Alle Storys
Keine Story von IREF-Ischemia Research and Education Fou mehr verpassen.

IREF-Ischemia Research and Education Fou

Aspirin shown to greatly reduce death and suffering from Ischemic Complications following heart bypass surgery


Landmark study published in the New England Journal of Medicine
identifies safe, inexpensive therapy to save lives and healthcare
Led by Dr. Dennis T. Mangano and the Ischemia Research & Education
Foundation, a massive, worldwide study involving 17 countries, 70
medical centers and more than 5'000 patients has shown that early
aspirin use following cardiac bypass surgery is associated with
greatly reduced risk of dying and suffering from ischemic (inadequate
blood supply) complications involving the heart, brain, kidney and
gastrointestinal tract. Furthermore, use of aspirin immediately
following surgery was found to be safe and cost-effective, allowing
for its immediate and widespread use.
Dr. Dennis T. Mangano, Ph.D., M.D., a world-renowned investigator
in association with investigators of the Ischemia Research and
Education Foundation (IREF) in San Francisco, and the Multicenter
Study of Perioperative Ischemia (McSPI) Research Group located
throughout the world conducted the groundbreaking EPI II Study. The
study appears as the lead article entitled "Aspirin and Mortality
from Cardiac Bypass Surgery" in tomorrow's New England Journal of
"For the first time, we have identified a therapy that can
substantially reduce both fatal and non-fatal outcomes associated
with cardiac surgery," said Dr. Mangano. "What's more, its use is
both safe and extremely cost-effective. If the clinical effect found
in EPI II were repeated, then every year 27'000 lives could be saved
and more than 51'000 serious ischemic events such as stroke or kidney
failure could be prevented through aspirin use immediately following
cardiac bypass surgery," he added.
Among patients receiving aspirin (up to 650 mg) within 48 hours of
coronary artery bypass graft (CABG) surgery, there was a 67%
reduction in subsequent mortality (1.3% versus 4.0%; P < 0.001)
compared with the non-aspirin group. Nonfatal ischemic complications
were also greatly reduced. The aspirin group experienced a 49%
reduction in myocardial infarctions (2.8% versus 5.4%; P < 0.001), a
48% reduction for stroke (1.3% versus 2.6%; P < 0.01), a 74%
reduction in for renal failure (0.87% versus 3.4%; P < 0.001), and a
68% reduction for bowel infarction (0.27% versus 0.84%; P = 0.01).
The aspirin benefit was similar among diverse subsets of patients,
including gender, race, age, disease acuity, insurance-type and
country. Multivariate analysis of the trial results showed that no
other factor or medication was independently associated with reduced
outcome. Most importantly, this analysis also showed that the risk
for hemorrhage, gastritis, infection or impaired wound healing was
not increased with aspirin use (odds ratio, 0.63; 95% confidence
interval, 0.54 - 0.74).
"The EPI II study is extremely noteworthy for a number of reasons.
First, it is the most comprehensive study ever performed in medicine,
collecting more than 7'500 pieces of data from every one of the 5'000
patients, or 40 million pieces of data. Second, the entire study was
privately (non-profit) funded, and included medical centers of the
United States, Canada, Mexico, South America, Europe, Eastern Europe,
the Middle East, India and the Far East. Third, and most importantly,
the breadth of effects shown by early aspirin use after cardiac
bypass surgery was very substantial," said Dr. Mangano. "Aspirin use
was shown to substantially mitigate both fatal and nonfatal damage
not only to the heart, but also other major organs. These findings
suggest a fundamental role of the platelet in orchestrating the
ischemic response to reperfusion injury among multiple organs in this
setting," he added.
Study Design
The EPI II Study was prospective and longitudinal, including 5'436
patients admitted with medically refractory coronary artery disease
and scheduled for CABG surgery at 70 medical institutions among 17
countries in North and South America, Europe, the Middle East, and
Asia. It was designed to determine the incidence of fatal and
nonfatal major ischemic events involving the heart, brain, kidney and
gastrointestinal tract and assess the impact of aspirin use
immediately following surgery on these outcomes, as well as estimate
any effect on healthcare costs.
For each enrolled patient, approximately 7'500 fields of data were
collected throughout the patient's hospitalization period by
independent investigators, with treating physicians blinded to
