Abstract: Background and Aims: Systemic sclerosis (SSc) is an autoimmune connective disease characterised by excessive extracellular matrix deposition and widespread skin and internal organ fibrosis including various cardiac manifestations. Heart involvement is one of the leading causes of death among patients with SSc. In this study, we aimed to assess the effect of various vasodilator treatments.
Methods: We used data from a national multicentric prospective study using the French SSc national database. We estimated the average treatment effect (ATE) of sildenafil, bosentan, angiotensin-converting enzyme (ACE) inhibitors and iloprost on diastolic dysfunction, altered ejection fraction <50% and pulmonary arterial hypertension (PAH) using a causal method, namely the longitudinal targeted minimum loss-based estimation, to adjust for confounding and informative censoring.
Results: We included 1048 patients with available data regarding treatment. Regarding sildenafil analyses, the ATE on diastolic dysfunction at 3 years was -2.83% (95% CI -4.06; -1.60, p<0.00001), and the estimated ATE on altered ejection fraction <50% was -0.88% (95% CI -1.70; -0.05, p=0.037). We did not find a significative effect on PAH. Regarding bosentan, ACE inhibitors and iloprost, none of them neither showed a significant effect on diastolic dysfunction, altered ejection fraction <50% or PAH.
Conclusions: Using causal methods, our study is the first and largest suggesting that sildenafil might have benefits among SSc patients regarding diastolic dysfunction and altered ejection fraction occurrence. However, further studies assessing the effect of vasodilators on heart-related outcome among SSc patients are needed to confirm those exploratory results.
Competing Interests: Competing interests: AM is the investigator of CELGENE, ROCHE and CHUGAI founded trials with APHP and Hopital 15-20 promotion; AM received several fees for congress travels and experts’ use from LFB, SANOFI, SHIRE and CELGENEEH; speakers bureau, Johnson & Johnson, GlaxoSmithKline, Roche-Chugai, Otsuka; consultant of Bayer, Boehringer Ingelheim, GlaxoSmithKline, Johnson & Johnson, Roche-Chugai, Sanofi-Genzyme, Novartis; grant/research support from CSL Behring, GlaxoSmithKline, Johnson & Johnson, Roche-Chugai, Sanofi-Genzyme, Sobi, Novartis, ED; and received fees as speaker in symposium from Boehringer Ingelheim. OL received several fees for congress travels and experts’ use from Amicus Therapeutics, Chiesi, Sanofi-Genzyme and Takeda.
(© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
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