Early antiarrhythmic drugs boost survival in shock-refractory cardiac arrest

CHICAGO – Paramedic-administered amiodarone or lidocaine during resuscitation of patients with shock-refractory ventricular fibrillation or ventricular tachycardia of out-of-hospital cardiac arrest significantly improves survival, according to the findings of the largest-ever clinical trial of out-of-hospital cardiac arrest.

However, the survival advantage was limited to bystander-witnessed arrest. The reason for this difference in the Amiodarone, Lidocaine or Placebo Study (ALPS) is that observed arrest is a good surrogate for earlier recognition and treatment of an out-of-hospital cardiac arrest (OHCA), Dr. Peter J. Kudenchuk explained in presenting the study findings at the annual meeting of the American College of Cardiology.

“The message from this trial is that, if you give these drugs to everyone across the board with out-of-hospital shock-refractory VF/VT cardiac arrest, you’ll help those who can be helped and you won’t hurt those who are beyond help,” said Dr. Kudenchuk, professor of medicine at the University of Washington, Seattle.

ALPS was a randomized, blinded, placebo-controlled clinical trial of 3,026 patients with shock-refractory VF/VT OHCA at 10 U.S. and Canadian sites participating in the Resuscitation Outcomes Consortium. Subjects were randomized to paramedic-administered treatment with prefilled syringes of amiodarone, lidocaine, or placebo. Time to treatment averaged 19 minutes from the initial call made to emergency services.

The primary endpoint in ALPS was survival to hospital discharge. Rates were 24.4% in the amiodarone group, 23.7% with lidocaine, and 21% with placebo. Differences in survival rates between the antiarrhythmic drug and placebo groups approached but did not achieve statistical significance.

Survival to hospital discharge in the 1,934 participants with bystander-witnessed arrest was a prespecified secondary endpoint. That outcome was achieved in 27.7% of the amiodarone group and 27.8% who got lidocaine, compared with 22.7% of placebo-treated patients. Those differences were statistically significant and clinically meaningful, Dr. Kudenchuk asserted.

“Though these differences – an absolute 5% improvement over placebo – may seem small, were we to implement this as policy, upwards of 1,800 more lives could potentially be saved each year in the United States alone,” said Dr. Kudenchuk, an electrophysiologist and cardiologist.

Bystander-witnessed OHCA was 2.3-fold more common than unwitnessed arrest. In the unwitnessed arrest subgroup there was no hint of benefit for either amiodarone or lidocaine.

“Many patients with unwitnessed arrest have already sustained mortal ischemic damage by the time they’re found,” he observed. “If you go into a morgue and give the best drug in the world, you’re not going to save anybody.”

Moreover, among the roughly 5% of patients whose OHCA was witnessed by EMS personnel, survival to hospital discharge was a whopping absolute 22% greater with antiarrhythmic drug therapy than with placebo.

“Taken together, these findings suggest that treatment sooner after heart collapse may be a critical determinant of drug effect,” Dr. Kudenchuk continued.

He said the ALPS findings are generalizable to all communities across North America where the local EMS system follows the Resuscitation Outcomes Consortium philosophy that early defibrillation and good CPR are the cornerstones of effective management of OHCA, without which no treatment can be effective.

Current use of these drugs across the United States is not standardized. “It is really a free-for-all,” according to Dr. Kudenchuk. “Some agencies strictly use lidocaine, others may use amiodarone. Some use both. And some use neither. I think in part that’s because current guideline recommendations give these drugs a class IIb recommendation – meaning they’re optional – because up until this point there have been no data to support their effectiveness in changing outcome.”

In his view, the ALPS data clearly warrant upgrading the strength of the recommendation for antiarrhythmic drug therapy in the next iteration of the guidelines. Although he is on the guideline committee, Dr. Kudenchuk added, he cannot predict what the committee as a whole will decide.

ALPS will not lead to a change in practice such that paramedic-administered antiarrhythmic agents are given only to patients with witnessed arrest, Dr. Kudenchuk said. It’s not practical for rescue personnel in the midst of the fray to try to figure out whether an OHCA was witnessed or not. Plus, there’s an ethical issue involved.

