Nineteen RCTs (n=70,385) were included.
Three trials (n=5,761) mandated ENaC inhibitor-hydrochlorothiazide combination therapy. ENaC inhibitor-hydrochlorothiazide combination therapy, compared to controls, was associated with significant reduction in both coronary mortality and sudden cardiac death in elderly patients: coronary mortality (OR 0.59, 95% CI 0.44 to 0.78); sudden cardiac death (OR 0.60, 95% CI 0.38 to 0.94).
Sixteen trials (n=64,624) did not mandate concomitant ENaC inhibitors. Thiazide diuretic therapy was not associated with significant reductions in coronary mortality or sudden cardiac death: coronary mortality (OR 0.94, 95% CI 0.81 to 1.09); sudden cardiac death (OR 1.27, 95% CI 0.93 to 1.75).
Meta-regression showed no significant effect of age (p=0.57) or blood pressure reduction (p=0.706) on outcomes in thiazide alone trials.