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Pulmonary Hypertension 2013 Update/Review
Part 2 of 2: Treatment of PH
There are 3 classes of pulmonary vasodilator drugs: phosphodiesterase-5 inhibitors (PDE-5 inhibitors, e.g. sildenafil, tadalafil), endothelin receptor antagonists (ERAs, e.g. bosentan, ambrisentan), and prostacyclins (epoprostenol, iloprost, treprostinil). Because the large trials have focused on PAH, currently only WHO group 1 has a clear indication for these medications. Their use in other WHO groups is an active area of research, but as of now their potential benefits and harms in these groups are largely unclear. Calcium channel blockers are a fourth class with specific indications.
The general approach to group 1 patients is to consider anticoagulation, diuretics, oxygen therapy, and digoxin. If patients have a vasodilator response during the catheterization procedure, this predicts long-term response to oral calcium channel blockers and a trial should be initiated and continued if there is a sustained response. If not, the therapeutic approach is guided by functional status (WHO symptom classification) and objective testing (e.g. 6MWT) as follows:
- Low risk, functional class I-III patients may be treated with oral PDE-5 inhibitors, oral ERAs, or inhaled prostacyclins
- High risk, functional class III-IV patients should be treated with intravenous or subcutaneous prostacyclins.
- Patients should be re-evaluated for improvement on therapy and considered for combination therapy. Clearly, these patients should be managed by clinicians with expertise in PH.
Group 2 patients with pulmonary venous hypertension are generally managed with therapies for left heart failure addressing systemic blood pressure control and volume management. The use of pulmonary vasodilators could actually worsen pulmonary venous hypertension and pulmonary edema by increasing pulmonary blood flow in the face of elevated left-sided filling pressures. That said, some of these patients will have developed intrinsic pulmonary vascular disease and could theoretically benefit from pulmonary vasodilator therapy. In fact, a small trial suggested potential benefit of PDE-5 inhibitors in patients with heart failure and a preserved ejection fraction if there was a >5 mmHg difference between PA diastolic pressure and PCWP after optimizing volume and blood pressure. ERAs and prostacyclins should not be used.
Management of patients with group 3 PH is directed at the underlying lung disease and hypoxemia. Pulmonary vasodilators do not have a role and in fact may worsen VQ matching in these patients, precipitating worsened oxygenation and symptoms.
Group 4 PH is potentially curable with thromboendartectomy. There may be a role for pulmonary vasodilators in those who are not surgical candidates.
Treatment of group 5 is directed at the underlying disease.
Management of RV dysfunction and failure is critical because of its association with increased mortality. Patients with RV failure have tenuous volume status and are prone to kidney injury (from renal venous congestion and decreased cardiac output), right ventricular ischemia, and arrhythmias. Severe PH and RV failure are particularly troublesome to manage during acute exacerbations and intercurrent critical illness.
Sanjiv J. Shah. Pulmonary Hypertension. JAMA 2012;308(13):1366-1374.