Comparison of primary and facilitated percutaneous coronary interventions for ST-elevation myocardial infarction: quantitative review of randomised trials

doi:10.1016/S0140-6736(06)68148-8

The Lancet

Volume 367, Issue 9510, 18–24 February 2006, Pages 579-588

https://doi.org/10.1016/S0140-6736(06)68148-8 Get rights and content

Summary

Background

Facilitated percutaneous coronary intervention for ST-segment-elevation myocardial infarction (STEMI) is defined as the use of pharmacological substances before a planned immediate intervention, to improve coronary patency. We undertook a meta-analysis of randomised controlled trials (published and unpublished) to compare facilitated and primary percutaneous coronary intervention.

Methods

We identified 17 trials of patients with STEMI assigned to facilitated (n=2237) or primary (n=2267) percutaneous coronary intervention. We identified short-term outcomes (up to 42 days) of death, stroke, non-fatal reinfarction, urgent target vessel revascularisation, and major bleeding. Grade 3 flow rates for prethrombolysis and post-thrombolysis in myocardial infarction (TIMI) were also analysed.

Findings

The facilitated approach resulted in a greater than two-fold increase in the number of patients with initial TIMI grade 3 flow, compared with the primary approach (832 patients [37%] vs 342 [15%], odds ratio 3·18, 95% CI 2·22–4·55); however, final rates did not differ (1706 [89%] vs 1803 [88%]; 1·19, 0·86–1·64). Significantly more patients assigned to the facilitated approach than those assigned to the primary approach died (106 [5%] vs 78 [3%]; 1·38, 1·01–1·87), had higher non-fatal reinfarction rates (74 [3%] vs 41 [2%]; 1·71, 1·16–2·51), and had higher urgent target vessel revascularisation rates (66 [4%] vs 21 [1%]; 2·39, 1·23–4·66); the increased rates of adverse events seen with the facilitated approach were mainly seen in thrombolytic-therapy-based regimens. Facilitated intervention was associated with higher rates of major bleeding than primary intervention (159 [7%] vs 108 [5%]; 1·51, 1·10–2·08). Haemorrhagic stroke and total stroke rates were higher in thrombolytic-therapy-containing facilitated regimens than in primary intervention (haemorrhagic stroke 15 [0·7%] vs two [0·1%], p=0·0014; total stroke 24 [1·1%] vs six [0·3%], p=0·0008).

Interpretation

Facilitated percutaneous coronary intervention offers no benefit over primary percutaneous coronary intervention in STEMI treatment and should not be used outside the context of randomised controlled trials. Furthermore, facilitated interventions with thrombolytic-based regimens should be avoided.

Introduction

Facilitated percutaneous coronary intervention for ST-segment-elevation myocardial infarction (STEMI) is defined as the administration of a pharmacological substance or a combination of substances before planned immediate percutaneous coronary intervention, with the intent to improve the coronary patency before the procedure. This approach is based on the hypothesis that pharmacologically induced reperfusion will occur during the time needed to transfer the patient to a facility for percutaneous coronary intervention, and that this early reperfusion will result in smaller infarcts, higher success rates, and better clinical outcomes for percutaneous coronary intervention. The drugs used to facilitate the procedure include high-dose heparin,¹ platelet glycoprotein IIb/IIIa inhibitors,2, 3, 4, 5, 6, 7, 8, 9, 10 full-dose and reduced-dose thrombolytic drugs,11, 12, 13, 14, 15, 16 and the combination of platelet glycoprotein IIb/IIIa inhibitors with reduced-dose thrombolytic drugs.17, 18

Guidelines from the American College of Cardiology/American Heart Association¹⁹ for the treatment of STEMI state that, although preliminary studies have not shown a benefit, “a strategy of facilitated PCI [percutaneous coronary intervention] holds promise in higher-risk patients when PCI is not immediately available” (a class IIb indication). The European Society of Cardiology²⁰ guidelines state that, “at the moment, there is no evidence for the recommendation of thrombolysis-facilitated PCI”, and “no evidence-based recommendation for GP [glycoprotein] IIb/IIIa inhibitor-facilitated primary PCI can be made at the present time to improve patients' outcome”.

