Remote ischemic preconditioning does no good

Remote ischemic preconditioning failed to improve outcomes among higher-risk patients undergoing elective cardiac surgery in two separate large clinical trials reported online Oct. 5 in the New England Journal of Medicine.

Both studies clearly showed that the technique did not provide greater protection of the heart, brain, or kidneys than did a sham technique, failing to improve any of the numerous primary or secondary endpoints or to produce a benefit in any of several subgroups of patients.

Remote ischemic preconditioning involves protecting the heart and other organs against surgery-related acute ischemia/reperfusion injury by first applying brief cycles of ischemia and reperfusion to a remote organ or tissue. It is thought that this stimulus produces a blood-borne response that conveys a protective effect from the remote area to the target organs. This remote preconditioning can be accomplished noninvasively by inflating and deflating a standard blood pressure cuff on the upper arm or thigh for brief periods.

Some early studies indicated that using this technique during cardiovascular surgery improved serum cardiac and renal biomarkers, which implied protection of these organs against ischemia/reperfusion injury. But more recent prospective clinical trials have shown no such benefit. None of these studies were adequately powered to assess the effect on hard clinical endpoints, and most were single center, unblinded, and had no standardized anesthesia regimen.

RIPHeart study

To address these study limitations, the RIPHeart Study investigators performed a prospective double-blind controlled trial among 1,385 adults undergoing elective cardiovascular surgery requiring cardiopulmonary bypass at 14 university hospitals in Germany during a 3-year period. The participants had a mean EuroSCORE (European System for Cardiac Operative Risk Evaluation) of 6 or higher, indicating that most of them were at higher than average risk, and all received the same anesthetic, intravenous propofol. A total of 692 patients were randomly assigned to undergo four 5-minute cycles of upper-arm ischemia/reperfusion after being anesthetized and 693 to undergo sham ischemia/reperfusion on a dummy arm hidden by surgical drapes, said Dr. Patrick Meybohm of the department of anesthesiology, intensive care medicine, and pain therapy at University Hospital Frankfurt and his associates.

The primary endpoint – a composite of death from any cause, nonfatal MI, stroke, or acute renal failure before hospital discharge – occurred in 14.3% of the intervention group and 14.6% of the control group, a nonsignificant difference. Furthermore, no significant differences between the two study groups were seen in any of the individual components of this composite measure, or in any secondary endpoints such as duration of mechanical ventilation, ICU length of stay, hospital length of stay, troponin levels, creatinine levels, onset of atrial fibrillation, or incidence of postoperative delirium. All outcome measures remained similar between the two study groups at 30-day, 90-day, and 1-year follow-ups (N Engl J Med 2015 Oct 5. doi: 10.1056/NEJMoa1413579).

In addition, estimated event-free survival at 30 days was 85.2% with the true intervention and 85.0% with the sham intervention, another nonsignificant difference. These estimates remained similar between the two study groups at 90 days and 1 year. The findings of the primary analysis were confirmed in the “completely concordant” per-protocol analysis, Dr. Meybohm and his associates noted.

ERICCA trial

In the Effect of Remote Ischemic Preconditioning on Clinical Outcomes in Patients Undergoing CABG (ERICCA) study, investigators assessed 1,612 adults undergoing on-pump CABG (with or without valve surgery) using blood cardioplegia at 30 cardiac surgery centers in the United Kingdom during a 3-year period. These patients were randomly assigned to undergo remote ischemic preconditioning with a standard blood pressure cuff on the upper arm for four 5-minute cycles (801 participants) or a sham procedure using a deactivated blood pressure cuff (811 participants) before surgery but while anesthetized, said Dr. Derek J. Hausenloy of the Hatter Cardiovascular Institute, University College London, and his associates.

The primary endpoint – a composite of death from cardiovascular causes, nonfatal MI, coronary revascularization, or stroke within 1 year – was 26.5% with true preconditioning and 27.7% with the sham procedure, a nonsignificant difference. There were no significant differences between the two study groups in any of the individual components of this composite or according to type of anesthesia or the interval between preconditioning and surgical incision.

These findings remained strongly consistent across all subgroups of patients evaluated, regardless of troponin levels, inotrope score, presence or absence of kidney injury, degree of kidney injury, length of ICU stay, length of hospital stay, or performance on 6-minute walk test, Dr. Hausenloy and his associates said (N Engl J Med. 2015 Oct 5. doi: 10.1056/NEJMoa1413534).

In both trials, the rate of adverse effects from remote ischemic preconditioning was the same between the true and the sham procedures, and the only adverse effect considered to be related to preconditioning was an increased incidence of skin petechiae (4.4% vs. 0.2%) in the ERICCA study.

The investigators’ financial disclosures are available at NEJM.org.

