Erectile-Dysfunction Drugs Also Give the Heart a Boost

October 22, 2014

ROME, ITALY — For individuals with left ventricular hypertrophy (LVH), long-term use of an erectile-dysfunction drug can prevent cardiac remodeling, while use of these phosphodiesterase type-5 (PDE-5) inhibitors, which include the popular sildenafil (Viagra, Pfizer), can also improve measures of cardiac performance in subjects with a range of clinical diagnoses[1].

Aside from its typical bedroom use, Dr Elisa Gianetta (Sapienza University of Roma, Italy) and colleagues say their "analyses reveal that the ideal target population to benefit from PDE-5 [inhibition] are patients with heart failure and LVH."

Their conclusions are based on a meta-analysis of 24 studies with 1622 individuals, of which 954 were treated with PDE-5 inhibitors and 772 with placebo. Their results are published October 19, 2014 in BMC Medicine.

The erectile-dysfunction drugs have been hypothesized to improve cardiac care outside the urological setting for many years now. In fact, sildenafil was first explored as an antianginal medication before gaining initial marketing approval for the treatment of erectile dysfunction and later for primary pulmonary arterial hypertension (PAH).

The rationale for evaluating sildenafil in patients with heart failure—as in PAH—stems from observations that PDE-5 is the main enzyme responsible for cyclic guanosine monophosphate (cGMP) catabolism in vascular smooth-muscle cells. Chronic left ventricular systolic dysfunction is characterized by impaired nitric-oxide (NO)-cGMP-mediated vasodilation in pulmonary and skeletal-muscle circulatory systems.

Benefit Best Among LVH Patients

Among the 24 studies included in the meta-analysis were studies administering the PDE-5 inhibitors to patients with heart failure (with and without preserved ejection fraction), diastolic dysfunction after MI, PAH, congestive heart failure, and diabetic cardiomyopathy, among others. The vast majority of patients were treated with sildenafil, while 218 received vardenafil (Levitra, GlaxoSmithKline) and 54 were treated with tadalafil (Cialis, Eli Lilly). Treatment ranged from 4 weeks to 1 year.

In the analysis, markers of cardiac performance improved with long-term use of the PDE-5 inhibitors. Six studies reported data on ejection fraction in 286 patients with left heart disease. In these, all of whom were treated with sildenafil, there was a 3.56% increase in ejection fraction over placebo. The increase in ejection fraction over placebo was 4.38% in patients with LVH. Treatment with PDE-5 inhibitors had no effect on heart rate, and there were no changes in systolic and diastolic blood pressure, mean arterial pressure, or the systemic vascular resistance index.

The most common side effects of treatment with the drugs were flushing, headache, nosebleeds, and gastric symptoms.

The researchers suggests that PDE-5 inhibitors "could be reasonably offered to men with cardiac hypertrophy and early-stage heart failure." Given that the drugs were tested in men, there is a need for additional studies in women, as well as a long-term study focusing on cardiovascular outcomes, they add.

In 2013, the National Heart, Lung, and Blood Institute-sponsored RELAX study fell short when sildenafil was tested in HF patients with preserved ejection fraction. In that study, as reported by heartwire , there was no improvement in cardiac performance, hospitalizations, or ventricular remodeling and diastolic function, among other end points.

The authors have reported they have no relevant financial relationships.

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