Lotrel, a Single-Pill Combination for Treating High Blood Pressure, Reduced Cardiovascular...

Lotrel, a Single-Pill Combination for Treating High Blood Pressure, Reduced
Cardiovascular Events by 20% in High-Risk Patients
- ACCOMPLISH first study to compare two single-pill combinations of commonly
used high blood pressure medicines in reduction of cardiovascular events

CHICAGO, March 31 /PRNewswire/ -- Interim results from the ACCOMPLISH
(Avoiding Cardiovascular Events through COMbination Therapy in Patients LIving
with Systolic Hypertension) trial demonstrate that high-risk, high blood
pressure patients treated with Lotrel(R) (amlodipine besylate and benazepril
HCl) had 20% fewer cardiovascular events than those taking a benazepril and
hydrochlorothiazide (HCTZ) combination. This is the first cardiovascular
outcomes trial in a hypertensive population where all patients were randomized
to receive a single-pill combination treatment at the onset of the trial as
opposed to a step care regimen.
"These results suggest that the combination of the angiotensin-converting
enzyme inhibitor (ACEI) and calcium channel blocker in Lotrel yielded better
patient outcomes in high-risk hypertensive patients than the ACEI and HCTZ
combination," explained Kenneth Jamerson, MD, professor of internal medicine
at the University of Michigan Medical Center in Ann Arbor and lead
investigator of the trial. "Further, a strategy of starting patients in the
trial on a single-pill combination proved to be very efficient in
significantly increasing blood pressure control rates."
Lotrel is approved for the treatment of high blood pressure. It should not
be used before other medications have been tried first.
Treatment with combination therapy resulted in exceptional blood pressure
control at 30 months. Before entering the study, almost all patients were
treated with multiple high blood pressure medicines. At study entry, only 37%
of the study population had a blood pressure of <140/90 mmHg, regarded in
treatment guidelines as the appropriate goal for most patients. After
switching to a single-pill combination of the study medications, 82% of
patients taking Lotrel and 79% of patients taking the benazepril and HCTZ
combination achieved blood pressure goal after 30 months. Some patients
received additional medication to treat their high blood pressure.
"Evidence from trials like ACCOMPLISH provides physicians with additional
information to better inform their treatment decisions in high-risk
hypertensive patients," said Marjorie Gatlin, MD, Vice President and Head of
Cardiovascular and Metabolism Medical Franchise US Medical and Drug Regulatory
Affairs at Novartis Pharmaceuticals Corporation. "Novartis is an innovator of
unique medications for the treatment of high blood pressure, including single-
pill combinations, and is committed to further develop this approach for
effective patient care."
The results were presented today in a late-breaking session at the
American College of Cardiology 57th Annual Scientific Session in Chicago.
ACCOMPLISH is the first large clinical outcomes trial to directly compare
two single-pill combinations of commonly used high blood pressure medicines in
the reduction of a composite endpoint including heart attacks, strokes,
hospitalizations for unstable angina and cardiovascular deaths in high blood
pressure patients at high cardiovascular risk. In October 2007, the study was
stopped early because the pre-defined efficacy outcome had been achieved.
The study was a multi-national, double-blind trial and included more than
11,000 patients at 550 study sites in the US and Scandinavia. One day after
stopping their current high blood pressure medication, patients received a
single-pill combination of either Lotrel or a combination of benazepril and
HCTZ. In the first two months of the study, doses of study medications were
increased. Patients in the Lotrel arm started on 5/20 mg. The dose was
increased to Lotrel 5/40 mg and, for patients not at goal blood pressure, then
to 10/40 mg. Patients taking benazepril and HCTZ started at 20/12.5 mg and
were increased to 40/12.5 mg and, for patients not at goal blood pressure, to
40/25 mg. The combination doses of benazepril and HCTZ 40/12.5 mg and 40/25 mg
used in this study were investigational. In both arms, patients were given
additional blood pressure medication if goal blood pressure was not attained
on the maximum dose of study medications.
The primary study endpoint was a composite of cardiovascular disease, non-
fatal heart attack, non-fatal stroke, and hospitalization for unstable angina
(chest pain that occurs when the heart muscle does not get enough blood) or
revascularization (a procedure that re-establishes blood flow to previously
restricted regions of the heart), and cardiovascular death. The full data will
be available later this year and further analyses will examine the effects on
specific patient populations.
Important safety information
LOTREL and the fixed dose combination of benazepril and HCTZ are
prescription medications for the treatment of high blood pressure. They
should not be used before other high blood pressure medications have been
tried first.
LOTREL and the fixed dose combination of benazepril and HCTZ can harm an
unborn baby and even cause death. If you get pregnant, stop taking LOTREL or
the benazepril and HCTZ combination. Call your doctor right away. Talk to
your doctor about other ways to lower your blood pressure if you plan to
become pregnant.
Don't take LOTREL or the benazepril and HCTZ combination if you are
allergic to any of the ingredients, or to any ACE inhibitor or for patients
taking LOTREL, amlodipine. Do not take the benazepril and HCTZ combination if
you have a history of reduced urine output, or have allergic reactions to
certain drugs known as sulfonamides and tell your doctor if you have liver
problems, lupus or if you take lithium. Your doctor or pharmacist can give you
a complete list of the ingredients in LOTREL or the benazepril and HCTZ
combination.
In rare cases with LOTREL or the benazepril and HCTZ combination, a
potentially life-threatening allergic reaction (swelling of the mouth and
throat) can occur. This potentially dangerous swelling of the mouth and
throat has been reported more often in African American patients receiving ACE
inhibitors than in non-African American patients.
