Direct Renin inhibition with aliskiren in obese patients with arterial hypertension.
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.
Jordan
Jens
J
Franz-Volhard Clinical Research Center, Medical Faculty of the Charité and Helios Klinikum, Berlin, Germany. jens.jordan@charite.de
Engeli
Stefan
S
Boye
Sam W
SW
Le Breton
Stephanie
S
Keefe
Deborah L
DL
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000577:Amides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D017311:Amlodipine / Q000009:adverse effects / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000627:therapeutic use; D001713:Biphenyl Compounds / Q000009:adverse effects / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D003971:Diastole; D004311:Double-Blind Method; D005260:Female; D005650:Fumarates / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D006852:Hydrochlorothiazide / Q000009:adverse effects / Q000627:therapeutic use; D006973:Hypertension / Q000097:blood / Q000150:complications* / Q000188:drug therapy* / Q000503:physiopathology; D000077405:Irbesartan; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000150:complications*; D012083:Renin / Q000097:blood*; D013599:Systole; D013777:Tetrazoles / Q000009:adverse effects / Q000627:therapeutic use; D016896:Treatment Outcome; D000092502:Renin Inhibitors
D000577:Amides; D017311:Amlodipine; D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D005650:Fumarates; D006852:Hydrochlorothiazide; D000077405:Irbesartan; D012083:Renin; D013777:Tetrazoles; D000092502:Renin Inhibitors; C446481:aliskiren