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.

Spironolactone

“…This is being investigated in the ESCAM trial (Effect of spironolactone on cardiovascular morbidity and mortality in patients with hypertension and glucose metabolism disorders). 6 At the time of writing, this large trial is due to finish at the end of 2023.…”

“…Patients with hypertension and diabetes have higher aldosterone concentrations than those with hypertension alone, and the deleterious effect of aldosterone on the vascular endothelium and cardiac function suggests a role for spironolactone in the management of hypertension in this group. This is being investigated in the ESCAM trial (Effect of spironolactone on cardiovascular morbidity and mortality in patients with hypertension and glucose metabolism disorders) 6 . At the time of writing, this large trial is due to finish at the end of 2023.…”

Redefining primary hyperaldosteronism as “The Syndrome of Inappropriate Aldosterone Secretion (SIALDS)”: A common but unrecognized cause of hypertension

“…However, randomized controlled trials investigating their long‐term benefits or harms, when used as antihypertensive agents are still lacking 32,33 . Ongoing trials in China and the University of Oxford aim to address this knowledge gap 34,35 …”

“…32,33 Ongoing trials in China and the University of Oxford aim to address this knowledge gap. 34,35 Future trials should investigate the long-term benefits of MRAs and aldosterone synthase inhibitors, particularly in low-renin hypertension.…”

Relation between blood pressure time in range and composite cardiovascular disease in patients with primary aldosteronism: a retrospective study

“…Composite CVD events were de ned as stroke (cerebral infarction, cerebral bleeding, and transient ischemic attack), aortic dissection, sustained arrhythmia (atrial brillation, atrial utter, supraventricular and ventricular tachycardia), symptomatic angina pectoris, myocardial infarction, revascularization procedure for coronary or peripheral artery diseases, hospitalization for congestive heart failure (CHF), and carotid or femoral atherosclerosis [13,14].…”