Three Out of Four Patients Uncontrolled on Monotherapy Achieved Blood Pressure Goal with Azor According to New Study Results
Study Including All Seven Major Subpopulations with High Prevalence for Hypertension Showed Significant Benefit in Switching Patients from Monotherapy to a Fixed-Dose Combination Therapy
PARSIPPANY, N.J., May 3 /PRNewswire/ -- Preliminary results from a dose titration study showed that treatment with the fixed-dose combination therapy AZOR® (amlodipine and olmesartan medoxomil) helped the majority (cumulative 75.8 percent) of hypertensive patients to reach systolic blood pressure goals of <140 mm hg (<130 hg for patients with diabetes) at any time point during the first 12 weeks and 66.1 percent non-cumulative week 12. the primary endpoint of the study was percentage patients achieving seated systolic blood pressure goal <140 cumulatively by a total 71.3 achieved a of <140>
The study enrolled 999 patients unable to attain blood pressure
control on monotherapy and switched to AZOR for a 20 week
duration.(1) Uncontrolled hypertension was defined as mean systolic
blood pressure (SBP) greater than or equal to 140 mm Hg and less
than or equal to 180 mm Hg AND mean diastolic blood pressure (DBP)
less than or equal to 110 mm Hg or mean SBP greater than or equal
to 130 mm Hg and < 180 mm Hg AND mean DBP less than or equal to
110 mm Hg for patients with diabetes. Data were presented during
the late breaker poster session of the American Society of
Hypertension (ASH) annual meeting in New York.
The prospective, open-label, multicenter, single-arm, dose
titration Blood Pressure Control in All Subgroups with Hypertension
(BP CRUSH) sought to examine whether there would be a benefit of
switching patients from monotherapy to AZOR without a washout
period. The findings showed that patients treated with AZOR 10/40
mg experienced significant reductions in systolic blood pressure
(SBP) of 20.3 mm Hg (mean baseline systolic blood pressure 154.0 mm
Hg) and diastolic blood pressure (DBP) of 11.3 mm Hg (mean baseline
diastolic blood pressure 92.3 mm Hg), P< 0.0001.(1)
A total of 229 patients in BP CRUSH underwent pre-specified
24-hour ambulatory blood pressure measurement (ABPM). Patients
achieved a mean 24-hour ambulatory blood pressure reduction of
14.8/9.4 mm Hg from baseline (136.2/81.6 mm Hg) to Week
12.(1)
"The results of this study may be of immediate practical use to
physicians, as they show that switching patients from monotherapy
to combination therapy was widely effective in helping patients
better achieve blood pressure control," said Dr. Joel Neutel, MD,
Director, Orange County Heart Institute and Research Center,
Tustin, CA. "What makes these results so valuable is that there was
no period of non-treatment before switching from one medication to
another, so it allows us to see that patients responded safely and
effectively to switching from monotherapy to AZOR."(1)
In BP CRUSH, treatment with AZOR was well tolerated, with no
deaths or drug-related serious adverse events (AEs). Treatment
emergent adverse events (TEAEs) occurred in 429 out of 999 (42.9
percent) patients, but the majority of TEAEs were mild-to-moderate
in severity. Treatment emergent adverse events leading to
discontinuation occurred in 53 out of 999 (5.3 percent) of
patients.(1)
Study Design
BP CRUSH was a prospective, open-label, multicenter, titration study evaluating blood pressure goal attainment after switching to the combination therapy AZOR in 999 patients with hypertension uncontrolled on monotherapy. The 20 week active treatment period consisted of consecutive four-week intervals with dosages up-titrated as follows: AZOR 5/20 mg; AZOR 5/40 mg; AZOR 10/40 mg (to achieve blood pressure <120>
Almost 38 percent (37.5 percent) of participants in the study
had previously been treated with an angiotensin receptor blocker or
calcium channel blocker. Male and female patients greater than or
equal to 18 to 80 years (patients without diabetes: 140 less than
or equal to SBP less than or equal to 180 mm Hg and DBP less than
or equal to 110mm Hg; patients with diabetes: 130 less than or
equal to SBP less than or equal to 180 mm Hg and DBP less than or
equal to 110 mm Hg) were eligible for randomization. At least 100
subjects in each of the following subpopulations were recruited:
elderly (greater than or equal to 65 years), Black, Hispanic,
Asian, obese (BMI greater than or equal to 30 kg/m2), type 2
diabetes, and metabolic syndrome, which is defined as a multiplex
of risk factor for cardiovascular disease.(1, 3)
The primary endpoint of the study was the proportion of subjects achieving cuff systolic blood pressure goal (<140 mm hg-patients without diabetes; <130 hg patients with diabetes) during the first 12 weeks. the secondary endpoints included: cuff diastolic blood pressure control (<90 hg-non-diabetics; <80 mm hg-diabetics) first weeks, and blood pressure goals (<140>
About Clinical Inertia
Many patients with high blood pressure can suffer from
under-treatment due to clinical inertia, which occurs when
medications or increased doses of existing medications are not
provided when blood pressure treatment goals are not met.(4)
Additionally, patients also may not be fully aware in understanding
the importance of adhering to prescribed treatment regimens and
making behavioral changes in order to meet blood pressure goals.
