Early Invasive Intervention Trumps Delayed Approach in NSTEMI Patients

A strategy of immediate invasive coronary angiography within 2 hours of admission to hospital for NSTEMI is superior to a protocol of delayed angiography, according to the results of a new study. Early Invasive Intervention Trumps Delayed Approach in NSTEMI Patients

Compared with the delayed intervention where patients underwent coronary angiography within 72 hours after presenting to the emergency department, the early invasive approach significantly reduced the occurrence of death and MI at 30 days. The benefit, according to investigators, was driven by lower rates of new MI in patients undergoing early invasive angiography, chiefly during the pre-catheterization period.

At 1 year, the benefit of early invasive angiography persisted, with the early approach associated with a 66% lower risk of death and MI compared with patients undergoing delayed angiography (HR 0.34; 95% CI 0.17-0.67). 

Senior investigator Goran Stankovic, MD, PhD, of the Clinical Center of Serbia in Belgrade, said that while studies have tested an early- vs delayed-invasive approach in this setting before, there is often a failure to discriminate among the different types of NSTE-ACS patients. The unstable angina patient differs from the high-risk NSTEMI patient who is experiencing myocardial necrosis as indicated by cardiac biomarkers, said Stankovic.

“For these patients with elevations in cardiac troponin, we know that we have to approach them differently,” he told TCTMD.  

 Necessary for NSTEMI Patient With High-Risk Features

Published online January 6, 2016, in JACC: Cardiovascular Interventions, the study randomized 162 patients to coronary angiography within 2 hours of presenting to the hospital (median time 1.4 hours) and 161 patients to a more conventional protocol of delayed angiography within 72 hours (median time 61 hours). All eligible patients presented to the hospital with chest pain occurring no more than 24 hours prior to admission. In addition to chest pain, patients had a documented elevation in cardiac troponin and ST-segment depression or T-wave inversion on ECG.

At 30 days, death or MI occurred in 4.3% of patients randomized to immediate angiography vs 13.0% of patients randomized to delayed angiography, a statistically significant difference (P = .008). Thirty-day mortality rates were equivalent in the 2 treatment arms at 3.1%, but the risk of MI was higher among those who underwent delayed coronary angiography (2.5% vs 9.9%, respectively; P = .01). A secondary endpoint, one that combined death, new MI, and recurrent ischemia, was also lower in the immediate-intervention arm (6.8% vs 26.7%, respectively; P < .001).

The largest difference in the rate of death or MI between the 2 treatment approaches occurred early in the pre-catheterization phase. For patients in the immediate intervention arm, there were no deaths or MIs prior to angiography, whereas 1 death and 10 MIs occurred in the pre-catheterization phase of the delayed-intervention arm. At 1 year, the rate of death or new MI was lower in the immediate-intervention group—6.8% vs 18.8%, respectively (P = .002)—but a landmark analysis revealed no significant difference in the event rates from 31 days to 1 year.

To TCTMD, Stankovic said previous studies investigating the early-vs-delayed approach in NSTEMI did not include clinical outcomes as the primary endpoint but instead focused on cardiac biomarkers. While their study does have limitations, including the relatively small sample size, he believes an early invasive approach is necessary for NSTEMI with high-risk features, such as those included in their trial. 

 Heterogeneity of NSTE-ACS Population Cited

To TCTMD, David E. Kandzari, MD, Piedmont Heart Institute (Atlanta, GA), said there is a fair amount of heterogeneity in NSTE-ACS patients, but the present study focused on patients with high-risk features, including elevations in cardiac troponin and ST-segment changes. These patients, he noted, typically have other comorbidities and are at increased risk of cardiovascular events compared with other patients who present to the hospital with ischemic-based chest pain alone.

In the present study, the immediate strategy, which could be considered “aggressive” given how quickly patients were taken to the cath lab, was associated with a significant reduction in reinfarction, suggesting “you salvage more heart muscle if you intervene early,” said Kandzari. In past studies testing early- vs delayed-intervention strategies, the benefit of an early invasive protocol was driven by a reduction in ischemia, he noted.

Sunil V. Rao, MD, Duke University Medical Center (Durham, NC), said the preferred strategy in the United States is early invasive risk stratification within 24 hours. This is based on trials conducted in the 1990s, such as FRISC II and TIMACS, that established the benefit of early coronary angiography. “This benefit varies with the baseline risk of the patient, so patients with higher GRACE scores get more absolute benefit from early invasive strategy,” he told TCTMD.

The 2014 American College of Cardiology/American Heart Association clinical guidelines for the management of NSTE-ACS recommend an “immediate invasive” strategy within 2 hours in patients with high-risk features, such as refractory angina, hemodynamic instability, recurrent angina or ischemia at rest or with low-level activities (despite medical therapy), worsening heart failure or mitral regurgitation, or sustained ventricular tachycardia or fibrillation (class 1A). An early strategy, within 24 hours, is a reasonable option in initially stabilized high-risk patients (class IIa) while a delayed approach (24 to 72 hours) is recommended in other patients not at high or intermediate risk.

In Europe, the guidelines are similar, with high-risk NSTE-ACS patients recommended to undergo invasive angiography within 24 hours and intermediate-risk patients within 72 hours. The European Society of Cardiology does suggest very-high-risk patients undergo invasive treatment within 2 hours. 

Kandzari said NSTEMI patients presenting to the hospital during daytime hours would likely be taken to the lab the same day, while those who present at night would typically undergo angiography the next day. In the present study, given that patients were randomized within 2 hours to early invasive management, a 24-hour lab would be necessary. While this would likely place some stress on the systems of care, the reduction in MI observed with the early invasive strategy “underscores the immediacy of treatment,” not unlike the importance of getting STEMI patients into the cath lab as quickly as possible, said Kandzari.

To TCTMD, Stankovic said his group performs approximately 3,000 PCIs each year, including anywhere from 1,200 to 1,400 primary PCIs. At their high-volume center, where they treat at least 3 or 4 STEMI patients every day with an experienced team of operators, the pathway is not dissimilar to the STEMI protocol. 

“This is why I believe we can follow the same path as STEMI patients for the NSTEMI patient who is high risk but stable,” said Stankovic. “We know how to move these patients quickly to the cath lab from the [coronary care unit] and then perform coronary angiography and proceed with culprit-vessel revascularization.”


Milosevic A, Vasiljevic-Pokrajcic Z, Milasinovic D, et al. Randomized study of immediate versus delayed invasive intervention in patients with non-ST-segment elevation myocardial infarction (RIDDLE-NSTEMI). J Am Coll Cardiol Intv. 2016;Epub ahead of print.


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Michael O’Riordan is the Associate Managing Editor for TCTMD and a Senior Journalist. He completed his undergraduate degrees at Queen’s…

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  • Stankovic reports no conflicts of interest.
  • Rao reports consulting to Astra Zeneca, Boehringer Ingelheim, Medtronic, Merck, Terumo Interventional Systems, and ZOLL.
  • Kandzari reports receiving consulting fees/honoraria from Boston Scientific, Medtronic, Micell Technologies, and Thoratec.