Benefit demonstrated in obese hypertensive patients
ROME—Aliskiren, an oral direct renin inhibitor, lowers BP more effectively than hydrochlorothiazide as monotherapy or with add-on amlodipine in obese patients with hypertension, according to results reported here at the 44th annual meeting of the European Association for the Study of Diabetes.
Roland E. Schmieder, MD, of the department of nephrology and hypertension at the University of Erlangen in Erlangen, Germany, and coworkers compared the long-term BP reduction and safety of aliskiren and hydrochlorothiazide in obese patients (BMI 30 kg/m2 or greater) with hypertension.
For the study, they used data from a 52-week, randomized, double-blind trial involving 1,124 hypertensive patients. The trial found that an aliskiren-based regimen, including optional add-on amlodipine, provided greater BP reductions than a hydrochlorothiazide-based regimen and was also well tolerated.
The present analysis looked at the long-term efficacy and safety of aliskiren- and hydrochlorothiazide-based treatment regimens in the obese and nonobese patient subgroups in this trial.
“Approximately 75% of obese patients have hypertension, but fewer than 20% of obese hypertensive [patients] have their blood pressure controlled to less than 140/90 mm Hg,” said Dr. Schmieder, head of the Clinical Research Center at the University of Erlangen. “Even so, current guidelines include no specific recommendation for first-line treatment of hypertension in obese patients.”
Following washout and placebo run-in periods, patients were randomized in a 2:2:1 ratio to double-blind, once-daily treatment with aliskiren 150 mg, hydrochlorothiazide 12.5 mg, or placebo. After three weeks, active treatment was force-titrated to double the initial dose. At week 6, patients receiving placebo were assigned in a 1:1 ratio to double-blind, once-daily aliskiren 300 mg or hydrochlorothiazide 25 mg. For patients with uncontrolled BP, amlodipine 5 mg was added starting at week 12 and titrated to 10 mg from week 18.
The analysis, which included 396 obese patients and 728 nonobese patients, showed that in obese patients, aliskiren 300 mg monotherapy provided significantly larger BP reductions than hydrochlorothiazide 25 mg monotherapy at week 12 (17/12 vs. 12/9 mm Hg) and aliskiren-based therapy lowered pressure more effectively than hydrochlorothiazide-based therapy at week 52 (20/16 vs. 18/13 mm Hg).
In addition, approximately 60% of obese patients achieved BP control with aliskiren after 12 weeks, and nearly 70% achieved BP control after 52 weeks.
Aliskiren-based therapy produced a similar BP decrease from baseline in obese and nonobese patients. Hydrochlorothiazide-based therapy was significantly less effective in obese patients. “This finding reflects the fact that these patients are relatively resistant to many commonly used antihypertensives,” Dr. Schmieder noted.
Aliskiren-based therapy was generally well tolerated in obese patients and was associated with a significantly lower incidence of headache than hydrochlorothiazide-based treatment.
The incidence of hypokalemia, a well-known side effect of thiazide diuretics, was significantly lower with aliskiren-based treatment than hydrochlorothiazide-based treatment in obese patients.
“Hydrochlorothiazide-associated hypokalemia has been linked with metabolic abnormalities and impaired glucose tolerance during long-term therapy as well as with sudden cardiac death and is therefore of particular clinical relevance in obese patients with hypertension,” Dr. Schmieder noted.
Overall, the results show that aliskiren with or without amlodipine is superior to hydrochlorothiazide in obese hypertensive patients, he added.