Effect of spironolactone on cardiovascular morbidity and mortality in patients with hypertension and glucose metabolism disorders (ESCAM): a study protocol for a pragmatic randomised controlled trial

Abstract

IntroductionHypertension combined with diabetes and hypokalemia is more likely to develop hyperaldosteronism and is at higher risk of cardiovascular events. There is evidence that activation of aldosterone and mineralocorticoid receptors may play a significant role in the occurrence of cardiovascular events in patients with hypertension and diabetes. Clinical studies have demonstrated that spironolactone can reduce the incidence of cardiovascular events in patients with chronic kidney diseases or severe heart failure. However, the effect of spironolactone on cardiovascular risk in patients with hypertension and glucose metabolism disorders (GMD) and low potassium has been scarcely studied. Therefore, this study aims to evaluate whether add-on spironolactone (conventional antihypertensive drugs alone vs conventional antihypertensive drugs+spironolactone) can reduce the morbidity and mortality of cardiovascular events in this population.Methods and analysisIn this multicentre, randomised, parallel-controlled study, a total of 7140 hypertensive patients aged 45–75 years with GMD and low potassium will be randomised in a 1:1 manner to the control or the spironolactone group (20 mg/day or with a maximum dose of 40 mg). The primary objective is to estimate the difference in the HR of composite cardiovascular events between the two groups. We will also assess the effects of spironolactone on individual cardiovascular events and the progression of diabetes and renal dysfunction.Ethics and disseminationThis protocol was approved by the Independent Ethics Committee of People’s Hospital of Xinjiang Uygur Autonomous Region (no. 2020020618). The results will be disseminated in peer-reviewed journals and at scientific conferences.Trial registration numberChiCTR2000028909.