Fibrinolytic Therapy in Patients With Definite NSTE-ACS: Recommendation Class III: Harm 1. In patients with NSTE-ACS (ie, without ST-elevation, true posterior MI, or left bundle-branch block not known to be old), intravenous fibrinolytic therapy should not be used.93,329 (Level of Evidence: A) There is no role for fibrinolytic therapy in patients with NSTE- ACS. Fibrinolysis with or without subsequent PCI in patients with NSTE-ACS was evaluated by the Fibrinolytic Trialists and There was no benefit for mortality or MI. Intracranial hemorrhage and fatal and nonfatal MI occurred more frequently in patients treated with fibrinolytic therapy. See Online Data Supplement 17 for additional informa- tion on parenteral anticoagulant and fibrinolytic therapy in patients with definite NSTE-ACS. 4.4. Ischemia-Guided Strategy Versus Early Invasive Strategies See Figure 3 for the management algorithm for ischemia- guided versus early invasive strategy. 4.4.1. General Principles Two treatment pathways have emerged for all patients with NSTE-ACS. The invasive strategy triages patients to an inva- sive diagnostic evaluation (ie, coronary angiography). In contrast, the initial ischemia-guided strategy calls for an inva- sive evaluation for those patients who 1) fail medical therapy (refractory angina or angina at rest or with minimal activity despite vigorous medical therapy), 2) have objective evidence of ischemia (dynamic electrocardiographic changes, myo- cardial perfusion defect) as identified on a noninvasive stress test, or 3) have clinical indicators of very high prognostic risk (eg, high TIMI or GRACE scores). In both strategies, patients should receive optimal anti-ischemic and antithrombotic medical therapy as outlined in Section 4.1. A subgroup of patients with refractory ischemic symptoms or hemodynamic or rhythm instability are candidates for urgent coronary angi- ography and revascularization. 4.4.2. Rationale and Timing for Early Invasive Strategy This strategy seeks to rapidly risk stratify patients by assess- ing their coronary anatomy. 