Lotrel, a Single-Pill Combination for Treating High Blood Pressure, Reduced Cardiovascular Events by 20% in High-Risk Patients

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 http://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 , 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/.