Prevention of vascular damage in scleroderma and autoimmune Raynaud's phenomenon: A multicenter, randomized, double‐blind, placebo‐controlled trial of the angiotensin‐converting enzyme inhibitor quinapril

Abstract

Objective. To evaluate the efficacy and tolerability of prolonged administration of quinapril, a long-acting angiotensin-converting enzyme inhibitor, in the management of the peripheral vascular manifestations of limited cutaneous systemic sclerosis (lcSSc) and in the prevention of the progression of visceral organ involvement in the disease.Methods. This was a multicenter, randomized, double-blind, placebo-controlled study evaluating quinapril 80 mg/day, or the maximum tolerated dosage, in 210 patients with lcSSc or with Raynaud's phenomenon (RP) and the presence of SSc-specific antinuclear antibodies. Treatment was for 2-3 years. The primary outcome measure was the number of new ischemic ulcers appearing on the hands; secondary measures were the frequency and severity of RP attacks, skin score, treatments for ischemia, health status (measured by the Short Form 36 instrument), measures of kidney and lung function, and echocardiographic estimates of pulmonary artery pressure. An intent-to-treat analysis was used.Results. Quinapril did not affect the occurrence of digital ulcers or the frequency or severity of RP episodes. It did not alter the treatments that were prescribed for either infected ulcers or severe RP symptoms. There was no apparent effect on the estimated tricuspid gradient. Health status was not affected by quinapril, and one-half of the patients who believed they had benefited from the trial treatment were in the placebo arm. Quinapril was not tolerated by one-fifth of the patients, with dry cough being the most frequent side effect.Conclusion. Administration of quinapril for up to 3 years had no demonstrable effects on the occurrence of upper limb digital ulcers or on other vascular manifestations of lcSSc in this patient population. ISRCTN: 57984704.

Raynaud’s phenomenon and digital ischaemia - pharmacologic approach and alternative treatment options

“…Although captopril and enalapril were shown to reduce the number of attacks in patients with primary RP, no such eff ect was observed in patients with secondary RP [39,40]. In addition, an RCT including 210 patients with limited cutaneous systemic sclerosis (SSc) or RP with the presence of SSc-specifi c antinuclear antibodies did not reveal benefi cial eff ects of quinapril treatment for up to 3 years with regard to the incidence of digital ulcers or to the frequency or severity of RP episodes [41].…”

“…It is noteworthy that approximately 95 % of all SSc patients suff er from RP; the prevalence of RP is also high in patients with mixed connective tissue disease (MCTD; 86 %), systemic lupus erythematosus (SLE; 31 %), undiff erentiated CTD (30 %), rheumatoid arthritis (22 %) and Sjögren syndrome (13 %) [1]. Landry et al followed a total of 1039 RP patients for a median of 3.2 years (range 0 -21 years) and stratifi ed the patients according to the presence or absence of structural vascular disease and according to the presence or absence of autoantibodies (i.e., ANAs, antibodies against extractable nuclear antigens [ENAs] or rheumatoid factor) [ ESM 2,41]. Digital skin ulcers occurred in 5.2 % of vasospastic/seronegative RP, 15.5 % of vasospastic/seropositive RP, 48.2 % in obstructive/seronegative RP and 55.6 % of obstructive/seropositive RP.…”

Lack of agreement between rheumatologists in defining digital ulceration in systemic sclerosis

“…These types of ulcers are often used as a primary end point in clinical trials of SSc-related digital ischemia and vasculopathy, as was the case in 2 recent multicenter placebo-controlled trials (3,4). Patient-assessed digital ulcer "activity" was among a core set of measures proposed for use in trials of SSc-related Raynaud's phenomenon (5).…”

Drug Treatment of Raynaud’s Phenomenon

“…Enalapril was ineffective in the treatment of primary RP in one trial [ 57 ], whereas in a crossover trial of primary and secondary RP, enalapril at 20 mg daily reduced in the frequency of Raynaud's attacks, especially in patients with primary Raynaud's [ 58 ]. Long term use of quinapril at 80 mg/day in a large placebo controlled trial was negative with respect to RP in patients with limited SSc or suspected SSc [ 59 ]. Overall the data does not support the use of an ACE inhibitor.…”