research data. Fatal and nonfatal outcomes occurring more than 48
hours after surgery and during the hospitalization were classified as
cardiac (myocardial infarction, heart failure), cerebral (stroke,
encephalopathy), renal (dysfunction, failure), gastrointestinal
(ischemia, infarction), or other (such as infections or pulmonary).
Clinical decisions were not controlled by study protocol, and all
patients qualifying for enrollment within the pre-specified
enrollment period were entered. Of the 5,436 patients enrolled in the
study, 371 were excluded due to either patient withdrawal, death
prior to surgery, cancellation of surgery, or incomplete data. Of the
remaining 5'065 patients, 3'001 received aspirin (from a total of 80
mg to 650 mg) within 48 hours of revascularization (restoration of
blood flow to the heart). All potential side effects associated with
aspirin use, such as blood loss, gastric irritation, infection and
impaired wound healing, were recorded daily by blinded investigators.
Adverse Outcomes
During the hospitalization period defined by the trial, 164
patients (3.2%) died, all of whom were associated with one or more
adverse ischemic events. Seventy-four percent of the deaths
(involving 121 patients) and 65% of the nonfatal ischemic events
(involving 539 additional patients) occurred after 48 hours of
First use of aspirin after 48 hours was not associated with a
significant reduction in subsequent mortality. The practices of
discontinuing aspirin use prior to surgery, transfusing platelets
(small blood cells that control bleeding) after reperfusion, and
using anti-fibrinolytic agents (blood clot stabilizers) to reduce
blood loss during hospitalization, were all associated with increased
risk of dying and suffering ischemic complications. Those risks are
substantially reduced, but still significant, when aspirin was used.
Pharmacoeconomic Clinical Implications
The pharmacoeconomic implications of the EPI II study results mean
that for every 1'000 CABG patients treated with aspirin within the
first 48 hours after surgery, 81 lives could be saved. Worldwide, if
the clinical effect found in EPI II were repeated, 26'700 lives could
be saved every year. Additionally, in 51'300 other patients, serious
ischemic events such as stroke or kidney failure could be prevented
each year resulting in savings of approximately 1'402'800 hospital
days, or approximately $3.3 billion annually. Given a hospital cost
of five cents per aspirin, the added cost of treating these patients
would be only $100,000 per year.
Using reasonable assumptions for life expectancy, the effect of
aspirin therapy on mortality alone would result in annual savings of
approximately 267'000 life-years, or 38 cents per life-year saved.
This is less than one percent of that associated with fibrinolytic
therapy and less than one-tenth of one percent of that associated
with kidney dialysis.
Coronary Artery Bypass Graft Surgery
First performed nearly four decades ago, CABG surgery now is
performed in nearly one million patients per year worldwide - a
growth rate likely to accelerate given worldwide aging and greater
availability of this therapy in India and China. Although substantial
advances have evolved for surgical techniques, heart preservation,
monitoring and intensive care, complication rates continue to be
troubling - especially for the older and sicker patients and those
not indicated for angioplasty (percutaneous coronary transluminal
angioplasty or PCTA). These high-risk patients now represent the
majority of surgical patients giving rise to complication rates of
15% or more.
The Ischemia Research and Education Foundation (IREF) is a
nonprofit, privately endowed research institution based in San
Francisco. IREF's mission is to improve the health and quality of
life throughout the world by conducting and publishing high quality
clinical research for the public benefit. Founded in 1987 by Dennis
T. Mangano, MD, PhD, IREF has 13 MDs, PhDs and PharmDs among its 19
full-time staff and a network of nearly 300 clinical sites
internationally. IREF has unique research capabilities in the areas
of cardiovascular medicine and anesthesiology and has specifically
addressed the problem of morbidity and mortality through the study of
perioperative ischemia. You may find out more about IREF on the web
Contact: Rick Roose 
Company: Chase Communications
Phone: 415-433-0333
Cell: 415-246-0474
Contact: Julie Chase 
Company: Chase Communications
Phone: 415-777-0607
Cell: 415-710-7108


Amy Berry
Company: Chase Communications
Phone: 415-433-0363
Cell: 415-505-6201