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Conservative vs Early Invasive Approach ³How early?´
Coronary Artery Disease
In the United States, nearly 1.0 million patients annually suffer from AMI Fatal event in approximately 1/3 of patients About 50 percent of the deaths associated with AMI occur within 1 hour of the event and are attributable to arrhythmias, most often ventricular fibrillation
22K pts STEMI 30-33% NSTEMI 25% UA 38-42% .the Euro Heart Survey and the GRACE registry. international surveys published in 2002 .AMI Continuum of disease: Ranging from chronic stable angina to STEMI Two multicenter.
AMI.8% 5% 9.4% 8% 8.6% 11.7% 2. GUSTO IIb trial performed in the early 1990s Mortality 30 day 6 months 1 year STEMI NSTEMI UA 6% 5. cont.1% 7% .
With or without ischemic ECG changes NSTEMI = UA with evidence of myocardial necrosis on the basis of the release of cardiac markers . (2) it is severe and described as frank pain and of new onset (i.e. poorly localized chest or arm discomfort (rarely described as pain) that is reproducibly associated with physical exertion or emotional stress and relieved within 5 to 15 minutes by rest and/or sublingual nitroglycerin.e. more severe.Definitions Stable angina pectoris = deep.. within 1 month). prolonged. and (3) it occurs with a crescendo pattern (i.. or frequent than previously). Unstable angina = angina pectoris (or equivalent type of ischemic discomfort) with at least one of three features: (1) it occurs at rest (or with minimal exertion) usually lasting more than 20 minutes (if not interrupted by nitroglycerin).
Pathophysiology UA/NSTEMI.Plaque rupture and coronary thrombosis compromise blood flow Infarct-related artery not generally completely occluded for prolonged period Thrombi are grayish white (platelet rich) .
STEMI Complete occlusion. reddish (fibrin-rich) thrombi .
NSTEMI Treatment Intense medical therapy ± ASA ± Plavix ± IV heparin/ LMWH ± BB ± IV ntg for symptoms ± IIB/IIIA inhibitor ± Conservative vs Invasive approach .
symptoms recur. IV meds are d/c¶d Exercise testing is performed Pts catheterized if symptoms persist.Conservative Approach Asymptomatic pts are given several days to ³cool off´ and plaque stabilization to occur. or a positive stress test .
Early Invasive Approach Intensive medical regimen with more widespread use of plavix and IIB/IIIA Prompt catheterization with subsequent revascularization Time to intervention 4-48 hrs .
2003 . 2002 VINO. 1998 FRISC II. 1995 VANQUISH. 2002 ISAR-COOL. 2001 RITA 3. 1998 MATE.Clinical Trials TIMI IIIB. 1999 TACTICS-TIMI 18.
1 P=. 58 % at 1 yr .9 14.7 10 18.8 within 6 wks *High rate of cross-over to invasive group.1 8.2 2.4 5.5 5.1 Rehospitalization 7.2 10.6 16.33 10.TIMI IIIB (Thrombolysis in MI Trial) *UA or NSTEMI <24 hrs of rest angina *Treated with heparin/ASA Early Invasive(18-48 hrs) N=740 Conservative* N= 733 Death Nonfatal MI + 6 wk ETT Total Hospital days 2.
no ST segment depression. Trend present at 1 yr and not at 2 yr Subset analysis of invasive population which did worse: Received thrombolysis. w/out hx of MI Large percentage of cross-over. 33% .8 vs 3.VANQWISH 920 pts with NSTEMI.2. Heparin No benefit in invasive group (only 44% of pts) At discharge: Death or Nonfatal MI 7. 97% men Early invasive w/in 72 hrs of last chest pain vs conservative ASA.
due to reduction in angina No significant difference in 21 mo endpts . IV heparin Triage angiography within 24 hrs 58% revascularization vs 37% in conservative group 45% reduction in in-hospital end-pts.MATE 210 pts with ACS not eligible for thrombolysis ASA.
randomly assigned after 48 hrs to invasive or conservative approach Intervention within 7 days LMWH Heparin/ASA/ +/-Dalteparin .FRISC II 2457 pts with unstable coronary disease.
