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DANAMI 3-iPOST: No significant benefit with ischemic postconditioning after STEMI

CHICAGO – Ischemic postconditioning in patients with ST-segment elevation myocardial infarction failed to significantly reduce death from any cause or hospitalization for heart failure in the randomized, controlled DANAMI 3-iPOST trial.

At a mean follow-up of 37.5 months, the primary composite endpoint of death from any cause and hospitalization for heart failure occurred in 69 of 617 patients with STEMI who received standard angioplasty and in 65 of 617 patients who received ischemic postconditioning in DANAMI 3-iPOST (the Third Danish Study of Optimal Acute Treatment of Patients With ST-Segment Elevation Myocardial Infarction: iPOST conditioning during primary PCI). The 7% difference (hazard ratio, 0.93) was not statistically significant, Dr. Thomas Engstrøm reported at the annual meeting of the American College of Cardiology.

Dr. Thomas Engstrom
Sharon Worcester/Frontline Medical News
Dr. Thomas Engstrom

For the individual component of all-cause mortality, the reduction in the ischemic postconditioning group was 25%, occurring in 50 patients, compared with 38 in the conventionally treated group (hazard ratio, 0.75), but this difference also did not reach statistical significance, Dr. Engstrøm said.

Thirty patients in each group required hospitalization for heart failure.

However, an improvement in a secondary endpoint of left ventricular ejection fraction above 45% in patients with anterior infarcts was statistically significant, occurring in 72% of patients in the standard angioplasty group and 80% of those in the ischemic postconditioning group, said Dr. Engstrøm of Rigshospitalet University of Copenhagen.

This finding may translate into improved survival with longer follow-up, he noted.

Patients in the DANAMI-3 iPOST trial, who had a mean age of age 61 years, had acute STEMI (ST-segment elevation MI) symptoms of less than 12 hours’ duration at the time of randomization. They were followed for at least 2 years.

Ischemic postconditioning – a variation on angioplasty that involves using 30-second bursts of blood flow interspersed with 30-second pauses to restore blood flow to the heart – was shown in earlier studies to improve ST-segment resolution, reduce damage to heart muscle, and – in some patients – limit the extent of reperfusion injury.

Whether these factors would reduce hospitalizations or improve patient survival remained unclear, Dr. Engstrøm said.

Abrupt reperfusion by angioplasty may itself damage the heart muscle. In fact, up to 35% of patients may experience such injury during angioplasty.

“The thinking was that performing the reperfusion in a gentle, graded fashion would protect the heart against reperfusion injury,” Dr. Engstrøm explained.

The findings of DANAMI 3-iPOST – the first large clinical trial designed to evaluate clinical outcomes in STEMI patients (as opposed to surrogate endpoints such as ST-segment resolution) were disappointing, but larger trials may be required to definitively establish whether ischemic postconditioning improves clinical outcomes, Dr. Engstrøm said.

The DANAMI 3-iPOST trial was funded by the Danish Agency for Science, Technology, and Innovation and the Danish Council for Strategic Research. Dr. Engstrøm reported having no relevant financial disclosures.

sworcester@frontlinemedcom.com

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CHICAGO – Ischemic postconditioning in patients with ST-segment elevation myocardial infarction failed to significantly reduce death from any cause or hospitalization for heart failure in the randomized, controlled DANAMI 3-iPOST trial.

At a mean follow-up of 37.5 months, the primary composite endpoint of death from any cause and hospitalization for heart failure occurred in 69 of 617 patients with STEMI who received standard angioplasty and in 65 of 617 patients who received ischemic postconditioning in DANAMI 3-iPOST (the Third Danish Study of Optimal Acute Treatment of Patients With ST-Segment Elevation Myocardial Infarction: iPOST conditioning during primary PCI). The 7% difference (hazard ratio, 0.93) was not statistically significant, Dr. Thomas Engstrøm reported at the annual meeting of the American College of Cardiology.

Dr. Thomas Engstrom
Sharon Worcester/Frontline Medical News
Dr. Thomas Engstrom

For the individual component of all-cause mortality, the reduction in the ischemic postconditioning group was 25%, occurring in 50 patients, compared with 38 in the conventionally treated group (hazard ratio, 0.75), but this difference also did not reach statistical significance, Dr. Engstrøm said.

Thirty patients in each group required hospitalization for heart failure.

However, an improvement in a secondary endpoint of left ventricular ejection fraction above 45% in patients with anterior infarcts was statistically significant, occurring in 72% of patients in the standard angioplasty group and 80% of those in the ischemic postconditioning group, said Dr. Engstrøm of Rigshospitalet University of Copenhagen.

This finding may translate into improved survival with longer follow-up, he noted.

Patients in the DANAMI-3 iPOST trial, who had a mean age of age 61 years, had acute STEMI (ST-segment elevation MI) symptoms of less than 12 hours’ duration at the time of randomization. They were followed for at least 2 years.

