ACE inhibitors in SSc patients display a risk factor for scleroderma renal crisis - A EUSTAR analysis

Lukas Bütikofer; Pierre A. Varisco; O. Distler; O. Kowal-Bielecka; Y. Allanore; G. Riemekasten; P. M. Villiger; S. Adler; Jérôme Avouac; Ulrich A. Walker; Serena Guiducci; Gabriele Riemekasten; Paolo Airò; Eric Hachulla; Gabriele Valentini; Patricia E. Carreira; Franco Cozzi; Alexandra Balbir Gurman; Yolanda Braun-Moscovici; Nemanja Damjanov; Lidia P. Ananieva; Raffaella Scorza; Sergio Jimenez; Joanna Busquets; Mengtao Li; Ulf Müller-Ladner; Britta Maurer; Alan Tyndall; Giovanni Lapadula; Florenzo Iannone; Radim Becvar; Stanislaw Sierakowsky; Otylia Kowal Bielecka; Maurizio Cutolo; Alberto Sulli; Giovanna Cuomo; Serena Vettori; Simona Rednic; Ileana Nicoara; P. Vlachoyiannopoulos; C. Montecucco; Roberto Caporali; Srdan Novak; László Czirják; Cecilia Varju; Carlo Chizzolini; Eugene J. Kucharz; Anna Kotulska; Magdalena Kopec-Medrek; Malgorzata Widuchowska; Blaz Rozman; Carmel Mallia; Bernard Coleiro; Armando Gabrielli; Dominique Farge; Adrian Hij; Roger Hesselstrand; Agneta Scheja; Frank Wollheim; Duska Martinovic; M. Govoni; Andrea Lo Monaco; Nicolas Hunzelmann; Raffaele Pellerito; Lisa Maria Bambara; Paola Caramaschi; Carol Black; Christopher Denton; Jörg Henes; Vera Ortiz Santamaria; Stefan Heitmann; Dorota Krasowska; Matthias Seidel; Mara Oleszowsky; Harald Burkhardt; Andrea Himsel; Maria J. Salvador; Bojana Stamenkovic; Aleksandra Stankovic; Mohammed Tikly; Maya N. Starovoytova; Merete Engelhart; Gitte Strauss; Henrik Nielsen; Kirsten Damgaard; Gabriella Szücs; Antonio Zea Mendoza; Carlos De La Puente Buijdos; Walter A. Sifuentes Giraldo; Øyvind Midtvedt; Torhild Garen; David Launay; Guido Valesini; Valeria Riccieri; Ruxandra Maria Ionescu; Daniela Opris; Laura Groseanu; Fredrick M. Wigley; Carmen M. Mihai; Roxana Sfrent Cornateanu; Razvan Ionitescu; Ana Maria Gherghe; Marilena Gorga; Rucsandra Dobrota; Mihai Bojinca; Georg Schett; Jörg H.W. Distler; Pierluigi Meroni; Silvana Zeni; Luc Mouthon; Filip De Keyser; Vanessa Smith; Francesco P. Cantatore; Ada Corrado; Susanne Ullman; Line Iversen; Maria R. Pozzi; Kilian Eyerich; Rüdiger Hein; Elisabeth Knott; Jacek Szechinski; Piotr Wiland; Magdalena Szmyrka-Kaczmarek; Renata Sokolik; Ewa Morgiel; Brigitte Krummel-Lorenz; Petra Saar; Martin Aringer; Claudia Günther; Branimir Anic; Marko Baresic; Miroslav Mayer; Sebastião C. Radominski; Carolina De Souza Müller; Valderílio F. Azevedo; Svetlana Agachi; Liliana Groppa; Lealea Chiaburu; Eugen Russu; Thierry Zenone; Simon Stebbings; John Highton; Lisa Stamp; Peter Chapman; Murray Baron; John O'Donnell; Kamal Solanki; Alan Doube; Douglas Veale; Marie O'Rourke; Esthela Loyo; Edoardo Rosato; Simonetta Pisarri; Cristina Mihaela Tanaseanu; Monica Popescu; Alina Dumitrascu; Isabela Tiglea; Rodica Chirieac; Codrina Ancuta; Daniel E. Furst; Suzanne Kafaja; Paloma García De La Peña Lefebvre; Silvia Rodriguez Rubio; Marta Valero Exposito; Jean Sibilia; Emmanuel Chatelus; Jacques Eric Gottenberg; Hélène Chifflot; Ira Litinsky; Algirdas Venalis; Irena Butrimiene; Paulius Venalis; Rita Rugiene; Diana Karpec; Eduardo Kerzberg; Fabiana Montoya; Vanesa Cosentino; Ivan Castellvi

doi:10.1186/s13075-020-2141-2

ACE inhibitors in SSc patients display a risk factor for scleroderma renal crisis - A EUSTAR analysis

