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Aprotinin Injection Therapy Associated with Reduced Risk of Stroke During Coronary Artery Bypass Graft Surgery

WEST HAVEN, Conn., Sept. 7 /PRNewswire/ -- Trasylol(R) (aprotinin injection) therapy was associated with a 47 percent relative risk reduction for stroke in patients undergoing coronary artery bypass graft (CABG) surgery, according to a study published today in the Journal of Thoracic and Cardiovascular Surgery.(1) Trasylol is the only drug treatment approved by the U.S. Food and Drug Administration (FDA) to reduce bleeding and the need for blood transfusions during CABG surgery.

The systematic review with meta-analysis evaluating data from 35 CABG clinical studies determined that use of Trasylol resulted in a 39 percent reduction in the risk for receiving any blood transfusion. Blood transfusions during CABG surgery have been associated with an increased risk of stroke.(2, 3) Stroke or symptomatic neurological injury occurs in about 5 percent(4) of the more than 300,000 CABG surgeries performed annually.(5)

"Our results highlight that use of aprotinin therapy might be recommended in all primary CABG surgeries following an assessment of the costs and applicability of these data to individual institutions and patients," said lead investigator Artyom Sedrakyan, M.D., Ph.D., researcher at Yale University School of Medicine and honorary lecturer at London School of Hygiene and Tropical Medicine. "About 10 strokes may be avoided in every 1,000 CABG patients with the use of aprotinin, according to these data."

The study also showed that Trasylol therapy was associated with a trend toward reduced atrial fibrillation and did not increase the risk of adverse event outcomes including mortality, myocardial infarction and renal failure.

"The effects of aprotinin therapy on neurological outcome and the contribution of aprotinin's anti-inflammatory effects have been reported in previous studies," said Sedrakyan.

Stroke Associated with CABG Surgery
Some predictors for stoke include advanced age, especially in patients 70 years or older, history of hypertension, presence of proximal aortic atherosclerosis, history of prior neurological disease, and history of unstable angina.(6) Strokes occurring several days after CABG surgery represent almost 25 percent of all cardiac surgery-related strokes.(7)

"The mission of National Stroke Association is to reduce the incidence and impact of stroke. Because stroke is an important complication of bypass surgery, any drug that might reduce this risk is very welcome," said James Baranski, CEO, National Stroke Association.

Stroke, the leading cause of adult long-term disability, is the third largest cause of death in the United States, ranking behind heart disease and cancer. About 750,000 people suffer a new or recurrent stroke each year, with approximately one-fourth of stroke survivors experiencing a recurrent attack within five years.(8, 9)

About the Study
A total of 35 randomized, placebo-controlled trials involving more than 3,800 CABG surgery patients were included in the meta-analysis. The data from all of the studies had been previously published, and most of the studies were double-blind.

Stroke was reported in 18 trials and evaluated in 2,976 patients. Trasylol use was associated with consistently fewer strokes in most of the individual trials. Use of Trasylol resulted in a 47 percent relative risk reduction compared to placebo. Stroke occurred in 1.1 percent of Trasylol and 2.2 percent of placebo groups.

The number of patients in need of a blood transfusion was evaluated in 25 trials involving 3,430 patients. Trasylol therapy was associated with a 39 percent risk reduction for receiving any blood transfusion.

About Trasylol
Trasylol, a natural broad-spectrum proteinase inhibitor, modulates the systemic inflammatory response (SIR) associated with cardiopulmonary bypass (CPB) surgery.

Approved by the FDA in 1993, Trasylol is indicated for prophylactic use to reduce perioperative blood loss and the need for blood transfusion in patients undergoing CPB in the course of CABG surgery. Full prescribing and warning information is also available at http://trasylol.com.(10)

The effects of Trasylol use in CPB involves a reduction of inflammatory response which translates into a decreased need for allogeneic blood transfusions, reduced bleeding and decreased mediastinal re-exploration for bleeding.

Important Safety Considerations
Trasylol is generally well tolerated. Adverse events reported are frequent sequelae of open heart surgery (eg, atrial fibrillation, myocardial infarction, and heart failure). The incidence of myocardial infarction, renal dysfunction and graft patency rates were comparable to placebo.

Anaphylactic or anaphylactoid reactions are possible when Trasylol(R) is administered. Hypersensitivity reactions are rare in patients with no prior exposure to aprotinin. The risk of anaphylaxis is increased in patients who are reexposed to aprotinin-containing products. The benefit of Trasylol(R) to patients undergoing primary CABG surgery should be weighed against the risk of anaphylaxis should a second exposure to aprotinin be required. (See WARNINGS and PRECAUTIONS in the Trasylol(R) prescribing information.)

Anaphylactic reactions are possible. In clinical studies, hypersensitivity and anaphylactic reactions were:

-- Rare ( -- 2.7% overall reaction rate upon re-exposure
-- Within 6 months, the incidence was 5 percent
-- After 6 months, the incidence was 0.9 percent(10)

(1) Sedrakyan, A, et al. "Effect of aprotinin on clinical outcomes in coronary artery bypass graft surgery: A systematic review and meta- analysis of randomized clinical trials." The Journal of Thoracic and Cardiovascular Surgery 2004; 128(2): 1-7.
(2) Spiess, B, et al. "Platelet transfusions during coronary artery bypass graft surgery are associated with serious adverse outcomes." Transfusion 2004; 44:1143-48.
(3) Bucerius J, Gummert JF, Borger MA, Walther T, Doll N, Onnasch JF, Metz S, Falk V, Mohr FW. Stroke after cardiac surgery: a risk factor analysis of 16,184 consecutive adult patients. Ann Thorac Surg. 2003 Feb;75(2):472-8.
(4) Medline Plus: Heart Bypass Surgery. Retrieved August 16, 2004 from https://medlineplus.gov/ency/article/002946.htm.
(5) Heart Disease and Stroke Statistics - 2004 Update. Retrieved August 16, 2004 from http://www.americanheart.org/downloadable/heart/1079736729696HDSStats2004Updat eREV3-19-04.pdf.
(6) Eagle KA, Guyton RA, Davidoff R, Edwards FH, Ewy GA, Gardner TJ, Hart JC, Herrmann HC, Hillis LD, Hutter AM Jr, Lytle BW, Marlow RA, Nugent WC, Orszulak TA. "ACC/AHA 2004 guideline update for coronary artery bypass graft surgery: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Update the 1999 Guidelines for Coronary Artery Bypass Graft Surgery)." American Heart Association Web Site. Available at: http://www.heart.org/HEARTORG/?identifier=9181. Retrieved September 2, 2004.
(7) "Reducing the Incidence of Perioperative Stroke in Cardiac Surgical Patients." Stroke Clinical Updates (National Stroke Association Bi- Monthly Publication) Mar.-Apr. 2004; XIIII(2).
(8) William GR, Jiang JG, Matchar DB, samsa GP. "Incidence and occurrence of Total (First-Ever and Recurrent) Stroke." Stroke 1999; 30: 2523- 2528.
(9) National Institutes of Health, National Institute of Neurological Disorders and Stroke. "Stroke: Hope Through Research." www.ninds.nih.gov, May 1999. Retrieved September 2, 2004.
(10) Trasylol Prescribing Information. Retrieved August 20, 2004 from http://trasylol.com.

Source: Bayer HealthCare Pharmaceuticals

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