Sildenafil Versus Placebo in Chronic Heart Failure (SilHF)

• Patient Global Assessment [ Time Frame: Baseline, 8 weeks, 24 weeks ] [ Designated as safety issue: No ]
  Analysis of change from baseline.
  
  
• Six minute walk test [ Time Frame: Baseline, 8 weeks, 24 weeks ] [ Designated as safety issue: No ]
  Analysis of change from baseline.
  
  

• Quality of Life (QoL) evaluation by EuroQol5D [ Time Frame: Baseline, 8 weeks and 24 weeks ] [ Designated as safety issue: No ]
  Analysis of change from baseline.
  
  
• Kansas City Questionaire [ Time Frame: Baseline, 8 weeks and 24 weeks ] [ Designated as safety issue: No ]
  Analysis of change from baseline.
  
  
• New York Heart Association (NYHA) function class [ Time Frame: Baseline, 8 weeks, 16 weeks and 24 weeks ] [ Designated as safety issue: No ]
  Analysis of change from baseline.
  
  

It is estimated that 2-3 % of the adult population suffers from heart failure (HF) and the prevalence is increasing. The European Society of Cardiology (ESC) represents countries with a population > 1,1 billion, and it is estimated that approximately 30 million patients have HF in these 53 countries. Heart failure is particularly prevalent in the elderly population and represents a major burden for both patients and the health services. HF is present in over 10% of patients admitted to hospital and accounts for ~ 2% of national health expenses. Approximately 50% of these costs are related to hospitalisation.

Despite optimal non-pharmacological, pharmacological and device therapy, the morbidity among HF patients is high with symptoms such as dyspnoea and fatigue that reduce quality of life. Following diagnosis approximately 50% are dead after 4 years. Forty percent of patients admitted to hospital with HF are either dead or rehospitalised within one year.

During the last decade, PDE5-inhibitors have been evaluated as a potential treatment for heart failure (see scientific rationale and reference). However, these investigations have been small and there is still limited data. Trials assessing the acute effects of PDE5-inhibition in patients with symptomatic HF due to systolic dysfunction have been performed primarily with sildenafil. Due to the short half-life of sildenafil the drug is administered 3 times daily when studying its chronic effects.

Previous studies have evaluated the 50 mg dose acutely and 50 mg 3 times daily during short-term chronic studies. Importantly, there is considerable off-label use of sildenafil in symptomatic heart failure patients in most European countries.

Revatio is currently licenced for pulmonary hypertension group 1. The dosing scheme is 20mg x 3. However, we suggest targeting a higher dose to achieve optimal clinical benefit in patients with heart failure and moderate congestion. As mentioned above most of the clinical literature in patients with symptomatic heart failure has been done using the 50mg x 3 regimen. However, it is believed that in the proposed study using 40mg x 3 should be equally efficacious. There is already considerable experience using this dosage scheme in heart failure patients locally.

The hemodynamic profile of PDE-5 inhibitors is favourable with reduction in filling pressures, both systemic and pulmonary, vascular resistance accompanied by improvement in symptoms and submaximal and peak exercise performance. This pilot study will evaluate the use of the PDE5-inhibitor sildenafil in patients with heart failure, systolic dysfunction and documented secondary pulmonary hypertension.