Lukas Bütikofer, Pierre A. Varisco, O. Distler, O. Kowal-Bielecka, Y. Allanore, G. Riemekasten, P. M. Villiger, S. Adler, Jérôme Avouac, Ulrich A. Walker, Serena Guiducci, Gabriele Riemekasten, Paolo Airò, Eric Hachulla, Gabriele Valentini, Patricia E. Carreira, Franco Cozzi, Alexandra Balbir Gurman, Yolanda Braun-Moscovici, Nemanja DamjanovLidia P. Ananieva, Raffaella Scorza, Sergio Jimenez, Joanna Busquets, Mengtao Li, Ulf Müller-Ladner, Britta Maurer, Alan Tyndall, Giovanni Lapadula, Florenzo Iannone, Radim Becvar, Stanislaw Sierakowsky, Otylia Kowal Bielecka, Maurizio Cutolo, Alberto Sulli, Giovanna Cuomo, Serena Vettori, Simona Rednic, Ileana Nicoara, P. Vlachoyiannopoulos, C. Montecucco, Roberto Caporali, Srdan Novak, László Czirják, Cecilia Varju, Carlo Chizzolini, Eugene J. Kucharz, Anna Kotulska, Magdalena Kopec-Medrek, Malgorzata Widuchowska, Blaz Rozman, Carmel Mallia, Bernard Coleiro, Armando Gabrielli, Dominique Farge, Adrian Hij, Roger Hesselstrand, Agneta Scheja, Frank Wollheim, Duska Martinovic, M. Govoni, Andrea Lo Monaco, Nicolas Hunzelmann, Raffaele Pellerito, Lisa Maria Bambara, Paola Caramaschi, Carol Black, Christopher Denton, Jörg Henes, Vera Ortiz Santamaria, Stefan Heitmann, Dorota Krasowska, Matthias Seidel, Mara Oleszowsky, Harald Burkhardt, Andrea Himsel, Maria J. Salvador, Bojana Stamenkovic, Aleksandra Stankovic, Mohammed Tikly, Maya N. Starovoytova, Merete Engelhart, Gitte Strauss, Henrik Nielsen, Kirsten Damgaard, Gabriella Szücs, Antonio Zea Mendoza, Carlos De La Puente Buijdos, Walter A. Sifuentes Giraldo, Øyvind Midtvedt, Torhild Garen, David Launay, Guido Valesini, Valeria Riccieri, Ruxandra Maria Ionescu, Daniela Opris, Laura Groseanu, Fredrick M. Wigley, Carmen M. Mihai, Roxana Sfrent Cornateanu, Razvan Ionitescu, Ana Maria Gherghe, Marilena Gorga, Rucsandra Dobrota, Mihai Bojinca, Georg Schett, Jörg H.W. Distler, Pierluigi Meroni, Silvana Zeni, Luc Mouthon, Filip De Keyser, Vanessa Smith, Francesco P. Cantatore, Ada Corrado, Susanne Ullman, Line Iversen, Maria R. Pozzi, Kilian Eyerich, Rüdiger Hein, Elisabeth Knott, Jacek Szechinski, Piotr Wiland, Magdalena Szmyrka-Kaczmarek, Renata Sokolik, Ewa Morgiel, Brigitte Krummel-Lorenz, Petra Saar, Martin Aringer, Claudia Günther, Branimir Anic, Marko Baresic, Miroslav Mayer, Sebastião C. Radominski, Carolina De Souza Müller, Valderílio F. Azevedo, Svetlana Agachi, Liliana Groppa, Lealea Chiaburu, Eugen Russu, Thierry Zenone, Simon Stebbings, John Highton, Lisa Stamp, Peter Chapman, Murray Baron, John O'Donnell, Kamal Solanki, Alan Doube, Douglas Veale, Marie O'Rourke, Esthela Loyo, Edoardo Rosato, Simonetta Pisarri, Cristina Mihaela Tanaseanu, Monica Popescu, Alina Dumitrascu, Isabela Tiglea, Rodica Chirieac, Codrina Ancuta, Daniel E. Furst, Suzanne Kafaja, Paloma García De La Peña Lefebvre, Silvia Rodriguez Rubio, Marta Valero Exposito, Jean Sibilia, Emmanuel Chatelus, Jacques Eric Gottenberg, Hélène Chifflot, Ira Litinsky, Algirdas Venalis, Irena Butrimiene, Paulius Venalis, Rita Rugiene, Diana Karpec, Eduardo Kerzberg, Fabiana Montoya, Vanesa Cosentino, Ivan Castellvi

