Post on 14-Jan-2016
description
Antiplatelet Interventions in Acute Coronary Syndromes
VBWG
Contents
I. Acute Coronary Syndromes: Tailoring Treatment to Level of Risk
II. Thrombus Susceptibility and the Vulnerable Plaque: Relationship Between Inflammation and Thrombosis
III. ACC/AHA UA/NSTEMI Guidelines: Role of GP IIb/IIIa Inhibitors
IV. Clinical Trials of GP IIb/IIIa Inhibition
V. Clinical Insights, Risk Stratification, and Enhancing Outcomes
VI. GP IIb/IIIa Inhibition in STEMI: Growing Clinical Trial Evidence
Acute Coronary Syndromes: Tailoring Treatment to Level of Risk
VBWG
US hospital discharges: Unstable angina/NSTEMI and STEMI
AHA. Heart Disease and Stroke Statistics–2005 Update.
STEMI = ST-elevation myocardial infarction (MI), or Q-wave MINSTEMI = non–ST-elevation MI, or non–Q-wave MI
1.67 million hospital discharges
STEMI
1.17 million discharges per year
500,000 discharges per year
Acute coronary syndromes
UA/NSTEMI
VBWG
Braunwald E et al. J Am Coll Cardiol. 2002;40:1366-74.
ACC/AHA 2002 UA/NSTEMI guidelines: High-risk indicators for early invasive strategy
• Recurrent angina/ischemia on treatment
• Elevated troponin levels
• New ST-segment depression
• Recurrent angina/ischemia with CHF symptoms, S3 gallop, pulmonary edema, worsening rales, new or worsening mitral regurgitation
• High-risk noninvasive test results
• Depressed LV function (EF <40%)
• Sustained ventricular tachycardia
• PCI within 6 months
• Prior CABG
Class I (Level of evidence: A)
VBWG
Odds ratio (95% CI)0.1 0.2 0.5 1 2 5 10
Favors routineinvasive
Favors selectiveinvasive
OR 1.60, P = 0.007
OR 0.76, P = 0.01
Mortality during hospitalization
Mortality after dischargeTIMI 3B 3.32.8VANQWISH 11.713.4MATE 6.910.0FRISC II 3.01.2TACTICS 2.81.9VINO 9.41.6RITA 3 7.35.2
Subtotal 1.11.8
TIMI 3B 1.92.2VANQWISH 1.34.5MATE 3.30.9FRISC II 0.91.1TACTICS 0.71.4VINO 4.51.6RITA 3 0.71.6
Subtotal 3.8 4.9
Cons (%)Inv (%)
Invasive Rx in ACS: Early and late mortality
Mehta SR et al. JAMA. 2005;293:2908-17.
7 trials, N = 9212
VBWG
Mehta SR et al. JAMA. 2005;293:2908-17.
7 trials, N = 9212
*TIMI 3B, VANQWISH, MATE†FRISC II, TACTICS, VINO, RITA 3‡Data by troponin status available only in FRISC II, TACTICS, RITA 3
Invasive management of UA/NSTEMI meta-analysis: Subgroups
Trial Routine (%) Selective (%) Odds ratio
Favorsroutine
invasive
Favorsselective invasive P
<0.001
0.0010.42
0.010.40
0.92After 1999† 12.49.4 0.73
Positive troponin‡ 10.0 14.0 0.69
Negative troponin 6.7 7.4 0.89
Marker positive 14.7 17.4 0.82
Marker negative 7.7 8.5 0.90
Before 1999* 19.3 19.6 0.99
0.001Overall 12.2 14.4 0.82
Odds ratio (95% Cl)0.5 1.0 2.0
Death or MI at follow-up
VBWG
RITA 3: Benefit of routine invasive strategy mainly in high-risk patients
Death or MI at 5 yrs
Risk score quartile* Event rate (%) OR (95% CI)
Invasive(n = 895)
Conservative(n = 915)
1st Q (1.71) 6.6 6.1 0.96 (0.44–2.10)
2nd Q (>1.71–2.20) 12.8 12.2 1.10 (0.62–1.95)
3rd Q (>2.20–2.83) 16.0 19.0 0.80 (0.49–1.30)
4th Q, lower (>2.83–3.28) 31.3 35.4 0.76 (0.44–1.35)
4th Q, upper (>3.28) 29.2 48.5 0.44 (0.25–0.76)
Fox KAA et al. Lancet. 2005;366:914-20.
