An initial combined treatment for pulmonary arterial hypertension provides better long-term results

A study published in the New England Journal of Medicine (NEJM) shows that the combination of two drugs (ambrisentan and tadalafil) is more effective than the use of one of these agents to treat pulmonary arterial hypertension. The combination therapy improves very significantly the outcome of patients with this disease and reduces by 50% the risk of clinical failure. Dr. Joan Albert Barberà, pulmonologist at Hospital Clínic and head of the IDIBAPS team Physiopathological mechanisms of respiratory illnesses is one of the authors of this study and coordinator of the trial in Spain.

Pulmonary hypertension is a disease characterized by the abnormal increase in blood pressure in the pulmonary arteries. It occurs in the form of primary diseases affecting these arteries, such as pulmonary arterial hypertension (PAH) and chronic thrombosis of the pulmonary arteries, or may develop in the context of other chronic cardiac or respiratory diseases. When not treated properly, the disease causes heart failure and can be a cause of death.

Current treatments target alterations in the synthesis of different substances that play a key role in the regulation of contractility and cell proliferation in the pulmonary arteries. The currently available drugs act on three of these substances involved in regulatory pathways. However, when these therapies are used separately, they have limited efficacy in controlling the disease, suggesting that more than one of these regulatory pathways are involved in disease onset. "So far previous studies have evaluated combinations of drugs administered sequentially. This is the first work proposing the use of a combination of drugs given to patients simultaneously and since the beginning", explains Dr. Joan Albert Barberá, who is also Coordinator of the new research program in pulmonary hypertension at the Networked Biomedical Research Center for Respiratory Diseases (CIBERES)

500 patients from different countries with pulmonary hypertension not treated previously have participated in the aforementioned study published in NEJM. They were divided into three groups: 250 were assigned to the combination of drugs –tadalafil and ambrisentan-, the second group, consisting of 126 patients, were given only ambrisentan and the rest, only tadalafil. The study evaluated the events indicative of clinical failure (death, hospitalization, need for transplant, clinical worsening, poor clinical response) for a long period of time. The results show that 18% of patients who received the drug combination had a clinical event of failure, whereas in the groups treated with monotherapy the rate reached 31%. This means that the risk of clinical failure from the start of treatment halved with the combined therapy.

"These results will have a major impact on the treatment of patients with pulmonary hypertension", explains Dr. Barberà. "In fact, the therapeutic strategy using an initial combined treatment has been incorporated into the new European Clinical Guidelines for pulmonary hypertension, presented last week in London", he concludes.

Article reference:

Initial Use of Ambrisentan plus Tadalafil in Pulmonary Arterial Hypertension.

Galiè N, Barberà JA, Frost AE, Ghofrani HA, Hoeper MM, McLaughlin VV, Peacock AJ, Simonneau G, Vachiery JL, Grünig E, Oudiz RJ, Vonk-Noordegraaf A, White RJ, Blair C, Gillies H, Miller KL, Harris JH, Langley J, Rubin LJ; AMBITION Investigators.

N Engl J Med. 2015 Aug 27;373(9):834-44. doi: 10.1056/NEJMoa1413687.