School of Medicine

Research output: Contribution to journal › Article › peer-review

7 Scopus citations

Abstract

Objectives: To investigate the effect of ACE inhibitors (ACEi) on the incidence of scleroderma renal crisis (SRC) when given prior to SRC in the prospectively collected cohort from the European Scleroderma Trial and Research Group (EUSTAR). Methods: SSc patients without prior SRC and at least one follow-up visit were included and analyzed regarding SRC, arterial hypertension, and medication focusing on antihypertensive medication and glucocorticoids (GC). Results: Out of 14,524 patients in the database, we identified 7648 patients with at least one follow-up. In 27,450 person-years (py), 102 patients developed SRC representing an incidence of 3.72 (3.06-4.51) per 1000 py. In a multivariable time-to-event analysis adjusted for age, sex, disease severity, and onset, 88 of 6521 patients developed SRC. The use of ACEi displayed an increased risk for the development of SRC with a hazard ratio (HR) of 2.55 (95% confidence interval (CI) 1.65-3.95). Adjusting for arterial hypertension resulted in a HR of 2.04 (95%CI 1.29-3.24). There was no evidence for an interaction of ACEi and arterial hypertension (HR 0.83, 95%CI 0.32-2.13, p = 0.69). Calcium channel blockers (CCB), angiotensin receptor blockers (ARB), endothelin receptor antagonists, and GC - mostly in daily dosages below 15 mg of prednisolone - did not influence the hazard for SRC. Conclusions: ACEi in SSc patients with concomitant arterial hypertension display an independent risk factor for the development of SRC but are still first choice in SRC treatment. ARBs might be a safe alternative, yet the overall safety of alternative antihypertensive drugs in SSc patients needs to be further studied.

Original language	English (US)
Article number	59
Journal	Arthritis Research and Therapy
Volume	22
Issue number	1
DOIs	https://doi.org/10.1186/s13075-020-2141-2
State	Published - Mar 24 2020

Keywords

ACE inhibitors
Antihypertensive drugs
Arterial hypertension
Outcome
Scleroderma renal crisis

ASJC Scopus subject areas

Rheumatology
Immunology and Allergy
Immunology

Access to Document

10.1186/s13075-020-2141-2

Cite this

Bütikofer, L., Varisco, P. A., Distler, O., Kowal-Bielecka, O., Allanore, Y., Riemekasten, G., Villiger, P. M., Adler, S., Avouac, J., Walker, U. A., Guiducci, S., Riemekasten, G., Airò, P., Hachulla, E., Valentini, G., Carreira, P. E., Cozzi, F., Gurman, A. B., Braun-Moscovici, Y., ... Castellvi, I. (2020). ACE inhibitors in SSc patients display a risk factor for scleroderma renal crisis - A EUSTAR analysis. Arthritis Research and Therapy, 22(1), Article 59. https://doi.org/10.1186/s13075-020-2141-2