“If we’d wanted to hit the headlines with a major trial with a positive outcome we would have selected only people with witnessed cardiac arrest from the get-go to do this trial, since we guessed that’s where the money was going to be. The reality is you can’t treat people that way. Everyone has to have a chance,” he said.

Asked which antiarrhythmic drug the next edition of the resuscitation guidelines should recommend preferentially, he said ALPS wasn’t powered to distinguish between amiodarone and lidocaine. “If I were writing the guidelines, I would simply say either or both happens to be okay.”

An important footnote is that ALPS utilized a new, Food and Drug Administration–approved formulation of amiodarone, known as Nexterone, designed to reduce hypotensive effects. Had investigators employed the more familiar version of the drug, the safety results wouldn’t have been as good.

Out-of-hospital cardiac arrest accounts for roughly 350,000 deaths per year in the United States

Simultaneously with Dr. Kudenchuk’s presentation of the ALPS findings at ACC 16 in Chicago, the results were published online (N Engl J Med. 2016 Apr 4; doi: 10.1056/NEJMoa1514204).

He reported having no financial conflicts regarding the ALPS study, which was funded by the National Heart, Lung, and Blood Institute, the Canadian Institutes of Health Research, the American Heart Association, the U.S. Army, and Defense Research and Development Canada.

[email protected]

CHICAGO – Paramedic-administered amiodarone or lidocaine during resuscitation of patients with shock-refractory ventricular fibrillation or ventricular tachycardia of out-of-hospital cardiac arrest significantly improves survival, according to the findings of the largest-ever clinical trial of out-of-hospital cardiac arrest.

However, the survival advantage was limited to bystander-witnessed arrest. The reason for this difference in the Amiodarone, Lidocaine or Placebo Study (ALPS) is that observed arrest is a good surrogate for earlier recognition and treatment of an out-of-hospital cardiac arrest (OHCA), Dr. Peter J. Kudenchuk explained in presenting the study findings at the annual meeting of the American College of Cardiology.

“The message from this trial is that, if you give these drugs to everyone across the board with out-of-hospital shock-refractory VF/VT cardiac arrest, you’ll help those who can be helped and you won’t hurt those who are beyond help,” said Dr. Kudenchuk, professor of medicine at the University of Washington, Seattle.

ALPS was a randomized, blinded, placebo-controlled clinical trial of 3,026 patients with shock-refractory VF/VT OHCA at 10 U.S. and Canadian sites participating in the Resuscitation Outcomes Consortium. Subjects were randomized to paramedic-administered treatment with prefilled syringes of amiodarone, lidocaine, or placebo. Time to treatment averaged 19 minutes from the initial call made to emergency services.

The primary endpoint in ALPS was survival to hospital discharge. Rates were 24.4% in the amiodarone group, 23.7% with lidocaine, and 21% with placebo. Differences in survival rates between the antiarrhythmic drug and placebo groups approached but did not achieve statistical significance.

Survival to hospital discharge in the 1,934 participants with bystander-witnessed arrest was a prespecified secondary endpoint. That outcome was achieved in 27.7% of the amiodarone group and 27.8% who got lidocaine, compared with 22.7% of placebo-treated patients. Those differences were statistically significant and clinically meaningful, Dr. Kudenchuk asserted.

“Though these differences – an absolute 5% improvement over placebo – may seem small, were we to implement this as policy, upwards of 1,800 more lives could potentially be saved each year in the United States alone,” said Dr. Kudenchuk, an electrophysiologist and cardiologist.

Bystander-witnessed OHCA was 2.3-fold more common than unwitnessed arrest. In the unwitnessed arrest subgroup there was no hint of benefit for either amiodarone or lidocaine.

“Many patients with unwitnessed arrest have already sustained mortal ischemic damage by the time they’re found,” he observed. “If you go into a morgue and give the best drug in the world, you’re not going to save anybody.”