Despite the lack of evidence regarding the safety and efficacy of facilitated percutaneous coronary intervention, patients with STEMI are being treated with the procedure in everyday clinical practice in many countries. This approach has become especially popular in the treatment of STEMI in patients being urgently transferred from community hospitals to tertiary-care centres for percutaneous coronary intervention. We did a meta-analysis of data from available randomised controlled trials to compare the angiographic and clinical outcomes between facilitated regimens and primary approaches of percutaneous coronary intervention.

Section snippets

Eligibility and search strategy

We identified all randomised trials, published and unpublished, comparing primary with facilitated percutaneous coronary intervention for the treatment of STEMI. Two of the investigators independently assessed the eligibility of identified trials. Trials were eligible for inclusion if patients with STEMI were randomly assigned to either primary or facilitated intervention. The facilitated approach was defined as the precardiac catheterisation laboratory (prehospital, pretransfer, or in

Results

We identified 20 randomised controlled trials that fulfilled our eligibility criteria. Three were subsequently omitted from the analysis. One of the omitted trials had assessed high-dose heparin,¹ which was not regarded as a facilitated regimen of percutaneous coronary intervention, according to STEMI guidelines of the American College of Cardiology/American Heart Association¹⁹ or the European Society of Cardiology,²⁰ because of the lack of improvement in initial TIMI grade 3 flow. The other

Discussion

The concept of pharmacological facilitation of percutaneous coronary intervention is based on the premise that pre-treatment will result in earlier reperfusion, namely, the achievement of TIMI grade 3 flow. Other potential advantages of this procedure include decreasing clot burden and distal embolisation, assistance in guide-wire passage (resulting in an angiographic roadmap not present when the infarct-related artery is occluded), and ultimately, the improvement of clinical outcomes. Our

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Cited by (475)

