Pulmonary hypertension · Initial combination therapy
Initial Use of Ambrisentan plus Tadalafil in Pulmonary Arterial Hypertension
| Design | Randomised, double-blind trial |
|---|---|
| Treatment | Initial combination of ambrisentan and tadalafil |
| Control | Ambrisentan monotherapy or tadalafil monotherapy |
| Population | 500 treatment-naive patients with pulmonary arterial hypertension |
| Follow-up | Event-driven, median approximately 517 days |
| Primary endpoint | Time to first clinical-failure event: death, hospitalisation for worsening PAH, disease progression, or unsatisfactory long-term clinical response |
| Result | A primary endpoint event occurred in 18% on combination therapy, 34% on ambrisentan and 28% on tadalafil, and in 31% of the pooled monotherapy group. Hazard ratio for combination versus pooled monotherapy 0.50 (95% CI 0.35 to 0.72). |
| Secondary endpoints | NT-proBNP, six-minute walk distance, WHO functional class |
Among participants with pulmonary arterial hypertension who had not received previous treatment, initial combination therapy with ambrisentan and tadalafil resulted in a significantly lower risk of clinical-failure events than the risk with ambrisentan or tadalafil monotherapy.
The trial authors, in the published abstract
Ended sequential add-on therapy as the default in PAH. Upfront dual therapy is now standard for most treatment-naive patients, and the subsequent question — what to add for those who remain high risk — is what ZENITH addresses.
Galiè N, Barberà JA, Frost AE, et al. Initial Use of Ambrisentan plus Tadalafil in Pulmonary Arterial Hypertension. N Engl J Med 2015 Aug 27;373(9):834-44.