ACC: Angiomax+ReoPro reduces infarct size, but Angiomax+aspiration thrombectomy does not
CHICAGO—In patients with large anterior STEMI presenting early after symptom onset and undergoing primary PCI with bivalirudin (Angiomax, The Medicines Company) anticoagulation, infarct size at 30 days was significantly reduced by bolus intracoronary (IC) abciximab (ReoPro, Eli Lilly) delivered to the infarct lesion site but not by manual aspiration thrombectomy, according to INFUSE-AMI, a late-breaking clinical trial presented March 25 at the 61st annual American College of Cardiology’s (ACC) scientific session.
According to the study’s lead investigator Gregg W. Stone, MD, of Columbia University Medical Center and NewYork-Presbyterian Hospital in New York City, myocardial recovery after primary PCI is often suboptimal despite restoration of TIMI 3 flow, in part due to thrombus embolization which results in impaired microvascular perfusion and increased infarct size.
While the two strategies of bolus IC abciximab and manual thrombus aspiration have been proposed to reduce embolization after primary PCI, prior studies have reported conflicting results as to whether they reduce infarct size or improve clinical outcomes, in part due to enrollment of a high proportion of small infarcts and/or patients presenting late (more than four to six hours after the MI). Stone pointed out that “single center thrombectomy trials have mostly been positive, whereas multicenter trials have mostly been negative.”
INFUSE-AMI used a 2 x 2 factorial design, which isolates the impact of each intervention to maximize the chance of identifying any reduction in heart attack size. The trial, conducted at 37 sites in six countries, screened 6,318 patients and enrolled 452 patients between Nov. 28, 2009, and Dec. 2, 2011. It is a single-blind study in which the operator knew the randomization assignments.
Participants were randomly assigned to one of four arms:
In the two abciximab arms, a “weeping” balloon catheter (ClearWay RX, Atrium Medical) delivered the drug right to the site of the lesion, which “invariably has a thrombus,” said Stone. All patients who had angioplasty were administered bivalirudin.
The researchers assessed infarct size by cardiac MR (cMR) at 30 days, after edema had lowered. The study authors wrote that infarct size “strongly correlates with subsequent mortality,” in the Journal of the American Medical Association, in which the trial was simultaneously published. During his press conference presentation, Stone added, “Infarct size is considered the strongest cardiovascular indicator of future survival.”
Evaluable cMR results at 30 days were present in 181 patients and 172 patients randomized to intracoronary abciximab vs. no abciximab, respectively, and in 174 patients and 179 patients randomized to manual aspiration vs. no aspiration, respectively.
The study authors reported that patients randomized to intracoronary abciximab compared with no abciximab had a significant reduction in 30-day infarct size (median, 15.1 percent [181 patients] vs. 17.9 percent [172 patients]). Patients randomized to intracoronary abciximab also had a significant reduction in absolute infarct mass (median, 18.7 g [184 patients] vs. 24 g [175 patients]), but not abnormal wall motion score (median, 7 [188 patients] vs. 8 [184 patients]). Patients randomized to aspiration thrombectomy vs. no aspiration had no significant difference in infarct size at 30 days (median, 17 percent [174 patients] vs. 17.3 percent [179 patients]), absolute infarct mass (median, 20.3 g [178 patients] vs. 21 g [181 patients) or abnormal wall motion score (median, 7.5 [186 patients] vs. 7.5 [186 patients]).
In explaining the trial’s limitations, Stone noted INFUSE-AMI was not powered for clinical events, and “a large randomized, controlled trial is required to determine whether the magnitude of the infarct size reduction seen with IC abciximab in this trial would translate into improved clinical outcomes without excessive bleeding.” During the press conference, Stone added this “is the not the definitive study, because we need a larger outcomes-based trial, such as the ongoing TOTAL and TASTE trials.”
Study discussant ACC Past-President Ralph G. Brindis, MD, complimented Stone for his “consistent appropriate call for an outcomes trial to determine the actual results of these therapies.” He also said that this trial is focused on “the patients that we worry about the most: the high-risk patients with large anteriors.” In terms of whether or not the strategies are cost-effective, Brindis said that these strategies may hold “use value for these higher risk patients, but not for the general PCI population.”
While Stone noted that the researchers did not assess the cost considerations with any of the four arms, Trevor Carlton, president of Atrium told Cardiovascular Business that the cost of the aspiration catheter is approximately $700 to $800, and the cost of combining the catheter with abciximab is approximately $1,000. “The hospitals are only reimbursed at DRG, so they are receiving a set reimbursement amount and will have to absorb the costs,” said Carlton, who added that the costs of using abciximab will decrease when its patent expires in a few years.
