Guédon Alexis F, Carrat Fabrice, Mouthon Luc, Launay David, Chaigne Benjamin, Pugnet Grégory, Lega Jean-Christophe, Hot Arnaud, Cottin Vincent, Agard Christian, Allanore Yannick, Fauchais Anne Laure, Lescoat Alain, Dhote Robin, Papo Thomas, Chatelus Emmanuel, Bonnotte Bernard, Kahn Jean-Emmanuel, Diot Elisabeth, Aouba Achille, Magy-Bertrand Nadine, Queyrel Viviane, Le Quellec Alain, Kieffer Pierre, Amoura Zahir, Granel Brigitte, Gaultier Jean Baptiste, Balquet Marie-Hélène, Wahl Denis, Lidove Olivier, Espitia Olivier, Cohen Ariel, Fain Olivier, Hachulla Eric, Mekinian Arsène, Rivière Sébastien
Institut Pierre Louis d'Epidemiologie et de Sante Publique, Paris, Île-de-France, France
Sorbonne Université, APHP, Service de Médecine Interne, Hopital Saint-Antoine, Paris, Île-de-France, France.
RMD Open. 2024 Dec 9;10(4):e004918. doi: 10.1136/rmdopen-2024-004918.
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.
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.
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.
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.
系统性硬化症（SSc）是一种自身免疫性结缔组织病，其特征为细胞外基质过度沉积以及皮肤和内脏广泛纤维化，包括各种心脏表现。心脏受累是SSc患者的主要死亡原因之一。在本研究中，我们旨在评估各种血管扩张剂治疗的效果。
我们使用了来自一项全国多中心前瞻性研究的数据，该研究使用了法国SSc国家数据库。我们采用一种因果方法，即基于纵向目标最小损失估计，来调整混杂因素和信息性删失，从而估计西地那非、波生坦、血管紧张素转换酶（ACE）抑制剂和伊洛前列素对舒张功能障碍、射血分数改变<50%以及肺动脉高压（PAH）的平均治疗效果（ATE）。
我们纳入了1048例有治疗相关可用数据的患者。关于西地那非的分析，3年时其对舒张功能障碍的ATE为-2.83%（95%CI -4.06；-1.60，p<0.00001），对射血分数改变<50%的估计ATE为-0.88%（95%CI -1.70；-0.05，p=0.037）。我们未发现其对PAH有显著影响。关于波生坦、ACE抑制剂和伊洛前列素，它们均未对舒张功能障碍、射血分数改变<50%或PAH显示出显著影响。
通过因果方法，我们的研究首次且规模最大地表明，西地那非可能对SSc患者的舒张功能障碍和射血分数改变的发生有益。然而，需要进一步研究评估血管扩张剂对SSc患者心脏相关结局的影响，以证实这些探索性结果。
