DANAMI3: Deferred Stenting, Ischemic Postconditioning No Help in STEMI
The results are seen as relatively definitive, although deeper looks at angiographic and electrocardiographic data are planned.
CHICAGO, IL—Physicians who treat patients with STEMI do not need to introduce routine deferred stenting or ischemic postconditioning, as both failed to improve outcomes in randomized trials conducted as part of the DANAMI3 program.
Although both DANAMI3-DEFER and DANAMI3-iPOST showed slight improvements in LV function with the interventions, clinical outcomes overall were unaffected, according to presentations made here at the American College of Cardiology 2016 Scientific Sessions.
The trials should not be considered negative, however, said Henning Kelbæk, MD (Roskilde Hospital, Roskilde, Denmark), who presented the DANAMI3-DEFER results. That’s because they demonstrate “that the way we treat patients today is optimal, or near optimal, and it’s very hard to show any difference in treatment modalities,” he said during a press conference.
He added that the investigators will be analyzing angiographic and electrocardiographic data to see whether there are any subgroups of patients who may benefit from deferred stenting or ischemic postconditioning.
Distal embolization and slow/no-flow can occur during primary PCI, and both are associated with poorer clinical outcomes, Kelbæk said during his presentation. Prior, mostly nonrandomized studies have suggested that deferring stent implantation for several hours or days may have benefits, and DANAMI3-DEFER was designed to study that approach.
The trial, which was conducted at four primary PCI centers in Denmark, included 1,215 patients with STEMI, symptoms lasting no more than 12 hours, and ST-segment elevation of 0.1 mV or more in at least two contiguous electrocardiographic leads. They were randomized to conventional PCI with immediate stent implantation or PCI with deferred stenting.
In the latter group, operators used minimal manipulation to restore stable flow in the infarct-related artery and then reassessed the need for stenting about 48 hours after the index procedure. Ultimately, 14% of patients in that group did not receive a stent compared with only 1% of patients in the conventional group.
The results, which were published simultaneously online in the Lancet, showed that deferred stenting did not reduce the rate of the primary composite outcome of all-cause mortality, hospital admission for heart failure, recurrent MI, or any unplanned revascularization of the infarct-related artery through a median follow-up of 42 months (17% vs 18%; HR 0.99; 95% CI 0.76-1.29). Of the individual components of the endpoint, only unplanned revascularization differed between study arms, with a higher rate in the deferred stenting group (7% vs 4%; HR 1.70; 95% CI 1.04-2.92).
Among patients in whom echocardiography was performed a median of 18 months after the index procedure, LVEF was slightly higher in deferred stenting group (median 60% vs 57%; P = 0.04). “Whether this will translate into improved outcomes in years to come, I cannot tell you right now,” Kelbæk said during the press conference.
Commenting during the press conference, David Kandzari, MD (Piedmont Heart Institute, Atlanta, GA), said the increases in LV function “are relatively clinically modest . . . and likely will have no significant [clinical] impact when we consider that the ejection fraction in both groups was relatively maintained and high.”
It remains to be seen whether there are mechanistic data regarding myocardial perfusion to support use of deferred stenting, Kandzari said, adding, however, that it is unlikely the trial “will have any major impact on clinical practice.”
J. Dawn Abbott, MD (Brown University, Providence, RI), said during a panel discussion following Kelbæk’s presentation that “we can now say definitively that a routine strategy of deferring stent implantation in an all-comers STEMI population is not beneficial.”
Thomas Engstrøm, MD, PhD (Rigshospitalet University Hospital, Copenhagen, Denmark) presented results of DANAM3-iPOST, in which ischemic postconditioning was performed by using four 30-second occlusions with a balloon to try to ease reperfusion injury to the myocardium.
The trial randomized 1,234 patients with STEMI, a symptom duration of 12 hours or less, and TIMI 0-1 flow in the infarct-related artery to conventional PCI or ischemic postconditioning.
The primary endpoint was a composite of all-cause mortality or hospitalization for heart failure. Ischemic postconditioning did not result in a lower rate of that endpoint through a median follow-up of 37.5 months (10.5% vs 11.2%; HR 0.93; 95% CI 0.66-1.30), a finding that was consistent across subgroups. The approach also had no impact on either of the individual components of the composite outcome or any other clinical outcomes.
Ischemic postconditioning did result in a slightly higher LVEF (52.7% vs 50.8%; P < 0.05) and percentage of patients with LVEF > 45% (80% vs 72%; P = 0.015).
During a panel discussion following Engstrøm’s presentation, Bernard Gersh, MBChB, DPhil (Mayo Clinic, Rochester, MN), called reperfusion injury “the last frontier” of reperfusion therapy. He pointed out that the results of many positive animal studies have not been translated into successful human studies.
Referring to DANAMI3-iPOST, Gersh said “this is, unfortunately, a very good definitively neutral study and probably does put the nail in the coffin of ischemic postconditioning.”
Engstrøm noted that event rates are very low in patients with STEMI in the modern era and that it might be possible to find a role for ischemic postconditioning by selecting patients prone to large reperfusion injuries. “Of course I’m not too optimistic today,” he said.
Kelbæk H, Høfsten DE, Køber L, et al. Deferred versus conventional stent implantation in patients with ST-segment elevation myocardial infarction (DANAMI 3-DEFER): an open-label randomised controlled trial. Lancet. 2016;Epub ahead of print.
Engstrøm T. DANAMI3-iPOST: the Third Danish Study of Optimal Acute Treatment of Patients with ST-segment Elevation Myocardial Infarction: Ischemic Postconditioning During Primary PCI. Presented at: American College Cardiology 2016 Scientific Sessions. April 3, 2016. Chicago, IL.
- The trials were funded by the Danish Agency for Science, Technology, and Innovation and the Danish Council for Strategic Research.
- Kelbæk and Engstrøm report no relevant conflicts of interest.