On this topic, Stone said to Cardiovascular Business, “To the extent that we can prevent clinical complications, then I’m sure it will be cost-effective.” He added that they are not looking to pursue a cost-effectiveness assessment of INFUSE-AMI, but hypothesizes that TOTAL or TASTE may include a cost-effectiveness follow-up.
Atrium funded and participated in the study’s design.
According to the study’s lead investigator Gregg W. Stone, MD, of Columbia University Medical Center and NewYork-Presbyterian Hospital in New York City, myocardial recovery after primary PCI is often suboptimal despite restoration of TIMI 3 flow, in part due to thrombus embolization which results in impaired microvascular perfusion and increased infarct size.
While the two strategies of bolus IC abciximab and manual thrombus aspiration have been proposed to reduce embolization after primary PCI, prior studies have reported conflicting results as to whether they reduce infarct size or improve clinical outcomes, in part due to enrollment of a high proportion of small infarcts and/or patients presenting late (more than four to six hours after the MI). Stone pointed out that “single center thrombectomy trials have mostly been positive, whereas multicenter trials have mostly been negative.”
INFUSE-AMI used a 2 x 2 factorial design, which isolates the impact of each intervention to maximize the chance of identifying any reduction in heart attack size. The trial, conducted at 37 sites in six countries, screened 6,318 patients and enrolled 452 patients between Nov. 28, 2009, and Dec. 2, 2011. It is a single-blind study in which the operator knew the randomization assignments.
Participants were randomly assigned to one of four arms:
- Aspiration plus abciximab;
- Aspiration without abciximab;
- No aspiration plus abciximab; and
- No aspiration or abciximab (control).
In the two abciximab arms, a “weeping” balloon catheter (ClearWay RX, Atrium Medical) delivered the drug right to the site of the lesion, which “invariably has a thrombus,” said Stone. All patients who had angioplasty were administered bivalirudin.
The researchers assessed infarct size by cardiac MR (cMR) at 30 days, after edema had lowered. The study authors wrote that infarct size “strongly correlates with subsequent mortality,” in the Journal of the American Medical Association, in which the trial was simultaneously published. During his press conference presentation, Stone added, “Infarct size is considered the strongest cardiovascular indicator of future survival.”
Evaluable cMR results at 30 days were present in 181 patients and 172 patients randomized to intracoronary abciximab vs. no abciximab, respectively, and in 174 patients and 179 patients randomized to manual aspiration vs. no aspiration, respectively.
The study authors reported that patients randomized to intracoronary abciximab compared with no abciximab had a significant reduction in 30-day infarct size (median, 15.1 percent [181 patients] vs. 17.9 percent [172 patients]). Patients randomized to intracoronary abciximab also had a significant reduction in absolute infarct mass (median, 18.7 g [184 patients] vs. 24 g [175 patients]), but not abnormal wall motion score (median, 7 [188 patients] vs. 8 [184 patients]). Patients randomized to aspiration thrombectomy vs. no aspiration had no significant difference in infarct size at 30 days (median, 17 percent [174 patients] vs. 17.3 percent [179 patients]), absolute infarct mass (median, 20.3 g [178 patients] vs. 21 g [181 patients) or abnormal wall motion score (median, 7.5 [186 patients] vs. 7.5 [186 patients]).
In explaining the trial’s limitations, Stone noted INFUSE-AMI was not powered for clinical events, and “a large randomized, controlled trial is required to determine whether the magnitude of the infarct size reduction seen with IC abciximab in this trial would translate into improved clinical outcomes without excessive bleeding.” During the press conference, Stone added this “is the not the definitive study, because we need a larger outcomes-based trial, such as the ongoing TOTAL and TASTE trials.”
Study discussant ACC Past-President Ralph G. Brindis, MD, complimented Stone for his “consistent appropriate call for an outcomes trial to determine the actual results of these therapies.” He also said that this trial is focused on “the patients that we worry about the most: the high-risk patients with large anteriors.” In terms of whether or not the strategies are cost-effective, Brindis said that these strategies may hold “use value for these higher risk patients, but not for the general PCI population.”
While Stone noted that the researchers did not assess the cost considerations with any of the four arms, Trevor Carlton, president of Atrium told Cardiovascular Business that the cost of the aspiration catheter is approximately $700 to $800, and the cost of combining the catheter with abciximab is approximately $1,000. “The hospitals are only reimbursed at DRG, so they are receiving a set reimbursement amount and will have to absorb the costs,” said Carlton, who added that the costs of using abciximab will decrease when its patent expires in a few years.
On this topic, Stone said to Cardiovascular Business, “To the extent that we can prevent clinical complications, then I’m sure it will be cost-effective.” He added that they are not looking to pursue a cost-effectiveness assessment of INFUSE-AMI, but hypothesizes that TOTAL or TASTE may include a cost-effectiveness follow-up.
Atrium funded and participated in the study’s design.