Bütikofer, L, Varisco, PA, Distler, O, Kowal-Bielecka, O, Allanore, Y, Riemekasten, G, Villiger, PM, Adler, S, Avouac, J, Walker, UA, Guiducci, S, Riemekasten, G, Airò, P, Hachulla, E, Valentini, G, Carreira, PE, Cozzi, F, Gurman, AB, Braun-Moscovici, Y, Damjanov, N, Ananieva, LP, Scorza, R, Jimenez, S, Busquets, J, Li, M, Müller-Ladner, U, Maurer, B, Tyndall, A, Lapadula, G, Iannone, F, Becvar, R, Sierakowsky, S, Bielecka, OK, Cutolo, M, Sulli, A, Cuomo, G, Vettori, S, Rednic, S, Nicoara, I, Vlachoyiannopoulos, P, Montecucco, C, Caporali, R, Novak, S, Czirják, L, Varju, C, Chizzolini, C, Kucharz, EJ, Kotulska, A, Kopec-Medrek, M, Widuchowska, M, Rozman, B, Mallia, C, Coleiro, B, Gabrielli, A, Farge, D, Hij, A, Hesselstrand, R, Scheja, A, Wollheim, F, Martinovic, D, Govoni, M, Monaco, AL, Hunzelmann, N, Pellerito, R, Bambara, LM, Caramaschi, P, Black, C, Denton, C, Henes, J, Santamaria, VO, Heitmann, S, Krasowska, D, Seidel, M, Oleszowsky, M, Burkhardt, H, Himsel, A, Salvador, MJ, Stamenkovic, B, Stankovic, A, Tikly, M, Starovoytova, MN, Engelhart, M, Strauss, G, Nielsen, H, Damgaard, K, Szücs, G, Mendoza, AZ, De La Puente Buijdos, C, Sifuentes Giraldo, WA, Midtvedt, Ø, Garen, T, Launay, D, Valesini, G, Riccieri, V, Ionescu, RM, Opris, D, Groseanu, L, Wigley, FM, Mihai, CM, Cornateanu, RS, Ionitescu, R, Gherghe, AM, Gorga, M, Dobrota, R, Bojinca, M, Schett, G, Distler, JHW, Meroni, P, Zeni, S, Mouthon, L, De Keyser, F, Smith, V, Cantatore, FP, Corrado, A, Ullman, S, Iversen, L, Pozzi, MR, Eyerich, K, Hein, R, Knott, E, Szechinski, J, Wiland, P, Szmyrka-Kaczmarek, M, Sokolik, R, Morgiel, E, Krummel-Lorenz, B, Saar, P, Aringer, M, Günther, C, Anic, B, Baresic, M, Mayer, M, Radominski, SC, De Souza Müller, C, Azevedo, VF, Agachi, S, Groppa, L, Chiaburu, L, Russu, E, Zenone, T, Stebbings, S, Highton, J, Stamp, L, Chapman, P, Baron, M, O'Donnell, J, Solanki, K, Doube, A, Veale, D, O'Rourke, M, Loyo, E, Rosato, E, Pisarri, S, Tanaseanu, CM, Popescu, M, Dumitrascu, A, Tiglea, I, Chirieac, R, Ancuta, C, Furst, DE, Kafaja, S, De La Peña Lefebvre, PG, Rubio, SR, Exposito, MV, Sibilia, J, Chatelus, E, Gottenberg, JE, Chifflot, H, Litinsky, I, Venalis, A, Butrimiene, I, Venalis, P, Rugiene, R, Karpec, D, Kerzberg, E, Montoya, F, Cosentino, V & Castellvi, I 2020, 'ACE inhibitors in SSc patients display a risk factor for scleroderma renal crisis - A EUSTAR analysis', Arthritis Research and Therapy, vol. 22, no. 1, 59. https://doi.org/10.1186/s13075-020-2141-2

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title = "ACE inhibitors in SSc patients display a risk factor for scleroderma renal crisis - A EUSTAR analysis",

