Читать книгу Interventional Cardiology - Группа авторов - Страница 329

It should be borne in mind that due to the pharmacological mechanism of action of fibrinolytics i.e. penetration of the thrombus and fracturing the links of the fibrin strands, early interventional is especially critical, and certainly after 12 h, fibrinolysis is of very limited benefit, as it can in most cases no longer effectively penetrate the thrombus [102].

A summary of currently available fibrinolytic agents available worldwide is provided in Table 13.2. The advantages of fibrin‐specific lytics over t‐PA in terms of mortality are small but unequivocal [103], and just as important is their relative ease of administration, e.g. single‐bolus weight‐adjusted tenecteplase [104]. ESC and AHA Guidelines recommend use of a fibrin specific agent [3]. Adjunctive therapy with aspirin [105], clopidogrel [106], and parental anti‐coagulation [107–109] has been shown to be safe and have additive benefits, whereas the adjunct of GP IIb/IIIa inhibitors shows no additional benefit with full dose fibrinolysis, principally due to the much increased risk of hemorrhage [110–112]. Specifically, a retrospective analysis of 548 patients who presented or were referred to the Erasmus Medical Centre, Rotterdam for rescue therapy following failed thrombolysis noted that rates of major hemorrhage with the combination of thrombolysis and GP IIb/IIIa inhibitors were as high as 31% (compared to 11% in rescue strategies that did not use GP IIb/IIIa inhibitors, p = 0.004) [113].

Table 13.2 Fibrinolytic agents in STEMI [4].

Fibrinolytic Agent	Dose	Fibrin specificity	Antigenic
Fibrin specific:
Tenecteplase (TNK‐tPA)	Single IV weight‐based bolus	++++	No
Reteplase (rPA)	10 U + 10 U IV boluses given 30 mins apart	++	No
Alteplase (tPA)	90‐min weight based infusion	++	No
Non‐fibrin specific
Streptokinase	1.5 million units IV given over 30–60 mins	No	Yes

Where available, pre‐hospital thrombolysis can significantly reduce mortality [114]. The STREAM trial [115] looked at 1892 patients with STEMI who presented within 3 h of symptom onset and who were unable to undergo primary PCI within 1 h, and randomized them to either primary PCI or prehospital fibrinolytic therapy with bolus tenecteplase. Emergency coronary angiography was performed if fibrinolysis failed, otherwise angiography was performed 6 to 24 h after randomization. The primary endpoint was a composite of death, shock, congestive heart failure, or reinfarction up to 30 days. There was no significant difference in the primary endpoint between both groups (relative risk for the fibrinolysis group 0.86, 95% CI 0.68‐1.09; p = 0.21) but more intracranial hemorrhage occurred in the fibrinolysis group (1.0% vs 0.2%; p = 0.04) to the point where the protocol was amended to half‐dose tenecteplase for patients aged ≥ 75 y.

A meta‐analysis of randomized controlled trials comparing fibrinolysis in the early prehospital setting vs primary PCI revealed that fibrinolysis was consistently associated with similar rates of short term (RR 0.94, 95% CI 0.67–1.31) and 1 year mortality (RR 1.01, 95% CI 0.75–1.34) albeit with an increased risk of hemorrhagic stroke (RR 4.37, 95% CI 1.25–15.26) [117].

Nonetheless, when expedient transfer to a primary PCI center is possible for patients who initially present to a non‐PCI center, then transfer for PCI has been shown in recent real‐world registries to have a survival advantage over fibrinolysis. In the Catalonia “CODI IAM” network registry of all‐comers (with STEMI) to a non‐capable PCI center with symptom onset to first medical contact <120 min, reperfusion with fibrinolysis rather than transfer to for primary PCI was found to be an independent 30‐day mortality predictive factor (odds ratio 1.91; 95% CI 1.01–3.50, p = 0.04) [119].

With the advent of more potent P2Y12 inhibitors, the TREAT trial [120], assessed the efficacy of ticagrelor when compared to clopidogrel in STEMI patients treated with fibrinolytic therapy. It enrolled 3799 patients (age <75 years) and randomized them to either ticagrelor or clopidogrel. Decisions as regards the choice of fibrinolytic agent were left to local availability and the discretion of the treating physician. In terms of a primary endpoint of cardiovascular mortality, MI, or stroke, no significant difference was found between treatment groups (HR for the ticagrelor group 0.93; 95% CI 0.73–1.18; p = 0.53). The rates of major, fatal, and intracranial bleeding were similar in both groups suggesting no incremental advantage of ticagrelor over clopidogrel.