Once-Daily Aliskiren Reduces Blood Pressure in Patients with Hypertension

Speaker: Byung-Hee Oh, MD, PhD, Professor of Medicine and Chief of Cardiology, Seoul National University College of Medicine, and Director, Cardiovascular Center, Seoul National Hospital, Seoul, South Korea

Aliskiren (Novartis), an investigational oral renin inhibitor, is an effective, once-daily antihypertensive drug for patients with mild-to-moderate hypertension. The medication reduced blood pressure (BP) throughout a 24-hour dosing period without serious adverse drug effects (ADEs).

A randomized, double-blind, placebo-controlled, parallel-group study was conducted at 68 centers in the U.S., Canada, Guatemala, Korea, and the Netherlands. A total of 833 persons with a sitting diastolic BP of between 95 and 110 mm Hg were enrolled in the study.
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Of these 833 individuals, 672 patients participated: 172 received aliskiren 150 mg once daily; 169 received aliskiren 300 mg once daily; 166 received aliskiren 600 mg once daily, and 165 received placebo. Existing antihypertensive therapies were withdrawn during a two-week washout period, and the patients were then enrolled in a two- to four-week, single-blind, placebo-run-in period to meet BP eligibility criteria and to establish BP values. Next, they received treatment for eight weeks, followed by a two-week treatment-free withdrawal period.

After eight weeks, all patients receiving aliskiren therapy had significantly lower mean sitting diastolic and systolic BP readings, compared with patients receiving placebo:

  • aliskiren 150 mg: diastolic BP reduced by 10.3 mm Hg; systolic BP reduced by 13 mm Hg
  • aliskiren 300 mg: diastolic BP reduced by 11.1 mm Hg; systolic BP reduced by 14.7 mm Hg
  • aliskiren 600 mg: diastolic BP reduced by 12.5 mm Hg; systolic BP reduced by 15.8 mm Hg
  • placebo: diastolic BP reduced by 4.9 mm Hg; systolic BP reduced by 3.8 mm Hg

In terms of overall dose-dependent effects, the proportion of patients responding to treatment was significantly higher with aliskiren 150 mg (59%), 300 mg (63°%), and 600 mg (69%) than with placebo (36%). The drug remained effective over the 24-hour dosing period and was associated with the same ADEs as placebo in doses up to 300 mg.

The incidence of diarrhea was elevated in patients taking aliskiren 600 mg (11.4%), compared with those taking lower doses (1.2% ) and placebo (1.8%), but symptoms were mild.
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Only one patient taking aliskiren 600 mg and one patient taking placebo discontinued therapy as a result of the diarrhea.

Darusentan Beneficial in Resistant Hypertension

Speaker: Henry Black, MD, Charles J. and Margaret Roberts Professor of Preventative Medicine, Rush University Medical Center, Chicago, Illinois; Adjunct Professor of Preventative Medicine, Northwestern University School of Medicine; and Adjunct Professor of Health Resources Management, School of Public Health, The University of Illinois at Chicago

Darusentan (Mycogen, Inc.), a novel, once-daily, oral endo-thelin-A receptor antagonist in clinical development, offers additional BP-lowering benefits as an add-on antihypertensive therapy.

A randomized study was performed to compare the efficacy of once-daily darusentan 104 to 300 mg with that of placebo in patients with “resistant” hypertension, as defined by the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of Hypertension (JNC 7) criteria. Overall, 115 patients who did not achieve treatment BP goals after taking three or more antihypertensive agents, including a diuretic at full doses, were assigned, in a 2:1 ratio, to receive oral darusen-tan or placebo once daily.

After a two-week, run-in phase with placebo, the darusentan dose was escalated every two weeks, starting with a dose of 10 mg daily until a maximum of 300 mg daily was attained. Over a two-week period, darusentan therapy and placebo therapies were withdrawn.

Sitting and standing BP and heart rates were measured at every study visit via standard sphygmomanometry and physical examination. Hematological laboratory tests and electro-cardiography were performed at screening and periodically throughout the study.

The co-primary efficacy endpoints were changes from baseline through weeks 8 and 10 (at doses of 150 and 300 mg) at the lowest (in trough) sitting systolic BP. Secondary variables included:

  • changes from baseline in 24-hour systolic BP, as measured by ambulatory BP monitoring.
  • the percentage of patients who achieved systolic BP goals.
  • changes from baseline in trough sitting diastolic BP.

Eighty-seven percent of patients completed the study. The mean duration of treatment was 78.6 ± 18 days (range, 60.6-96.6 days).

At the baseline evaluation, mean systolic BP was 149.4 ± 13.1 mm Hg and mean diastolic BP was 81.5 ± 13 mm Hg. Beginning at the fourth week of therapy, significant improvements in mean trough sitting diastolic BP, compared with placebo, were evident (-6.2 mm Hg; P < .001) and were maintained throughout the study. Kamagra Oral Jelly

At the 10th week of darusentan therapy, the placebo-corrected mean trough sitting systolic BP at a dose of 300 mg was 11.5 ± 3.1 mm Hg (P = .015); the diastolic BP, at the same dose, was reduced by 6.3 ± 2 mm Hg (P = .004). Also at week 10, 51% of the darusentan-treated patients achieved JNC 7 systolic BP goals, compared with only 33% of those in the placebo group (P = .069).