Primary percutaneous intervention (PCI) is better than thrombolytic therapy to treat most patients with ST-segment myocardial infarction.
1
, 2
, 3
Still, primary PCI is far from perfect. Despite the evolution of adjunctive antithrombotic therapy, the slow-flow or no-flow phenomenon frequently occurs during primary PCI and remains associated with recurrent infarction and increased mortality.4
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Although manual thrombectomy has been associated with beneficial effects on coronary flow, it has failed to improve clinical outcomes in recent clinical trials.6
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Proponents of delayed stenting believe that a stent abruptly implanted in a thrombus-laden artery ruins everything. When a strategy of delayed stenting is attempted, flow is first restored in the infarct-related coronary artery (typically by thrombectomy or with a small-size balloon angioplasty catheter), but aggressive angioplasties and stenting are withheld until after the thrombus has melted down, in the hope of preventing distal embolization, microvascular obstruction (MVO), and ensuing myocardial damage. This strategy assumes that clot lysis by the in situ endothelial fibrinolytic system combined with an adjunctive systemic anticoagulation will reduce the thrombus burden,9
, 10
stabilize the plaque,- Tang L.
- Zhou S.H.
- Hu X.Q.
- Fang Z.F.
- Shen X.Q.
Effect of delayed vs immediate stent implantation on myocardial perfusion and cardiac function in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous intervention with thrombus aspiration.
Can J Cardiol. 2011; 27: 541-547
11
and minimize the chances of no reflow after stenting. Another advantage of withholding stent implantation is to allow referral for surgical revascularization in patients with complex coronary artery disease, with no fear of acute stent thrombosis in the perioperative period.- Gibson C.M.
- Pride Y.B.
- Hochberg C.P.
- et al.
Effect of intensive statin therapy on clinical outcomes among patients undergoing percutaneous coronary intervention for acute coronary syndrome: PCI-PROVE IT: A PROVE IT–TIMI 22 (Pravastatin or Atorvastatin Evaluation and Infection Therapy–Thrombolysis In Myocardial Infarction 22) Substudy.
J Am Coll Cardiol. 2009; 54: 2290-2295
Whether delayed stenting prevents myocardial damage remains uncertain.
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In the present issue of the Journal, Cassese et al.15
report that delayed stenting, compared with immediate stenting, improves coronary flow acutely but does not reduce longer-term myocardial damage. By pooling the study-level estimates of 4 trials (n = 797 participants), they show that delayed stenting yielded the same risk of MVO compared with immediate stenting, when measured by cardiac magnetic resonance imaging (risk ratio [RR], 0.93; 95% confidence interval [CI], 0.76-1.14; P = 0.51). Notably, the current study presents the largest magnetic resonance imaging–based comparative analysis of MVO after immediate versus delayed stenting in patients with ST-segment myocardial infarction. None of these estimates were obtained from patient-level data and therefore should be interpreted with caution.15
Of the trials included in the meta-analysis, only the DANAMI-3–DEFER trial (Third Danish Study of Optimal Acute Treatment of Patients With ST-elevation Myocardial Infarction) was powered to compare the efficacy of delayed stenting (n = 603) versus routine immediate stenting (n = 612) on hard clinical outcomes. Over a median follow-up of 42 months, 17% of participants assigned to delayed stenting compared with 18% of participants assigned to immediate stenting experienced the primary end point of all-cause death, heart failure, recurrent infarction, or any unplanned target vessel revascularization (hazard ratio, 0.99; 95% CI, 0.76-1.29; P = 0.92). The DANAMI-3 trial was instructive in many ways. The strategy of delayed stenting was associated with a clinically potentially meaningful yet not statistically significant reduction in all-cause death (from 9% to 7%, hazard ratio, 0.83; 95% CI, 0.56-1.20; P = 0.37), with no significant change in the rates of heart failure (from 5% to 4%, hazard ratio, 0.82; 95% CI, 0.47-1.40).
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The paradigm of delayed stenting is multifaceted. It remains unclear if, when, and how delayed stenting should be attempted. Important variations have been described in the execution of delayed stenting, including the time interval between the index reperfusion and stenting (ranging from 12 hours to 7 days),
16
the type of adjunctive antithrombotic therapy used (bivalirudin vs unfractionated heparin; infrequent vs mandatory use of glycoprotein IIb/IIIa inhibitors), and the thrombus burden at baseline. Using meta-regression, Cassese et al. observed that although an important proportion of participants presented with a low thrombus burden at baseline (43.3% presented with a Thrombolysis in Myocardial Infarction [TIMI] thrombus grade ≤ 3), a favourable treatment effect on slow flow or no reflow (P interaction = 0.047) and MVO (P interaction = 0.03) with delayed stenting was predominantly seen in participants with a high thrombus burden (TIMI thrombus grade > 3).In the context of uncertain efficacy of delayed stenting, can it be reasonably attempted in selected subgroups, such as those with high thrombus burden? One additional contribution of the meta-analysis by Cassese et al. is that it quantifies the hazards associated with delayed stenting and points toward a nonsignificant increase in the risks of recurrent myocardial ischemia and of unplanned target vessel revascularization in the interval between reperfusion and stenting (RR, 2.42; 95% CI, 0.88-6.63; P = 0.09 and RR, 1.63; 95% CI, 1.00-2.66; P = 0.051, respectively). Although these trends are not statistically significant, they are large enough to suggest potential clinical importance. In the Impact of Immediate Stent Implantation Versus Deferred Stent Implantation on Infarct Size and Microvascular Perfusion in Patients With ST-Segment Elevation Myocardial Infarction (INNOVATION) study alone, the target vessel re-occluded in 7% of patients assigned to delayed stenting.
