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

Research output: Contribution to journalArticlepeer-review

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 languageEnglish (US)
Article number59
JournalArthritis Research and Therapy
Volume22
Issue number1
DOIs
StatePublished - Mar 24 2020

Keywords

  • ACE inhibitors
  • Antihypertensive drugs
  • Arterial hypertension
  • Outcome
  • Scleroderma renal crisis

ASJC Scopus subject areas

  • Rheumatology
  • Immunology and Allergy
  • Immunology

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