Early Invasive Approach After Cardiac Arrest Gains Support

Patients resuscitated after an out-of-hospital cardiac arrest appear to fare better both during the initial hospital stay and up to several years after discharge if they are brought to the cardiac cath lab early for angiography and revascularization, according to 2 observational studies.

The studies, published in the October issue of Circulation: Cardiovascular Interventions, are concordant with many—but not all—prior analyses, but they do not effectively address whether an early invasive approach improves outcomes in patients without ST-segment elevation, Christopher B. Granger, MD, of the Duke Clinical Research Institute (Durham, NC), commented in a telephone interview with TCTMD.

“My conclusion from these 2 studies is that they add fuel to the debate and they add to the rationale for doing randomized trials to determine if and to what extent there may be benefit from early cath and revascularization in the setting of cardiac arrest for patients who do not have ST elevation,” he said. 

Long-term Impact of Immediate PCI

In the first study, Alain Cariou, MD, PhD, of Cochin Hospital (Paris, France), and colleagues examined data on 1,722 patients (71.5% men; median age 60) with non-trauma-related out-of-hospital cardiac arrest admitted to a cardiac arrest center in Paris after the return of spontaneous circulation between 2000 and 2013. About one-third of patients (35.6%) did not undergo immediate coronary angiography, 35.7% underwent immediate angiography without PCI, and 27.8% underwent angiography and PCI within 6 hours of collapse. Median time from collapse to PCI was 1.5 hours.

Thirty-day mortality was lowest among patients who underwent immediate PCI (57.0%), increasing to 64.5% for those who underwent angiography only and 79.5% for those who were not taken immediately to the cath lab (P < .01 for differences). Similar patterns were seen at 3 and 10 years of follow-up among patients who survived to at least 30 days. Median length of follow-up among 30-day survivors was 3.2 years (maximum 13.5 years).

After multivariate adjustment, immediate PCI was associated with lower 30-day mortality (adjusted OR 0.61; 95% CI 0.43-0.85) and long-term mortality (adjusted HR 0.40; 95% CI 0.23-0.70). In a propensity-matched analysis, immediate PCI remained associated with less long-term mortality (adjusted HR 0.29; 95% CI 0.14-0.61), but the relationship with 30-day mortality was no longer significant (adjusted HR 0.64; 95% CI 0.38-1.08).

Angiography without PCI was not predictive of either short- or long-term mortality.

“These findings should suggest physicians to consider immediate coronary angiography and PCI if indicated in these patients,” Dr. Cariou and colleagues say.

Short-term Survival After Early Angiography

In the second study, Ankur Vyas, MD, of the University of Iowa Hospitals and Clinics (Iowa City, IA), and colleagues examined data from the Cardiac Arrest Registry to Enhance Survival (CARES) on 4,029 adult patients admitted to 374 US hospitals after successful resuscitation from cardiac arrest due to shockable rhythms between 2010 and 2013.

Early angiography, defined as occurring within 1 calendar day of arrest, was used in 48.5% of patients. Among them, 64.2% underwent revascularization.

In the overall cohort, 67.5% of patients survived to hospital discharge; the proportion surviving with a favorable neurological outcome was 48.8%.

A propensity-matched analysis that included 1,312 patient pairs showed that early angiography was associated with greater chances of survival to discharge (OR 1.52; 95% CI 1.28-1.80) and survival with a favorable neurological outcome (OR 1.47; 95% CI 1.25-1.71). Further adjustment for revascularization weakened both relationships, “suggesting that revascularization was a key mediator of the survival benefit,” the authors write.

In an analysis of patients without ST-segment elevation, early angiography remained associated with survival with a favorable neurological outcome (OR 1.60; 95% CI 1.14-2.26) but not overall survival (OR 1.29; 95% CI 0.87-1.90).

Dr. Vyas and colleagues acknowledge that, because of its observational design, the study cannot establish causal relationships. “However,” they say, “given our study findings and the potential to improve survival in out-of-hospital cardiac arrest victims, there is an urgent need for randomized controlled trials to confirm the benefit of coronary angiography in patients with out-of-hospital cardiac arrest including its timing (immediate [< 2 hours], early [< 24 hours], or after neurological prognostication), especially in patients who are not identified to have ST-elevation on admission.”

Field Awaits Randomized Data

In an accompanying editorial, Kapiledo Lotun, MD, and Karl B. Kern, MD, of the University of Arizona (Tucson, AZ), point out that the optimal management approach for patients resuscitated from cardiac arrest remains uncertain, resulting in practice variation across centers. “An aggressive approach to simultaneously cool and cath such patients on arrival at the hospital is favored by some interventional cardiologists,” they write. “Others remain unconvinced that such therapy is beneficial or needed.”

The 2 studies roughly double the number of patients reported in the literature on an early invasive approach after cardiac arrest, they say. “[E]ven more importantly, both have raised the bar of evidence by using propensity-score matching and, as expected, have shown slightly less impressive odds ratios or hazard ratios, but still statistically significant differences in favor of early coronary angiography and revascularization” compared with prior observational studies.

Drs. Lotun and Kern say the debate about the right treatment approach after cardiac arrest centers on uncertainty about which specific types of patients derive benefit from early angiography and revascularization. They note that US and European guidelines contain strong recommendations for immediate coronary angiography at admission in patients resuscitated after cardiac arrest if they have ST-segment elevation, regardless of whether they are comatose or awake. The European guidelines also recommend considering early angiography in patients without ST-segment elevation.

The editorialists call into question whether the US study shows that early angiography does not have a survival benefit in patients without ST-segment elevation, pointing out that about half of the patients did not have post-resuscitation ECG information available. Also, 2 recent studies showed that early angiography was, in fact, associated with improved outcomes in patients without ST-segment elevation.

“Despite the consistency of these cohort studies, the cardiology interventional community seems to not only want, but even demand, a randomized controlled trial of early coronary angiography post arrest before it is willing to fully accept this approach,” Drs. Lotun and Kern write, adding that such studies are ongoing, including DISCO in Sweden and PEARL in the United States.

“Though both trials are admittedly small, with anticipated randomization of about 300 patients each, the organizers have prospectively communicated to make them reasonably similar to maximize the opportunity for combining results in a potential meta-analysis,” they note.

The ongoing trials will not be definitive, but they will provide the most informative and reliable information to date, Dr. Granger said. Randomized trials are necessary, he said, because all observational studies “are fundamentally limited by the fact that unmeasured confounders can never be accounted for no matter how careful the analysis, no matter how good the propensity model, no matter how good the adjustment.”

He likened the situation to that surrounding PCI of nonculprit lesions during primary PCI for STEMI. Early observational data indicated that more complete revascularization was harmful, resulting in a class III recommendation against the practice. That recommendation was recently overturned in a focused update after randomized trials published in the last few years demonstrated a benefit from intervening on nonculprit lesions.

“That’s an example of where we see in these observational analyses dealing with revascularization that there are these substantial confounding effects,” Dr. Granger said.

 

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Sources: 
1. Geri G, Dumas F, Bougouin W, et al. Immediate percutaneous coronary intervention is associated with improved short- and long-term survival after out-of-hospital cardiac arrest. Circ Cardiovasc Interv. 2015;8:e002303.
2. Vyas A, Chan PS, Cram P, et al. Early coronary angiography and survival after out-of-hospital cardiac arrest. Circ Cardiovasc Interv. 2015;8:e002321.
3. Lotun K, Kern KB. How much is enough… what more is needed [editorial]? Circ Cardiovasc Interv. 2015;8:003075.