Controlling Perioperative Hypertension with Cleviprex Reduces Risk of Heart Attack and of Death Following Cardiac Surgery, According to New AnalysesVANCOUVER, British Columbia--(BUSINESS WIRE)--Jun 20, 2008 - The Medicines Company (NASDAQ: MDCO) today announced that data from two post-hoc analyses of the ECLIPSE trial showed that use of Cleviprex(TM) (clevidipine butyrate) injectable emulsion to control blood pressure during cardiac surgery may be associated with a reduced risk of heart attack compared to two of three currently used IV antihypertensive agents. In a separate sub-analysis, Cleviprex was associated with a lower 30-day mortality compared to two nitrovasodilators.
The two sub-analyses from ECLIPSE were presented during a poster session held at the annual meeting of the Society of Cardiovascular Anesthesiologists (SCA). In the first analysis, investigators examined the relationship between perioperative blood pressure control and postoperative myocardial infarction (MI) in the 30-day postoperative period. In the second analysis, investigators evaluated 30-day mortality in patients who received IV antihypertensive therapy for blood pressure control before cardiac surgery (n=282). ECLIPSE is a large safety trial which compared three intravenous antihypertensive therapies involving 1,964 cardiac surgery patients, each enrolled in one of three randomized, open-label trials which compared Cleviprex to nitroglycerin, sodium nitroprusside or nicardipine. Overall results were presented in March at the American College of Cardiology meeting.
"Perioperative hypertension is recognized as a risk factor in cardiac surgery patients; however, its contribution to cardiac complications such as postoperative myocardial infarction (MI) is unclear," said lead investigator Edwin Avery, MD, Massachusetts General Hospital, Boston, MA. "These new data suggest the critical importance of controlling blood pressure in this setting."
30-Day Mortality Analysis (n=282)
Researchers examined 30-day mortality among a subset of ECLIPSE patients who received an IV hypertensive for blood pressure control prior to surgery (before skin incision). Patients were randomized to receive Cleviprex, sodium nitroprusside or nitroglycerin. No patients received nicardipine prior to cardiac surgery; therefore, they were excluded from this analysis. Of the 282 patients included in the analysis, overall 30-day mortality was 5 percent, with a significant difference between groups: 3/137 (2 percent) of Cleviprex patients and 11/145 (8 percent) of nitroglycerin or sodium nitroprusside patients (p less than 0.03). The researchers concluded that in patients requiring pre-incision treatment for BP that Cleviprex was associated with significantly reduced risk of 30-day mortality after surgery compared to either sodium nitroprusside or nitroglycerin.
"This analysis points to potential difference in antihypertensive treatments options to manage hypertension before and during cardiac surgery, which needs to be confirmed with future studies," says lead investigator Solomon Aronson, MD, Duke University Medical Center, Durham, North Carolina.
Postoperative MI Analysis (n=1413)
For the analysis investigating the relationship between perioperative hypertension and 30-day postoperative MI, researchers calculated blood pressure "excursions" in cardiac surgery patients during the first 24 hours after the perioperative use of either the investigational drug, Cleviprex, or controlled therapy with sodium nitroprusside, nicardipine or nitroglycerin. Blood pressure control was quantified using the area under the curve (AUC) method, capturing magnitude and duration of blood pressure excursions outside predefined, systolic ranges. Cleviprex was more effective at keeping patients' blood pressures within acceptable ranges than nitroglycerin and sodium nitroprusside. Cleviprex was equally as effective as nicardipine. The researchers concluded that less precise blood pressure control was an independent and significant predictor of an increased rate of MI within the 30-day postoperative period.
Cleviprex is a novel investigational IV antihypertensive for the treatment of acutely elevated blood pressure, when the use of oral therapy is not feasible or desirable. Cleviprex has a rapid onset and offset of action and can be titrated for predictable blood pressure control. Unlike current antihypertensive treatments which are metabolized by the kidney or liver, Cleviprex is metabolized in the blood and does not accumulate in the body.
Six Phase III trials of Cleviprex met all of their primary endpoints. The most common adverse reactions seen with Cleviprex use were headache, sinus tachycardia, hypotension, nausea, polyuria, flushing, dizziness and vomiting.
About The Medicines Company
The Medicines Company (NASDAQ: MDCO) is focused on advancing the treatment of critical care patients through the delivery of innovative, cost-effective medicines to the worldwide hospital marketplace. The Company markets Angiomax(R) (bivalirudin) in the United States and other countries for use in patients undergoing coronary angioplasty, a procedure to clear restricted blood flow in arteries around the heart. The Company also has two products in late-stage development, Cleviprex(TM) (clevidipine butyrate) injectable emulsion and cangrelor. The Company's website is www.themedicinescompany.com.
Statements contained in this press release about The Medicines Company that are not purely historical, and all other statements that are not purely historical, may be deemed to be forward-looking statements for purposes of the safe harbor provisions under The Private Securities Litigation Reform Act of 1995. Without limiting the foregoing, the words "believes," "anticipates" and "expects" and similar expressions are intended to identify forward-looking statements. These forward-looking statements involve known and unknown risks and uncertainties that may cause the Company's actual results, levels of activity, performance or achievements to be materially different from those expressed or implied by these forward-looking statements. Important factors that may cause or contribute to such differences include whether the Company's products will advance in the clinical trials process on a timely basis or at all, whether clinical trial results will warrant submission of applications for regulatory approval, whether the Company will be able to obtain regulatory approvals, whether physicians, patients and other key decision-makers will accept clinical trial results, and such other factors as are set forth in the risk factors detailed from time to time in the Company's periodic reports and registration statements filed with the Securities and Exchange Commission including, without limitation, the risk factors detailed in the Company's Quarterly Report on Form 10-Q filed on May 12, 2008, which are incorporated herein by reference. The Company specifically disclaims any obligation to update these forward-looking statements.
Posted: June 2008