DANAMI-3 Studies of Ischemic Postconditioning and Deferred Stenting Presented

April 11, 2016—Findings from the DANAMI-3 DEFER and DANAMI-3 iPOST investigations were presented at ACC.16, the American College of Cardiology’s 65th Annual Scientific Session held April 2–4 in Chicago, Illinois. DANAMI-3, the Danish Study of Optimal Acute Treatment of Patients With ST-Elevation Myocardial Infarction (STEMI) 3 trial, was funded by the Danish Agency for Science, Technology and Innovation and Danish Council for Strategic Research.

The DANAMI-3-DEFER trial showed that delayed or deferred stent implantation in patients experiencing STEMI failed to reduce death from any cause, hospitalization for heart failure, subsequent heart attacks, or the need for a repeat procedure to restore blood flow to the heart. DANAMI-3 DEFER was published online ahead of print in The Lancet.

The DANAMI-3 iPOST trial found that ischemic postconditioning (iPOST) in patients who had STEMI reduced death from any cause or hospitalization for heart failure by 7% in patients who received iPOST compared with those who received standard angioplasty, but this result did not reach statistical significance. Although the primary endpoint was not met, a statistically significant 4% improvement was seen in a secondary endpoint, left ventricular ejection fraction rate, in patients whose STEMIs involved the front wall of the left ventricle.

The DANAMI-3-DEFER trial was the largest trial yet to evaluate whether delaying stent implantation would improve patients' survival and reduce their risk of heart failure or another heart attack.

In the trial, which took place in Denmark, 1,234 patients (average age, 61 years; 75% men) with acute STEMI symptoms of < 12-hours duration were randomly assigned to undergo standard angioplasty with immediate stent implantation or angioplasty followed by stent implantation after a re-examination 24 to 48 hours later. After an average follow-up time of 43 months, 105 patients (17%) in the DEFER group and 109 (18%) in the standard treatment group met the primary endpoint, a composite of death from any cause, hospitalization for heart failure, a second heart attack, and unplanned repeat angioplasty—a nonsignificant difference.

Although the trial was the largest so far to address the issue of delayed stent implantation, it may not have been large enough to detect a difference between the two treatment groups. Another limitation is that the trial did not select patients who were at the highest risk for developing another arterial blockage, such as those older than 65 years, those who have had more than one heart attack, or those known to have a large number of blood clots, noted DANAMI-3 DEFER’s Lead Investigator, Henning Kelbaek, MD, of Roskilde Hospital, University of Copenhagen, Denmark.

In the ACC announcement, Dr. Kelbaek stated, “The take-home message from this study is that deferred stent implantation cannot be recommended as a routine procedure for STEMI patients treated with primary percutaneous coronary intervention. Our results completely rebut the promising findings of preliminary studies that suggested deferred stenting should translate to clinical benefit.”

“We cannot rule out that a fraction of our patients who met these criteria might have benefited from delayed stent placement, especially because we found a small improvement in heart muscle function 18 months after treatment among patients who underwent deferred stenting,” Dr. Kelbaek said.

The study was not powered to detect this improvement, but Dr. Kelbaek advised the investigators would now look carefully for possible “hypothesis-generating” findings in subsets of patients––both those who might have benefited from the deferred-treatment strategy and, equally important, those in whom this strategy might have worsened their condition.

In the ACC press release, DANAMI-3 iPOST’s Lead Investigator, Thomas Engstrøm, MD, of Rigshospitalet University of Copenhagen in Copenhagen, Denmark, commented, “Abrupt reperfusion by angioplasty may itself damage the heart muscle. The thinking was that performing the reperfusion in a gentle, graded fashion would protect the heart against reperfusion injury.”

The DANAMI-3 iPOST trial, which took place in Denmark, included 1,234 patients (average age, 61 years; 79% men) with acute STEMI symptoms of < 12-hours duration who were randomly assigned to receive standard angioplasty or ischemic postconditioning before stent implantation in the blocked artery. The primary endpoint was a composite of death from any cause and hospitalization for heart failure. Patients were followed for a minimum of 2 years, with an average follow-up time of 39 months. Dr. Engstrøm observed, “This may translate into improved survival over more years of follow-ups.”

He added that DANAMI iPOST was the first large clinical trial designed to evaluate clinical outcomes in STEMI patients, as opposed to surrogate endpoints such as ST-segment resolution. Larger trials may be required to definitely establish whether ischemic postconditioning improves clinical outcomes. A limitation of the study is that the physicians performing the angioplasties cannot be blinded to the treatment group that patients are assigned to, noted Dr. Engstrøm in the ACC announcement.