Intracoronary antithrombotic therapy during primary percutaneous coronary intervention in patients with STEMI: A systematic review and network meta-analysis
2024, Thrombosis Research
The efficacy of intracoronary (IC) antithrombotic therapy, which may best prevent the no-reflow phenomenon during percutaneous coronary intervention (PCI), remains unclear. Therefore, we compared the efficacy and safety of different IC antithrombotic agents.
This systematic review and network meta-analysis of randomized controlled trials (RCTs) compared IC fibrinolytic agents (recombinant tissue plasminogen activators [rtPAs] and non-rtPAs) or glycoprotein IIb/IIIa inhibitors (small molecules and monoclonal antibodies) with placebo by searching the relevant studies published before September 21, 2022. Bayesian network meta-analyses were performed using random-effects models.
Twenty-five RCTs with 4546 patients were included. Non-rtPAs and small molecules were significantly more effective in achieving thrombolysis in myocardial infarction (TIMI) grade 3 flow than placebo (odds ratio [OR] 2.28, 95 % credible intervals [CrI] 1.24–4.13; OR 2.06, 95 % CrI 1.17–3.46). Moreover, these agents' efficacy was observed in other microcirculation-related outcomes, including TIMI myocardial perfusion grade 3, complete ST-segment resolution, and corrected TIMI frame counts. Within 6 months, small molecules were associated with both an improved left ventricular ejection fraction (MD 3.90, 95 % CrI 0.48–7.46) and major adverse cardiac events (MACE) reduction (OR 0.36, 95 % CrI 0.20–0.61). Non-rtPAs demonstrated a reduced MACE incidence within 6 months (OR 0.51, 95 % CrI 0.31–0.81). The results were consistent in the subgroup with a total ischemic time > 6 h. No significant differences in mortality or bleeding events were observed.
IC non-rtPAs and small molecules may be effective for adjunctive therapy to PCI, particularly in patients with longer ischemia periods.
Efficacy and safety of a bolus of half-dose r-SAK prior to primary PCI in ST-elevation myocardial infarction: Rationale and design of the OPTIMA-6 trial
2023, American Heart Journal
Time to reperfusion is the key to the treatment of patients with ST-elevation myocardial infarction (STEMI). It is uncertain whether adjunctive thrombolytic therapy combined with contemporary antiplatelet agent ticagrelor improves outcomes as administered prior to primary percutaneous coronary intervention (PCI) expected to be performed within 120 minutes.
OPTIMA-6 is a multicenter, randomized, double-blind, placebo-controlled, and superiority trial to evaluate the efficacy of a bolus of half-dose recombinant staphylokinase (r-SAK) vs placebo prior to timely primary PCI in patients with STEMI. Enrollment began in April 2023 and is expected to enroll 2,260 patients at approximately 50 centers. Patients with acute STEMI presenting ≤12 hours of symptom onset and expected to undergo primary PCI within 120 minutes but more than 30 minutes are to be randomized to a bolus of half-dose r-SAK or placebo. All recruited patients will be mandatory to take aspirin and ticagrelor and receive a bolus of loading dose heparin before the thrombolytic therapy. The primary efficacy endpoint is major adverse cardiovascular events (MACE) within 90 days, and the MACE is defined as a composite of all-cause death, reinfarction, unplanned target vessel revascularization, heart failure or cardiogenic shock, and major ventricular arrhythmia. The primary safety endpoints are major bleeding events (BARC 3, 5) within 90 days.
OPTIMA-6 will reveal the efficacy and safety of a contemporary facilitated PCI with a bolus of half-dose r-SAK in combination with ticagrelor in patients with STEMI.
Percutaneous Coronary Intervention Versus Coronary Artery Bypass Grafting in Non–ST-Elevation Coronary Syndromes and Multivessel Disease: A Systematic Review and Meta-Analysis
2023, American Journal of Cardiology
There is lack of evidence regarding the optimal revascularization strategy in patients with non–ST-elevation acute coronary syndrome (NSTE-ACS) and multivessel disease (MVD). This systematic review and meta-analysis compares the clinical impact of percutaneous coronary intervention (PCI) with that of coronary artery bypass graft surgery (CABG) in this subset of patients. EMBASE, MEDLINE, and Web of Knowledge were searched for studies including patients with NSTE-ACS and MVD who underwent PCI or CABG up to September 1, 2021. The primary end point of the meta-analysis was all-cause mortality at 1 year. The secondary end points were myocardial infarction (MI), stroke, or repeat revascularization at 1 year. The analysis was conducted using the Mantel-Haenszel random-effects model to calculate the odds ratio (OR) with 95% confidence interval (CI). Four prospective observational studies met the inclusion criteria, including 1,542 patients who underwent CABG and 1,630 patients who underwent PCI. No significant differences were found in terms of all-cause mortality (OR 0.91, 95% CI 0.68 to 1.21, p = 0.51), MI (OR 0.78, 95% CI 0.40 to 1.51, p = 0.46), or stroke (OR 1.54, 95% CI 0.55 to 4.35, p = 0.42) between PCI and CABG. Repeat revascularization was significantly lower in the CABG group (OR 0.21, 95% CI 0.13 to 0.34, p <0.00001). In patients presenting with NSTE-ACS and MVD, 1-year mortality, MI, and stroke were similar between patients treated with either PCI or CABG, but the repeat revascularization rate was higher after PCI.
Antiplatelet Agents in Acute ST Elevation Myocardial Infarction
2022, American Journal of Medicine
Platelet aggregation and thrombus formation represent the basic mechanism for clinical, electrocardiographic, and biomarker changes consistent with acute coronary syndrome. Various oral and intravenous formulations of platelet function inhibitors have been developed to help decrease platelet aggregation due to acute atherosclerotic plaque rupture. In this article, we review the various mechanisms, pharmacokinetics/pharmacodynamics, and the key clinical trials related to the platelet inhibitors that form the basis for current recommendations of their use in the ST elevation myocardial infarction guidelines by the American College of Cardiology/American Heart Association.
Safety and Efficacy of Intracoronary Thrombolysis as Adjunctive Therapy to Primary PCI in STEMI: A Systematic Review and Meta-analysis
2021, Canadian Journal of Cardiology
