Combination Therapy in Pulmonary Artery Hypertension

In her excellent article Iona Preston1 systematically evaluates the current status of combination therapy in the treatment of patients with pulmonary artery hypertension (PAH) in the United States. The United Kingdom recently published its own consensus statement on the management of PAH in clinical practice, which included the current use of combination therapy.2

Despite the current lack of definitive clinical trial data, combination therapy remains an attractive option for the clinician faced with a patient who is getting worse or a patient who is failing to improve on monotherapy. In the UK, the most common way to combine therapies is to add a second drug when the patient is not improving or getting worse on optimal doses of single therapy. Despite the concerns over pharmacological interactions, the most common combination in the UK is the addition of an endothelin receptor antagonist (ETRA) to sildenafil or vice versa, which accounts for 65% of combination therapy prescriptions.

In rapidly deteriorating patients, a parenteral prostanoid may be added to the original oral therapy. The combination of a prostanoid with sildenafil accounts for 23% of combination prescriptions in the UK. Combined use of a prostanoid and ETRA accounts for the remaining 12% of prescriptions. It is of some concern that the funding arrangements in the UK are making it harder to prescribe combination therapy in the absence of definitive trial data and a favourable cost-benefit analysis. Thus it is recommended that where combination therapy is being considered that all patients should be entered into a clinical trial where possible. When it is not possible to include patients in clinical trials, we recommend that at the very least the patient's response to treatment is carefully monitored and that data are submitted to national databases for audit purposes.