Efficacy and safety of tadalafil when used in monoand initial combination therapy regimens in patients with pulmonary arterial hypertension

Objective. To evaluate the efficacy and safety of tadalafil in 24-week mono- and initial combination therapy in newly diagnosed patients with pulmonary arterial hypertension (PAH).

Material and Methods. A single-center, open-label, prospective study at the E.I. Chazov National Medical Research Center of Cardiology of the Ministry of Health of the Russian Federation in 2024-2025 enrolled patients over 18 years of age with newly diagnosed idiopathic pulmonary arterial hypertension (IPAH) and PAH associated with systemic sclerosis (PAH-SSc) in functional class II-III (WHO) who were prescribed tadalafil-based therapy (Tadacardil Canon, Canonpharma Production, Russia). A total of 47 pts aged 43.8 [37.5; 53.6] yrs were enrolled (28 IPAH pts, 19 PAH-SSD pts). The dose of tadalafil 20 mg once daily, if well tolerated and without hypotension, was increased to 40 mg once in all patients after 4 weeks. Starting monotherapy with tadalafil was prescribed to 11 low-risk patients, combination therapy with tadalafil and macitentan 10 mg/day – to 36 intermediate risk patients. Clinical and instrumental data [functional class, 6-minute walk test (6MWT) with determination of the degree of dyspnea according to Borg, capillary blood oxygen saturation (SpO2); NT-proBNP assessment, echocardiography (Echo), right heart catheterization (RHC)] were assessed at baseline and after 24±2 wks of therapy.

Results. After 24 wks of treatment, the 6MWT distance in IPAH and PAH-SSD groups increased by 49.9 m (p=0.00003) and 30.7 m (p=0.024), respectively. At the control point, as at baseline, significant differences in FC, 6MWT distance, and SpO₂ before and after 6MWT remained between the IPAH and PAH-SSD groups, indicating more pronounced functional impairment in PAH-SSD. In IPAH group, both at baseline and after 24 wks, Echo revealed significantly higher pulmonary artery systolic pressure (SPAP) values and greater right chambers dilation with a lower proportion of patients with pericardial effusion. Tadalafil therapy in IPAH group resulted in a significant increase in stroke volume (SV) and cardiac index (CI), resulting in a decrease in pulmonary vascular resistance (PVR), as well as an increase in SvO₂. In patients with PAH-SSD, in addition to a significant improvement in SV, CI, PVR, a significant decrease in mean pulmonary artery pressure (mPAP) was observed. By week 24, IPAH group maintained higher mPAP and PVR and higher SV and CI compared to the PAH-SSD group.

At baseline, 23.4% of patients in the overall group (35.7% in IPAH group) and 5.3% of patients (PAH-SSD group) had a low-risk profile; the remaining patients had an intermediate risk of 1-year mortality. After 24 wks, a significant increase was observed in the proportion of patients in the overall group who achieved low risk (53.2%). Moreover, the improvement of risk profile in the overall group was achieved primarily in patients with IPAH, in whom the percentage of low risk patients increased to 71.4% after 24 wks of treatment. High risk at the control point was observed in one patient with IPAH and one patient with PAH-SSD, both of whom received initial therapy with tadalafil and macitentan, which required the addition of a third drug.

Tadalafil monotherapy led to a significant improvement in functional capacity without a significant increase in the 6MWT distance; a significant decrease in the percentage of patients with persistent pericardial effusion according to Echo and positive RHC parameters dynamics – SPAP, PVR, CI, SV, SvO₂. In the initial dual therapy group the improvement in functional capacity was accompanied by the 6MWT distance increase +32 m (p<0.05). Despite the absence of Echo changes, as in the tadalafil monotherapy group, improvements were observed in NT-proBNP and a wide range of parameters of the RHC-SPAP, PVR, CI, SV, SvO₂, and mean right atrial pressure.

Conclusion: 24-wk tadalafil-based therapy in newly diagnosed IPAH and PAH-SSD patients resulted in significant improvements in clinical, functional, and hemodynamic status, as well as the risk profile, with treatment goals achieved in the majority of patients with IPAH (71.4%) and 26.3% of pts with PAH-SSD. Tadacardil Canon (Canonpharma Production) was shown to be highly effective and well-tolerated when administered both as monotherapy and in combination with macitentan.

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