Primary percutaneous coronary intervention (PPCI) is the preferred method of reperfusion in ST-elevation myocardial infarction. However, microvascular perfusion is often impaired due to distal embolization of thrombus. Intracoronary (IC) thrombolysis may attenuate thrombotic burden. We conducted a meta-analysis comparing the benefits and risks of IC thrombolytic therapy as an adjunct to PPCI.
Randomized controlled trials (RCTs) were identified through search of Medline, EMBASE, Scopus, Web of Science, Cochrane Library (Cochrane Reviews and Cochrane Protocols), PROSPERO, and clinicaltrials.gov from 1946 to January 2019. Studies included patients with ST-elevation myocardial infarction undergoing primary PCI receiving IC thrombolytic agents. Both safety and efficacy outcomes were explored. Data were combined using a fixed-effects model.
Of 1278 citations identified, 6 RCTs (890 patients; 519 IC thrombolytic and 371 IC placebo) were included. Post-PCI thrombolysis in myocardial infarction (TIMI) flow grade 2/3 occurred in 97.1% of the IC thrombolytic group vs 95.1% of the IC placebo group (odds ratio [OR], 0.57; 95% confidence interval [CI], 0.28-1.17; P = 0.13). Complete ST-segment resolution was more common with IC thrombolysis (OR, 0.29; 95% CI, 0.15-0.57; P = 0.0003). There was a strong trend favouring fewer in-hospital major adverse cardiac events with IC thrombolysis when compared with IC placebo (OR, 0.64; 95% CI, 0.41-1.01; P = 0.05). There was no difference in bleeding (TIMI major, TIMI minor, and Bleeding Academic Research Consortium [BARC] 3-5 bleeds) between the 2 groups (OR, 1.36; 95% CI, 0.38-3.54; P = 4.84).
Given the limited studies to date, our meta-analysis suggests that a targeted IC thrombolytic approach is safe and potentially effective to augment PPCI. However, these findings deserve confirmation in a larger RCT.
L’intervention coronarienne percutanée (ICP) primaire est la méthode de reperfusion privilégiée dans les cas d’infarctus du myocarde avec élévation du segment ST (STEMI). Cependant, la perfusion microvasculaire est souvent altérée par l’embolisation distale du thrombus. La thrombolyse intracoronarienne peut atténuer la charge thrombotique. Une méta-analyse comparant les avantages et les risques du traitement thrombolytique intracoronarien comme un complément à l’ICP primaire a été réalisée.
Une recherche dans les bases de données Medline, EMBASE, Scopus, Web of Science, Cochrane Library (Cochrane Reviews et Cochrane Protocols), PROSPERO et clinicaltrials.gov a permis d’effectuer un recensement d’essais contrôlés à répartition aléatoire (ECRA) menés entre 1946 et janvier 2019. Les études incluaient des patients victimes d’un STEMI ayant subi une ICP primaire et reçu des agents thrombolytiques par voie intracoronarienne. Les résultats en matière d’innocuité et d’efficacité ont été examinés. Les données ont été traitées à l’aide d’un modèle à effets fixes.
À partir de 1 278 citations, six ECRA ont été recensés (890 patients; 519 ayant reçu des agents thrombolytiques par voie intracoronarienne et 371 ayant reçu un placebo par voie intracoronarienne). Un flux TIMI (thrombolysis in myocardial infarction) de 2 ou 3 a été noté après l’ICP chez 97,1 % des patients du groupe ayant reçu des agents thrombolytiques par voie intracoronarienne vs 95,1 % des patients du groupe ayant reçu un placebo par voie intracoronarienne (rapport de cotes [RC] : 0,57; intervalle de confiance [IC] à 95 % : 0,28-1,17; p = 0,13). La résolution complète du segment ST était plus fréquente dans le contexte de la thrombolyse intracoronarienne (RC : 0,29; IC à 95 % : 0,15-0,57; p = 0,0003). Une forte tendance à la baisse des événements cardiaques indésirables majeurs survenant à l’hôpital a été notée chez les patients qui avaient reçu par voie intracoronarienne des agents thrombolytiques plutôt qu’un placebo (RC : 0,64; IC à 95 % : 0,41-1,01; p = 0,05). Aucune différence au chapitre des hémorragies (hémorragies majeures selon les critères TIMI, hémorragies mineures selon les critères TIMI et hémorragies de type 3 à 5 selon la classification du BARC [Bleeding Academic Research Consortium]) n’a été relevée entre les deux groupes (RC : 1,36; IC à 95 % : 0,38-3,54; p = 4,84).
Compte tenu du nombre limité d’études réalisées à ce jour, cette méta-analyse donne à penser qu’une thrombolyse intracoronarienne ciblée est sûre et potentiellement efficace comme complément à l’ICP primaire. Néanmoins, les constatations qui s’en dégagent devront être confirmées par un ECRA mené à plus grande échelle.
Management and outcomes of uncomplicated ST-segment elevation myocardial infarction patients transferred after fibrinolytic therapy
2020, International Journal of Cardiology
This study sought to assess the contemporary outcomes of patients transferred after receiving fibrinolytic therapy (‘drip-and-ship’) for ST-segment elevation myocardial infarction (STEMI) in the United States.
During 2009–2016, adults (>18 years) with STEMI (>18 years) without cardiac arrest and cardiogenic shock that received fibrinolytic therapy and were subsequently transferred were identified using the National Inpatient Sample (NIS). These admissions were divided into those undergoing fibrinolysis alone, subsequent coronary angiography (CA) without revascularization and subsequent CA with revascularization. Outcomes of interest included in-hospital mortality, resource utilization, and discharge disposition.
A total of 27,454 STEMI admissions receiving a ‘drip-and-ship strategy’, 96.3% and 85.8% received subsequent coronary angiography and revascularization Admissions receiving CA and revascularization were younger, male, and with lower comorbidity. The fibrinolysis alone cohort had higher rates of organ failure, hemorrhagic sequelae, and intracranial hemorrhage. Compared to the fibrinolysis cohort, CA with revascularization (adjusted odds ratio [aOR] 0.17 [95% confidence interval {CI} 0.11–0.27]; p < .001) but not CA without revascularization (OR 0.72 [95% CI 0.42–1.21]; p = .21) was associated with lower in-hospital mortality. The fibrinolysis alone cohort had higher use of do-not-resuscitate status (12.8%) and fewer discharges to home (56.6%) compared to cohorts undergoing CA without (1.7%; 86.9%) and with (0.3% and 91.2%) revascularization, respectively. Presence of complications, do-not-resuscitate status, and higher comorbidity were predictive of lower CA and revascularization use.
Fibrinolysis with subsequent revascularization is associated with excellent outcomes in STEMI. Admissions receiving fibrinolysis alone were systematically different, sicker and had poorer outcomes.

