Latest Strategies and Patient Outcomes in the Treatment of ST-segment-elevation Myocardial Infarction
angioplasty versus thrombolysis, the benefit on long-term mortality is reduced, and seems to be dependent on an effect on infarct size limitation.5
To achieve optimal results with primary PCI, time from the first hospital door to the balloon inflation should be as short as possible, with a goal of within 90 minutes (up to 120 minutes when the patient is transferred to a second non-PCI-capable hospital).3
However, data from the
American College of Cardiology National Cardiovascular Data Registry (2005–2006) show that in the US, primary PCI is failing to achieve the established benchmarks, with >40% of patients achieving a door-to- balloon time of >90 minutes even in the presenting hospital. A greater proportion of patients with longer door-to-balloon times were treated on a weekday between 4pm and 8am, at weekends and at community centres.6
Similar data were presented in Europe.1
Several specific considerations are important when primary PCI is performed. First, although there is no evidence to suggest that primary stenting reduces mortality compared with balloon angioplasty, major adverse cardiac events are reduced, driven by the reduction in subsequent target vessel revascularisation (TVR) with stenting.7 Compared with conventional bare-metal stents, drug-eluting stents decrease TVR with no differences in death, reinfarction or stent thrombosis rates.8
Second, evidence has emerged about the use of
bivalirudin as an effective alternative to unfractionated heparin during primary PCI (Harmonizing Outcomes with RevascularIZatiON and Stents in Acute Myocardial Infarction [HORIZONS-AMI] study).9
The risk of
stent thrombosis associated with bivalirudin appeared to be mitigated by the prior use of unfractionated heparin, by the use of a 600mg loading dose of clopidogrel or by the maintenance of bivalirudin shortly after the PCI ending. Third, new thienopyridines (prasugrel) are currently being tested during primary PCI with no clear nested benefit compared with clopidogrel (TRial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel- Thrombolysis In Myocardial Infarction [TRITON-TIMI-38] study).10 Fourth, trials evaluating glycoprotein GPIIb/IIIa antagonists as adjuncts to oral antiplatelet therapy in the setting of primary PCI question whether GPIIb/IIIa antagonists provide significant additional benefit to STEMI patients who have received dual antiplatelet therapy before catheterisation (HORIZONS-AMI, Value of Abciximab in Patients With Acute MI Undergoing PCI After High Dose Clopidogrel Pretreatment [BRAVE-3], Ongoing tirofiban in myocardial infarction evaluation [On- TIME], etc.).9,11–14
Thus, current evidence indicates that adjunctive use of a GPIIb/IIIa antagonist can be useful at the time of primary PCI, but cannot be recommended as routine therapy. Finally, great controversy exists with the use of proton pump inhibitors and dual antiplatelet therapy. Proton pump inhibitors have been found to interfere with the metabolism of clopidogrel.15 test its clinical implications.
Randomised clinical trials are needed to
Overall, the time delay from first medical contact to balloon inflation constitutes the Achilles’ heel of primary PCI, especially for patients who need to be transferred. This led researchers to question whether administrating thrombolytics to bridge the delay between first medical contact and primary PCI would improve outcomes. Thus, the concept of facilitated angioplasty came into being. This strategy involves full- or half-dose thrombolytic therapy with or without a GPIIb/IIIa receptor antagonist, followed by primary PCI. Two large studies addressed this matter: Assessment of the Safety and Efficacy of a New Treatment Strategy with Percutaneous Coronary Intervention
EUROPEAN CARDIOLOGY
(ASSENT-4 PCI)16 Reperfusion Speed to Stop Events (FINESSE) trial.13
and the Facilitated Intervention with Enhanced In the ASSENT-4 PCI
trial, therapy with full-dose tenecteplase associated with PCI was randomly compared with primary PCI. The trial was terminated prematurely because of a higher in-hospital mortality rate in the facilitated PCI group. It has been theorised that some factors could have strongly influenced this observation, i.e. the lack of heparin infusion after the bolus in the facilitated group, the regimen of antithrombotic therapy used with no loading dose of clopidogrel, the prohibition of concomitant treatment with GPIIb/IIIa inhibitors except for bailout and, most importantly, an adequate delay between thrombolysis and PCI. In addition, FINESSE showed that neither PCI preceded by abciximab and reteplase nor PCI preceded by abciximab alone was superior to abciximab used at the time of PCI among patients presenting within four hours of medical contact. Thus, at the moment facilitated PCI offers no evidence-based clinical benefit, but further studies are necessary to clarify these matters. In this sense, we are convinced that the optimal timing between fibrinolysis and PCI is crucial for the results of any pharmaco-invasive PCI.
Thrombolysis as Primary Reperfusion Therapy
It is of critical importance to recognise that worldwide reperfusion continues to be performed with thrombolytics in the vast majority of patients, even when tertiary centres with PCI facilities are available.17
In
poor countries, thrombolysis should be administered to STEMI patients with symptom onset within the previous 12 hours, and optimisation of thrombolysis (including promotion of the ‘golden hour’ and reducing the substantial proportion of patients who do not receive reperfusion) can still reduce mortality from acute MI before angioplasty is introduced. Moreover, bearing in mind the current availability of new, more easily administered thrombolytic agents, the efficacy and application of drug reperfusion can be expected to grow substantially in the near future. A strategy of pre-hospital fibrinolysis provides a clinical benefit over in-hospital fibrinolysis in STEMI.18
Furthermore, if the
emergency medical services personnel who attempt first patient contact have fibrinolytic capability, we believe that pre-hospital fibrinolysis should always be started immediately in patients with symptom duration of less than three hours.
If thrombolysis is performed as the primary reperfusion therapy, it should not be considered to be the final treatment. In about 45–50% of patients who receive fibrinolytics, adequate coronary reperfusion (epicardial thrombolysis in myocardial infarction [TIMI] 3 flow) is not achieved.19
Therefore, it is important to be aware of the signs of
adequate reperfusion in terms of clinical parameters (relief of pain), electrocardiography (ST resolution >50%), enzymatic signs (rapid elevation of myocardial damage markers) and tissue perfusion. The combination of clinical data, electrocardiography and measurement of enzyme activity helps to better evaluate whether or not adequate reperfusion has been achieved, although in the majority of cases clinical and electrocardiographic assessments guided us in estimating the probability of adequate reperfusion. In fact, complete ST resolution is an excellent predictive factor of recovery of coronary patency, with a predictive value of >90% for an epicardial flow of TIMI 2 or 3 and 70–80% for TIMI 3. However, its negative predictive value is very low (about 50%), mainly due to the fact that ST resolution depends not only on epicardial perfusion, but also on microvascular perfusion. In any event, in the absence of clear reperfusion criteria 60–90 minutes after the administration of fibrinolytics, failure to restore patency must be ruled out by emergency catheterisation and
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