Moreover, among the roughly 5% of patients whose OHCA was witnessed by EMS personnel, survival to hospital discharge was a whopping absolute 22% greater with antiarrhythmic drug therapy than with placebo.

“Taken together, these findings suggest that treatment sooner after heart collapse may be a critical determinant of drug effect,” Dr. Kudenchuk continued.

He said the ALPS findings are generalizable to all communities across North America where the local EMS system follows the Resuscitation Outcomes Consortium philosophy that early defibrillation and good CPR are the cornerstones of effective management of OHCA, without which no treatment can be effective.

Current use of these drugs across the United States is not standardized. “It is really a free-for-all,” according to Dr. Kudenchuk. “Some agencies strictly use lidocaine, others may use amiodarone. Some use both. And some use neither. I think in part that’s because current guideline recommendations give these drugs a class IIb recommendation – meaning they’re optional – because up until this point there have been no data to support their effectiveness in changing outcome.”

In his view, the ALPS data clearly warrant upgrading the strength of the recommendation for antiarrhythmic drug therapy in the next iteration of the guidelines. Although he is on the guideline committee, Dr. Kudenchuk added, he cannot predict what the committee as a whole will decide.

ALPS will not lead to a change in practice such that paramedic-administered antiarrhythmic agents are given only to patients with witnessed arrest, Dr. Kudenchuk said. It’s not practical for rescue personnel in the midst of the fray to try to figure out whether an OHCA was witnessed or not. Plus, there’s an ethical issue involved.

“If we’d wanted to hit the headlines with a major trial with a positive outcome we would have selected only people with witnessed cardiac arrest from the get-go to do this trial, since we guessed that’s where the money was going to be. The reality is you can’t treat people that way. Everyone has to have a chance,” he said.

Asked which antiarrhythmic drug the next edition of the resuscitation guidelines should recommend preferentially, he said ALPS wasn’t powered to distinguish between amiodarone and lidocaine. “If I were writing the guidelines, I would simply say either or both happens to be okay.”

An important footnote is that ALPS utilized a new, Food and Drug Administration–approved formulation of amiodarone, known as Nexterone, designed to reduce hypotensive effects. Had investigators employed the more familiar version of the drug, the safety results wouldn’t have been as good.

Out-of-hospital cardiac arrest accounts for roughly 350,000 deaths per year in the United States

Simultaneously with Dr. Kudenchuk’s presentation of the ALPS findings at ACC 16 in Chicago, the results were published online (N Engl J Med. 2016 Apr 4; doi: 10.1056/NEJMoa1514204).

He reported having no financial conflicts regarding the ALPS study, which was funded by the National Heart, Lung, and Blood Institute, the Canadian Institutes of Health Research, the American Heart Association, the U.S. Army, and Defense Research and Development Canada.

[email protected]

CHICAGO – Paramedic-administered amiodarone or lidocaine during resuscitation of patients with shock-refractory ventricular fibrillation or ventricular tachycardia of out-of-hospital cardiac arrest significantly improves survival, according to the findings of the largest-ever clinical trial of out-of-hospital cardiac arrest.

However, the survival advantage was limited to bystander-witnessed arrest. The reason for this difference in the Amiodarone, Lidocaine or Placebo Study (ALPS) is that observed arrest is a good surrogate for earlier recognition and treatment of an out-of-hospital cardiac arrest (OHCA), Dr. Peter J. Kudenchuk explained in presenting the study findings at the annual meeting of the American College of Cardiology.

“The message from this trial is that, if you give these drugs to everyone across the board with out-of-hospital shock-refractory VF/VT cardiac arrest, you’ll help those who can be helped and you won’t hurt those who are beyond help,” said Dr. Kudenchuk, professor of medicine at the University of Washington, Seattle.

ALPS was a randomized, blinded, placebo-controlled clinical trial of 3,026 patients with shock-refractory VF/VT OHCA at 10 U.S. and Canadian sites participating in the Resuscitation Outcomes Consortium. Subjects were randomized to paramedic-administered treatment with prefilled syringes of amiodarone, lidocaine, or placebo. Time to treatment averaged 19 minutes from the initial call made to emergency services.

