title: Blood pressure response with fixed-dose combination therapy: comparing hydrochlorothiazide with amlodipine through individual-level meta-analysis.
abstract: BACKGROUND
  Although fixed-dose combination drug therapy is commonly used to treat hypertension, the efficacy of head-to-head comparisons of dual fixed-dose combinations has not been well described. We hypothesized that when used in combination with an angiotensin receptor blocker (ARB) olmesartan medoxomil, hydrochlorothiazide (HCTZ) will be as effective as the dihydropyridine calcium channel blocker (CCB) amlodipine to lower both clinic and 24-h ambulatory blood pressure (BP). Furthermore, we hypothesized that response to ARB along with HCTZ or ARB along with CCB may be heterogeneous depending on clinical characteristics.
  
  
  METHODS
  An individual-level meta-analysis was performed among 559 individuals treated with dual combination therapy in five trials. A forced titration scheme was used in each of these trials and blood BP was measured both in the clinic and outside using 24-h ambulatory BP monitors.
  
  
  RESULTS
  The mean age was 62 years, 55% were men, 46% had diabetes mellitus, 17% were black, clinic BP averaged 159.5/89.5 mmHg and 24-h ambulatory BP 145.0/82.5 mmHg. Overall, baseline-adjusted lowering of mean 24-h ambulatory BP was 22.0/11.7 mmHg. BP reductions were similar between ARB along with HCTZ and ARB along with CCB groups. However, clinic BP was lowered 4.3/1.8 mmHg more with ARB along with CCB combination (28.4/13.0 mmHg drop) than with ARB along with HCTZ combination (24.1/11.2 mmHg drop). The white coat effect (WCE) was therefore mitigated 3.8/1.7 mmHg more with ARB along with CCB combination. Heterogeneity in ambulatory BP response was noted. Compared with men, women had a greater ambulatory and clinic BP lowering with either combination. ARB along with HCTZ produced a greater BP-lowering effect among men, elderly, nonobese and nondiabetic. On the contrary, ARB along with CCB produced a greater BP-lowering effect among women, young, obese and diabetic individuals. This heterogeneity in response was often undetectable with clinic BP measurements. In multivariable analysis, sex and diabetes mellitus remained independent measures of heterogeneity.
  
  
  CONCLUSIONS
  Overall, the combination of olmesartan and HCTZ is as effective as olmesartan and CCB in lowering 24-h, daytime, and night-time ambulatory BP. However, greater lowering is noted with the olmesartan and CCB combination for clinic BP. Thus, out-of-office BP monitoring is necessary to provide better assessment of overall BP and response to treatment. Women and diabetic individuals may have slightly better 24-h ambulatory BP response with the olmesartan and CCB combination therapy.
authors.affiliation: Indiana University School of Medicine and Richard L. Roudebush Veterans Administration Medical Center, Indianapolis, IN 46202, USA. ragarwal@iupui.edu
authors.forename: Rajiv
authors.initials: R
authors.lastname: Agarwal
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Weir
mesh_terms: D000368:Aged; D017311:Amlodipine / Q000008:administration & dosage*; D057911:Angiotensin Receptor Antagonists / Q000008:administration & dosage; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects*; D018660:Blood Pressure Monitoring, Ambulatory; D015992:Body Mass Index; D002121:Calcium Channel Blockers / Q000008:administration & dosage; D048909:Diabetes Complications / Q000188:drug therapy; D004359:Drug Therapy, Combination / Q000379:methods*; D005260:Female; D006801:Humans; D006852:Hydrochlorothiazide / Q000008:administration & dosage*; D007093:Imidazoles / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D000068557:Olmesartan Medoxomil; D012737:Sex Factors; D013777:Tetrazoles / Q000008:administration & dosage
chemical_list: D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D007093:Imidazoles; D013777:Tetrazoles; D006852:Hydrochlorothiazide; D017311:Amlodipine; D000068557:Olmesartan Medoxomil