Study of Deferred Versus Immediate Stenting in Acute STEMI Conventional Treatment With Immediate Stenting - DEFER-STEMI


Given the high thrombus burden in patients with ST-segment elevation myocardial infarction (STEMI), there is a high incidence of no/slow-reflow due to distal embolization, microvascular spasm, and thrombosis. Recently, there has been interest in exploring the role of deferred percutaneous coronary intervention (PCI) following restoration of infarct-related artery (IRA) patency in these patients. The current trial sought to compare outcomes following deferred PCI versus immediate PCI (conventional primary PCI) in patients presenting with STEMI.


A strategy of deferred PCI would be superior to immediate PCI (conventional primary PCI) in patients presenting with STEMI.

Study Design

  • Randomized
  • Parallel

Patient Populations:

  • STEMI patient undergoing primary PCI
  • Radial access
  • High-risk for no-reflow as defined by:
    - Clinical history: previous MI, increased age (i.e., age ≥65 years), duration of symptoms >6 hours
    - Culprit coronary artery abnormalities: an occluded artery (TIMI grade 0/1) at initial angiography, heavy thrombus burden (TIMI ≥grade 2), long lesion length (≥24 mm), small vessel diameter (i.e., ≤2.5 mm)
    - Clinical signs of acute microvascular injury after initial reperfusion: persistent ST-elevation >50%

    Number screened: 411
    Number of enrollees: 101
    Duration of follow-up: 6 months
    Mean patient age: 60 years
    Percentage female: 30%


  • Cardiogenic shock
  • Absence of normal (TIMI grade 3) coronary blood flow after initial reperfusion with aspiration thrombectomy with or without balloon angioplasty; the residual severity of the culprit stenosis was not relevant to participation provided TIMI grade 3 flow was evident
  • Contraindication to MRI (e.g., permanent pacemaker)

Primary Endpoints:

  • Incidence of no/slow-reflow, defined as absent flow (TIMI flow grade 0), incomplete filling (TIMI flow grade 1) or slow-reflow, but complete filling (TIMI 2) of the culprit coronary artery during or at the end of PCI, as revealed by the coronary angiogram

Secondary Endpoints:

  • Angiographic: no-reflow (TIMI flow grade 0/1), final TIMI flow grade, corrected TIMI frame count, TIMI myocardial blush grade, the occurrence of intraprocedural thrombotic events
  • ECG: occurrence of complete (≥70), partial (30% to <70%), or no (≤30%) ST-segment resolution on the ECG assessed 60 minutes after reperfusion compared to the baseline ECG before reperfusion
  • MRI: occurrence of microvascular obstruction with late gadolinium enhancement on CMR 2 days after reperfusion, final infarct size at 6 months, myocardial salvage, and myocardial salvage index

Drug/Procedures Used:

All patients underwent radial access. Patients were included if they were at high risk for no-reflow following primary PCI. Patients were randomized to a deferred strategy (PCI 4-16 hours following initial coronary reperfusion) or immediate PCI, as per conventional standards. All patients received tirofiban (0.15 mcg/kg/min) (for 12 hours post-PCI in all patients, and also until the second procedure in the deferred arm). In addition, patients in the deferred PCI arm received enoxaparin 1 mg/kg BID for up to 16 hours following the first procedure. All patients received 300 mg aspirin, 600 mg clopidogrel, and 5000 U of unfractionated heparin in the ambulance.

Principal Findings:

A total of 101 patients were randomized, 49 to immediate PCI and 52 to deferred PCI. Baseline characteristics were similar between the two arms, with some important exceptions. Approximately 13% had diabetes mellitus and 4% had undergone prior PCI. Patients in the immediate PCI arm were older, more likely to be male, and less likely to have experienced prior MI (4.1% vs. 9.6%). The median ischemic time was also higher (183 minutes vs. 166 minutes), and a higher proportion had an ischemic time >12 hours (10.2% vs. 1.9%). The IRA was right coronary artery in 50%, and left anterior descending artery in approximately 33% (36.7% vs. 28.8%). Nearly 50% of the patients had multi-vessel disease. Baseline Thrombolysis in Myocardial Infarction (TIMI) 0/1 flow was observed in 78% of patients, with thrombus observed in close to 97% of all patients. Thrombus burden was moderate to high (TIMI grade 3/4) in nearly 50% of the patients, and aspiration thrombectomy was performed in nearly 87% of all patients. Predilation was less common in the immediate PCI arm (73.5% vs. 88.5%), whereas postdilation was more common (71.4% vs. 57.7%). Three patients in the deferred PCI arm did not require any stenting.