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Of note, delayed stenting was not associated with an increased bleeding risk compared with immediate stenting, despite the prolonged systemic anticoagulation used with the former.The upcoming PRIMACY trial (Primary Reperfusion Secondary Stenting Trial; NCT01542385) and its Bayesian patient-level pooled analysis are expected to bring additional insights into these complex questions.
Disclosures
Dr Jolicoeur is supported by research grants from les Fonds la Recherche du Québec en santé, the Canadian Institutes for Health Research, and la Fondation de l’Institut de Cardiologie de Montréal. Dr Ben-Shoshan has no conflicts of interest to disclose.
References
- Primary angioplasty versus intravenous thrombolytic therapy for acute myocardial infarction: a quantitative review of 23 randomised trials.Lancet. 2003; 361: 13-20
- Contemporary mortality differences between primary percutaneous coronary intervention and thrombolysis in ST-segment elevation myocardial infarction.Arch Intern Med. 2011; 171: 544-549
- Reperfusion therapy for STEMI: is there still a role for thrombolysis in the era of primary percutaneous coronary intervention?.Lancet. 2013; 382: 624-632
- Clinical and angiographic correlates and outcomes of suboptimal coronary flow inpatients with acute myocardial infarction undergoing primary percutaneous coronary intervention.J Am Coll Cardiol. 2003; 42: 1739-1746
- Incidence and outcomes of no-reflow phenomenon during percutaneous coronary intervention among patients with acute myocardial infarction.Am J Cardiol. 2013; 111: 178-184
- Aspiration thrombectomy prior to percutaneous coronary intervention in ST-elevation myocardial infarction: a systematic review and meta-analysis.BMC Cardiovasc Disord. 2016; 16: 121
- Thrombus aspiration in STEMI revisited: impact on coronary microcirculation?.Open Heart. 2015; 2e000274
- Meta-analysis of the long-term effect of routine aspiration thrombectomy in patients undergoing primary percutaneous coronary intervention.Am J Cardiol. 2016; 118: 23-31
- Is delayed facilitated percutaneous coronary intervention better than immediate in reperfused myocardial infarction? Six months follow up findings.J Thromb Thrombolysis. 2006; 2: 147-157
- Effect of delayed vs immediate stent implantation on myocardial perfusion and cardiac function in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous intervention with thrombus aspiration.Can J Cardiol. 2011; 27: 541-547
- Effect of intensive statin therapy on clinical outcomes among patients undergoing percutaneous coronary intervention for acute coronary syndrome: PCI-PROVE IT: A PROVE IT–TIMI 22 (Pravastatin or Atorvastatin Evaluation and Infection Therapy–Thrombolysis In Myocardial Infarction 22) Substudy.J Am Coll Cardiol. 2009; 54: 2290-2295
- Immediate vs. delayed stenting in acute myocardial infarction: a systematic review and meta-analysis.EuroIntervention. 2013; 8: 1207-1216
- Deferred versus conventional stent implantation in patients with ST-segment elevation myocardial infarction (DANAMI 3-DEFER): an open-label, randomised controlled trial.Lancet. 2016; 387: 2199-2206
- Myocardial damage in patients with deferred stenting after STEMI: a DANAMI-3–DEFER Substudy.J Am Coll Cardiol. 2017; 69: 2794-2804
- Deferred vs immediate stenting in primary percutaneous coronary intervention: a collaborative meta-analysis of randomized trials with cardiac magnetic resonance imaging data.Can J Cardiol. 2018; 34: 1573-1580
- A randomized trial of deferred stenting versus immediate stenting to prevent no- or slow-reflow in acute ST-segment elevation myocardial infarction (DEFER-STEMI).J Am Coll Cardiol. 2014; 63: 2088-2098
- INNOVATION Study (Impact of Immediate Stent Implantation Versus Deferred Stent Implantation on Infarct Size and Microvascular Perfusion in Patients With ST-Segment–Elevation Myocardial Infarction).Circ Cardiovasc Interv. 2016; 9 (pii: e004101)
Article info
Publication history
Published online: November 08, 2018
Accepted:
October 29,
2018
Received:
October 29,
2018
Footnotes
See article by Cassese et al., pages 1573–1580 of this issue.
See page 1542 for disclosure information.
Identification
Copyright
© 2018 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.
