Description of studies
The study selection process is detailed in a flow chart as per PRISMA guidelines (Figure 1). The initial MEDLINE search returned 191 results, Embase 384 and Central 564 (1139 in total). After removal of duplicates there were 967 articles of which 769 were excluded based on title and abstract. The remaining 198 full-text articles were assessed for eligibility and 153 were excluded for various reasons (Figure 1). The remaining 45 articles were included in the qualitative synthesis. MRA and potassium-sparing diuretics were grouped together for the analysis as only one study had measurements for a potassium-sparing diuretic (amiloride) with the remainder MRAs. The most commonly used diuretic class was the MRA/potassium-sparing class. Classes of diuretic were thiazide/thiazide-like (24/45, 53%), MRA/potassium-sparing (28/45, 62%), loop (4/45, 9%) and combination (3/45, 7%). Individual diuretics were hydrochlorothiazide, amiloride, indapamide, bendroflumethiazide, chlorthalidone, canrenone, furosemide, spironolactone, eplerenone, tielinic acid and torsemide. Details of individual trials are summarised in table 1. In those studies where patients where previously treated with another antihypertensive medication before the diuretic was added, an ACE/ARB was included in over 50%. For renin sub-analysis, plasma renin activity (PRA) was used as this was the most common measure of renin in the studies.