abstract = "Objectives: To investigate the effect of ACE inhibitors (ACEi) on the incidence of scleroderma renal crisis (SRC) when given prior to SRC in the prospectively collected cohort from the European Scleroderma Trial and Research Group (EUSTAR). Methods: SSc patients without prior SRC and at least one follow-up visit were included and analyzed regarding SRC, arterial hypertension, and medication focusing on antihypertensive medication and glucocorticoids (GC). Results: Out of 14,524 patients in the database, we identified 7648 patients with at least one follow-up. In 27,450 person-years (py), 102 patients developed SRC representing an incidence of 3.72 (3.06-4.51) per 1000 py. In a multivariable time-to-event analysis adjusted for age, sex, disease severity, and onset, 88 of 6521 patients developed SRC. The use of ACEi displayed an increased risk for the development of SRC with a hazard ratio (HR) of 2.55 (95% confidence interval (CI) 1.65-3.95). Adjusting for arterial hypertension resulted in a HR of 2.04 (95%CI 1.29-3.24). There was no evidence for an interaction of ACEi and arterial hypertension (HR 0.83, 95%CI 0.32-2.13, p = 0.69). Calcium channel blockers (CCB), angiotensin receptor blockers (ARB), endothelin receptor antagonists, and GC - mostly in daily dosages below 15 mg of prednisolone - did not influence the hazard for SRC. Conclusions: ACEi in SSc patients with concomitant arterial hypertension display an independent risk factor for the development of SRC but are still first choice in SRC treatment. ARBs might be a safe alternative, yet the overall safety of alternative antihypertensive drugs in SSc patients needs to be further studied.",

keywords = "ACE inhibitors, Antihypertensive drugs, Arterial hypertension, Outcome, Scleroderma renal crisis",

author = "Lukas B{\"u}tikofer and Varisco, {Pierre A.} and O. Distler and O. Kowal-Bielecka and Y. Allanore and G. Riemekasten and Villiger, {P. M.} and S. Adler and J{\'e}r{\^o}me Avouac and Walker, {Ulrich A.} and Serena Guiducci and Gabriele Riemekasten and Paolo Air{\`o} and Eric Hachulla and Gabriele Valentini and Carreira, {Patricia E.} and Franco Cozzi and Gurman, {Alexandra Balbir} and Yolanda Braun-Moscovici and Nemanja Damjanov and Ananieva, {Lidia P.} and Raffaella Scorza and Sergio Jimenez and Joanna Busquets and Mengtao Li and Ulf M{\"u}ller-Ladner and Britta Maurer and Alan Tyndall and Giovanni Lapadula and Florenzo Iannone and Radim Becvar and Stanislaw Sierakowsky and Bielecka, {Otylia Kowal} and Maurizio Cutolo and Alberto Sulli and Giovanna Cuomo and Serena Vettori and Simona Rednic and Ileana Nicoara and P. Vlachoyiannopoulos and C. Montecucco and Roberto Caporali and Srdan Novak and L{\'a}szl{\'o} Czirj{\'a}k and Cecilia Varju and Carlo Chizzolini and Kucharz, {Eugene J.} and Anna Kotulska and Magdalena Kopec-Medrek and Malgorzata Widuchowska and Blaz Rozman and Carmel Mallia and Bernard Coleiro and Armando Gabrielli and Dominique Farge and Adrian Hij and Roger Hesselstrand and Agneta Scheja and Frank Wollheim and Duska Martinovic and M. Govoni and Monaco, {Andrea Lo} and Nicolas Hunzelmann and Raffaele Pellerito and Bambara, {Lisa Maria} and Paola Caramaschi and Carol Black and Christopher Denton and J{\"o}rg Henes and Santamaria, {Vera Ortiz} and Stefan Heitmann and Dorota Krasowska and Matthias Seidel and Mara Oleszowsky and Harald Burkhardt and Andrea Himsel and Salvador, {Maria J.} and Bojana Stamenkovic and Aleksandra Stankovic and Mohammed Tikly and Starovoytova, {Maya N.} and Merete Engelhart and Gitte Strauss and Henrik Nielsen and Kirsten Damgaard and Gabriella Sz{\"u}cs and Mendoza, {Antonio Zea} and {De La Puente Buijdos}, Carlos and {Sifuentes Giraldo}, {Walter A.} and {\O}yvind Midtvedt and Torhild Garen and David Launay and Guido Valesini and Valeria Riccieri and Ionescu, {Ruxandra Maria} and Daniela Opris and Laura Groseanu and Wigley, {Fredrick M.} and Mihai, {Carmen M.} and Cornateanu, {Roxana Sfrent} and Razvan Ionitescu and Gherghe, {Ana Maria} and Marilena Gorga and Rucsandra Dobrota and Mihai Bojinca and Georg Schett and Distler, {J{\"o}rg H.W.} and Pierluigi Meroni and Silvana Zeni and Luc Mouthon and {De Keyser}, Filip and Vanessa Smith and Cantatore, {Francesco P.} and Ada Corrado and Susanne Ullman and Line Iversen and Pozzi, {Maria R.} and Kilian Eyerich and R{\"u}diger Hein and Elisabeth Knott and Jacek Szechinski and Piotr Wiland and Magdalena Szmyrka-Kaczmarek and Renata Sokolik and Ewa Morgiel and Brigitte Krummel-Lorenz and Petra Saar and Martin Aringer and Claudia G{\"u}nther and Branimir Anic and Marko Baresic and Miroslav Mayer and Radominski, {Sebasti{\~a}o C.} and {De Souza M{\"u}ller}, Carolina and Azevedo, {Valder{\'i}lio F.} and Svetlana Agachi and Liliana Groppa and Lealea Chiaburu and Eugen Russu and Thierry Zenone and Simon Stebbings and John Highton and Lisa Stamp and Peter Chapman and Murray Baron and John O'Donnell and Kamal Solanki and Alan Doube and Douglas Veale and Marie O'Rourke and Esthela Loyo and Edoardo Rosato and Simonetta Pisarri and Tanaseanu, {Cristina Mihaela} and Monica Popescu and Alina Dumitrascu and Isabela Tiglea and Rodica Chirieac and Codrina Ancuta and Furst, {Daniel E.} and Suzanne Kafaja and {De La Pe{\~n}a Lefebvre}, {Paloma Garc{\'i}a} and Rubio, {Silvia Rodriguez} and Exposito, {Marta Valero} and Jean Sibilia and Emmanuel Chatelus and Gottenberg, {Jacques Eric} and H{\'e}l{\`e}ne Chifflot and Ira Litinsky and Algirdas Venalis and Irena Butrimiene and Paulius Venalis and Rita Rugiene and Diana Karpec and Eduardo Kerzberg and Fabiana Montoya and Vanesa Cosentino and Ivan Castellvi",

