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CHICAGO -- Data from the DANAMI 3 investigation suggest that neither delayed stent implantation nor ischemic postconditioning improves outcomes for patients with ST-elevation myocardial infarction (STEMI).

Deferred stenting had been hypothesized to time to prevent distal embolization by allowing more time to dissolve a thrombus, yet the combined odds of death, heart failure, new heart attack, and retreatment in the same artery were no better in a group of patients experiencing a 48-hour delay after initial coronary reperfusion before stenting than those stented with conventional timing (hazard ratio 0.99, 95% CI 0.75-1.29).

There was no difference between groups for procedure-related myocardial infarction, bleeding, contrast-induced nephropathy, or stroke, though left ventricular ejection fractions (LVEFs) at 18 months were slightly greater in the deferred stent cohort (60% versus 57% for conventional timing, P=0.04).

Importantly, however, unplanned target vessel revascularization was more common in deferred stenting patients (HR 1.7, 95% CI 1.04-2.92), according to Henning Kelbaek, MD, DMSci, of Denmark's Roskilde Hospital, who presented the results of DANAMI 3-DEFER at the American College of Cardiology (ACC) 2016 Scientific Sessions. The study was simultaneously published online in The Lancet.

"We can now say definitively that a routine strategy of deferred stent implantation in all-comers STEMI is not beneficial," said panelist , of Rhode Island Hospital in Providence.

She noted that early trials that showed early TIMI flow with a deferred stenting strategy "were using quite old stainless-steel, thicker strut stents," which is why "we may not see that as much with thinner strut stents, improved deployment, and better sizing. Technical expertise and device technology are taking away a little of the limitations of stenting," she said.

DANAMI 3-DEFER included 1,207 patients followed over a median period of 42 months.

Ischemic Postconditioning Fails Too

Also of no benefit for STEMI patients was ischemic postconditioning, according to the separate DANAMI 3-iPOST trial.

Patients who received ischemic postconditioning to reduce reperfusion injury after PCI had greater LVEFs (52.7% versus 50.8% who went without, P<0.05). This group was also somewhat more likely to exhibit a LVEF greater than 45% (80% versus 72%, P=0.015) over follow-up.

However, Thomas Engstrøm, MD, DMSci, PhD, of The Heart Center in Denmark, and colleagues found that ischemic postconditioning was -- as seen in prior studies -- not associated with reduced rates of:

• All-cause mortality (6.2% versus 8.1%, HR 0.75, 95% CI 0.49-1.14)
• Heart failure hospitalization (4.9% versus 4.9%, HR 0.99, 95% CI 0.60-1.64)
• Cardiovascular mortality (4.2% versus 4.9%, HR 0.86, 95% CI 0.51-1.45)
• Recurrent MI (5.4% versus 4.7%, HR 1.13, 95% CI 0.68-1.86)

Indeed, 1 year of event-free survival was equally likely between patients who received postconditioning and their counterparts that didn't (10.5% versus 11.2%, HR 0.93, 95% CI 0.66-1.30).

"Ischemic postconditioning during primary angioplasty in STEMI patients failed to reduce the rate of the primary composite endpoint of all-cause mortality and hospitalization for heart failure," the authors included.

"This is a definitively neutral study," said , of Mayo Clinic in Rochester, Minn., as "it does put the nail on the coffin for ischemic postconditioning," no matter how good it looks in animal studies.

Calling reperfusion injury "the last frontier" in treatment of acute ischemic events, he said, "I don't know any area where there are so many positive animal studies but no clinical trials that reach their clinical endpoints."

Speaking during the panel following Engstrøm's presentation, Gersh conceded, however, that "remote ischemic postconditioning may stil have a role" in clinical therapy.

DANAMI 3-iPOST included 1,243 patients, randomized to PCI with or without ischemic postconditioning, with a median follow-up of 37.5 months.

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