Factorial antihypertensive study of an extended-release metoprolol and hydrochlorothiazide combination.
BACKGROUND
To attain goal blood pressure (BP), many hypertensive patients require combination antihypertensive therapy. Thiazide diuretic/beta-blocker regimens lower BP, and clinical studies indicate that they reduce the risk for cardiovascular consequences of hypertension. Fixed-dose combination tablets can simplify multidrug treatment regimens.


METHODS
This multicenter, randomized, double-blind, placebo-controlled, unbalanced factorial study (N = 1571) was designed to determine whether hydrochlorothiazide (HCT) and extended release (ER) metoprolol both contribute to an antihypertensive effect. Hypertensive adults with sitting diastolic BP (SiDBP) 95 to 114 mm Hg and systolic BP (SiSBP) <180 mm Hg received one of three hydrochlorothiazide doses (6.25 mg, 12.5 mg, or 25 mg), one of four ER-metoprolol doses (25 mg, 50 mg, 100 mg, 200 mg), or one of nine of the combinations or placebo for 8 weeks.


RESULTS
Blood pressure decreased with all combinations (P < .001 v placebo); reductions were dose related, ranging from 8.7 to 15.7 mm Hg (SiDBP) and 9.7 to 18.9 mm Hg (SiSBP) (model-derived values). Reductions with placebo were 5.3 (SiDBP) and 4.2 mm Hg (SiSBP). Both active agents contributed to the combination effect (P = .0015 for SiDBP; P = .0006 for SiSBP). Several low-dose combinations were approximately as effective as high doses of the individual agents (differences within 1 to 2.5 mm Hg). The adverse event discontinuation rate was 2.9%. Serum potassium decreased and uric acid increased with increasing doses of HCT.


CONCLUSIONS
Extended-release metoprolol/hydrochlorothiazide is an effective antihypertensive combination that offers additive antihypertensive contributions from both components.
Papademetriou
Vasilios
V
Hypertension Research, VA Medical Center and Georgetown University Medical Center, Washington, DC 20422, USA. papavip@aol.com
Hainer
James W
JW
Sugg
Jennifer
J
Munzer
Deborah
D
D000293:Adolescent; D000319:Adrenergic beta-Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D003692:Delayed-Action Preparations; D004232:Diuretics / Q000009:adverse effects / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006852:Hydrochlorothiazide / Q000009:adverse effects / Q000627:therapeutic use*; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008790:Metoprolol / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D015233:Models, Statistical; D016896:Treatment Outcome; D014481:United States
D000319:Adrenergic beta-Antagonists; D000959:Antihypertensive Agents; D003692:Delayed-Action Preparations; D004232:Diuretics; D006852:Hydrochlorothiazide; D008790:Metoprolol