title: Antihypertensive efficacy of hydrochlorothiazide vs chlorthalidone combined with azilsartan medoxomil.
abstract: BACKGROUND
  Chlorthalidone has proven efficacy to reduce cardiovascular morbidity and mortality, yet it is infrequently used in practice. This study provides a direct comparison of chlorthalidone with hydrochlorothiazide, each combined with the angiotensin receptor blocker azilsartan medoxomil, on blood pressure reduction and control rates.
  
  
  METHODS
  This is a randomized, double-blind, titrate-to-target blood pressure trial comparing the single-pill combination of azilsartan medoxomil and chlorthalidone versus co-administration of azilsartan medoxomil and hydrochlorothiazide in participants with stage 2 primary hypertension. After 2 weeks of treatment with azilsartan medoxomil 40 mg alone, all participants also received 12.5 mg of diuretic for 4 weeks (up to week 6) and were titrated to 25 mg for another 4 weeks (up to week 10) if they failed to achieve target blood pressure. The primary end point was change in clinic systolic blood pressure. Target blood pressure was defined as clinic blood pressure <140/90 mm Hg for participants without diabetes or chronic kidney disease or <130/80 mm Hg for participants with diabetes or chronic kidney disease.
  
  
  RESULTS
  The mean age of the 609 participants was 56.4 years, and the mean baseline clinic blood pressure was 164.6/95.4 mm Hg. The primary end point analysis at week 6 demonstrated a greater reduction of clinic systolic blood pressure for the chlorthalidone (-35.1 mm Hg) versus hydrochlorothiazide combination (-29.5 mm Hg) (mean difference, -5.6 mm Hg; 95% confidence interval, -8.3 to -2.9; P <.001). The mean difference in 24-hour ambulatory systolic blood pressure at week 6 was -5.8 mm Hg (95% confidence interval, -8.4 to -3.2; P <.001), favoring the azilsartan medoxomil/chlorthalidone group. The percentage of participants achieving target clinic blood pressure at week 6 was greater for the chlorthalidone versus hydrochlorothiazide combination (64.1% vs 45.9%, P <.001). Drug discontinuations due to adverse events were not statistically significantly different between groups (9.3% vs 7.3%, P = .38), and hypokalemia was uncommon in both groups.
  
  
  CONCLUSIONS
  Chlorthalidone combined with azilsartan medoxomil provides better blood pressure reduction and a higher likelihood of achieving blood pressure control than hydrochlorothiazide combined with azilsartan medoxomil. This benefit occurred without a difference in safety measurements.
authors.affiliation: The University of Chicago Medicine, Chicago, IL 60637, USA. gbakris@gmail.com
authors.forename: George L
authors.initials: GL
authors.lastname: Bakris
authors.forename: Domenic
authors.initials: D
authors.lastname: Sica
authors.forename: William B
authors.initials: WB
authors.lastname: White
authors.forename: William C
authors.initials: WC
authors.lastname: Cushman
authors.forename: Michael A
authors.initials: MA
authors.lastname: Weber
authors.forename: Alison
authors.initials: A
authors.lastname: Handley
authors.forename: Eric
authors.initials: E
authors.lastname: Song
authors.forename: Stuart
authors.initials: S
authors.lastname: Kupfer
mesh_terms: D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000627:therapeutic use*; D018660:Blood Pressure Monitoring, Ambulatory; D002752:Chlorthalidone / Q000627:therapeutic use*; D003404:Creatinine / Q000097:blood; D004311:Double-Blind Method; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006852:Hydrochlorothiazide / Q000627:therapeutic use*; D006973:Hypertension / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010069:Oxadiazoles / Q000627:therapeutic use*; D011188:Potassium / Q000097:blood; D013599:Systole
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D004338:Drug Combinations; D010069:Oxadiazoles; D006852:Hydrochlorothiazide; D003404:Creatinine; C557413:azilsartan medoxomil; D002752:Chlorthalidone; D011188:Potassium