New Heart Failure Guidelines Support the Use of BiDil(R)
Aug 18, 2005, 11:35, Reviewed by: Dr.
|"We hope that the use of BiDil according to the new heart failure guidelines will contribute to improved outcomes for black heart failure patients, who face a disproportionate burden from this serious disease."
Updated heart failure guidelines released on Tuesday by the of Cardiology (ACC) and the American Heart Association (AHA) support the combined use of isosorbide dinitrate and hydralazine, now available as a proprietary fixed-dose formulation known as BiDil(R) (isosorbide dinitrate/hydralazine hydrochloride), as an adjunct to current standard heart failure therapy for black patients. BiDil was recently approved by the U.S. Food and Drug Administration (FDA) and launched by NitroMed, Inc. in July 2005.
"NitroMed is pleased that these most prestigious groups in the heart failure community -- the ACC and the AHA -- have recognized the important role that BiDil therapy can play in treating heart failure in self-identified black patients," said Manuel Worcel, M.D., Chief Medical Officer of NitroMed. "We hope that the use of BiDil according to the new heart failure guidelines will contribute to improved outcomes for black heart failure patients, who face a disproportionate burden from this serious disease."
According to the 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult, the addition of the combination to standard medical therapy for heart failure, including ACE inhibitors and beta- blockers, is "reasonable and can be effective in blacks with New York Heart Association (NYHA) functional class III or IV heart failure."
Although not mandatory, these heart failure practice guidelines are made available to help physicians and health care professionals make clinical decisions by providing a range of generally accepted approaches for the prevention, diagnosis and management of the disease. According to ACC and AHA, the guidelines focus on defining practices that meet the needs of most heart failure patients, in most cases.
In citing the results of the African American Heart Failure Trial (A- HeFT), the new guidelines further validate the landmark trial conducted by NitroMed in conjunction with the Association of Black Cardiologists, Inc. In A-HeFT, BiDil, a proprietary fixed-dose combination of isosorbide dinitrate and hydralazine, was shown to decrease the risk of mortality by 43 percent, reduce the risk of first hospitalization for heart failure by 39 percent and improve patient-reported functional status for self-identified black patients when taken as adjunctive therapy with current standard heart failure therapies. The trial was halted early by the study's safety review board due to the significant survival benefit seen with the drug.
Although the mechanism underlying the beneficial effects of BiDil in the treatment of heart failure is not known, the guidelines noted that the benefits seen with this treatment may be related to an improvement in nitric oxide bioavailability.
The issuance of these important guidelines for the management of heart failure comes within months of BiDil's approval by the FDA. NitroMed officially launched BiDil on July 1 and commercial product is now available in pharmacies.
About the ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult
The newly updated set of practice guidelines were developed by an expert panel of the ACC and AHA to reflect the most recent scientific findings on heart failure and guide physicians in its evaluation and management. The guidelines were developed in collaboration with the of Chest Physicians and the International Society for Heart and Lung Transplantation.
BiDil is indicated for the treatment of heart failure as an adjunct to current standard therapy in self-identified black patients, to improve survival, prolong time to hospitalization for heart failure and improve patient-reported functional status. There is little experience in patients with New York Heart Association (NYHA) class IV heart failure. Most patients in the clinical trial supporting effectiveness, referred to as A-HeFT, received, in addition to BiDil or placebo, a loop diuretic, an angiotensin converting enzyme inhibitor or an angiotensin II receptor blocker, and a beta blocker, and many also received a cardiac glycoside or an aldosterone antagonist. BiDil is a fixed-dose combination of isosorbide dinitrate and hydralazine hydrochloride. While the exact mechanism of action underlying the beneficial effects of BiDil in the treatment of heart failure is unknown, it is known that isosorbide dinitrate is a vasodilator with effects on both arteries and veins. The dilator properties of nitrates result from the release of nitric oxide that leads to the relaxation of vascular smooth muscle. Hydralazine is an arterial vasodilator.
In A-HeFT, self-identified black patients taking BiDil in addition to current standard heart failure therapies experienced a significant 43 percent decrease in the risk of mortality (P=.012) (absolute mortality rate: BiDil, 6.2% vs. placebo, 10.2%), a 39 percent reduction in the risk of first hospitalization for heart failure (P less than .001) (absolute first hospitalization rate: BiDil, 16.4% vs. placebo, 24.4%) and a statistically significant improvement at most time points in response to the Minnesota Living with Heart Failure Questionnaire, which is a self-report of the patient's functional status, versus patients taking placebo in addition to current standard therapies.
BiDil treatment is orally-administered and is initiated at a dose of one tablet, three times per day, and may be increased to a maximum of two tablets, three times per day, based on patient tolerance. Adjustments to maximum dosage may occur in three to five days; however, adverse side effects, which may include headaches and dizziness, may require that some patients take more time to reach their highest tolerated dose.