While BP CRUSH did not evaluate the impact of AZOR on clinical
inertia, it provides evidence that fixed-dose combination
antihypertensive therapy can get patients to blood pressure
goal.
The Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure (JNC 7) guidelines recommend that patients with high blood pressure achieve a goal blood pressure of <140>
Despite 50 years of treating hypertension and seven evolutions
of the Joint National Committee on Prevention, Detection,
Evaluation and Treatment of High Blood Pressure (JNC) guidelines, a
gap remains between guidelines and their implementation to achieve
optimal blood pressure goals.(7) It is thought that clinical
inertia is a major contributing factor in this gap. Recent work
suggests that clinical inertia related to the management of
diabetes, hypertension and lipid disorders may contribute to up to
80 percent of heart attacks and strokes. As a result, clinical
inertia is considered a leading cause of potentially preventable
adverse events, disability, death and excess medical care costs.
Contributing factors to the inertia may include inaccurate
understanding of normal blood pressure control, side effects
associated with aggressive treatment, or the belief that higher
blood pressure levels in some patients is acceptable.(2)
About AZOR
AZOR is a convenient, once daily, single tablet combination of
amlodipine, the most prescribed CCB on the market, which inhibits
the entrance of calcium into the blood vessel walls, with
olmesartan medoxomil, the active ingredient in Benicar®, 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.
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 may be used as initial therapy in patients who are
likely to need multiple antihypertensive agents to achieve their
blood pressure goals. Initial therapy with AZOR is not recommended
in patients greater than or equal to 75 years old or hepatically
impaired patients. 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
amlodipine (or another dihydropyridine CCB) alone or with
olmesartan medoxomil (or another ARB) 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. There are
no studies with AZOR demonstrating a reduction in cardiovascular
events.
IMPORTANT SAFETY INFORMATION ABOUT AZOR USE IN PREGNANCY
When used in pregnancy during the second and third trimesters,
drugs that act directly on the renin-angiotensin system can cause
injury and even death to the developing fetus. When pregnancy is
detected, AZOR should be discontinued as soon as possible. See
WARNINGS AND PRECAUTIONS, Fetal/Neonatal Morbidity and
Mortality.
Hypotension in Volume- or Salt-Depleted Patients
In patients with an activated renin-angiotensin system, such as
volume- and/or salt-depleted patients, symptomatic hypotension due
particularly to the olmesartan component may occur after initiation
of treatment with AZOR®. Treatment should start under close
medical supervision.
Vasodilation
Since the vasodilation attributable to amlodipine in AZOR is
gradual in onset, acute hypotension has rarely been reported after
oral administration. Nonetheless, caution, as with any other
peripheral vasodilator, should be exercised when administering
AZOR, particularly in patients with severe aortic stenosis.
Severe Obstructive Coronary Artery Disease
Patients, particularly those with severe obstructive coronary
artery disease, may develop increased frequency, duration, or
severity of angina or acute myocardial infarction on starting
calcium channel blocker therapy or at the time of dosage
increase.
Congestive Heart Failure
In general, calcium channel blockers should be used with caution
in patients with heart failure.
Impaired Renal Function
In studies of ACE inhibitors in patients with unilateral or
bilateral renal artery stenosis, increases in serum creatinine or
blood urea nitrogen (BUN) have been reported. There has been no
long-term use of olmesartan medoxomil in patients with unilateral
or bilateral renal artery stenosis, but similar effects would be
expected with AZOR because of the olmesartan medoxomil
component.
Hepatic Impairment
Since amlodipine is extensively metabolized by the liver and the
plasma elimination half-life (t1/2) is 56 hours in patients with
severely impaired hepatic function, caution should be exercised
when administering AZOR to patients with severe hepatic impairment.
