INTRODUCTION: In animal studies, aldosterone enhanced neointimal proliferation by increasing extracellular accumulation of collagen and potentiating the effects of angiotensin II. Spironolactone, an aldosterone antagonist, is a potent inhibitor of neointimal proliferation. We conducted a placebo-controlled, double-blind, randomised study to assess the effect of spironolactone on angiographic 6-month in-stent restenosis. MATERIALS AND METHODS: Of the 310 randomised patients with significant coronary artery disease, 258 patients were available for analysis: 128 constituted the placebo group and 130 were assigned to receivespironolactone. Eligible patients were randomly assigned to receive a dose of 50 mg spironolactone or placebo orally twice a day for 6 months. The primary endpoint was the angiographic restenosis (>50% stenosis) rate at follow-up angiography. RESULTS: At 6-month follow-up angiography after stenting, there was no difference between the 2 groups in minimal lumen diameter, percent diameter stenosis, late loss, and net gain. Angiographic restenosis occurred in 46 (35.4%) of 130 patients receiving spironolactone and 50 (39.0%) of 128 in the placebo group with an odds ratio (OR) of 0.85 with a 95% confidence interval (CI) of 0.49 to 1.46 (P = 0.62). Restenosis rate was found in 60 (32.9%) of 182 lesions in the spironolactone group, and 61 (35.5%) of 172 lesions in the placebo group with an OR of 0.89 with a 95% CI of 0.56 to 1.42 (P = 0.89). CONCLUSIONS:Spironolactone did not reduce the incidence of in-stent restenosis as compared with placebo in human, contrary to the fact that reduction of neointimal formation in animal models has been observed upon administration of spironolactone.
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INTRODUCTION: In animal studies, aldosterone enhanced neointimal proliferation by increasing extracellular accumulation of collagen and potentiating the effects of angiotensin II. Spironolactone, an aldosterone antagonist, is a potent inhibitor of neointimal proliferation. We conducted a placebo-controlled, double-blind, randomised study to assess the effect of spironolactone on angiographic 6-month in-stent restenosis. MATERIALS AND METHODS: Of the 310 randomised patients with significant coronary artery disease, 258 patients were available for analysis: 128 constituted the placebo group and 130 were assigned to receive spironolactone. Eligible patients were randomly assigned to receive a dose of 50 mg spironolactone or placebo orally twice a day for 6 months. The primary endpoint was the angiographic restenosis (>50% stenosis) rate at follow-up angiography. RESULTS: At 6-month follow-up angiography after stenting, there was no difference between the 2 groups in minimal lumen diameter, percent diameter stenosis, late loss, and net gain. Angiographic restenosis occurred in 46 (35.4%) of 130 patients receiving spironolactone and 50 (39.0%) of 128 in the placebo group with an odds ratio (OR) of 0.85 with a 95% confidence interval (CI) of 0.49 to 1.46 (P = 0.62). Restenosis rate was found in 60 (32.9%) of 182 lesions in the spironolactone group, and 61 (35.5%) of 172 lesions in the placebo group with an OR of 0.89 with a 95% CI of 0.56 to 1.42 (P = 0.89). CONCLUSIONS:Spironolactone did not reduce the incidence of in-stent restenosis as compared with placebo in human, contrary to the fact that reduction of neointimal formation in animal models has been observed upon administration of spironolactone.
Authors: Jochen Dutzmann; Robert-Jonathan Musmann; Marco Haertlé; Jan-Marcus Daniel; Kristina Sonnenschein; Andreas Schäfer; Peter Kolkhof; Johann Bauersachs; Daniel G Sedding Journal: PLoS One Date: 2017-09-19 Impact factor: 3.240