65 (p=.4%) 94 (7.FRISC II cont. MI.77 .78 124(10.or both MI Death Invasive (1222 pts) 113 (9. 6 256 (22%) months Readmission. 6 357 (31%) months .62 Angina.1%) .56 .1%) 36(2.9%) 455 (39%) 594 (49%) .8%) 23 (1.1) . Death.9%) Non-invasive Risk (1235 pts) Ratio 148 (12.
FRISC II .
tirofiban Benefit only noted if positive Troponin Invasive Death.TACTICS-TIMI 18 2220 pts UA/NSTEMI undergoing invasive (4-48 hrs) or conservative approach ASA.4 15. Rehosp for ACS* Death or nonfatal MI* *6 months Conservative 19.5 . IV heparin.9 7.3 9. MI.
3) and MI reduced (9.1) .6 vs 8.6 vs 14. or refractory angina (9. nonfatal MI.Improved combined end pt of death.4 vs 14. ASA 4 months.RITA 3 1810 pts with NSTEMI randomized within 48 hrs of initial chest pain Enoxaparin.5) Results due to angina reduction 1 year.Death+nonfatal MI (7.
VINO 131 pts with NSTEMI within 24 hrs of last chest pain ASA/ IV heparin/ Ticlopidine if stented Six month improvement in mortality (3.4%) death or reinfarction (6 vs 22% in conservative) Despite 40% of conservative pts undergoing catheterization by then .1 vs 13.
6% Early RRI intervention 5.4 hrs) vs. Tirofiban Early invasive (2. delayed invasive (86 hrs) Difference due to reduced events prior to catheterization (0.ISAR-COOL 410 pts with NSTEMI treated with Heparin. ASA.9% 96% NNH 18 .3) Outcomes at 30 d Lg MI or death Prolonged pretreatment 11.5 vs 6. Plavix.
and TIMI IIIB ± Age> 65: TIMI IIIB . TACTICS-TIMI 18.Summary Benefit in all but VANQWISH and TIMI-IIIB in the early invasive group Advancements in anticoagulation and stents could have some role Most benefit in moderate to high risk groups ± Elevated Troponin: FRISC II & TACTICS-TIMI 18 ± ST depression ( > 0.1 mm or >0.05 mm) on the ECG in >1 lead: FRISC II.
TIMI Risk Score Derived from several large cardiac databases Seven Variables: ± ± ± ± ± ± ± Age >65 Presence of at least 3 risk factors for CHD Prior coronary stenosis >50% ST segment deviation 2 anginal episodes in last 24 hrs Elevated serum cardiac biomarkers Use of ASA in last 7 days .
2% Score 6/7= 40. new or recurrent MI.3% Score 3= 13.TIMI Score Score correlated with increased numbers of events at 14 days (all-cause mortality.9% Score 5= 26.2% Score 4=19.9% .7 % Score 2= 8. severe recurrent ischemia requiring revascularization) Score 0/1= 4.
worsening rales.2002 ACC/AHA guidelines Class I indication to early invasive therapy in pts with UA/NSTEMI plus: ± Recurrent angina/ischemia at rest or with low-level activity despite intensive anti-ischemic tx ± Elevated Troponin I or T ± New or presumably new ST-segment depression ± Recurrent angina/ischemia with CHF sx. S3 gallop. pulmonary edema. new or worsening mitral regurgitation ± High-risk findings on non-invasive study ± Depressed LVSF ± Hemodynamic instability or angina at rest accompanied by hypotension ± Sustained VT ± PCI within 6 months ± Prior CABG .
Time to intervention? ISAR-COOL<6 hrs compared with RITA 3 and TACTICS-TIMI 18 (4-48 hrs) Within ³next working day´ is probably acceptable. less than 48 hrs Specialized centers of excellence for treating ACS may be future in providing best evidence-based care .
Thanks Fellow residents and friends Faculty and Staff Mark Wilson Sarah and Samuel Leonard .