Deferred Stenting, Postconditioning Strike Out for STEMI in DANAMI 3

Patrice Wendling

April 04, 2016

CHICAGO, IL — Postponing stent implantation for 48 hours after primary angioplasty did not improve clinical outcomes in patients with ST-segment-elevation MI (STEMI) in the Danish Study of Optimal Acute Treatment of Patients with ST-segment Elevation Myocardial Infarction: DEFER (DANAMI 3-DEFER) trial[1].

Deferred stenting was actually associated with a higher rate of target vessel revascularization (TVR) than standard primary PCI (P=0.03), lead author Dr Henning Kelbæk (Rigshospitalet University of Copenhagen, Denmark) reported at the American College of Cardiology (ACC) 2016 Scientific Sessions.

"We can now say definitively that a routine strategy of deferring stent implantation in an all-comer STEMI population is not beneficial," panelist Dr J Dawn Abbott (Brown University, Providence, RI) said.

The Danish investigators tried a second strategy to improve STEMI outcomes with ischemic postconditioning in DANAMI 3-iPOST, but it too failed to meet its primary end point[2].

"This probably does put the nail in the coffin for ischemic postconditioning, which really looks extremely good in the animal lab, but this is now one of two or three large studies showing it is not beneficial," said panelist Dr Bernard Gersh (Mayo Clinic, Rochester, MN). The reasons for this disconnect are likely complex and multifactorial, "but some of it has to do with the fact that in the experimental lab you can reperfuse within minutes, but you're not going to be able to do that clinically."

DANAMI 3-DEFER

DANAMI 3-DEFER assessed whether deferred stent implementation would reduce the risk of jeopardized myocardial vascular flow and improve the clinical course of STEMI patients compared with conventional PCI.

The two strategies were evaluated in 1215 patients presenting with chest pain for less than 12 hours and ST-segment elevation >0.1 mV in at least two contiguous leads in whom a stabilized TIMI 2–3 flow could be achieved after minimal acute manipulation. Their mean age was 62 years, and three-fourths were men.

After a median of 42 months, deferred stenting did not improve the composite primary end point of all-cause death, hospitalization for heart failure, reinfarction, or TVR compared with immediate stenting (hazard ratio [HR] 0.99; P=0.92), Kelbæk said.

Mortality and heart-failure hospitalizations numerically favored deferred stenting, but this was offset by the significantly higher TVR rate, mainly due to a small fraction of patients (n=11) who returned prematurely for stent implantation because of recurrent symptoms or ST-segment elevation, he observed.

Left ventricular function was slightly better after deferred stent implementation when evaluated in two-thirds of patients 18 months after treatment (median 60% vs. 57%; P=0.04).

"The difference was small, and I really don't know what the clinical significance is," remarked Gersh.

Kelbæk said analyses are planned in patients with large thrombus burden, a population that has shown benefit in prior studies, and in those with complete ST resolution. It's also possible that detailed selection of patients with increased risk of slow or no flow might have produced different results, the authors write in their report, published online in Lancet.

DANAMI 3-iPOST

There have been several small trials of postconditioning in STEMI patients with mixed results, but the DANAMI 3-iPOST trial is the largest to test whether gentle, graded ischemic postconditioning would protect the heart against reperfusion injury, thus lessening the development of myocardial heart failure and improving survival.

A total of 1234 patients (TIMI 0–1) with acute-STEMI symptoms for less than 12 hours were randomly assigned to standard PCI or ischemic postconditioning prior to stent implantation. Within 60 seconds of reperfusion in the postconditioning group, a low-pressure balloon was inflated four times for 30 seconds, interspersed with 30-second bursts of reperfusion.

After a median follow-up of 39 months, ischemic postconditioning led to a nonsignificant 7% reduction in the primary composite end point of all-cause mortality and heart-failure hospitalizations (HR 0.93; P=0.66), lead author Dr Thomas Engstrøm (University of Copenhagen, Denmark) reported at the meeting.

All-cause mortality alone was reduced by 25% with postconditioning (HR 0.75; P=0.18).

There was no difference in the primary end point in predefined subgroups, nor were there between-group differences in heart-failure hospitalization, cardiovascular mortality, recurrent MI, or TVR by PCI or CABG.

Once again, though, LVEF at 18 months was higher in the experimental arm than with standard care (52.7% vs 50.8%; P<0.05). LVEF >45% was also more common with ischemic postconditioning (80% vs 72%; P=0.015), Engstrøm said.

Session chair Dr Gregg Stone (Columbia University Medical Center, New York City) said the results were highly anticipated because, unlike delayed stenting, ischemic postconditioning is very simple to do in the catheter lab, but added, "We have to be a little careful when we talk about a 25% reduction in mortality when it was nowhere close to statistically significant."

When the DANAMI 3 trialists were asked in a press briefing whether the results truly spell the end for the two strategies, Kelbæk said, "In general, yes, there is no proof for ischemic postconditioning, but maybe a subset of patients might benefit in the future."

Dr David Kandzari (Piedmont Heart Institute, Atlanta, GA), who was not involved in the study, told heartwire from Medscape it would be difficult to replicate such large trials with these particular modalities in more select subgroups.

"One of the broader issues, too, is that when we think of implementing these potentially game-changing practices in acute-myocardial-infarction care, given the acuity of these patients, these get folded into treatment algorithms, and to parcel it out for patients with large anterior myocardial infarctions or specific subgroups really starts to challenge the application in clinical practice," he added.

The studies were funded by the Danish Agency for Science, Technology, and Innovation and Danish Council for Strategic Research. Kelbæk and coauthors report no relevant financial relationships. Engstrøm reports consultant fees/honoraria from St Jude and Zealand Pharma and serving as a speaker for Bayer Healthcare; the coauthors report no relevant financial relationships. Abbott reports serving on a data safety monitory board for Pfizer. Gersh reports consultant fees/honoraria from Xenon Pharmaceuticals and serving on a safety monitoring board for Armetheon, Baxter Healthcare, Cardiovascular Research Foundation, and Janssen. Stone reports consultant fees/honoraria from Ablative Solutions and Guided Delivery. Kandzari reports consultant fees/ honoraria from Boston Scientific, the Medicines Company, and Medtronic.

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