EARLY INVASIVE VERSUS INITIAL CONSERVATIVE STRATEGIES IN UA/NSTEMI

EARLY INVASIVE VERSUS INITIAL CONSERVATIVE STRATEGIES IN UA/NSTEMI Dr. Mayuresh

In patients with unstable angina and non-ST elevation myocardial infarction (UA/NSTEMI) two strategies are possible, either a routine invasive strategy where all patients undergo coronary angiography shortly after admission and, if indicated, coronary revascularization; or a conservative strategy where medical therapy alone is used initially, with selection of patients for angiography based on clinical symptoms or investigational evidence of persistent myocardial ischemia.Evidence for early invasive versus conservative strategy in management of NSTEMI

7Fragmin during Instability in Coronary Artery Disease (FRISC-2) 1999Patients within 48 h UA/NSTEMI Early inv vs conserv & dalteparin vs placebo3048 patients dalteparin for 57 d 2457 continued dalteparin/placebo & received either inv or conserv rx strategyMeds: ASA, -blockers unless contraindicatedNo death/MI @ 3 mo by dalteparin Death/MI @ 6 mo, 1 y & 5 y for inv strategy Benefit confined to men, nonsmokers, and patients with 2 risk factorsWallentin L, et al. Lancet 2000;356:916 (1-year results). Lagerqvist B, et al. J Am Coll Cardiol 2001;38:418 (women vs men). Lagerqvist B, et al. Lancet 2006;368:9981004 (5-yr follow-up).8Treat Angina with Aggrastat and Determine Cost of Therapy with an Invasive or Conservative Strategy (TACTICS-TIMI-18) 20012,220 patients within 24 h UA/NSTEMIEarly inv or conserv (selective invasive) strategyMeds: ASA, heparin and tirofiban Death, MI, and rehosp for an ACS @ 6 mo for inv strategy Benefit in medium and high-risk patients (TnT of > 0.01 ng/mL, ST-segment deviation, TIMI risk score > 3) No high-risk features, outcomes similar Death/MI @ 6 mo for older adults with early inv strategy Benefit of early inv strategy for high-risk women ( TnT); low-risk women tended to have worse outcomes, incl risk of major bleedingCannon CP, et al. N En gl J M N Engl J Med. 2001 Jun 21;344(25):1879-87.: ed 2001;344:187987. 9Third RandomizedIntervention Treatment of Angina (RITA-3) 20021,810 moderate- high risk ACS patientsEarly inv or conserv (ischemia-driven) within 48 hrs. strategyExclusions: CK-MB > 2X ULN @ randomization, new Q-waves, MI w/in 1 mo, PCI w/in 1 y, any prior CABG Death, MI, & refractory angina for inv strategy @ 4 months Benefit driven primarily by in refractory angina Death/MI @ 5 y for early inv armNo benefit of early inv strategy in womenLancet. 2002 Sep 7;360(9335):743-51Lancet. 2005 Sep 10-16;366(9489):914-20ISAR-COOL (Intracoronary Stenting with AntithromboticRegimen Cooling-Off) trial 2003Prolonged (3 to 5 days) antithrombotic pretreatment (Cooling-Off strategy) before intervention V/S early intervention after pretreatment for less than 6 hoursAspirin, clopidogrel , tirofiban , unfractionated heparin (UFH).410 patients with symptoms of unstable angina plus either ST-segment depression or elevation of cardiac troponin T levels.By 30 days follow-up, the primary endpoint of death or large MI occurred in 11.6% of patients randomized to delayed catheterization versus 5.9% of those in the early angiography group.strategy of coolingoff for 3 to 5 days before angiography does not improve outcome in this setting.small sample size and the prolonged delay before angiography in the medical pretreatment arm.

THE RIGHT TIMINGTIMACS STUDY, 2009Early invasive management: angiography within 24 hours followed by PCI or CABG as appropriatev/s delayed invasive strategy: angiography after 36 hours followed by PCI or CABG as appropriate.3031 patients.Superior outcome among patients managed by early rather than delayed intervention in the setting of UA/NSTEMI,Refractory ischemia was reduced by an early approach, as were the risks of death, MI, and stroke among patients at the highest tertile of ischemic risk as defined by the GRACE risk score

ABOARD TRIAL, 2009To assess whether a more aggressive strategy of very early intervention, analogous to the standard of primary PCI for STEMI, would lead to improved outcomes in patients with nonST-elevation ACS.To determine whether immediate intervention (primary PCI strategy) is superior to delayed intervention (next day strategy) in patients with moderate-to-high risk (TIMI score > 3) non-ST segment elevation ACS.A primary PCI strategy in NSTE-ACS (compared with a rapid intervention on the next day):352 ptsis feasible, but does not reduce the risk of MI (primary outcome)is not associated with significant differences in other efficacy or safety outcomesdoes not benefit to a particular subgroup of patientsshortens significantly hospital stay

Recommendations for Initial Invasive Versus Initial Conservative Strategies(2012)Class I1. An early invasive strategy (ie, diagnostic angiography with intent to perform revascularization) is indicated in UA/NSTEMI patients who have refractory angina or hemodynamic or electrical instability (without serious comorbidities or contraindications to such procedures). (Level of Evidence: B)

2. An early invasive strategy (ie, diagnostic angiography with intent to perform revascularization) is indicated in initially stabilized UA/NSTEMI patients (without serious comorbidities or contraindications to such procedures) who have an elevated risk for clinical events (Level of Evidence : A)

2007 recommendation remains current.

Class IIa1. It is reasonable to choose an early invasive strategy (within 12 to 24 hours of admission) over a delayed invasive strategy for initially stabilized high-risk patients with UA/NSTEMI.* For patients not at high risk, a delayed invasive approach is also reasonable (Level of Evidence: B)Class III: No Benefit1. An early invasive strategy (ie, diagnostic angiography with intent to perform revascularization) is not recommended in patients with extensive comorbidities (eg, liver or pulmonary failure, cancer), in whom the risks of revascularization and comorbid conditions are likely to outweigh the benefits of revascularization. (Level of Evidence: C)

2. An early invasive strategy (ie, diagnostic angiography with intent to perform revascularization) is not recommended in patients with acute chest pain and a low likelihood of ACS. (Level of Evidence: C)

3. An early invasive strategy (ie, diagnostic angiography with intent to perform revascularization) should not be performed in patients who will not consent to revascularization regardless of the findings. (Level of Evidence: C)2007 recommendation remains current.

CONCLUSIONSThese trials, taken together with earlier studies, do provide support for a strategy of early angiography and intervention to reduce ischemic complications in patients who have been selected for an initial invasive strategy, particularly among those at high risk (defined by a GRACE score 140), whereas a more delayed approach is reasonable in low- to intermediate risk patients. The early time period in this context is considered to be within the first 24 hours after hospital presentation, although there is no evidence that incremental benefit is derived by angiography and intervention performed within the first few hours of hospital admission. The advantage of early intervention was achieved in the context of intensive background antithrombotic therapy.