talk to your prescriber, who may be able to adjust the dose or switch to another option.

Are ED drugs safe if you have heart disease?

The ED drugs sildenafil (Viagra), tadalafil (Cialis), vardenafil (Levitra, Staxyn) and avanafil (Stendra) belong to a class called PDE5 inhibitors. They relax blood vessels and increase blood flow to the penis. According to the American Heart Association, sexual activity is reasonable for many people with stable heart disease, and ED drugs can be used by many men with stable cardiovascular disease after their heart health has been assessed. Your doctor will consider how well you tolerate physical activity before prescribing an ED drug.

ED drugs may also benefit the brain. In a UK study of nearly 270,000 men with ED, those who started an ED drug were 18% less likely to develop Alzheimer’s disease, and the risk was even lower in men who used them most often. An analysis of insurance records for more than 7 million people also linked sildenafil use to a lower risk of Alzheimer’s disease. Clinical trials are needed to confirm this benefit.

Which medications should never be combined with ED drugs?

• Nitrates, such as nitroglycerin spray or tablets, isosorbide mononitrate and isosorbide dinitrate. Together with ED drugs, they can cause a sudden, severe drop in blood pressure. This combination must be avoided. If you develop chest pain after taking an ED drug, tell the emergency team which drug you took and when: nitrates should not be given within 24 hours of sildenafil or within 48 hours of tadalafil.
• Riociguat, a drug for pulmonary hypertension, for the same reason.

Which combinations need caution?

• Alpha-blockers, such as tamsulosin (Flomax) and doxazosin (Cardura), used for an enlarged prostate or high blood pressure. Both drug types lower blood pressure, so you should be on a stable alpha-blocker dose first and start the ED drug at a low dose.
• Other blood pressure medications, such as amlodipine, ACE inhibitors (for example, ramipril and perindopril) and angiotensin receptor blockers or ARBs (for example, losartan and valsartan). These can usually be used with ED drugs, but they may add a small extra drop in blood pressure. Tell your prescriber about all your medications.
• Drugs that block the CYP3A4 enzyme. All four ED drugs are broken down by CYP3A4 in the liver. Some medications slow down this enzyme, so more of the ED drug stays in your body. These include certain antifungals (ketoconazole, itraconazole), the antibiotic clarithromycin and some HIV medications (ritonavir). If you take one of them, your doctor may lower the ED drug dose or choose another option. Some heart medications, such as diltiazem and verapamil, and grapefruit juice also slow down this enzyme.

How do genes affect ED drugs and heart medications?

Many heart medications are affected by genes that control how drugs are broken down or moved through the body:

• Statins: the CPIC guideline recommends choosing the statin and dose based on SLCO1B1, ABCG2 and CYP2C9 to lower the risk of muscle pain and other muscle side effects. SLCO1B1 is a transporter that moves statins into the liver. Read more in Are statins safe? It depends on your genetics.
• Beta-blockers such as metoprolol and carvedilol are broken down by CYP2D6. Poor metabolizers can have higher drug levels and more side effects.
• ED drugs depend on CYP3A4, and natural differences in CYP3A4 and CYP3A5 activity, as well as drug interactions, can affect their levels. There are no genetic dosing guidelines for ED drugs yet, but knowing your CYP3A4 status and medication interactions can help your prescriber choose a safe starting dose.

Can a pharmacogenetic test help?

Pillcheck reports on CYP3A4, CYP3A5, CYP2D6, CYP2C9, CYP2C19, SLCO1B1 and ABCG2, along with other genes that affect heart, blood pressure and ED medications. A Pillcheck pharmacist reviews your results and all your medications, flags risky combinations and recommends options and doses to discuss with your doctor. Your results and medication history are kept strictly confidential.

Summary

• ED is common in men with heart disease and can be an early warning sign of cardiovascular problems.
• Some heart medications, such as thiazide diuretics, spironolactone and digoxin, can contribute to ED, while statins may modestly improve erectile function.
• ED drugs can be used by many men with stable heart disease after a heart health assessment.
• Never combine ED drugs with nitrates or riociguat. Use caution with alpha-blockers and drugs that block CYP3A4.
• Genes such as SLCO1B1, CYP2D6 and CYP3A4 affect heart and ED medications, and a pharmacist review can flag risky combinations.

Frequently asked questions

Can I take Viagra or Cialis if I have heart disease?

Many men with stable heart disease can, after their doctor has assessed their heart health. They must not be taken with nitrates or riociguat.

Can I take an ED drug with nitroglycerin?

No. The combination can cause a dangerous drop in blood pressure. Nitrates should not be given within 24 hours of sildenafil or 48 hours of tadalafil.

Can I take ED drugs with amlodipine or other blood pressure pills?

Usually yes, but blood pressure may drop a little more. Alpha-blockers, such as tamsulosin (Flomax) and doxazosin (Cardura), need extra caution. Always tell your prescriber about all your medications.

Do heart medications cause erectile dysfunction?

Some can, including thiazide diuretics, spironolactone and digoxin. The effect of beta-blockers is smaller than often believed. Do not stop a heart medication without talking to your prescriber.

Do statins cause ED?

Studies suggest the opposite: statins may modestly improve erectile function.

Can a genetic test help with ED and heart medications?

Yes. A pharmacogenetic test shows how your body handles statins, beta-blockers, ED drugs and many other medications, and a pharmacist review can flag risky combinations.

References

Levine GN, Steinke EE, Bakaeen FG, et al. Sexual activity and cardiovascular disease: a scientific statement from the American Heart Association. Circulation. 2012;125(8):1058-1072.

Nehra A, Jackson G, Miner M, et al. The Princeton III Consensus recommendations for the management of erectile dysfunction and cardiovascular disease. Mayo Clin Proc. 2012;87(8):766-778.

Vlachopoulos CV, Terentes-Printzios DG, Ioakeimidis NK, et al. Prediction of cardiovascular events and all-cause mortality with erectile dysfunction: a systematic review and meta-analysis of cohort studies. Circ Cardiovasc Qual Outcomes. 2013;6(1):99-109.

Ko DT, Hebert PR, Coffey CS, et al. Beta-blocker therapy and symptoms of depression, fatigue, and sexual dysfunction. JAMA. 2002;288(3):351-357.

Kostis JB, Dobrzynski JM. The effect of statins on erectile dysfunction: a meta-analysis of randomized trials. J Sex Med. 2014;11(7):1626-1635.

Dadkhah F, Safarinejad MR, Asgari MA, et al. Atorvastatin improves the response to sildenafil in hypercholesterolemic men with erectile dysfunction not initially responsive to sildenafil. Int J Impot Res. 2010;22(1):51-60.

Cooper-DeHoff RM, Niemi M, Ramsey LB, et al. The Clinical Pharmacogenetics Implementation Consortium Guideline for SLCO1B1, ABCG2, and CYP2C9 genotypes and Statin-Associated Musculoskeletal Symptoms. Clin Pharmacol Ther. 2022;111(5):1007-1021.

Adesuyan M, Jani YH, Alsugeir D, et al. Phosphodiesterase Type 5 Inhibitors in Men With Erectile Dysfunction and the Risk of Alzheimer Disease: A Cohort Study. Neurology. 2024;102(4):e209131.

Fang J, Zhang P, Zhou Y, et al. Endophenotype-based in silico network medicine discovery combined with insurance record data mining identifies sildenafil as a candidate drug for Alzheimer's disease. Nat Aging. 2021;1(12):1175-1188.

Burnett AL, Nehra A, Breau RH, et al. Erectile Dysfunction: AUA Guideline. J Urol. 2018;200(3):633-641.