Ischemic postconditioning – a variation on angioplasty that involves using 30-second bursts of blood flow interspersed with 30-second pauses to restore blood flow to the heart – was shown in earlier studies to improve ST-segment resolution, reduce damage to heart muscle, and – in some patients – limit the extent of reperfusion injury.

Whether these factors would reduce hospitalizations or improve patient survival remained unclear, Dr. Engstrøm said.

Abrupt reperfusion by angioplasty may itself damage the heart muscle. In fact, up to 35% of patients may experience such injury during angioplasty.

“The thinking was that performing the reperfusion in a gentle, graded fashion would protect the heart against reperfusion injury,” Dr. Engstrøm explained.

The findings of DANAMI 3-iPOST – the first large clinical trial designed to evaluate clinical outcomes in STEMI patients (as opposed to surrogate endpoints such as ST-segment resolution) were disappointing, but larger trials may be required to definitively establish whether ischemic postconditioning improves clinical outcomes, Dr. Engstrøm said.

The DANAMI 3-iPOST trial was funded by the Danish Agency for Science, Technology, and Innovation and the Danish Council for Strategic Research. Dr. Engstrøm reported having no relevant financial disclosures.

sworcester@frontlinemedcom.com

CHICAGO – Ischemic postconditioning in patients with ST-segment elevation myocardial infarction failed to significantly reduce death from any cause or hospitalization for heart failure in the randomized, controlled DANAMI 3-iPOST trial.

At a mean follow-up of 37.5 months, the primary composite endpoint of death from any cause and hospitalization for heart failure occurred in 69 of 617 patients with STEMI who received standard angioplasty and in 65 of 617 patients who received ischemic postconditioning in DANAMI 3-iPOST (the Third Danish Study of Optimal Acute Treatment of Patients With ST-Segment Elevation Myocardial Infarction: iPOST conditioning during primary PCI). The 7% difference (hazard ratio, 0.93) was not statistically significant, Dr. Thomas Engstrøm reported at the annual meeting of the American College of Cardiology.

Dr. Thomas Engstrom
Sharon Worcester/Frontline Medical News
Dr. Thomas Engstrom

For the individual component of all-cause mortality, the reduction in the ischemic postconditioning group was 25%, occurring in 50 patients, compared with 38 in the conventionally treated group (hazard ratio, 0.75), but this difference also did not reach statistical significance, Dr. Engstrøm said.

Thirty patients in each group required hospitalization for heart failure.

However, an improvement in a secondary endpoint of left ventricular ejection fraction above 45% in patients with anterior infarcts was statistically significant, occurring in 72% of patients in the standard angioplasty group and 80% of those in the ischemic postconditioning group, said Dr. Engstrøm of Rigshospitalet University of Copenhagen.

This finding may translate into improved survival with longer follow-up, he noted.

Patients in the DANAMI-3 iPOST trial, who had a mean age of age 61 years, had acute STEMI (ST-segment elevation MI) symptoms of less than 12 hours’ duration at the time of randomization. They were followed for at least 2 years.

Ischemic postconditioning – a variation on angioplasty that involves using 30-second bursts of blood flow interspersed with 30-second pauses to restore blood flow to the heart – was shown in earlier studies to improve ST-segment resolution, reduce damage to heart muscle, and – in some patients – limit the extent of reperfusion injury.

Whether these factors would reduce hospitalizations or improve patient survival remained unclear, Dr. Engstrøm said.

Abrupt reperfusion by angioplasty may itself damage the heart muscle. In fact, up to 35% of patients may experience such injury during angioplasty.

“The thinking was that performing the reperfusion in a gentle, graded fashion would protect the heart against reperfusion injury,” Dr. Engstrøm explained.

The findings of DANAMI 3-iPOST – the first large clinical trial designed to evaluate clinical outcomes in STEMI patients (as opposed to surrogate endpoints such as ST-segment resolution) were disappointing, but larger trials may be required to definitively establish whether ischemic postconditioning improves clinical outcomes, Dr. Engstrøm said.

The DANAMI 3-iPOST trial was funded by the Danish Agency for Science, Technology, and Innovation and the Danish Council for Strategic Research. Dr. Engstrøm reported having no relevant financial disclosures.

sworcester@frontlinemedcom.com

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Key clinical point: Ischemic postconditioning in patients with STEMI failed to significantly reduce death from any cause or hospitalization for heart failure in the randomized, controlled DANAMI 3-iPOST trial.

Major finding: No significant difference was seen in the primary composite endpoint of death from any cause and hospitalization for heart failure in standard angioplasty and ischemic postconditioning patients (HR, 0.93).

Data source: A randomized, controlled, open-label study of 1,234 patients from the DANAMI 3-iPOST trial.

Disclosures: The DANAMI 3-iPOST trial was funded by the Danish Agency for Science, Technology, and Innovation and the Danish Council for Strategic Research. Dr. Engstrøm reported having no relevant financial disclosures.