Randomized Intervention Trial of unstable Angina
*Based on age, diabetes, prior MI, smoking, ST, pulse, grade 3/4 angina, sex, left bundle branch block, transient ST
VBWG
Clayton TC et al. Eur Heart J. 2004;25:1641-50.
HR 0.61(95% CI 0.44–0.85)
HR 1.09(95% CI 0.70–1.71)
20
0
12
16
8
4
0 1 32Time (years)
Invasive
Men
Conservative
Invasive
545 491 354 189 350 316 228 125
Conservative 583 507 356 194 332 305 230 119
20
0
12
16
8
4
0 1 32Time (years)
Women
Invasive
Conservative
Deathor MI(%)
No. patients
RITA 3: Greater benefit of early invasive strategy in men vs women with ACS
n = 682 women, 1128 men with UA/NSTEMI
VBWG
Death or MI(%)
Lagerqvist B et al. J Am Coll Cardiol. 2001;38:41-8.
Time (days)
20
16
12
8
4
00
4
8
12
20
0 60 120 180 240 300 360
n = 749 women, 1708 men with UA/NSTEMI
Time (days)
Fragmin and fast Revascularization during InStability in Coronary artery disease
16
0 60 120 180 240 300 360
Men Women
Invasive (n = 348)
Noninvasive (n = 401)Invasive (n = 874)
Noninvasive (n = 834)
P < 0.001ns
15.8%
9.6%
12.4%
10.5%
FRISC II: Men with ACS show greater benefit from early invasive strategy than women
VBWG
Multiples of the upper
reference limit
Days after onset of acute MI
50
20
10
5
2
1
0 1 2 3 4 5 6 7 8
Antman EM. N Engl J Med. 2002;346:2079-82.
Upperreference
limit
Cardiac troponin after“classic” acute MI
CK-MB after acute MI
Cardiac troponin after“microinfarction”
Release of cardiac troponins and CK-MB in acute MI
0
VBWG
Roe MT et al. Arch Intern Med. 2005;165:1870-6.Reference limit: maximum troponin ratio 0–1x upper limit of normal
Maximum troponin ratio
7
6
5
4
3
2
1
00 1 2 3 4 5 6 7 8 9 10
In-hospital mortality
(%)
CRUSADE: N = 23,298
In-hospital mortality higher with any degree of troponin elevation in NSTEMI patients
VBWG
*Family history of CAD, hypertension, elevated cholesterol, diabetes, current smoker†Creatine-kinase MB and/or cardiac troponins Antman EM et al. JAMA. 2000;284:835-42.
TIMI risk score for UA/NSTEMI
• Age ≥65 years
• ≥3 CAD risk factors*
• Significant coronary stenosis
• ST-segment deviation
• Severe angina (≥2 anginal events in last 24 hours)
• Daily use of aspirin in prior 7 days
• Elevated serum cardiac markers†
VBWG
Antman EM et al. JAMA. 2000;284:835-42.n = 1957 ACS patients
Risk factors (n)
0
45
35
25
15
5
0/1 2 3 4 5 6/7
Death/MI/severe ischemia
at 14 days (%)
4.78.3
13.2
19.9
26.2
40.9
TIMI risk score in UA/NSTEMI
VBWG
OPUS-TIMI 16
Sabatine MS et al. Circulation. 2002;105:1760-3.
TACTICS-TIMI 18
1
1.8
3.5
6
12.1
5.7
13
1 2 301 2 30
14
10
6
2
BNP = B-type natriuretic peptideCRP = C-reactive protein
6
4
2
0
30-day mortality relative
risk
Elevated cardiac biomarkers (n) Elevated cardiac biomarkers (n)
P = 0.014 P < 0.001
67 150 155 78 504 717 324 90
0
Multimarker strategy: Identifying high-risk patients by troponin I, CRP, and BNP
n =
VBWG
Hemodynamic stress
Giugliano RP et al. J Am Coll Cardiol. 2005;46:906-19.
Troponin +++ ++ +++BNP +++ ++ 0Renal dysfunction ++ + +Glucose metabolism + 0 +CRP ++ ++ ++
Blood glucose
Myocyte necrosis
Acceleratedatherosclerosis
Vasculardamage
Inflammation
hs-CRP, CD40L
Troponin
BNP, NT-proBNP
CrClMicroalbuminuria
A1C
BiomarkerIndependent
predictor of riskUseful in
multimarker strategyTherapeuticimplication
Multimarker approach in ACS