Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Mar 24;22(1):59.
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  1 , Pierre A Varisco  2 , O Distler  3 , O Kowal-Bielecka  4 , Y Allanore  5 , G Riemekasten  6 , P M Villiger  7   8 , S Adler  9   10   11 ; EUSTAR collaborators
Collaborators, Affiliations

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

Lukas Bütikofer et al. Arthritis Res Ther. .

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.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Patient flow. *Does not sum up as categories are not exclusive
Fig. 2
Fig. 2
Kaplan-Meier failure plot for mortality with 95% confidence intervals of patients with and without scleroderma renal crisis (SRC) based on the complete dataset
Fig. 3
Fig. 3
Cumulative incidence of SRC with 95% confidence intervals depending on whether patients have arterial hypertension (AH) based on the complete dataset or are treated with ACE inhibitors (ACE), calcium channel blockers (CCB), or glucocorticoids (GC) based on the medication dataset
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Steen VD, Costantino JP, Shapiro AP, Medsger TA., Jr Outcome of renal crisis in systemic sclerosis: relation to availability of angiotensin converting enzyme (ACE) inhibitors. Ann Intern Med. 1990;113(5):352–357. doi: 10.7326/0003-4819-113-5-352. - DOI - PubMed
    1. Hudson M, Baron M, Tatibouet S, Furst DE, Khanna D. International scleroderma renal crisis study I. Exposure to ACE inhibitors prior to the onset of scleroderma renal crisis-results from the international scleroderma renal crisis survey. Semin Arthritis Rheum. 2014;43(5):666–672. doi: 10.1016/j.semarthrit.2013.09.008. - DOI - PubMed
    1. Guillevin L, Berezne A, Seror R, Teixeira L, Pourrat J, Mahr A, et al. Scleroderma renal crisis: a retrospective multicentre study on 91 patients and 427 controls. Rheumatology. 2012;51(3):460–467. doi: 10.1093/rheumatology/ker271. - DOI - PubMed
    1. Mouthon L, Berezne A, Bussone G, Noel LH, Villiger PM, Guillevin L. Scleroderma renal crisis: a rare but severe complication of systemic sclerosis. Clin Rev Allergy Immunol. 2011;40(2):84–91. doi: 10.1007/s12016-009-8191-5. - DOI - PubMed
    1. Khalaf M, Chowdhary S, Elias PS, Castell D. Distal esophageal spasm: a review. Am J Med. 2018;131(9):1034–1040. doi: 10.1016/j.amjmed.2018.02.031. - DOI - PubMed

Publication types

Substances