CHICAGO — Nearly three-fourths of patients with uncontrolled hypertension on monotherapy achieved national blood pressure targets on a fixed-dose combination of amlodipine and valsartan that will soon be available, Dr. Joseph L. Izzo Jr. reported at the annual meeting of the American Society of Hypertension.
Two different formulations of Novartis' single-tablet combination drug, which will be marketed as Exforge, were evaluated in a double-blind, multicenter study that randomized 443 patients to amlodipine 5 mg/valsartan 160 mg and 451 patients to amlodipine 10 mg/valsartan 160 mg.
After 8 weeks, hydrochlorothiazide (HCTZ) could be added, first at 12.5 mg and then at 25 mg.
The majority of the patients, including 145 (16%) of whom had type 2 diabetes, had been previously treated with a β-blocker, angiotensin receptor antagonist, ACE inhibitor, calcium channel blocker, or diuretic.
At admission, their mean age was 58 years and their mean blood pressure was 150/90 mm Hg, said Dr. Izzo, who has received research support and is a consultant for Novartis, which sponsored the study. More than 90% of the patients were white.
The study's primary end point was the proportion of patients after 8 and 16 weeks who had reached a blood pressure of 140/90 mm Hg or 130/80 mm Hg for those with diabetes—the currently recommended dual BP targets in the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC7).
In an intent-to-treat analysis at week 16, 322 of 440 patients (73%) on the 5-mg/160-mg dose and 338 of 449 patients (75%) on the 10-mg/160-mg dose achieved the dual JNC7 targets, the investigators reported.
Among those with diabetes, 25 of the 61 patients (41%) on the low-dose combination and 27 of the 59 patients (46%) on the high-dose combination reached a BP of less than 130 mm Hg.
Switching patients to the combination therapy resulted in an average additional 20-mm Hg drop in systolic BP, compared with reductions seen with their previous medications.
“Obviously those are pretty good responses when one looks at the control rates in the United States, which are just about half these control rates,” Dr. Izzo, a professor of medicine at the State University of New York at Buffalo, said at a press briefing.
Blood pressure control rates were similar when stratified by prior medication, age, or ethnicity.
There was little increased response after 8 weeks that could be attributed to the addition of HCTZ therapy.
There was an incremental response with the amlodipine 10-mg dose. But the incremental response was smaller than expected, meaning that the 5-mg/160-mg dosage is effective, Dr. Izzo said.
Adverse events were similar between groups, although the incidence of edema was higher in patients taking the 10-mg/160-mg dose than in those taking the lower dose (25% vs. 8%).
Exforge was approved by the Food and Drug Administration this summer. It is indicated for the treatment of hypertension in patients whose blood pressure has not been adequately controlled with a calcium channel blocker or angiotensin II receptor blocker alone.
The pills will be available in four strengths: 5 mg amlodipine/60 mg valsartan, 10 mg/160 mg, 5 mg/320 mg, and 10 mg/320 mg. Exforge has been launched by Novartis in select European countries.
The products will be available in the United States no earlier than Sept. 25 of this year, the FDA specified in a December 2006 letter to Novartis, because amlodipine (Norvasc, Pfizer Inc.) remains under patent protection until then.