note = "Publisher Copyright: {\textcopyright} 2020 The Author(s).",

year = "2020",

month = mar,

day = "24",

doi = "10.1186/s13075-020-2141-2",

language = "English (US)",

volume = "22",

journal = "Arthritis Research and Therapy",

issn = "1478-6354",

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TY - JOUR

T1 - ACE inhibitors in SSc patients display a risk factor for scleroderma renal crisis - A EUSTAR analysis

AU - Bütikofer, Lukas

AU - Varisco, Pierre A.

AU - Distler, O.

AU - Kowal-Bielecka, O.

AU - Allanore, Y.

AU - Riemekasten, G.

AU - Villiger, P. M.

AU - Adler, S.

AU - Avouac, Jérôme

AU - Walker, Ulrich A.

AU - Guiducci, Serena

AU - Riemekasten, Gabriele

AU - Airò, Paolo

AU - Hachulla, Eric

AU - Valentini, Gabriele

AU - Carreira, Patricia E.

AU - Cozzi, Franco

AU - Gurman, Alexandra Balbir

AU - Braun-Moscovici, Yolanda

AU - Damjanov, Nemanja

AU - Ananieva, Lidia P.

AU - Scorza, Raffaella

AU - Jimenez, Sergio

AU - Busquets, Joanna

AU - Li, Mengtao

AU - Müller-Ladner, Ulf

AU - Maurer, Britta

AU - Tyndall, Alan

AU - Lapadula, Giovanni

AU - Iannone, Florenzo

AU - Becvar, Radim

AU - Sierakowsky, Stanislaw

AU - Bielecka, Otylia Kowal

AU - Cutolo, Maurizio

AU - Sulli, Alberto

AU - Cuomo, Giovanna

AU - Vettori, Serena

AU - Rednic, Simona

AU - Nicoara, Ileana

AU - Vlachoyiannopoulos, P.

AU - Montecucco, C.

AU - Caporali, Roberto

AU - Novak, Srdan

AU - Czirják, László

AU - Varju, Cecilia

AU - Chizzolini, Carlo

AU - Kucharz, Eugene J.