Heart Failure Burden in Black Patients
Heart failure, or end-stage cardiovascular disease, affects approximately five million Americans, including an estimated 750,000 African Americans. Each year, over 550,000 people are diagnosed with heart failure for the first time, and there is no cure for this disease -- with more than 50 percent of patients dying within five years of diagnosis. With respect to heart failure, blacks are affected at a rate greater than that of the corresponding non-black population, presenting with the disease earlier and dying sooner. According to the Centers for Disease Control and Prevention (CDC), African Americans between the ages of 45 and 64 are 2.5 times more likely to die from heart failure than Caucasians in the same age range.
Important Safety Information
BiDil is contraindicated in patients who are allergic to organic nitrates. Augmentation of the vasodilatory effects of isosorbide dinitrate by phosphodiesterase inhibitors (e.g., Viagra(R)/RevatioTM, Levitra(R), Cialis(R)) could result in severe hypotension. Treatment with hydralazine may produce a clinical picture simulating systemic lupus erythematosus (SLE) including glomerulonephritis. If SLE-like symptoms occur, discontinuation of BiDil should be considered. Residua have been detected many years after discontinuation of hydralazine. Symptomatic hypotension may occur with even small doses of BiDil. BiDil should be used with caution in volume depleted or hypotensive patients. Hydralazine can cause tachycardia potentially leading to myocardial ischemia and anginal attacks. Hydralazine hydrochloride has been associated with peripheral neuritis, evidenced by paresthesia, numbness and tingling, which may be related to an antipyridoxine effect. Caution should be exercised if BiDil is used with MAO inhibitors, alcohol, sildenafil, vardenafil or tadalafil.
Headache (50%) and dizziness (32%) were the two most frequent adverse events and were more than twice as frequent in the BiDil group.
Viagra is a registered trademark and Revatio is a trademark of Pfizer, Inc.; Levitra is a registered trademark of Bayer HealthCare, GlaxoSmithKline, and Schering-Plough; Cialis is a registered trademark of Lilly ICOS LLC.
- The updated heart failure guidelines was released on Tuesday by the of Cardiology (ACC) and the American Heart Association (AHA)
The guidelines are available on the ACC Web site at http://www.acc.org/clinical/guidelines/failure/index.pdf.
About NitroMed, Inc.
NitroMed is an emerging pharmaceutical company focused on the research, development and commercialization of proprietary pharmaceuticals based on the therapeutic benefits of the naturally occurring molecule nitric oxide. BiDil, the Company's lead product, is approved for the treatment of heart failure as an adjunct to standard therapy in self-identified black patients and is marketed by NitroMed through a nationwide, dedicated sales force. The Company uses its expertise in nitric oxide biology and chemistry in an effort to develop both new pharmaceuticals, as well as safer, more effective versions of existing drugs. Research and development efforts focus on major diseases that are characterized by a deficiency in nitric oxide, such as cardiovascular and inflammatory diseases. Corporate collaborations are also an element of the Company's business strategy, and NitroMed has an agreement with Boston Scientific to jointly develop nitric oxide-enhanced cardiovascular stents.
Forward Looking Statements
Statements in this press release about future expectations, plans and prospects for the Company, including statements regarding the Company's expectations about the benefits of BiDil and its plans to make BiDil available to patients who can gain from its therapeutic benefits, constitute forward- looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including risks relating to: unanticipated difficulties in maintaining regulatory approvals to market and sell BiDil; the Company's ability to develop and maintain the necessary sales, marketing and manufacturing capabilities to launch and commercialize BiDil; patient, physician and third- payer acceptance of BiDil as a safe and effective therapeutic; adverse side effects experienced by patients taking BiDil; the Company's ability to obtain or maintain intellectual property protection and required licenses; the Company's ability to obtain the substantial additional funding required to conduct manufacturing, marketing and sales of BiDil and other factors discussed in its Quarterly Report on Form 10-Q for the Quarter ended June 30, 2005, which is filed with the SEC. In addition, the forward-looking statements included in this press release represent the Company's views as of the date of this release. The Company anticipates that subsequent events and developments will cause the Company's views to change. However, while the Company may elect to update these forward-looking statements at some point in the future, the Company specifically disclaims any obligation to do so. These forward-looking statements should not be relied upon as representing the Company's views as of any date subsequent to the date of this release.
For full prescribing information, visit: http://www.BiDil.com. BiDil is a registered trademark of NitroMed, Inc.
CONTACT: Investor Relations: Lawrence E. Bloch, M.D., J.D., ChiefFinancial Officer and Chief Business Officer of NitroMed, Inc.,+1-781-266-4197; Media: Amanda Sellers or Leslie Priest of Spectrum ScienceCommunications, +1-202-955-6222, for NitroMed, Inc.
Web site: http://www.BiDil.com/http://www.acc.org/http://www.americanheart.org/http://www.acc.org/clinical/guidelines/failure/index.pdf/
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