Effectiveness and safety of tadalafil in comparison with sildenafil in the group -3 pulmonary hypertension patients: A randomized, open label, parallel group study

Pulmonary hypertension is defined as a mean Pulmonary Artery Pressure greater than 20 mmHg at rest, measured by right heart catheterization. It is clinically classified into 5 groups. Those are 1) Pulmonary Arterial Hypertension; 2) Pulmonary Hypertension due to Left Heart Disease; (3) Pulmonary Hypertension caused by lung disease and/or hypoxia (PH-LD); 4) chronic thromboembolic Pulmonary Hypertension (CTEPH); and 5) Pulmonary Hypertension with unclear and/or multifactorial mechanisms. It is classified functionally by World Health Organization (WHO-FC) into 4 class which can be used for the assessment of severity. The recent global prevalence of it is estimated to be around 1% which increases up to 10% in individuals over 65 years. The incidence of PAH varies among countries. It depends on risk factors like air pollution, cigarette smoking and others like various lung diseases. The right heart catheterization, an invasive gold standard technique and the doppler echocardiography, a non-invasive test is available for diagnosis. Other supporting investigations comprise of Chest X-Ray, ECG and CT angiography, this aids in differential diagnosis. Pulmonary Function Test (PFT) and 6-minute walk test are the markers in the assessment of the severity of the lung disease and exercise capacity respectively. Oxygen supplementation is the main therapy that relieves hypoxemic pulmonary vasoconstriction. This leads to improved cardiac output, lessens sympathetic vasoconstriction, alleviates tissue hypoxemia, and improves renal perfusion. The Pharmacological treatment includes Pulmonary Arterial Hypertension (PAH) directed therapy like prostacyclin analogs (Teprostinil, Epoprostenol), endothelin receptor blockers (Bosentan, Ambrisentan), Phosphodiesterase-5 (PDE-5) inhibitors (Sildenafil, Tadalafil). This PAH-directed therapy is approved for the group-1 Pulmonary Hypertension patients where the primary etiology is in the pulmonary vasculature. However, in the clinical practice many centres prescribe Sildenafil or Tadalafil in the Group-3 PH like COPD associated Pulmonary Hypertension patients. Treatment with pulmonary vasodilators remains controversial in the group 3 PH patients as some studies has shown benefits and some studies has shown adverse events like deterioration of oxygenation due to the inhibition of hypoxic pulmonary vasoconstriction leads to impaired gas exchange and it has shown no significant improvement in the Six-minute walk distance test and WHO-FC. The present study is planned to determine the effectiveness and safety of Tadalafil in comparison with the Sildenafil in the group 3 PH patients.