Remote ischemic preconditioning failed to improve outcomes among higher-risk patients undergoing elective cardiac surgery in two separate large clinical trials reported online Oct. 5 in the New England Journal of Medicine.

Both studies clearly showed that the technique did not provide greater protection of the heart, brain, or kidneys than did a sham technique, failing to improve any of the numerous primary or secondary endpoints or to produce a benefit in any of several subgroups of patients.

Remote ischemic preconditioning involves protecting the heart and other organs against surgery-related acute ischemia/reperfusion injury by first applying brief cycles of ischemia and reperfusion to a remote organ or tissue. It is thought that this stimulus produces a blood-borne response that conveys a protective effect from the remote area to the target organs. This remote preconditioning can be accomplished noninvasively by inflating and deflating a standard blood pressure cuff on the upper arm or thigh for brief periods.

Some early studies indicated that using this technique during cardiovascular surgery improved serum cardiac and renal biomarkers, which implied protection of these organs against ischemia/reperfusion injury. But more recent prospective clinical trials have shown no such benefit. None of these studies were adequately powered to assess the effect on hard clinical endpoints, and most were single center, unblinded, and had no standardized anesthesia regimen.

RIPHeart study

To address these study limitations, the RIPHeart Study investigators performed a prospective double-blind controlled trial among 1,385 adults undergoing elective cardiovascular surgery requiring cardiopulmonary bypass at 14 university hospitals in Germany during a 3-year period. The participants had a mean EuroSCORE (European System for Cardiac Operative Risk Evaluation) of 6 or higher, indicating that most of them were at higher than average risk, and all received the same anesthetic, intravenous propofol. A total of 692 patients were randomly assigned to undergo four 5-minute cycles of upper-arm ischemia/reperfusion after being anesthetized and 693 to undergo sham ischemia/reperfusion on a dummy arm hidden by surgical drapes, said Dr. Patrick Meybohm of the department of anesthesiology, intensive care medicine, and pain therapy at University Hospital Frankfurt and his associates.

The primary endpoint – a composite of death from any cause, nonfatal MI, stroke, or acute renal failure before hospital discharge – occurred in 14.3% of the intervention group and 14.6% of the control group, a nonsignificant difference. Furthermore, no significant differences between the two study groups were seen in any of the individual components of this composite measure, or in any secondary endpoints such as duration of mechanical ventilation, ICU length of stay, hospital length of stay, troponin levels, creatinine levels, onset of atrial fibrillation, or incidence of postoperative delirium. All outcome measures remained similar between the two study groups at 30-day, 90-day, and 1-year follow-ups (N Engl J Med 2015 Oct 5. doi: 10.1056/NEJMoa1413579).

In addition, estimated event-free survival at 30 days was 85.2% with the true intervention and 85.0% with the sham intervention, another nonsignificant difference. These estimates remained similar between the two study groups at 90 days and 1 year. The findings of the primary analysis were confirmed in the “completely concordant” per-protocol analysis, Dr. Meybohm and his associates noted.

ERICCA trial

In the Effect of Remote Ischemic Preconditioning on Clinical Outcomes in Patients Undergoing CABG (ERICCA) study, investigators assessed 1,612 adults undergoing on-pump CABG (with or without valve surgery) using blood cardioplegia at 30 cardiac surgery centers in the United Kingdom during a 3-year period. These patients were randomly assigned to undergo remote ischemic preconditioning with a standard blood pressure cuff on the upper arm for four 5-minute cycles (801 participants) or a sham procedure using a deactivated blood pressure cuff (811 participants) before surgery but while anesthetized, said Dr. Derek J. Hausenloy of the Hatter Cardiovascular Institute, University College London, and his associates.

The primary endpoint – a composite of death from cardiovascular causes, nonfatal MI, coronary revascularization, or stroke within 1 year – was 26.5% with true preconditioning and 27.7% with the sham procedure, a nonsignificant difference. There were no significant differences between the two study groups in any of the individual components of this composite or according to type of anesthesia or the interval between preconditioning and surgical incision.

These findings remained strongly consistent across all subgroups of patients evaluated, regardless of troponin levels, inotrope score, presence or absence of kidney injury, degree of kidney injury, length of ICU stay, length of hospital stay, or performance on 6-minute walk test, Dr. Hausenloy and his associates said (N Engl J Med. 2015 Oct 5. doi: 10.1056/NEJMoa1413534).

In both trials, the rate of adverse effects from remote ischemic preconditioning was the same between the true and the sham procedures, and the only adverse effect considered to be related to preconditioning was an increased incidence of skin petechiae (4.4% vs. 0.2%) in the ERICCA study.

The investigators’ financial disclosures are available at NEJM.org.