AU - Kotulska, Anna

AU - Kopec-Medrek, Magdalena

AU - Widuchowska, Malgorzata

AU - Rozman, Blaz

AU - Mallia, Carmel

AU - Coleiro, Bernard

AU - Gabrielli, Armando

AU - Farge, Dominique

AU - Hij, Adrian

AU - Hesselstrand, Roger

AU - Scheja, Agneta

AU - Wollheim, Frank

AU - Martinovic, Duska

AU - Govoni, M.

AU - Monaco, Andrea Lo

AU - Hunzelmann, Nicolas

AU - Pellerito, Raffaele

AU - Bambara, Lisa Maria

AU - Caramaschi, Paola

AU - Black, Carol

AU - Denton, Christopher

AU - Henes, Jörg

AU - Santamaria, Vera Ortiz

AU - Heitmann, Stefan

AU - Krasowska, Dorota

AU - Seidel, Matthias

AU - Oleszowsky, Mara

AU - Burkhardt, Harald

AU - Himsel, Andrea

AU - Salvador, Maria J.

AU - Stamenkovic, Bojana

AU - Stankovic, Aleksandra

AU - Tikly, Mohammed

AU - Starovoytova, Maya N.

AU - Engelhart, Merete

AU - Strauss, Gitte

AU - Nielsen, Henrik

AU - Damgaard, Kirsten

AU - Szücs, Gabriella

AU - Mendoza, Antonio Zea

AU - De La Puente Buijdos, Carlos

AU - Sifuentes Giraldo, Walter A.

AU - Midtvedt, Øyvind

AU - Garen, Torhild

AU - Launay, David

AU - Valesini, Guido

AU - Riccieri, Valeria

AU - Ionescu, Ruxandra Maria

AU - Opris, Daniela

AU - Groseanu, Laura

AU - Wigley, Fredrick M.

AU - Mihai, Carmen M.

AU - Cornateanu, Roxana Sfrent

AU - Ionitescu, Razvan

AU - Gherghe, Ana Maria

AU - Gorga, Marilena

AU - Dobrota, Rucsandra

AU - Bojinca, Mihai

AU - Schett, Georg

AU - Distler, Jörg H.W.

AU - Meroni, Pierluigi

AU - Zeni, Silvana

AU - Mouthon, Luc

AU - De Keyser, Filip

AU - Smith, Vanessa

AU - Cantatore, Francesco P.

AU - Corrado, Ada

AU - Ullman, Susanne

AU - Iversen, Line

AU - Pozzi, Maria R.

AU - Eyerich, Kilian

AU - Hein, Rüdiger

AU - Knott, Elisabeth

AU - Szechinski, Jacek

AU - Wiland, Piotr

AU - Szmyrka-Kaczmarek, Magdalena

AU - Sokolik, Renata

AU - Morgiel, Ewa

AU - Krummel-Lorenz, Brigitte

AU - Saar, Petra

AU - Aringer, Martin

AU - Günther, Claudia

AU - Anic, Branimir

AU - Baresic, Marko

AU - Mayer, Miroslav

AU - Radominski, Sebastião C.

AU - De Souza Müller, Carolina

AU - Azevedo, Valderílio F.

AU - Agachi, Svetlana

AU - Groppa, Liliana

AU - Chiaburu, Lealea

AU - Russu, Eugen

AU - Zenone, Thierry

AU - Stebbings, Simon

AU - Highton, John

AU - Stamp, Lisa

AU - Chapman, Peter

AU - Baron, Murray

AU - O'Donnell, John

AU - Solanki, Kamal

AU - Doube, Alan

AU - Veale, Douglas

AU - O'Rourke, Marie

AU - Loyo, Esthela

AU - Rosato, Edoardo

AU - Pisarri, Simonetta

AU - Tanaseanu, Cristina Mihaela

AU - Popescu, Monica

AU - Dumitrascu, Alina

AU - Tiglea, Isabela

AU - Chirieac, Rodica

AU - Ancuta, Codrina

AU - Furst, Daniel E.

