{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T06:52:36Z","timestamp":1791355956515,"version":"4.3.1"},"reference-count":38,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"19","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2026,10,6]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">Diuretics are widely used alone or in combination with other medications to lower blood pressure (BP). The dosing ratio between hydrochlorothiazide and chlorthalidone for lowering BP, as well as the effects of different amiloride doses on BP and their ability to counteract thiazide's adverse metabolic effects, remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p xml:lang=\"en\">In a factorial superiority randomized clinical trial with blinded participants and investigators, we compared the effects of chlorthalidone 25\u2009mg with hydrochlorothiazide 50\u2009mg and amiloride 5\u2009mg with 10\u2009mg on BP measured by office and ambulatory BP monitoring and laboratory parameters. Patients were followed for 12\u2009weeks.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      The treatments showed no statistically significant interaction; comparisons were evaluated separately. Hydrochlorothiazide and chlorthalidone had similar effects on systolic and diastolic BP measured at the office and by ambulatory BP monitoring. The between\u2010group \u03b4s (hydrochlorothiazide minus chlorthalidone) for systolic 24\u2010hour and nighttime BP were \u22121.1 (95% CI, \u22128.0 to 5.9;\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      =0.8), and \u22122.3 (95% CI, \u221210.3 to 5.7;\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      =0.6), respectively. The effects of amiloride 5\u2009mg and 10\u2009mg on BP were similar. Laboratory parameters did not differ between hydrochlorothiazide and chlorthalidone. Comparing amiloride doses, serum sodium decreased more with 10\u2009mg, while the remaining parameters were similar between doses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">Chlorthalidone and hydrochlorothiazide, administered at a 1:2 dosing ratio, show similar effects on BP and laboratory parameters. Amiloride 5 and 10\u2009mg show similar effects on BP and most metabolic parameters, with no clear dose\u2013response relationship, suggesting that any independent BP\u2010lowering effect of amiloride is, at best, weak.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Registration<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      URL:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/clinicaltrials.gov\/\">https:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n                      ; Unique Identifier: NCT03928145.\n                    <\/jats:p>\n                  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