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Fast track — ArticlesComparison of primary and facilitated percutaneous coronary interventions for ST-elevation myocardial infarction: quantitative review of randomised trials

Summary

Background

Methods

Findings

Interpretation

Introduction

Section snippets

Eligibility and search strategy

Results

Discussion

J Am Coll Cardiol

Am J Cardiol

Am J Cardiol

J Am Coll Cardiol

Am J Cardiol

J Am Coll Cardiol

Am J Cardiol

Am J Cardiol

Facilitation of primary coronary angioplasty by early start of a glycoprotein 2b/3a inhibitor: results of the ongoing tirofiban in myocardial infarction evaluation (On-TIME) trial

Eur Heart J

Adjunctive platelet glycoprotein IIb/IIIa receptor inhibition with tirofiban before primary angioplasty improves angiographic outcomes: results of the TIrofiban Given in the Emergency Room before Primary Angioplasty (TIGER-PA) pilot trial

Circulation

Early administration of abciximab bolus in the emergency room improves microperfusion after primary percutaneous coronary intervention, as assessed by TIMI frame count: results of the ERAMI trial

Eur Heart J

Prehospital versus periprocedural administration of abciximab in STEMI: early and late results from the randomised REOMOBILE study

Eur Heart J

Use of abciximab prior to primary angioplasty in STEMI results in early recanalization of the infarct-related artery and improved myocardial tissue reperfusion—results of the Austrian multi-centre randomized ReoPro-BRIDGING Study

Eur Heart J

Early eptifibatide improves TIMI 3 patency before primary percutaneous coronary intervention for acute ST elevation myocardial infarction: results of the randomized integrilin in acute myocardial infarction (INTAMI) pilot trial

Eur Heart J

Fast track — Articles
Comparison of primary and facilitated percutaneous coronary interventions for ST-elevation myocardial infarction: quantitative review of randomised trials