AU - Kafaja, Suzanne

AU - De La Peña Lefebvre, Paloma García

AU - Rubio, Silvia Rodriguez

AU - Exposito, Marta Valero

AU - Sibilia, Jean

AU - Chatelus, Emmanuel

AU - Gottenberg, Jacques Eric

AU - Chifflot, Hélène

AU - Litinsky, Ira

AU - Venalis, Algirdas

AU - Butrimiene, Irena

AU - Venalis, Paulius

AU - Rugiene, Rita

AU - Karpec, Diana

AU - Kerzberg, Eduardo

AU - Montoya, Fabiana

AU - Cosentino, Vanesa

AU - Castellvi, Ivan

PY - 2020/3/24

Y1 - 2020/3/24

N2 - Objectives: To investigate the effect of ACE inhibitors (ACEi) on the incidence of scleroderma renal crisis (SRC) when given prior to SRC in the prospectively collected cohort from the European Scleroderma Trial and Research Group (EUSTAR). Methods: SSc patients without prior SRC and at least one follow-up visit were included and analyzed regarding SRC, arterial hypertension, and medication focusing on antihypertensive medication and glucocorticoids (GC). Results: Out of 14,524 patients in the database, we identified 7648 patients with at least one follow-up. In 27,450 person-years (py), 102 patients developed SRC representing an incidence of 3.72 (3.06-4.51) per 1000 py. In a multivariable time-to-event analysis adjusted for age, sex, disease severity, and onset, 88 of 6521 patients developed SRC. The use of ACEi displayed an increased risk for the development of SRC with a hazard ratio (HR) of 2.55 (95% confidence interval (CI) 1.65-3.95). Adjusting for arterial hypertension resulted in a HR of 2.04 (95%CI 1.29-3.24). There was no evidence for an interaction of ACEi and arterial hypertension (HR 0.83, 95%CI 0.32-2.13, p = 0.69). Calcium channel blockers (CCB), angiotensin receptor blockers (ARB), endothelin receptor antagonists, and GC - mostly in daily dosages below 15 mg of prednisolone - did not influence the hazard for SRC. Conclusions: ACEi in SSc patients with concomitant arterial hypertension display an independent risk factor for the development of SRC but are still first choice in SRC treatment. ARBs might be a safe alternative, yet the overall safety of alternative antihypertensive drugs in SSc patients needs to be further studied.

AB - Objectives: To investigate the effect of ACE inhibitors (ACEi) on the incidence of scleroderma renal crisis (SRC) when given prior to SRC in the prospectively collected cohort from the European Scleroderma Trial and Research Group (EUSTAR). Methods: SSc patients without prior SRC and at least one follow-up visit were included and analyzed regarding SRC, arterial hypertension, and medication focusing on antihypertensive medication and glucocorticoids (GC). Results: Out of 14,524 patients in the database, we identified 7648 patients with at least one follow-up. In 27,450 person-years (py), 102 patients developed SRC representing an incidence of 3.72 (3.06-4.51) per 1000 py. In a multivariable time-to-event analysis adjusted for age, sex, disease severity, and onset, 88 of 6521 patients developed SRC. The use of ACEi displayed an increased risk for the development of SRC with a hazard ratio (HR) of 2.55 (95% confidence interval (CI) 1.65-3.95). Adjusting for arterial hypertension resulted in a HR of 2.04 (95%CI 1.29-3.24). There was no evidence for an interaction of ACEi and arterial hypertension (HR 0.83, 95%CI 0.32-2.13, p = 0.69). Calcium channel blockers (CCB), angiotensin receptor blockers (ARB), endothelin receptor antagonists, and GC - mostly in daily dosages below 15 mg of prednisolone - did not influence the hazard for SRC. Conclusions: ACEi in SSc patients with concomitant arterial hypertension display an independent risk factor for the development of SRC but are still first choice in SRC treatment. ARBs might be a safe alternative, yet the overall safety of alternative antihypertensive drugs in SSc patients needs to be further studied.

KW - ACE inhibitors

KW - Antihypertensive drugs

KW - Arterial hypertension

KW - Outcome

KW - Scleroderma renal crisis

UR - http://www.scopus.com/inward/record.url?scp=85082380829&partnerID=8YFLogxK

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U2 - 10.1186/s13075-020-2141-2

DO - 10.1186/s13075-020-2141-2

M3 - Article

C2 - 32209135

AN - SCOPUS:85082380829

SN - 1478-6354

VL - 22

JO - Arthritis Research and Therapy

JF - Arthritis Research and Therapy

IS - 1

M1 - 59

ER -

ACE inhibitors in SSc patients display a risk factor for scleroderma renal crisis - A EUSTAR analysis

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