Healthcare Industry News:  bivalirudin 

Biopharmaceuticals Cardiology Surgery

 News Release - October 15, 2007

Improved Perioperative Blood Pressure Control Associated with Reduced Risk of Kidney Dysfunction in Cardiac Surgery Patients

Retrospective Analysis from the ECLIPSE Trial Presented at Annual Meeting of the American Society of Anesthesiologists

SAN FRANCISCO--(HSMN NewsFeed)--A retrospective analysis from ECLIPSE*, the largest safety trial of intravenous antihypertensive therapies, showed that improved perioperative blood pressure control in patients undergoing cardiac surgery is strongly associated with a reduced risk of kidney dysfunction within 30 days following the procedure.1 Perioperative hypertension - severely high blood pressure just before, during and/or after surgery - affects as many as 56 percent of cardiac surgery patients.2 The findings were presented today at the 2007 Annual Meeting of the American Society of Anesthesiologists (ASA).

"ECLIPSE is the first study to examine the relationship between perioperative blood pressure control and clinical outcomes such as kidney dysfunction," said Solomon Aronson, MD, lead author of the presentation and professor and vice chairman, Department of Anesthesiology, Duke University Medical Center. "The analysis we presented today suggests that better blood pressure control may reduce the risk of renal dysfunction, which has a major impact on quality of life and is very costly to treat."

"Data from ECLIPSE underscore the importance of tight blood pressure control in cardiac surgery patients," said John Kelley, President and Chief Operating Officer of The Medicines Company. "There is a clear need for new and better IV antihypertensive agents that provide rapid and predictable blood pressure control, and we are working to address that need."

Study and Findings

This ECLIPSE trial included a total of 1,512 cardiac surgery patients enrolled in one of three randomized, open-label studies comparing Cleviprex(TM) (clevidipine butyrate injectable emulsion) to current intravenous antihypertensive agents: nitroglycerin, sodium nitroprusside or nicardipine. Investigators monitored each patient's blood pressure (BP) beginning just before the patient went into cardiac surgery, and administered the assigned antihypertensive agent, at their discretion, if it became too high. The dose of antihypertensive agent was adjusted as necessary to achieve the desired BP response over a 24-hour period. The magnitude and duration of systolic BP excursions above or below predefined perioperative systolic BP ranges (85-145 mm Hg pre- and post-operatively, and 75-135 mm Hg during surgery) were calculated for each patient.

The analysis presented today showed a statistically significant association between BP excursions and kidney dysfunction (defined by creatinine being above 2.0 mg/dL, with minimum increase of 0.7mg/dL) at 30 days. Specifically, the risk of kidney dysfunction was more than 75 percent greater in patients with the worst BP control - those in the top 25 percent of BP excursions (odds ratio 1.785, confidence interval 1.132-2.815, p = 0.0126). The findings are consistent with others reported from a separate retrospective analysis of ECLIPSE data showing that poor BP control is associated with greater 30-day mortality risk.3

About Perioperative Hypertension

Perioperative hypertension affects patients in the operating room, post-anesthesia care unit and intensive care unit. It is thought to be caused by the rapid shifts in blood volume and increased activity of the sympathetic nervous system that accompany surgery, which in turn increase vasoconstriction, vascular resistance, and both systolic and diastolic BP. The increased pressure can damage blood vessels, resulting in inflammation and leaking of fluid or blood into tissues, and complications such as hemorrhagic stroke, ischemic stroke, encephalopathy, myocardial ischemia or infarction, heart arrhythmia, congestive heart failure, and bleeding at the surgical site.

Perioperative hypertension is treated using intravenous antihypertensive agents, but current therapies have various shortcomings. For example, nitroglycerin and sodium nitroprusside dilate both arteries and veins, which can result in less predictable BP control. Nicardipine is selective for arteries, but because it has a slower onset and longer duration of action, and accumulates over time in the body, it is rarely used to control BP during surgery, and is only used occasionally after surgery.

About Cleviprex

Cleviprex is a novel investigational IV antihypertensive for the treatment of acute hypertension 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, making it suitable for patients with end-organ damage.

Cleviprex has been studied in more randomized clinical trials and in more patients than any other intravenous antihypertensive agent. 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.

MDCO-G

About The Medicines Company

The Medicines Company meets the demands of the world's most advanced medical practitioners by developing products that improve acute hospital care. The Company markets Angiomax® (bivalirudin) in the United States and recently reacquired rights to the product in Europe, where it is marketed as Angiox® (bivalirudin). Angiomax is used in patients undergoing coronary angioplasty, a procedure to clear restricted blood flow in arteries around the heart. In addition to Cleviprex, the Company also has another product in late-stage development, cangrelor. The Company's Web site is http://www.themedicinescompany.com.

Statements contained in this press release about The Medicines Company and Cleviprex 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 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 August 9, 2007, which are incorporated herein by reference. The Company specifically disclaims any obligation to update these forward-looking statements.

References

* Evaluation of CLevidipine In the Postoperative Treatment of Hypertension Assessing Safety Events

(1) Aronson S, Cheung A, Stierer K, Levy JH, Lumb P, Investigators for DCRI-GPRO. Perioperative blood pressure control predicts renal dysfunction in cardiac surgery patients. Poster (A1253). Annual Meeting of the American Society of Anesthesiologists; 2007 Oct 13-17, 2007; San Francisco.

(2) Cheung AT. Exploring an optimum intra/postoperative management strategy for acute hypertension in the cardiac surgery patient. J Card Surg 2006; 21:S8-S14.

(3) Aronson S, Dyke C, Kereiakes D, Levy JH, Lumb P, Cheung A, Corwin H, Stierer K, Newman M. Blood pressure control is an independent predictor of short-term mortality in cardiac surgery patients: Analysis from the three randomized ECLIPSE trials. Late-breaking clinical trials. American College of Cardiology; 2007 Mar 24-27; New Orleans, LA.


Source: The Medicines Company

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