AZOR(R) (Amlodipine And Olmesartan Medoxomil) Significantly Improves 24-Hour Ambulatory Blood Pressure

Main Category: Hypertension
Article Date: 11 May 2009 - 5:00 PDT

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Daiichi Sankyo, Inc. announced today that data presented at the American Society of Hypertension, Inc. (ASH) Twenty-Fourth Annual Scientific Meeting and Exposition (ASH 2009) in San Francisco from the AZOR(R) Trial Evaluating Blood Pressure Reductions and Control (AZTEC) demonstrated that a stepwise amlodipine and olmesartan medoxomil-based titration regimen provided mean 24-hour ambulatory reductions in systolic blood pressure (SBP) of 21.4 mm Hg and diastolic blood pressure (DBP) of 12.7 mm Hg. In addition, 71 percent of patients in the study were able to safely and effectively achieve a 24-hour ambulatory target blood pressure (BP) of less than 130/80 mm Hg. The study also showed large mean 24-hour ambulatory BP reductions in patients with hypertension from two groups with elevated risk for developing hypertension, Blacks (20.7/11 mm Hg) and patients with type 2 diabetes (21.5/12.6 mm Hg).

AZTEC was the first time researchers have analyzed the effect of AZOR on 24-hour ambulatory BP measurement (ABPM), which provides a 24-hour measurement of patient BP and is generally considered a better indicator of target organ injury than cuff measurement.(1) ABPM can give physicians a clearer picture of 24-hour BP control in patients with hypertension.(2) According to the Seventh Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure (JNC 7), ABPM patients whose 24-hour BP is greater than 135/85 mm Hg are nearly twice as likely to have a cardiovascular event as those with BP less than 135/85 mm Hg.(3) There are no studies with AZOR demonstrating a reduction in cardiovascular events.

"Analyzing ambulatory BP gives physicians a clear picture of how well a patient's BP is controlled through a full 24-hour dosing period," said Dr. Joel Neutel, MD, director, Orange County Heart Institute and Research Center. "Most patients require treatment with at least two antihypertensive agents to achieve their recommended goal BP. The results of this study demonstrated the ability of a stepwise amlodipine and olmesartan medoxomil-based titration regimen to maintain BP reductions over 24 hours. This study also showed that an amlodipine and olmesartan medoxomil-based titration regimen can be an effective tool for treating hypertension in more challenging patient populations, such as patients with type 2 diabetes and Blacks."

During the study, AZOR demonstrated significant reductions in seated blood pressure (SeBP), also known as cuff BP. Unlike ABPM, SeBP is only recorded once during the course of a day. AZOR 10/40 mg provided a mean reduction in seated systolic blood pressure (SeSBP) of 24.6 mm Hg and the seated diastolic blood pressure (SeDBP) reading of 12.3 mm Hg.

In AZTEC, the amlodipine and olmesartan medoxomil-based titration regimen was well tolerated, with only three (1 amlodipine patient, 2 AZOR patients) of the 185 patients discontinuing treatment because of drug-related adverse events. In this trial, occurrence of drug-related AEs included: peripheral edema (2.2 percent) and dizziness (1.1 percent).

High blood pressure can cause permanent changes to blood vessels and the heart that may create serious problems elsewhere in the body.(4) Hypertension is one of the most prevalent conditions in the United States, affecting approximately one in three American adults (about 73 million people age 20 and older) and approximately one billion people worldwide.(5)(6) It is often difficult to control, and of those with high blood pressure, approximately 55 percent do not reach recommended BP levels.(7) The number of people with high blood pressure is expected to reach about 1.6 billion worldwide by 2025.(8)

Black Patients

In the U.S., the rate of high blood pressure is disproportionately high in the Black community and affects 41 percent of the population.(9) A further analysis of the AZTEC trial on the basis of race found that treatment with an amlodipine and olmesartan medoxomil-based titration regimen was well tolerated and produced similar 24-hour ambulatory BP reductions from baseline in both Black and non-Black patients. Black patients had a higher mean baseline BP than non-Black patients. The amlodipine and olmesartan medoxomil-based titration regimen produced mean 24-hour ambulatory BP reductions of 20.7/11 mm Hg in Black patients from a baseline of 148.6/85.7 mm Hg. Non-Black patients experienced a mean 24-hour ambulatory BP reduction of 21.5/13 mm Hg from a baseline of 144.2/85.7 mm Hg.

