Current guidelines from the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of
High Blood Pressure recommend first-line treatment with a
thiazide diuretic but do not provide specific guidance for obese patients. The
renin system is activated in
obesity-associated arterial
hypertension. Therefore, we tested the hypothesis that the oral
direct renin inhibitor aliskiren could provide additive blood pressure lowering in obese patients with
hypertension (body mass index >or=30 kg/m(2); mean sitting diastolic blood pressure: 95 to 109 mm Hg) who had not responded to 4 weeks of treatment with
hydrochlorothiazide (
HCTZ) 25 mg. After a 2- to 4-week washout, 560 patients received single-blind
HCTZ (25 mg) for 4 weeks; 489 nonresponders were randomly assigned to double-blind
aliskiren (150 mg),
irbesartan (150 mg),
amlodipine (5 mg), or placebo for 4 weeks added to
HCTZ (25 mg), followed by 8 weeks on double the initial doses of
aliskiren,
irbesartan, or
amlodipine. After 8 weeks of double-blind treatment (4 weeks on the higher dose),
aliskiren/
HCTZ lowered blood pressure by 15.8/11.9 mm Hg, significantly more (P<0.0001) than placebo/
HCTZ (8.6/7.9 mm Hg).
Aliskiren/
HCTZ provided blood pressure reductions similar to those with
irbesartan/
HCTZ and
amlodipine/
HCTZ (15.4/11.3 and 13.6/10.3 mm Hg, respectively), with similar tolerability to placebo/
HCTZ. Adverse event rates were highest with
amlodipine/
HCTZ because of a higher incidence of peripheral
edema (11.1% versus 0.8% to 1.6% in other groups). In conclusion, combination treatment with
aliskiren is a highly effective and well-tolerated therapeutic option for obese patients with
hypertension who fail to achieve blood pressure control with first-line
thiazide diuretic treatment.