Immediate Versus Delayed Invasive Intervention for Non-STEMI Patients - RIDDLE-NSTEMI


The goal of the trial was to assess efficacy of an immediate versus delayed invasive intervention in patients presenting with non-ST-segment elevation myocardial infarction (NSTEMI).

Contribution to the Literature: The RIDDLE-NSTEMI trial showed that an immediate invasive strategy may be superior to a delayed invasive strategy in improving cardiovascular outcomes in NSTEMI patients, mainly driven by a reduction in the rate of reinfarction.

Study Design

Patients with NSTEMI were randomized in a 1:1 fashion to either immediate (within 2 hours) intervention (n = 162) or delayed (within 72 hours) intervention (n = 161).

Inclusion criteria:

  • Episode of chest pain occurring no more than 24 hours before admission with elevation of cardiac troponin I greater than the upper limit of normal (ULN) and new ST-segment depression at least 1 mV and/or T-wave inversion in ≥2 contiguous leads
  • Total number of enrollees: 323
  • Duration of follow-up: 1 year
  • Mean patient age: 62 years
  • Percentage female: 32%

Exclusion criteria:

  • Persistent ST-segment elevation
  • Posterior MI
  • Hemodynamic instability or cardiogenic shock
  • Life-threatening ventricular arrhythmias
  • Refractory angina on admission
  • Active bleeding
  • Any contraindication for the use of dual antiplatelet therapy
  • Presence of comorbidities with a life expectancy <6 months

Other salient features/characteristics:

  • ST-segment depression: 79%
  • GRACE score: 130; GRACE >140: 38%; TIMI score: 4; TIMI ≥5: 23%
  • Single-vessel disease: 26%
  • Median times to angiography: 1.4% vs. 61.0%, p < 0.0001
  • Percutaneous coronary intervention (PCI): 78.4% vs. 65.0%, p = 0.01 (of this, bare-metal stent [BMS] PCI: 68.5% vs. 57.7%, plain old balloon angioplasty [POBA]: 8.7% vs. 8.6%)
  • Coronary artery bypass grafting (CABG): 12.3% vs. 23.8%, p = 0.01

Principal Findings:

  • Primary endpoint, 30-day death or MI, for immediate vs. delayed intervention: 4.3% vs. 13.0%, p = 0.008
  • Death: 3.1% vs. 3.1%, p = 0.97
  • MI: 2.5% vs. 9.9%, p = 0.01

Secondary outcomes (for immediate vs. delayed intervention, respectively):  

  • 30-day recurrent ischemia: 3.7% vs. 15.5%, p = 0.001
  • 30-day major bleeding: 0.6% vs. 0.6%, p = 0.99
  • 1-year death or MI: 6.8% vs. 18.8%, p = 0.002
  • 1-year recurrent ischemia: 9.9% vs. 16.9%, p = 0.002


The results of this relatively small single-center trial indicate that an immediate invasive strategy (median time 1.4 hours) is superior in improving cardiovascular outcomes compared with a delayed invasive strategy (median time 61.0 hours), mainly driven by a reduction in the rates of reinfarction. All patients had received clopidogrel loading. The majority of patients in this trial were not high risk (GRACE score >140 present in approximately one-third) since patients with ongoing chest pain or hemodynamic/electrical instability were excluded.  

Earlier trials have suggested a benefit, mostly in the need for revascularization, but not in death or MI, with earlier revascularization in NSTEMI patients. However, there are important differences from earlier trials. For instance, the time difference between the two arms compared with earlier trials was longer (for example, 14 vs. 50 hours in TIMACS, 1.2 vs. 21 hours for ABOARD, compared with 1.4 vs. 61 hours in the current trial).

Furthermore, the definition of reinfarction may have contributed to the positive outcome, particularly since nearly one-quarter of patients in the delayed group required CABG, in whom MI can be particularly hard to define. Also, it is unclear why this trial had a high rate of non-DES PCI (nearly two-thirds of PCI patients got either BMS PCI or POBA).

This is an important topic, and further well-powered trials are needed to further address this issue.


Milosevic A, Vasiljevic-Pokrajcic Z, Milasinovic D, et al. Immediate Versus Delayed Invasive Intervention for Non-ST-Segment Elevation Myocardial Infarction Patients: The RIDDLE-NSTEMI Study (Randomized study of ImmeDiate versus DeLayed invasivE intervention in patients with Non-ST-segment Elevation Myocardial Infarction). JACC Cardiovasc Interv 2016;9:541-9.

Clinical Topics: Acute Coronary Syndromes, Cardiac Surgery, Invasive Cardiovascular Angiography and Intervention, Aortic Surgery, Interventions and ACS, Interventions and Imaging, Angiography, Nuclear Imaging

Keywords: Acute Coronary Syndrome, Angiography, Angioplasty, Balloon, Coronary, Chest Pain, Coronary Artery Bypass, Hemodynamics, Myocardial Infarction, Percutaneous Coronary Intervention, Stents, Drug-Eluting Stents, Ticlopidine, Troponin I

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