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inpatient invasive strategy is recommended. Conversely, for patients with a low index of suspicion, a selective invasive approach is recommended. 5.3 Fibrinolysis and pharmaco-invasive strategy in patients with ST-elevation myocardial infarction 5.3.1. Benefit and indication of fibrinolysis Fibrinolytic therapy is an important reperfusion strategy for STEMI patients presenting within 12 h of symptom onset when PPCI cannot be performed in a timely manner; it prevents 30 early deaths per 1000 patients treated within 6 h of symptom onset.205 The largest absolute treatment benefit is seen among those patients at the highest risk, including the elderly. Successful reperfusion is generally associated with significant improvement in ischaemic symptoms, ≥50% ST-segment resolution, and haemodynamic stability. The doses of fibrinolytic agents and concomitant antithrombotic therapies are given in the Fibrinolysis and Pharmacoinvasive Strategy provided in the Supplementary data online, Section 6.3. 5.3.1.1 Pre-hospital fibrinolysis If trained medical or allied health staff can interpret the ECG on site, or transmit the ECG for remote interpretation, it is recommended to initiate fibrinolytic therapy in the pre-hospital setting. A fibrin-specific agent (i.e. tenecteplase, alteplase, or reteplase) is the preferred agent. The goal is to start fibrinolytic therapy within 10 min of the STEMI diagnosis. Fibrinolytic therapy initiation should not be delayed by waiting for the results of cardiac biomarker testing. In a meta-analysis of six randomized trials (n = 6434), pre-hospital fibrinolysis compared with inhospital fibrinolysis reduced early mortality by 17%, particularly when administered in the first 2 h after symptom onset.51,206 These, and more recent, data support the pre-hospital initiation of fibrinolytic treatment when a reperfusion strategy is indicated.145,207–209 The STREAM (Strategic Reperfusion Early After Myocardial Infarction) trial demonstrated that pre-hospital fibrinolysis followed by an early PCI strategy was associated with a similar outcome to transfer for PPCI in STEMI patients presenting within 3 h of symptom onset who could not undergo PPCI within 1 h of FMC, although a slight excess of intracranial bleeding was observed with the investigational strategy.184,210 This excess in intracranial bleeding was blunted by halving the dose of tenecteplase in patients >75 years of age. 5.3.1.2 Angiography and percutaneous coronary intervention after fibrinolysis (pharmaco-invasive strategy) It is recommended that patients should be transferred to a PCI centre immediately after initiation of lytic therapy (Figure 7). In cases of failed fibrinolysis or evidence of re-occlusion or re-infarction with recurrence of ST-segment elevation, immediate angiography and rescue PCI are indicated.185,211 In this setting, re-administration of fibrinolysis is not beneficial and is discouraged.185 Even if it is likely that fibrinolysis is successful (e.g. ST-segment resolution >50% at 60–90 min; typical reperfusion arrhythmia; and disappearance of chest pain), routine early angiography (i.e. within 2–24 h) is recommended. Several randomized trials have shown that routine early angiography with subsequent PCI (if required) after fibrinolysis reduced the rates of re-infarction and recurrent ischaemia in comparison to a ‘watchful waiting’ strategy (i.e. a strategy in which angiography and revascularization were performed only in patients with spontaneous or induced severe ischaemia or LV dysfunction, or in patients with a positive outpatient ischaemia test).186,209,212–215 A network meta-analysis including 15 357 STEMI patients treated with fibrinolytic therapy (n = 4212), PPCI (n = 6139), or fibrinolysis followed by routine immediate or early PCI (n = 5006) investigated whether STEMI patients should be transferred to a PCI-capable facility immediately (defined as a facilitated PCI approach) or within a day (e.g. <24 h, defined as a pharmaco-invasive approach).209 After PPCI, the pharmaco-invasive strategy was the second most favourable approach, with an odds ratio (OR) for death of 0.79 (95% confidence interval [CI], 0.59–1.08) compared with conventional fibrinolytic therapy. This supports the safety of transferring STEMI patients to a PCI-capable centre for angiography within 2–24 h. The benefit of routine early PCI after fibrinolysis was demonstrated without an increased risk of adverse events (stroke or major bleeding), and across the spectrum of the investigated patient subgroups.209,216 Therefore, early angiography with subsequent PCI if required is the recommended standard of care after successful fibrinolysis (Figure 7). Observational analysis of registry data has also provided some further support for the use of a pharmaco-invasive strategy.130 The optimal time delay between successful fibrinolysis and PCI has not been clearly defined; there has been a wide variation in this time delay in trials, ranging from a median of 1.3 to 17 h.184,185,206,215,217 Based on these data, a time window for PCI of 2–24 h after successful lysis is recommended. 5.3.1.2.1 Comparison of fibrinolytic agents. Some information on comparisons of fibrinolytic agents is provided in the Supplementary data online, Section 6.3.1. 5.3.1.2.2 Hazards of fibrinolysis and contraindications. Some infor- mation regarding the hazards of, and contraindications to, fibrinolysis is provided in the Supplementary data online, Section 6.3.2. 5.4 Patients not undergoing reperfusion The management of ACS patients not undergoing reperfusion is discussed in the Supplementary data online, Section 5.2. 5.4.1 Patients who are not candidates for invasive coronary angiography Information regarding the management of NSTE-ACS patients who are not candidates for invasive angiography is provided in the Supplementary data online, Section 5.2.1. 5.4.2 Patients with coronary artery disease not amenable to revascularization Information regarding the management of ACS patients with CAD that is not amenable to revascularization is provided in the Supplementary data online, Section 5.2.2. 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