Initial therapy with AZOR is not recommended in hepatically
impaired patients.
Laboratory Tests
There was a greater decrease in hemoglobin and hematocrit in the
combination product compared to either component alone.
Adverse Reactions
The only adverse reaction that occurred in greater than or equal
to 3 percent of patients treated with AZOR and more frequently than
placebo was edema. The placebo-subtracted incidence was 5.7 percent
(5/20 mg), 6.2 percent (5/40 mg), 13.3 percent (10/20 mg), and 11.2
percent (10/40 mg). The edema incidence for placebo was 12.3
percent.
Adverse reactions seen at lower rates but at about the same or
greater incidence as in patients receiving placebo included
hypotension, orthostatic hypotension, rash, pruritus, palpitation,
urinary frequency, and nocturia.
In individual clinical trials of amlodipine and olmesartan
medoxomil, other commonly reported adverse reactions included
headache, dizziness, and flushing.
Geriatric Use
Elderly patients have decreased clearance of amlodipine. Initial
therapy with AZOR is not recommended in patients greater than or
equal to 75 years old.
For more information on AZOR®, call 877-4-DSPROD
(877-437-7763) or go to the web site www.azor.com.
About Daiichi Sankyo
In keeping with its vision of becoming a "Global Pharma
Innovator," the Daiichi Sankyo Group is dedicated to the creation
and supply of innovative pharmaceutical products to address the
diversified, unmet medical needs of customers in both developed and
emerging markets. While maintaining its portfolio of marketed
pharmaceuticals for hypertension, hyperlipidemia, and bacterial
infections, the Group is engaged in the development of treatments
for thrombotic disorders and focused on the discovery of novel
oncology and cardiovascular-metabolic therapies. Furthermore, the
Daiichi Sankyo Group has created a "Hybrid Business Model," which
will respond to market and customer diversity and optimize growth
opportunities across the value chain. For more information, please
visit www.daiichisankyo.com.
Daiichi Sankyo, Inc., headquartered in Parsippany, New Jersey,
is the U.S. subsidiary of Daiichi Sankyo Company, Ltd. For more
information on Daiichi Sankyo, Inc., please visit
www.dsi.com.
(1) BP CRUSH Abstract: Effects on BP Control of Amlodipine
(AML)/Olmesartan Medoxomil (OM), with or without
Hydrochlorothiazide (HCTZ), In Patients Not Controlled by Prior
Antihypertensive Monotherapy. Presented at ASH 2010.
(2) BP-CRUSH Poster: Rationale and Design of Blood Pressure
Control in All Subgroups with Hypertension Study (BP CRUSH)
Evaluating the Efficacy and Safety of Amlodipine (AML)/Olmesartan
Medoxomil (OM) in Patients Who are Non-Responders to
Antihypertensive Monotherapy.
(3) American Heart Association. Metabolic Syndrome. Available
at: http://www.americanheart.org/presenter.jhtml?identifier=3063528.
Accessed April 19, 2010.
(4) U.S. Department of Health and Human Services. Advances in
Patient Safety: From Research to Implementation. Vol 2. AHRQ
Publication Nos. 050021 (1-4). February 2005, pg. 293. Available at
http://www.ahrq.gov/downloads/pub/advances/vol2/OConnor.pdf.
Accessed April 21, 2009.
(5) The Seventh Report of the Joint National Committee on
Prevention, Detection, Evaluation and Treatment of High Blood
Pressure. Bethesda, MD: National Institutes of Health: National
Heart, Lung, and Blood Institute; National High Blood Pressure
Education Program; May 2003. NIH Publication 03-5233.
(6) American Heart Association. High Blood Pressure Statistics.
Available at: http://www.americanheart.org/presenter.jhtml?identifier=4621.
Accessed March 29, 2010.
(7) McInnes, GT et al. How Important is Optimal BP Control?
Clinical Therapeutics, Vol 26, Supplement 1, 2004, Pages
A3-A11.
Source: Daiichi Sankyo, Inc.
CONTACT: Jennifer Brennan, Daiichi Sankyo, Inc., +1-973-944-2511
or
+1-201-709-9309 (cell), jbrennan@dsi.com; or Matthew
Gold, Hill & Knowlton,
+1-212-885-0564 or +1-631-804-3639 (cell), matthew.gold@hillandknowlton.com
Web Site: http://www.daiichisankyo.com/
Posted: May 2010
