Vasodilator drugs and heart-related outcomes in systemic sclerosis: an exploratory analysis.
A. F. Guédon
(1, 2)
,
F. Carrat
(1)
,
L. Mouthon
(3)
,
David Launay
(4, 5)
,
B. Chaigne
(3)
,
G. Pugnet
(6)
,
J. C. Lega
(7)
,
A. Hot
(7)
,
V. Cottin
(7, 8)
,
C. Agard
(9)
,
Y. Allanore
(3)
,
A. L. Fauchais
(10)
,
A. Lescoat
(11)
,
R. Dhote
(12)
,
T. Papo
(13)
,
E. Chatelus
(14)
,
B. Bonnotte
(15)
,
J. E. Kahn
(16)
,
E. Diot
(12)
,
A. Aouba
(17)
,
N. Magy-Bertrand
(18)
,
V. Queyrel
(19)
,
A. Le Quellec
(20)
,
P. Kieffer
(21)
,
Z. Amoura
(22)
,
B. Granel
(23)
,
J. B. Gaultier
(24)
,
M. H. Balquet
(25)
,
D. Wahl
(26)
,
O. Lidove
(27)
,
O. Espitia
(9)
,
A. Cohen
,
O. Fain
(2)
,
Eric Hachulla
(4, 5)
,
A. Mekinian
(2)
,
S. Rivière
(2)
1
iPLESP -
Institut Pierre Louis d'Epidémiologie et de Santé Publique
2 CHU Saint-Antoine [AP-HP]
3 Hôpital Cochin [AP-HP]
4 Centre de référence des maladies auto-immunes systémiques rares d'Île-de-France / National Reference Center for Rare Systemic Autoimmune Diseases
5 CHRU Lille - Centre Hospitalier Régional Universitaire [CHU Lille]
6 CHU Toulouse - Centre Hospitalier Universitaire de Toulouse
7 HCL - Hospices Civils de Lyon
8 Centre de Référence des Maladies Pulmonaires Rares [Hôpital Louis Pradel - HCL]
9 CHU Nantes - Centre Hospitalier Universitaire de Nantes = Nantes University Hospital
10 Hôpital Dupuytren [CHU Limoges]
11 Centre Hospitalier Universitaire [Rennes]
12 CHRU Tours - Centre Hospitalier Régional Universitaire de Tours
13 AP-HP - Hôpital Bichat - Claude Bernard [Paris]
14 CHU Strasbourg - Centre Hospitalier Universitaire [Strasbourg]
15 CHU Dijon - Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand
16 Hôpital Ambroise Paré [AP-HP]
17 CHU Caen
18 CHRU Besançon - Centre Hospitalier Régional Universitaire de Besançon
19 CHU Nice - Centre Hospitalier Universitaire de Nice
20 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
21 Groupe hospitalier de la région de Mulhouse et Sud-Alsace
22 CHU Pitié-Salpêtrière [AP-HP]
23 APHM - Assistance Publique - Hôpitaux de Marseille
24 CHU ST-E - Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne]
25 Centre Hospitalier de Lens
26 CHRU Nancy - Centre Hospitalier Régional Universitaire de Nancy
27 Groupe Hospitalier Diaconesses Croix Saint-Simon
2 CHU Saint-Antoine [AP-HP]
3 Hôpital Cochin [AP-HP]
4 Centre de référence des maladies auto-immunes systémiques rares d'Île-de-France / National Reference Center for Rare Systemic Autoimmune Diseases
5 CHRU Lille - Centre Hospitalier Régional Universitaire [CHU Lille]
6 CHU Toulouse - Centre Hospitalier Universitaire de Toulouse
7 HCL - Hospices Civils de Lyon
8 Centre de Référence des Maladies Pulmonaires Rares [Hôpital Louis Pradel - HCL]
9 CHU Nantes - Centre Hospitalier Universitaire de Nantes = Nantes University Hospital
10 Hôpital Dupuytren [CHU Limoges]
11 Centre Hospitalier Universitaire [Rennes]
12 CHRU Tours - Centre Hospitalier Régional Universitaire de Tours
13 AP-HP - Hôpital Bichat - Claude Bernard [Paris]
14 CHU Strasbourg - Centre Hospitalier Universitaire [Strasbourg]
15 CHU Dijon - Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand
16 Hôpital Ambroise Paré [AP-HP]
17 CHU Caen
18 CHRU Besançon - Centre Hospitalier Régional Universitaire de Besançon
19 CHU Nice - Centre Hospitalier Universitaire de Nice
20 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
21 Groupe hospitalier de la région de Mulhouse et Sud-Alsace
22 CHU Pitié-Salpêtrière [AP-HP]
23 APHM - Assistance Publique - Hôpitaux de Marseille
24 CHU ST-E - Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne]
25 Centre Hospitalier de Lens
26 CHRU Nancy - Centre Hospitalier Régional Universitaire de Nancy
27 Groupe Hospitalier Diaconesses Croix Saint-Simon
Résumé
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.