The most serious side effect with LOTREL and the benazepril and HCTZ
combination is low blood pressure.
The most common side effects in patients taking LOTREL and the benazepril
and HCTZ combination include cough, dizziness, and headache, additionally with
the benazepril and HCTZ combination fatigue and additionally with LOTREL,
edema (swelling of the feet, ankles, legs, or hands).
Please see full prescribing information about Lotrel and Lotensin HCT at
www.pharma.us.novartis.com or contact Christine Cascio at 862-778-8026 or
christine.cascio@novartis.com. The combination doses of benazepril and HCTZ
40/12.5 mg and 40/25 mg used in this study were investigational and do not
have approved prescribing information available.
About high blood pressure and treatment
High blood pressure increases a person's risk of experiencing a
cardiovascular event. For example, it has been reported that the risk of heart
attack and stroke doubles with every 20/10 mmHg increase in blood pressure,
starting at 115/75 mmHg. Blood pressure treatment guidelines sponsored by the
National Heart, Lung and Blood Institute recommend initial combination therapy
of two medications that work differently for patients who have a systolic
blood pressure of 20 mmHg and a diastolic blood pressure of 10 mmHg over
target goal. Systolic blood pressure is the pressure of blood flow as the
heart beats and pushes blood throughout the body. Diastolic blood pressure is
between heart beats, as your heart rests and refills with blood.
Approximately 73 million adults (nearly one in three) in the US have high
blood pressure. It has been estimated that most adults with high blood
pressure also have additional health problems that increase their risk for
cardiovascular events.
Novartis: strength in cardiovascular and metabolic diseases
Novartis is focused on improving the lives of the hundreds of millions of
people with diseases of the cardiovascular and metabolic systems. As a global
leader and innovator in cardiovascular and metabolic health, Novartis provides
novel therapies and support programs to treat high blood pressure and major
public health issues. The strength of Novartis lies in its broad range of
renin-angiotensin system (RAS) based therapies for the treatment of high blood
pressure, which include the most prescribed angiotensin-receptor-blocker, the
first approved oral direct renin inhibitor and a single agent combining two of
the most prescribed antihypertensive medicines. Novartis has an extensive
clinical research program in hypertension involving more than 100,000
patients. Novartis is dedicated to helping physicians and patients address
cardiovascular and metabolic health through effective medicines and an ongoing
commitment to education, support and research.
Disclaimer
The foregoing release contains forward-looking statements that can be
identified by terminology such as "will", "suggest", "committed", or similar
expressions, or by express or implied discussions regarding potential new
indications or labeling for Lotrel or regarding potential future revenues from
Lotrel. Such forward-looking statements reflect the current views of the
Company regarding future events, and involve known and unknown risks,
uncertainties and other factors that may cause actual results with Lotrel to
be materially different from any future results, performance or achievements
expressed or implied by such statements. There can be no guarantee that Lotrel
will be submitted or approved for any additional indications or labeling. Nor
can there be any guarantee that Lotrel will achieve any particular levels of
revenue in the future. In particular, management's expectations regarding
Lotrel could be affected by, among other things, the company's ability to
obtain or maintain patent or other proprietary intellectual property
protection, including for the Lotrel 5/40 mg and 10/40 mg capsules; unexpected
regulatory actions or delays or government regulation generally; unexpected
clinical trial results, including unexpected new clinical data and unexpected
additional analysis of existing clinical data; competition in general;
government, industry and general public pricing pressures, and other risks and
factors referred to in Novartis AG's current Form 20-F on file with the US
Securities and Exchange Commission. Should one or more of these risks or
uncertainties materialize, or should underlying assumptions prove incorrect,
actual results may vary materially from those anticipated, believed, estimated
or expected. Novartis is providing the information in this press release as of
this date and does not undertake any obligation to update any forward-looking
statements contained in this press release as a result of new information,
future events or otherwise.
About Novartis
Novartis Pharmaceuticals Corporation researches, develops, manufactures
and markets leading innovative prescription drugs used to treat a number of
diseases and conditions, including those in the cardiovascular, metabolic,
cancer, organ transplantation, central nervous system, dermatological,
gastrointestinal and respiratory areas. The company's mission is to improve
people's lives by pioneering novel healthcare solutions.
Located in East Hanover, New Jersey, Novartis Pharmaceuticals Corporation
is an affiliate of Novartis AG (NYSE: NVS), a world leader in providing
healthcare solutions that address the evolving needs of patients and
societies. Focused solely on growth areas in healthcare, Novartis offers a
diversified portfolio to best meet these needs: innovative medicines,
cost-saving generic pharmaceuticals, preventive vaccines and diagnostic tools,
and consumer health products. Novartis is the only company with leading
positions in these areas. In 2007, the Group's continuing operations
(excluding divestments in 2007) achieved net sales of USD 38.1 billion and net
income of USD 6.5 billion. Approximately USD 6.4 billion was invested in R&D
activities throughout the Group. Headquartered in Basel, Switzerland, Novartis
Group companies employ approximately 98,200 full-time associates and operate
in over 140 countries around the world. For more information, please visit
http://www.novartis.com.
SOURCE Novartis Pharmaceuticals Corporation

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for Novartis Pharmaceuticals Corporation