update on the medical management of acute coronary syndrome
TRANSCRIPT
Update on the Medical Management of
Acute Coronary Syndrome
Worldwide Statistics
Each year:
• > 4 million patients are admitted with unstable angina and acute MI
• > 900,000 patients undergo PTCA with or without stent
Myocardial Ischemia
• Spectrum of presentation– silent ischemia– exertion-induced angina– unstable angina– acute myocardial infarction
Cumulative 6-month mortality from ischemic heart disease
0 1 2 3 4 5 6
5
10
0
15
20
25
Months after hospital admission
Dea
ths
/ 100
pts
/ m
onth
Acute MIUnstable anginaStable angina
Duke Cardiovascular Database
N = 21,761; 1985-1992Diagnosis on adm to hosp
Ischemic Heart Diseaseevaluation
• Based on the patient’s– history / physical exam– electrocardiogram
• Patients are categorized into 3 groups– non-cardiac chest pain– unstable angina– myocardial infarction
Acute Coronary Syndrome
Ischemic DiscomfortUnstable Symptoms
No ST-segmentelevation
ST-segmentelevation
Unstable Non-Q Q-Waveangina AMI AMI
ECG
AcuteReperfusion
HistoryPhysical Exam
Acute Coronary Syndrome
• The spectrum of clinical conditions ranging from:– unstable angina– non-Q wave MI– Q-wave MI
• characterized by the common pathophysiology of a disrupted atheroslerotic plaque
Unstable AnginaAnti-platelet Therapy
• Abciximab – EPIC Trial
effective in preventing death, MI, and abrupt closure associated with coronary angioplasty (see also EPIC slides)
– EPISTENT Trial
Unstable AnginaAnti-platelet Therapy
• Abciximab – CAPTURE – At 30 days, there was a 29% reduction in the
primary composite endpoint of death, MI, or urgent revascularization in the abciximab group
– At 6 months, this benefit was not evident
Lancet 1997;349:1429-1435
Unstable AnginaAnti-platelet Therapy
• Tirofiban – PRISM (Platelet Receptor Inhibition for
Ischemic Syndrome Management)– 3,200 patients with unstable angina were
treated with either heparin or tirofiban– At 48 hours, there was significant risk
reduction (5.9% to 3.6%) in the rate of death, MI, or refractory ischemia. The benefit was lost at 30 days.
N Engl J Med 1998;338:1498-505
Unstable AnginaAnti-platelet Therapy
• Tirofiban– PRISM -PLUS (Platelet Receptor Inhibition
for Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms)
– randomized 1,915 patients with UA and non-Q-MI to tirofiban alone, heparin alone, or a combination of the two (all received aspirin)
N Engl J Med 1998;338:1488-97
Unstable AnginaAnti-platelet Therapy
• Eptifibatide – PURSUIT (Platelet IIb/IIIa Underpinning the
Receptor for Suppression of Unstable Ischemia Trial)
– ~11,000 patients admitted with unstable angina or non-Q-wave myocardial infarction
– a broad-based trial encompassing a variety of clinical practices and practice styles
NEJM 1998;339:436-443
Unstable AnginaAnti-platelet Therapy
• Eptifibatide PURSUIT– randomized to eptifibatide or placebo; all
patients received aspirin and heparin – significantly reduced the risk of death and MI
at 30 days from 15.7% to 14.2%, a 9% risk reduction
NEJM 1998;339:436-443
Platelet Inhibition and Bleeding Time
IMPACT II PURSUIT
135 / 0.5 180 / 2.0
Inhibition of platelet aggregation
15 minutes after bolus 69% 84%
at steady state 40-50% >90%
4h after infusion discontinuation <30% <50%
Bleeding-time prolongation
at steady state <5x <5x
6h after infusion discontinuation 1x 1.4x
Fibanincidence of intracranial bleeding
Treatment (%)
Study Compound Placebo Active Heparin
RESTORE Tirofiban 0.3 0.1
EPIC Abciximab 0.3 0.1
0.4
EPILOG Abciximab 0.0 0.1
IMPACT II Integrelin 0.07 0.07 0.15
The EXCITE Trial Investigators
Bolus
Low dose
High dose
Bolus + Infusion
Unstable AnginaAnti-platelet Therapy
• Summary – the four “P trials” (PRISM, PRISM-PLUS,
PARAGON, PURSUIT)– all show reduction of death rate between
1.3% and 3.4% - in addition to the benefit of aspirin
– useful in the management of patients with unstable angina and MI without ST elevation
Unstable AnginaAnti-coagulant Therapy
• Heparin– recommendation is based on documented
efficacy in many trials of moderate size– meta-analyses (1,2) of six trials showed a
33% risk reduction in MI and death, but with a two fold increase in major bleeding
– titrate PTT to 2x the upper limits of normal
1. Circulation 1994;89:81-882. JAMA 1996;276:811-815
Unstable AnginaAnti-coagulant Therapy
• Low-molecular-weight heparinadvantages over heparin:– better bio-availability– higher ratio (3:1) of anti-Xa to anti-IIa activity– longer anti-Xa activity, avoid rebound– induces less platelet activation– ease of use (subcutaneous - qd or bid)– no need for monitoring
ESSENCE Trialincidence of death, MI, or recurrent angina
N Eng J Med 1997;337:447-452
0
5
10
15
20
25
0
5
10
15
20
25
heparin Lovenox heparin Lovenox
n=1564 n=1607 n=1564 n=1607
19.8%
16.6%P=0.019
23.3%
19.8%P=0.016
Day 14 Day 30