|
||||||
|
|
|
|
|||||||||||
|
|||||||||||||
| ||||||||||||||||||||||||||||||||||||
The novel oral renin inhibitor aliskiren (Rasilez, Novartis) shows smooth, even blood pressure control throughout the 24-hour day, researchers reported at the 21st Annual Scientific Meeting of the American Society of Hypertension (ASH), held May 16–20 in New York.1
|
Early morning blood pressure surges, associated with cardiovascular events, were not seen with the drug, according to the report. "Once-daily aliskiren has the potential to maximize end-organ protective benefits through continuous, smooth blood pressure lowering," researchers conclude.
Their study, funded by Novartis, involved 672 adults with mild to moderate hypertension, or mean diastolic pressures of 95–109 mmHg. All subjects had similar diastolic and systolic blood pressures at baseline.
After a 2–4-week placebo run-in phase, patients were randomized to 150 mg, 300 mg, or 600 mg aliskiren or placebo once a day for 8 weeks. A subgroup of 216 patients wore 24-hour ambulatory monitors so the investigators could assess blood pressures throughout the diurnal cycle.
The primary end point was change in mean 24-hour diastolic and systolic pressure (MADBP and MASBP, respectively). MADBP dropped 6.55 mmHg with the 150 mg dose, 5.96 mmHg with the 300 mg dose, and 7.43 mmHg with the 600 mg dose. MASBP dropped 9.63 mmHg with 150 mg, 8.77 mmHg with 300 mg, and 9.92 mmHg with 600 mg at the end of the 8-week trial.
"All doses were highly statistically effective," says lead investigator Jerry Mitchell, MD, PhD, of the Texas Center for Drug Development in Austin, who presented the results. "Blood pressure was very smooth and even throughout."
Trough-to-peak ratios for 150 mg, 300 mg, and 600 mg doses were 0.64, 0.98, and 0.86, respectively. "About two-thirds of patients on the 150 mg dose have good blood pressure control at aliskiren's trough. Nearly all of patients on the 300 mg and 600 mg doses [have even control]," Mitchell says.
Adverse events were similar with active drug and placebo.
SECOND ALISKIREN STUDY
A further reduction in blood pressure was seen with the addition of hydrochlorothiazide to aliskiren, Argentinean researchers told ASH attendees.
Alberto Villamil, MD, and colleagues at Fundapres in Buenos Aires randomized 2,776 patients to 75 mg, 150 mg, or 300 mg aliskiren plus 6.25 mg, 12.5 mg, or 25 mg hydrochlorothiazide or placebo in an 8-week trial funded by Novartis.2 Mean sitting diastolic blood pressures (MSDBPs) were 95–109 mmHg at baseline.
With aliskiren monotherapy, diastolic blood pressure reductions were in the 8.7–10.3 mmHg range, in a dose-response fashion, compared with a 6.9 mmHg drop with placebo.
With the addition of hydrochlorothiazide, the greatest reductions in blood pressure were with the 300 mg aliskiren/25 mg hydrochlorothiazide regimen, with a mean drop of 21.2/14.3 mmHg. Combination therapy was superior to monotherapy for all dose combinations, the study found.
"You get some vasodilation with aliskiren; that's why you need a diuretic," Mitchell explains.
"The decreases in variability decrease the risk of adverse cardiovascular events that typically peak in the early morning," he says. "Variability is a major risk factor for end-organ damage. For every 10 mmHg surge, you get a 20% increase in risk of stroke."
Novartis submitted a new drug application for aliskiren as both monotherapy and in combination with diuretics in April 2006.
"What's not known is how aliskiren might interact with ACE
[angiotensin-converting enzyme] inhibitors and the ARBs [angiotensin-receptor
blockers]. Both of those cause the body to release more renin," Mitchell
says. 
References
2. Villamil A, Chrysant S, Calhoun D, et al.: The novel oral renin inhibitor aliskiren provides effective blood pressure control in patients with hypertension when used alone or in combination with hydrochlorothiazide. J Clin Hypertens 8 (Suppl. A): A100, 2006.
CiteULike 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
| ||||||||||||||||||||||||||||||||||||
|
||||||
|
| DOC News | Diabetes | Diabetes Care | Clinical Diabetes | Diabetes Spectrum |
