Vasodilator drugs and heart-related outcomes in systemic sclerosis: an exploratory analysis

Area of Science:

• Cardiology
• Rheumatology
• Pharmacology

Background:

• Systemic sclerosis (SSc) is an autoimmune disease causing fibrosis and heart problems, a leading cause of mortality.
• Cardiac manifestations in SSc significantly impact patient outcomes and survival rates.
• Assessing the efficacy of various vasodilator treatments is crucial for managing SSc-related cardiac complications.

Purpose of the Study:

• To evaluate the impact of sildenafil, bosentan, ACE inhibitors, and iloprost on cardiac function in SSc patients.
• To determine the average treatment effect (ATE) on diastolic dysfunction, reduced ejection fraction, and pulmonary arterial hypertension (PAH).
• To utilize causal inference methods for robust adjustment of confounding factors and informative censoring.

Main Methods:

• Analysis of data from a national multicentric prospective study of the French SSc database.
• Application of longitudinal targeted minimum loss-based estimation (TMLE) for causal effect estimation.
• Inclusion of 1048 SSc patients with available treatment data for analysis.

Main Results:

• Sildenafil showed a significant ATE in reducing diastolic dysfunction (-2.83%) and altered ejection fraction (<50%) (-0.88%) at 3 years.
• No significant effect of sildenafil was observed on pulmonary arterial hypertension (PAH).
• Bosentan, ACE inhibitors, and iloprost did not demonstrate significant effects on diastolic dysfunction, altered ejection fraction, or PAH.

Conclusions:

• This study suggests sildenafil may offer benefits for diastolic dysfunction and altered ejection fraction in SSc patients.
• The findings highlight sildenafil as a potential therapeutic option for specific cardiac manifestations in SSc.
• Further research is warranted to confirm these exploratory findings and assess long-term heart-related outcomes with vasodilators in SSc.