Hyperinvasive Approach May Boost Survival in OHCA

A “hyperinvasive” approach to treating refractory out-of-hospital cardiac arrest (OHCA)—one that relies on mechanical chest compressions during transport and extracorporeal CPR, if needed, followed by swift invasive tests and treatment—is more likely to lead to survival with neurological recovery at 6 months in some patients, as compared with standard protocols done at the site of the cardiac arrest, the Prague OHCA trial suggests.

The benefits of the hyperinvasive approach were particularly marked in patients requiring 45 or more minutes of resuscitation efforts, said Jan Bělohlávek, MD, PhD (Charles University, Prague, Czech Republic), who presented the findings Monday during the American College of Cardiology 2021 Scientific Session.

Prague OHCA actually missed its predefined primary endpoint—6-month survival with Cerebral Performance Category (CPC) 1 or 2—but the trial was in fact stopped early after an interim analysis showed the benefits of the hyperinvasive approach. “A prerequisite for such a high survival . . . includes highly effective prehospital care, high percentage of bystander CPR, dispatch center-directed CPR, and a close cooperation between experienced cardiac arrest centers,” he stressed.

Moreover, Bělohlávek noted, the expected effect of the hyperinvasive approach, for which the team had been training for over a 2-year period before randomizing their first patient, improved outcomes by more than twofold compared with the standard approach.

Efforts to improve the notoriously poor outcomes following OHCA have produced mixed results. An early invasive strategy is recommended in STEMI patients with an out-of-hospital cardiac arrest, but this approach in NSTEMI has not yet born fruit. Whether the addition of ECPR, consisting of veno-arterial extracorporeal membrane oxygenation (VA-ECMO), to support the heart during hospital transfer could augment an early invasive approach remains to be determined.

“What's kind of unique in this randomized trial is it's really studying a package [of] resuscitation therapies rather than just a single element,” noted Julia Indik, MD, PhD (University of Arizona College of Medicine, Tucson), who discussed the trial following its presentation. “It makes it a particularly ambitious trial to carry out as well and then to understand the nuances and the possible meanings behind the results.”

The fact that the trial didn’t quite meet its primary endpoint here is less important than the signal of what is “clearly a very important trend,” she continued, adding that the trial also reported “absolutely phenomenal” rates of bystander CPR.

Primary Endpoint Not Met

For the Prague OHCA study, Bělohlávek and colleagues randomized 264 patients with out-of-hospital cardiac arrest of presumed cardiac cause who were undergoing on-scene chest compressions to a hyperinvasive treatment approach or standard care between March 2013 and October 2020. Crossover was allowed and occurred at a rate of about 8% in both arms.

The patient groups were well balanced in terms of baseline characteristics. More than three-quarters were men, more than one-third of cardiac arrests happened in a public place, and the rates of bystander CPR strikingly were 97.7% and 99.2% in the standard and hyperinvasive groups, respectively.

More than half of patients in the standard care group (55.3%) and 73.4% in the hyperinvasive group underwent resuscitation for at least 45 minutes, with the average time of CPR being longer in the latter (median 46 vs 58 minutes; P = 0.037). More patients in the standard care group had sustained return of spontaneous circulation (ROSC) on admission (43.9% vs 27.4%; P = 0.012). ACS was the cause of cardiac arrest in about half of all patients, and bleeding was reported more often in the hyperinvasive arm (14.5% vs 31.0%; P = 0.014).

In the intention-to-treat analysis, there was no difference between the study groups for the primary endpoint of survival at 180 days with CPC scores of 1 or 2 (22.0% vs 31.5%; P = 0.09). At 30 days, however, there was a benefit observed for neurologic recovery for the hyperinvasive approach (18.2% vs 30.6%; P 0.02). Thirty-day cardiac recovery was numerically higher but not statistically so for the hyperinvasive group.

Kaplan-Meier analysis showed a benefit with regard to survival at 180 days with the hyperinvasive approach compared with standard care (P = 0.014).

Among the 26 patients who underwent CPR for at least 45 minutes and survived to 180 days with a CPC score of 1 or 2, 20 were randomized to the hyperinvasive strategy and six to standard care (P = 0.018). Notably, four of the survivors in the standard-care group had actually crossed over to the hyperinvasive treatment protocol, Bělohlávek said.

Digging Into the Details

In a press briefing, Rachel Lampert, MD (Yale University School of Medicine, New Haven, CT), pointed out that because the hyperinvasive approach patients had a slightly longer CPR time prior to randomization, this “would have biased the results against the intervention.”

Additionally, while it’s understandable why the study was stopped early given the benefit seen among patients who underwent at least 45 minutes of CPR, this “also seemed to be somewhat unusual as the overall numbers were solid but not extremely large,” Lampert said. “It might have been helpful to continue the study as planned and to see whether other groups might benefit, as well, both as far as differences in resuscitation time but perhaps other clinical factors.”

“What has certainly struck me as probably the most prominent element of a hyperinvasive approach is the use of VA-ECMO upon arrival to the cath lab,” Indik commented. “It's well known that [VA-ECMO] has its own set of potential complications—bleeding complications, vascular access, limb ischemia—and these are also brought up in one of your slides, but it's thought that VA-ECMO's downside could be balanced by some potential positive benefit on survival of course.”

She speculated that the trial findings might have been different if the requirement to initiate VA-ECMO had only been restricted to patients who still needed CPR when they got to the cath lab and excluding those who were still in shock, but who had achieved ROSC. “I think that's an intriguing thought that might have just changed the whole trial,” Indik suggested.

The trial had “very strict criteria” for cardiogenic shock, and all but a handful of patients who received ECMO were in persistent cardiac arrest, Bělohlávek explained. “There is still a chance that during the CPR en route [to the hospital] you get the ROSC on the compressed patients and the rest of them were implanted with ECMO,” he said.

The other benefit seen with the hyperinvasive protocol, Bělohlávek said, was they expected that only 10% of patients being resuscitated for 45 minutes would survive, yet more than double that percentage did so, even in the comparator group. “The protocol training actually improved outcomes in the standard arm, and I consider this the most beneficial byproduct of the study even though we did not prove a difference in the outcome,” he commented.