ACE inhibitors heighten risk of renal crisis in systemic sclerosis
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Angiotensin-converting enzyme inhibitors in patients with systemic sclerosis and concomitant arterial hypertension demonstrate an independent risk factor for developing scleroderma renal crisis, according to data published in Arthritis Research & Therapy.
Despite this, ACE inhibitors remain the first choice for scleroderma renal crisis treatment, the researchers added.
“ACE inhibitors (ACEi) are the mainstay of therapy in scleroderma renal crisis (SRC),” Lukas Bütikofer, PhD, of the CTU Bern and Institute of Social and Preventive Medicine at Bern University, in Switzerland, and colleagues wrote. “Initiation of their use allowed for major increased survival rates of SRC over the last decades yet with mostly lasting sequelae.”
“Nevertheless, the incidence of SRC remained almost unchanged over the last decades and SRC risk factors are still poorly understood,” they added. “Among those, the use of ACEi in hypertensive SSc patients prior to any SRC episode is meanwhile contradictorily discussed. While ACEi are supposed to lower the risk of SRC at the same time as they lower blood pressure, there are a few data that SRC outcome is worse in patients with prior ACEi intake.”
To determine whether the impact of ACE inhibitors on the incidence of scleroderma renal crisis when administered prior to condition among patients with SSc, Bütikofer and colleagues analyzed the European Scleroderma Trials and Research (EUSTAR) database. According to the researchers, EUSTAR is an online source of prospectively collected data from more than 15,000 patients with SSc from more than 200 international centers.
For their own investigation, the researchers studied data on patients with SSc and without prior scleroderma renal crisis, and who had at least one follow-up visit, focusing on the development of scleroderma renal crisis, arterial hypertension and medication use.
To accomplish this, Bütikofer and colleagues used two datasets. First, they analyzed the so-called “complete” dataset, including all information within EUSTAR up to Nov. 15, 2017. The second dataset was the co-called “medication” subset, for which medication was recorded with data collected on or after Jan. 1, 2009, when EUSTAR begin documentation of medication. Among 14,524 eligible EUSTAR participants with SSc, 9,690 and 7,648 individuals were included in the complete and medication datasets, respectively.
According to the researchers, among the 7,648 participants with at least one follow-up, 102 patients developed scleroderma renal crisis throughout 27,450 person-years, representing an incidence of 3.72 (95% CI, 3.06-4.51) per 1,000 patient years. In a multivariable, time-to-event analysis, which was adjusted for age, sex, disease severity and onset, 88 of 6,521 patients developed scleroderma renal crisis. The use of ACE inhibitors increased the risk for scleroderma renal crisis incidence (HR = 2.55; 95% CI, 1.65-3.95). After adjusting for arterial hypertension, the hazard ratio was 2.04 (95% CI, 1.29-3.24).
Additionally, there was no evidence for an interaction between ACR inhibitors and arterial hypertension (HR = 0.83; 95% CI, 0.32-2.13). Calcium channel blockers, angiotensin receptor blockers, endothelin receptor antagonists and glucocorticoids — especially in daily dosages below 15mg of prednisolone — failed to impact the hazard for scleroderma renal crisis.
“ACEi in SSc patients with concomitant arterial hypertension display an independent risk factor for the development of SRC,” Bütikofer and colleagues wrote. “Still, they are the mainstay of treatment once SRC is established. [Angiotensin receptor blockers] might be a safe option in the treatment of arterial hypertension with a possibly lower risk for development of SRC. Yet, the overall safety of alternative antihypertensive drugs in SSc patients needs to be studied.” – by Jason Laday
Disclosures: The researchers report no relevant financial disclosures.
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