Practical Cardiovascular Medicine. Elias B. Hanna

DTB delay, e.g., between DTB of 30 min and 60 min).³⁶ This is the rationale behind the ESC recommendations, which go beyond DTB <90 min. ESC recommends a STEMI diagnosis-to-wire crossing time <60 min in patients self-presenting to PCI centers and <90 min in patients transported by paramedics or from non-PCI centers. While this is valuable in early presenters with definite STEMI, keep in mind that aggressive reduction of DTB in all comers on a system level has not been consistently associated with improvement of outcomes,^34,35,37,38 particularly in registries comparing the modern DTB era with a previous era of longer DTB. Overzealous reduction of DTB should not preclude proper clinical and ECG assessment and should not lead to a rushed procedure in a patient whose clinical and ECG picture is not definite for STEMI.

      Elderly patients (age >75) – In fibrinolytic trials, the benefit from fibrinolytic therapy was much less striking in the elderly than in the young.^10,39 Conversely, primary PCI remains effective in the elderly, with more absolute mortality reduction in the elderly than in young patients. This makes fibrinolytic therapy, whether standalone or combined with PCI, a less attractive alternative to primary PCI in the elderly. Studies of combined fibrinolytic therapy and PCI included very few patients over the age 75.⁴⁰ In the modern STREAM trial of fibrinolysis vs. PCI, the dose of TNK was reduced by 50% in the elderly midway through the trial, which attenuated intracranial hemorrhage without reducing TNK efficacy.41 Hence, ESC guidelines suggest a half-dose of TNK in the elderly ≥ 75 (class IIa).²

      E. Combination of PCI and fibrinolytic therapy

Three different combinations of PCI and fibrinolytics have been studied in STEMI (Figure 2.4):⁴⁰

       Facilitated PCI is a strategy of emergent PCI with a planned door-to-balloon time of <120 minutes. Fibrinolytic therapy is administered “on the way” to a timely PCI.42,43

       Pharmacoinvasive therapy means that fibrinolytic therapy is administered at a non-PCI facility, then the patient is promptly and sys- tematically transferred to a PCI facility, where PCI is performed 2–3 to 24 hours after the start of fibrinolytic therapy, regardless of whether fibrinolysis results in successful reperfusion. Thus, the time to PCI is longer than with facilitated PCI. Facilitated PCI addresses patients primarily treated with a timely PCI, and looks at the value of pre-treatment with fibrinolytics or glycoprotein IIb/IIIa inhibitors (GPI), whereas pharmacoinvasive therapy addresses patients who are primarily treated with fibrinolytics, as they cannot undergo a timely PCI, and looks at the value of routine early PCI after fibrinolysis.44–46

       Rescue PCI refers to PCI that is performed urgently if fibrinolysis fails, failure being defined as persistent hemodynamic or electrical instability, persistent ischemic symptoms, or failure to achieve at least a 50–70% resolution of the maximal ST-segment elevation 90 minutes after fibrinolysis is started.⁴⁷ Approximately 35% of patients treated with fibrinolysis require rescue PCI.30,44,45

      Facilitated PCI has been associated with worse outcomes than primary PCI, probably because the administration of fibrinolytics before a timely PCI cannot offer any ischemic advantage yet increases the bleeding risk. Also, fibrinoytics expose clot-bound thrombin, a potent platelet activator, which heightens platelet activation and aggregation. PCI facilitated with fibrinolytics is associated with increased mortal- ity, ischemic complications, HF, and bleeding (ASSENT-4 trial). Even PCI facilitation with a brief upstream GPI therapy leads to increased bleeding without any ischemic benefit (FINESSE trial).^42,43 Conversely, pharmacoinvasive therapy, also called routine early PCI 2–24 hours after fibrinolytics, has been shown to improve outcomes, mainly recurrent MI and recurrent ischemia in high-risk STEMI, without increasing the bleeding risk (despite the use of femoral access in the trials). Patients who achieve successful reperfusion with fibrinolytics are actually left with severe residual disease in ~85% of the cases, and benefit from early PCI.

Figure 2.4 The timing of PCI in relation to thrombolysis in the pharmacoinvasive strategy, rescue PCI strategy, and facilitated PCI strategy, with the clinical trials that addressed and defined these strategies.

      F. Putting it all together: management of patients presenting to non-PCI-capable hospitals

      1 If there is a pre-established transfer system with a predicted DTB <120 minutes, a transfer for primary PCI is the best strategy and is superior to fibrinolysis (DANAMI-2 and PRAGUE trials).²⁷ This usually implies a distance <60 miles, often with a helicopter transfer, a door-in door-out time <30 minutes, direct activation of the outside PCI team through a central pager, and direct transfer to the outside cath lab.⁴⁸

      2 When DTB is expected to be >120 minutes, administer primary fibrinolytic therapy and immediately transfer the patient to allow the performance of routine early PCI 2–24 hours later, or to allow immediate rescue PCI if no response to fibrinolysis. Several registries suggest that timely fibrinolysis followed by semiurgent transfer for PCI offers a benefit similar to that seen in patients presenting to a PCI hospital and undergoing a timely primary PCI.48,49Beside fibrinolytics, the patient should receive aspirin, heparin bolus and infusion, and 300 mg of clopidogrel. Prasugrel, ticagrelor, or 600 mg of clopidogrel have not been studied in the first 24 hours of fibrinolytic therapy and may only be used if PCI is performed >24 hours later. Subcutaneous enoxaparin is not appropriate in patients undergoing early PCI. Glycoprotein IIb/IIa inhibitors may be used during PCI (rather than upstream of PCI).⁴⁴

      3 When DTB is expected to be >120 minutes but the patient is presenting >3–4 hours after symptom onset and has a non-anterior MI with low-risk clinical features (Killip class I, heart rate <100 bpm, SBP >100 mmHg), a transfer for primary PCI without preceding fibrinolytic therapy may be reasonable in individual cases, although not clearly expressed in the guidelines.

      4 If fibrinolytic therapy is contraindicated, immediately transfer for primary PCI regardless of the expected DTB.

      5 For cardiogenic shock or acute severe HF (Killip class III or IV), administer fibrinolytic therapy if DTB is expected to be >120 minutes, and immediately transfer for PCI.

      6 In patients presenting early, prehospital fibrinolytic therapy delivered by paramedics and followed by early transfer to a PCI facility has been associated with further reduction in mortality compared with in-hospital fibrinolytic therapy according to a meta-analysis of randomized trials, and a mortality comparable to that of primary PCI (STREAM, CAPTIM trial).30,50 This is the preferred strategy in patients unable to undergo timely PCI, in regions where such a system can be implemented, as per ESC guidelines.⁴⁹

      To prevent the dilemma of non-PCI hospitals, emergency medical systems are encouraged to triage STEMI patients to a PCI center and to bypass non-PCI hospitals, even if a non-PCI hospital is closer (class I ACC and ESC guidelines). In a statewide registry, bypassing a closer non-PCI hospital in favor of a PCI hospital led to an additional 16 min drive, yet was associated with significant reduction of time to reperfusion (31 min) and lower mortality. In fact, only 35% of patients brought to non-PCI hospitals received fibrinolytics; the majority were transferred for primary PCI, resulting in much longer time to reperfusion.⁵¹ Nonetheless, to meet the DTB guidelines, the drive to the PCI hospital should not exceed 45-60 min.

      Also, consider bypassing the emergency department and taking the patient directly to the catheterization laboratory when the diagnosis is certain, as this results in a 20-min or a third reduction of DTB.⁵²

VII. Coronary angiography and PCI later than 24 hours after presentation-role