PASSION Trial's Premature End Highlights Tadalafil's Ineffectiveness and Possible Risks for HFpEF Patients

While the results did not reveal a significant difference in the risk of the primary endpoint between the tadalafil and placebo groups, there was a potential indication of a higher risk of all-cause mortality in the tadalafil group, the researchers wrote in Circulation.

Marius M. Hoeper, Hannover Medical School, Germany, and colleagues aimed to assess the safety and efficacy of tadalafil, a phosphodiesterase type 5 inhibitor, in patients with heart failure with preserved ejection fraction and combined postcapillary and precapillary pulmonary hypertension.

In the double-blind PASSION study (Phosphodiesterase-5 Inhibition in Patients With Heart Failure With Preserved Ejection Fraction and Combined Post- and Pre-Capillary Pulmonary Hypertension), patients with HFpEF and combined postcapillary and precapillary pulmonary hypertension were randomly assigned in a 1:1 ratio to receive either tadalafil at a target dose of 40 mg or a placebo.

The primary endpoint was the time to the first composite event, which included adjudicated heart failure hospitalization or all-cause mortality. Secondary endpoints assessed included all-cause mortality and improvements in the New York Heart Association functional class or a ≥10% improvement in the 6-minute walking distance from baseline.

The study revealed the following findings:

• Initially targeting 372 patients, the study was terminated early because of a disruption in the study's medication supply. At that point, 125 patients had been randomized (placebo: 63; tadalafil: 62).
• Combined primary endpoint events occurred in 32% of patients assigned to placebo and 27% of patients assigned to tadalafil (hazard ratio, 1.02).
• There was a possible signal of higher all-cause mortality in the tadalafil group (hazard ratio, 5.10).
• There were no significant between-group differences in other secondary endpoints.
• Serious adverse events occurred in 48% of participants in the tadalafil group and 56% in the placebo group.

"This study does not support the use of tadalafil for patients with HFpEF and combined postcapillary and precapillary pulmonary hypertension, highlighting potential safety concerns," the researchers concluded.

Reference:

Hoeper MM, Oerke B, Wissmüller M, Leuchte H, Opitz C, Halank M, Seyfarth HJ, Baldus S, Bauersachs J, Böhm M, Ghofrani HA, Konstantinides S, Olsson KM, Wachter R, Lam CSP, Aminossadati B, Rosenkranz S. Tadalafil for Treatment of Combined Postcapillary and Precapillary Pulmonary Hypertension in Patients With Heart Failure and Preserved Ejection Fraction: A Randomized Controlled Phase 3 Study. Circulation. 2024 Jun 28. doi: 10.1161/CIRCULATIONAHA.124.069340. Epub ahead of print. PMID: 38939948.