Patients with Diabetes

Seventy five percent of adults diagnosed with diabetes in the U.S. have hypertension.(10)(11) A further analysis of the AZTEC trial found that treatment with an amlodipine and olmesartan medoxomil-based titration regimen was well tolerated and produced similar 24-hour ambulatory BP reductions from baseline in hypertensive patients with and without diabetes. Patients with diabetes treated with the amlodipine and olmesartan medoxomil-based titration regimen also achieved mean 24-hour ambulatory BP reductions of 21.5/12.6 mm Hg from a baseline of 145.6/83.1 mm Hg. Patients without diabetes experienced a mean 24-hour ambulatory BP reduction of 21.3/12.8 mm Hg from a baseline of 144.6/86.6 mm Hg.

Study Design

AZTEC was a 15-16-week (3- to 4-week placebo run-in and 12-week active treatment periods), open label, prospective, single-arm, titrate-to-goal study, conducted in 185 patients with mild to moderate (Stage 1) and challenging (Stage 2) hypertension. The study evaluated the safety and efficacy of an amlodipine and olmesartan medoxomil-based titration algorithm. Of the total study population, 26 patients were Black and 43 patients were diagnosed as having type 2 diabetes (populations are not mutually exclusive). The primary endpoint was change in mean systolic blood pressure (SBP) from baseline after 12 weeks of treatment as measured by 24-hour ABPM. Secondary endpoints included change from baseline in mean 24-hour DBP as measured by ABPM; change from baseline in mean daytime, nighttime, and last 2, 4, and 6 hours ambulatory SBP and DBP; achievement of ABPM prespecified BP targets; change from baseline mean SeSBP and SeDBP at each titration step; and achievement of BP goals.

Following placebo run-in, patients were started on amlodipine (AML) 5 mg, and were up-titrated at three week intervals if mean cuff BP was greater than or equal to 120/80 mm Hg to AML/olmesartan medoxomil (OM) 5/20 mg, AML/OM 5/40 mg then AML/OM 10/40 mg. If BP was less than 120/80 mm Hg, patients were not up-titrated to the next dose level and remained at the assigned dose (maintenance dose). Patients on maintenance doses were up-titrated if BP subsequently became uncontrolled (SBP greater than or equal to 140 mm Hg and/or DBP greater than or equal to 90 mm Hg). Twenty-four hour ABPM was performed at baseline and end of study (Week 12). One hundred seventy two patients had ABPM values for baseline and end of study. A total of 134 patients (72.4%) were titrated to AML/OM 10/40 mg.

About AZOR(R)

AZOR is a convenient, once daily, single tablet combination of amlodipine, the most prescribed CCB on the market(12), which inhibits the entrance of calcium into the blood vessel walls, with olmesartan medoxomil, the active ingredient in Benicar(R), which blocks angiotensin II receptors. Angiotensin II is a hormone that causes blood vessels to tighten and narrow. Together the two medicines relax the blood vessels so that blood can flow more easily. Benicar (olmesartan medoxomil), Daiichi Sankyo's flagship ARB product, is the fastest growing medication in the fastest growing class of blood pressure-lowering drugs.(13)

The U.S. Food and Drug Administration (FDA) granted marketing approval for AZOR in September 2007. AZOR is indicated for the treatment of hypertension, alone or with other antihypertensive agents. AZOR is not indicated for the initial therapy of hypertension. AZOR may be substituted for its individually titrated components. AZOR may also be used to provide additional blood pressure lowering for patients not adequately controlled with any calcium channel blocker or any angiotensin receptor blocker alone. In the pivotal registrational trial, AZOR demonstrated that eight weeks of double-blind treatment with combination therapy resulted in larger mean reductions in seated blood pressure and brought more patients to goal in comparison to the corresponding monotherapies.

Source
Daiichi Sankyo