The primary endpoint of no- or slow-reflow post-PCI was significantly higher in the immediate PCI compared with deferred PCI arms (28.6% vs. 5.9%, p = 0.005). TIMI 0/1 flow was numerically higher (14.3% vs. 2.0%, p = 0.052). All intraprocedural thrombotic events were higher with immediate PCI, including at least one thrombotic event (32.7% vs. 9.8%, p = 0.01) and distal embolization (20.4% vs. 2.0%, p = 0.006). Within the deferred stenting group, there was a significant reduction in the proportion of patients with angiographic evidence of thrombus at the start of the second versus the first procedure (98.1% vs. 62.7%; p < 0.0001). Complete ST-segment resolution on electrocardiogram (ECG) 60 minutes post-PCI was similar (38.8% vs. 50.0%). On cardiac magnetic resonance (CMR), compared with immediate stenting, myocardial salvage (% left ventricular mass) (14.7% vs. 19.7%, p = 0.027) and salvage indexes (56% vs. 68%, p = 0.031) at 6 months were greater in the deferred group.

Total contrast volume was higher in the deferred arm (205 vs. 278 ml, p < 0.0001). Recurrent ST-elevation in patients in the deferred PCI arm prior to the second procedure occurred in two patients (3.8%). There were no bleeding events or in-hospital mortality. On follow-up, one patient in the immediate PCI arm and three in the deferred PCI arm experienced a recurrent infarction.


The results of the DEFER-STEMI trial indicate that a strategy of deferred PCI following establishment of TIMI 3 flow in the IRA (by 4-16 hours) results in a significant improvement in the incidence of no- and slow-reflow post-PCI, compared with a conventional strategy of immediate PCI post-reperfusion in patients with STEMI and at high risk for no/slow-reflow. All patients received antiplatelet therapy with tirofiban infusion and low molecular weight heparin (LMWH) (only in the deferred PCI arm), in addition to aspirin and clopidogrel. Infarct size on CMR at 6 months was similarly lower in the deferred strategy arm.

This is a small, open-label, single-center hypothesis-generating trial, but requires further study before it can inform/change clinical practice. Intuitively, it is an appealing concept. No- or slow-reflow is reported in nearly 10% of STEMI patients post-primary PCI, and can be higher in patients with high thrombus burdens and long ischemic times. It has been linked with worse outcomes post-PCI. Thus, after restoring TIMI 3 flow with aspiration thrombectomy or gentle balloon predilation, these patients were “medically treated” with tirofiban and LMWH. After a few hours, the patients were taken for a definitive procedure, and observed to have a significant improvement in thrombus burden. PCI in this deferred setting resulted in less distal embolization, and less overall no-flow or slow-reflow. However, several limitations/caveats exist. For one, it is unknown if this benefit would be observed in patients pretreated with stronger antiplatelet agents such as prasugrel and ticagrelor versus clopidogrel.

Secondly, the choice of tirofiban for medical therapy is interesting. A similar upstream strategy of “facilitated PCI” with abciximab was not beneficial in the FINESSE trial. In the ON-TIME trial, upstream tirofiban was superior to in-lab administration of the drug in STEMI patients in improving TIMI flow and reducing thrombus burden. It is possible that the small molecule glycoprotein IIb/IIIa inhibitors behave differently than abciximab in this setting. In the context of the primary outcome, this appears somewhat biased towards the deferred PCI arm. A fairer comparison would have been a second angiography in all patients, with only a difference in timing of PCI between the two arms. Thus, the primary endpoint of angiographic no- or slow-reflow would be compared in both arms at the same time point after the initial procedure.

Importantly, this is a small single-center trial with no blinding, although outcome assessors were blinded to the study assignment. This may have introduced certain biases, and will need to be tested in larger blinded settings. Finally, a deferred strategy may be more expensive due to the need for prolonged administration of tirofiban and a second angiographic procedure; future studies will need to assess its cost-effectiveness.


Carrick D, Oldroyd KG, McEntegart M, et al. A randomized trial of deferred stenting versus immediate stenting to prevent no- or slow reflow in acute ST-elevation myocardial infarction (DEFER-STEMI). J Am Coll Cardiol 2014;Mar 5:[Epub ahead of print].

Clinical Topics: Anticoagulation Management, Cardiac Surgery, Invasive Cardiovascular Angiography and Intervention, Aortic Surgery

Keywords: Spasm, Myocardial Infarction, Follow-Up Studies, Platelet Aggregation Inhibitors, Heparin, Low-Molecular-Weight, Ticlopidine, Piperazines, Electrocardiography, Immunoglobulin Fab Fragments, Cost of Illness, Tyrosine, Percutaneous Coronary Intervention, Thrombectomy, Thrombosis, Enoxaparin, Magnetic Resonance Spectroscopy, Myocardial Reperfusion, Diabetes Mellitus, Platelet Glycoprotein GPIIb-IIIa Complex

< Back to Listings