The primary endpoint in ALPS was survival to hospital discharge. Rates were 24.4% in the amiodarone group, 23.7% with lidocaine, and 21% with placebo. Differences in survival rates between the antiarrhythmic drug and placebo groups approached but did not achieve statistical significance.

Survival to hospital discharge in the 1,934 participants with bystander-witnessed arrest was a prespecified secondary endpoint. That outcome was achieved in 27.7% of the amiodarone group and 27.8% who got lidocaine, compared with 22.7% of placebo-treated patients. Those differences were statistically significant and clinically meaningful, Dr. Kudenchuk asserted.

“Though these differences – an absolute 5% improvement over placebo – may seem small, were we to implement this as policy, upwards of 1,800 more lives could potentially be saved each year in the United States alone,” said Dr. Kudenchuk, an electrophysiologist and cardiologist.

Bystander-witnessed OHCA was 2.3-fold more common than unwitnessed arrest. In the unwitnessed arrest subgroup there was no hint of benefit for either amiodarone or lidocaine.

“Many patients with unwitnessed arrest have already sustained mortal ischemic damage by the time they’re found,” he observed. “If you go into a morgue and give the best drug in the world, you’re not going to save anybody.”

Moreover, among the roughly 5% of patients whose OHCA was witnessed by EMS personnel, survival to hospital discharge was a whopping absolute 22% greater with antiarrhythmic drug therapy than with placebo.

“Taken together, these findings suggest that treatment sooner after heart collapse may be a critical determinant of drug effect,” Dr. Kudenchuk continued.

He said the ALPS findings are generalizable to all communities across North America where the local EMS system follows the Resuscitation Outcomes Consortium philosophy that early defibrillation and good CPR are the cornerstones of effective management of OHCA, without which no treatment can be effective.

Current use of these drugs across the United States is not standardized. “It is really a free-for-all,” according to Dr. Kudenchuk. “Some agencies strictly use lidocaine, others may use amiodarone. Some use both. And some use neither. I think in part that’s because current guideline recommendations give these drugs a class IIb recommendation – meaning they’re optional – because up until this point there have been no data to support their effectiveness in changing outcome.”

In his view, the ALPS data clearly warrant upgrading the strength of the recommendation for antiarrhythmic drug therapy in the next iteration of the guidelines. Although he is on the guideline committee, Dr. Kudenchuk added, he cannot predict what the committee as a whole will decide.

ALPS will not lead to a change in practice such that paramedic-administered antiarrhythmic agents are given only to patients with witnessed arrest, Dr. Kudenchuk said. It’s not practical for rescue personnel in the midst of the fray to try to figure out whether an OHCA was witnessed or not. Plus, there’s an ethical issue involved.

“If we’d wanted to hit the headlines with a major trial with a positive outcome we would have selected only people with witnessed cardiac arrest from the get-go to do this trial, since we guessed that’s where the money was going to be. The reality is you can’t treat people that way. Everyone has to have a chance,” he said.

Asked which antiarrhythmic drug the next edition of the resuscitation guidelines should recommend preferentially, he said ALPS wasn’t powered to distinguish between amiodarone and lidocaine. “If I were writing the guidelines, I would simply say either or both happens to be okay.”

An important footnote is that ALPS utilized a new, Food and Drug Administration–approved formulation of amiodarone, known as Nexterone, designed to reduce hypotensive effects. Had investigators employed the more familiar version of the drug, the safety results wouldn’t have been as good.

Out-of-hospital cardiac arrest accounts for roughly 350,000 deaths per year in the United States

Simultaneously with Dr. Kudenchuk’s presentation of the ALPS findings at ACC 16 in Chicago, the results were published online (N Engl J Med. 2016 Apr 4; doi: 10.1056/NEJMoa1514204).

He reported having no financial conflicts regarding the ALPS study, which was funded by the National Heart, Lung, and Blood Institute, the Canadian Institutes of Health Research, the American Heart Association, the U.S. Army, and Defense Research and Development Canada.

[email protected]