Remote ischemic preconditioning failed to improve outcomes among higher-risk patients undergoing elective cardiac surgery in two separate large clinical trials reported online Oct. 5 in the New England Journal of Medicine.

Both studies clearly showed that the technique did not provide greater protection of the heart, brain, or kidneys than did a sham technique, failing to improve any of the numerous primary or secondary endpoints or to produce a benefit in any of several subgroups of patients.

Remote ischemic preconditioning involves protecting the heart and other organs against surgery-related acute ischemia/reperfusion injury by first applying brief cycles of ischemia and reperfusion to a remote organ or tissue. It is thought that this stimulus produces a blood-borne response that conveys a protective effect from the remote area to the target organs. This remote preconditioning can be accomplished noninvasively by inflating and deflating a standard blood pressure cuff on the upper arm or thigh for brief periods.

Some early studies indicated that using this technique during cardiovascular surgery improved serum cardiac and renal biomarkers, which implied protection of these organs against ischemia/reperfusion injury. But more recent prospective clinical trials have shown no such benefit. None of these studies were adequately powered to assess the effect on hard clinical endpoints, and most were single center, unblinded, and had no standardized anesthesia regimen.

RIPHeart study

To address these study limitations, the RIPHeart Study investigators performed a prospective double-blind controlled trial among 1,385 adults undergoing elective cardiovascular surgery requiring cardiopulmonary bypass at 14 university hospitals in Germany during a 3-year period. The participants had a mean EuroSCORE (European System for Cardiac Operative Risk Evaluation) of 6 or higher, indicating that most of them were at higher than average risk, and all received the same anesthetic, intravenous propofol. A total of 692 patients were randomly assigned to undergo four 5-minute cycles of upper-arm ischemia/reperfusion after being anesthetized and 693 to undergo sham ischemia/reperfusion on a dummy arm hidden by surgical drapes, said Dr. Patrick Meybohm of the department of anesthesiology, intensive care medicine, and pain therapy at University Hospital Frankfurt and his associates.

The primary endpoint – a composite of death from any cause, nonfatal MI, stroke, or acute renal failure before hospital discharge – occurred in 14.3% of the intervention group and 14.6% of the control group, a nonsignificant difference. Furthermore, no significant differences between the two study groups were seen in any of the individual components of this composite measure, or in any secondary endpoints such as duration of mechanical ventilation, ICU length of stay, hospital length of stay, troponin levels, creatinine levels, onset of atrial fibrillation, or incidence of postoperative delirium. All outcome measures remained similar between the two study groups at 30-day, 90-day, and 1-year follow-ups (N Engl J Med 2015 Oct 5. doi: 10.1056/NEJMoa1413579).

In addition, estimated event-free survival at 30 days was 85.2% with the true intervention and 85.0% with the sham intervention, another nonsignificant difference. These estimates remained similar between the two study groups at 90 days and 1 year. The findings of the primary analysis were confirmed in the “completely concordant” per-protocol analysis, Dr. Meybohm and his associates noted.

ERICCA trial

In the Effect of Remote Ischemic Preconditioning on Clinical Outcomes in Patients Undergoing CABG (ERICCA) study, investigators assessed 1,612 adults undergoing on-pump CABG (with or without valve surgery) using blood cardioplegia at 30 cardiac surgery centers in the United Kingdom during a 3-year period. These patients were randomly assigned to undergo remote ischemic preconditioning with a standard blood pressure cuff on the upper arm for four 5-minute cycles (801 participants) or a sham procedure using a deactivated blood pressure cuff (811 participants) before surgery but while anesthetized, said Dr. Derek J. Hausenloy of the Hatter Cardiovascular Institute, University College London, and his associates.

The primary endpoint – a composite of death from cardiovascular causes, nonfatal MI, coronary revascularization, or stroke within 1 year – was 26.5% with true preconditioning and 27.7% with the sham procedure, a nonsignificant difference. There were no significant differences between the two study groups in any of the individual components of this composite or according to type of anesthesia or the interval between preconditioning and surgical incision.

These findings remained strongly consistent across all subgroups of patients evaluated, regardless of troponin levels, inotrope score, presence or absence of kidney injury, degree of kidney injury, length of ICU stay, length of hospital stay, or performance on 6-minute walk test, Dr. Hausenloy and his associates said (N Engl J Med. 2015 Oct 5. doi: 10.1056/NEJMoa1413534).

In both trials, the rate of adverse effects from remote ischemic preconditioning was the same between the true and the sham procedures, and the only adverse effect considered to be related to preconditioning was an increased incidence of skin petechiae (4.4% vs. 0.2%) in the ERICCA study.

The investigators’ financial disclosures are available at NEJM.org.