Erectile Dysfunction Medicines as Cardio Protective Agents?

Phosphodiesterase type 5 inhibitor (PDE5i): is a drug that blocks the degradative action of cGMP- specific phosphodiesterase 5 on cyclic GMP in the smooth muscle cells lining the blood vessels of corpus cavernosum of the penis. These drugs are being used for the treatment of erectile dysfunction. These agents are also given for treating pulmonary hypertension, because of the presence of PDE5 in the arterial wall smooth muscles within the lungs.

Examples of drugs containing PDE5i: Sildenafil(Viagra), Vardenafil(Levitra), Tadalafil(Cialis).

 Chronic treatment with PDE5i have shown to improve the cardiovascular function, particularly in patients suffering from the heart failure and left ventricular hypertrophy LVH ( a condition in which the muscle wall of heart’s left pumping chamber, the ventricle becomes thickened, leading to its hypertrophy). 

New research published in BMC medicine suggests that treatment with PDE5i for a prolonged time can provide protection at different stages of cardio vascular diseases.

Presence of PDE5 in heart is leading to the questions that whether the mechanism involved in the blockade of this enzyme be used for the treatment of conditions other than the urological ones.

The myocardial effects of PDE5i have recently received considerations in several preclinical studies.The risk/benefit ratio in humans is still unclear.

Studies: the researchers found out that the drug was increasing the heart’s efficiency of pumping blood into the vessels, and was able to cause relaxation between beats.

A meta analysis of 24 randomized trials was done by Dr. Andrea M. Isidori (associate Professor of endocrinology at Sapienza University of Rome) team. The analysis constitute of cardiovascular data, which included 2 with vardenafil, 18 with sildenafil and 4 with tadalafil. When compared with placebo, treatment with PDE5i showed attenuation in left ventricle mass index in patients having LVH. End diastolic volume index (end diastolic volume is the volume of blood in the right and/or  left ventricle at the end load or the amount of blood in the ventricles just before systole) was seen to be increased in patients without hypertrophy. But no effect on diastolic function was seen [ as it was measured by E/A ratio ( E/A ratio is a marker of the function of the left ventricle of the heart)]. LVH patients also showed reduction in the levels of NT-pro BNP ( the N terminal of the prohormone brain natriuretic peptide).The clinical trials are highly required now to discover the complete efficacy and safety of these drugs in cardiac conditions, because presently in cardiology, only few drugs are able to affect these parameters. So, more work needs to be done to find out the benefits of these drugs in the treatment and prevention of heart failures. The lower dosage is needed for the cardiac problems as compared to the doses being used for erectile dysfunction.

According to Dr. Andrea, animal testing have shown that long term use of Sildenafil is involved in reducing the cardiac remodeling, along with an anti fibrotic effect and also an anti hypertrophic effect. Animal data have also shown that PDE5i can be a cardio protective agent in conditions like ischemic cardiomyopathy, ischemia/ reperfusion injury and doxorubicin induced cardiomyopathy.

Dr. Isidori said ” PDE5i could also be helpful in patients affected by heart failure with reduced ejection fraction (is a measurement of the percentage of blood leaving the heart each time it contracts) in which the cardiac pump has stopped working – for the improvement in cardiac performance.”

This shows that PDE5i could be reasonably used in men with cardiac hypertrophy and early stage of heart failure. But for now, until more stronger and adequate data and results are obtained, PDE5i should be prescribed only for its approved indications, which are erectile dysfunction and pulmonary hypertension.

Side effects: the trial having 1,622 subjects, out of which 954 were randomized to PDE5i and 722 to placebo showed only common side effects like flushing, gastric symptoms, headache, epistaxis. In these 1600 subjects, increased risk for photo-sensitivity or visual disturbances was absent.

Further trials: controlled randomized prospective studies are required both in men & women before giving these drugs the rightful approval for the treatment of cardiac conditions.

Gender differences in the impact of viagra for the treatment of heart failure: new animal studies done by John Hopkins CV researchers showed that sildenafil affects males & females in a totally different way.

 According to Takimoto, MD, PhD… in female mice modeling human heart failure, the results of sildenafil were practically non existent. It appeared that the action of the drug was dependent on the animal’s estrogen levels. Estrogen is present in both females & males but their quantity differs to great extents. The cardio protective mechanism of sildenafil in female mice was dependent on the estrogen’s presence via mechanism that involves myocyte eNOS- dependent cGMP synthesis and the cGMP dependent protein kinase 1a.

Summary: according to analysis the authors concluded that sustained PDE5i produced;

1. an anti remodeling effect by decreasing the cardiac mass in subjects with LVH & by increasing end diastolic volume in non LVH patients.

2. an improvement in cardiac performance.

3. betterment in flow mediated vasodilation.

4. with no necessary changes in the hemodynamics. 

Reference: the following information is obtained from various published medical articles.

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