STREAM Substudy: Lytic Failure Means Worse Outcomes for Pharmacoinvasively Treated STEMI Patients

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Among patients with ST-segment elevation myocardial infarction (STEMI) treated with a pharmacoinvasive strategy, those who have successful fibrinolysis have better short-term outcomes than patients who require rescue percutaneous coronary intervention (PCI), according to a substudy of the STREAM trial published online July 10, 2014, ahead of print in the American Journal of Cardiology.

Methods
In the main STREAM trial, 1,892 STEMI patients who presented early after symptom onset, but were unable to undergo primary PCI within 1 hour, were randomized to primary PCI or fibrinolysis prior to transport to a PCI-capable hospital. Angiography was performed 6 to 24 hours after randomization except for those in whom lysis failed and who instead underwent urgent angiography.
The results, which were presented at the American College of Cardiology Scientific Sessions/i2 Summit in March 2013 and published simultaneously online in the New England Journal of Medicine, showed that the fibrinolysis group had a 30-day rate of combined death, cardiogenic shock, CHF, or reinfarction similar to patients who received primary PCI.
For the prespecified subanalysis, investigators led by Paul W. Armstrong, MD, of the University of Alberta (Edmonton, Canada), compared the characteristics and outcomes of patients with failed (n = 348)  vs successful lysis (n = 516).

 

Overall, rescue patients had angiography within a median of 140 minutes after randomization, while successfully reperfused patients underwent scheduled angiography about a median of 18 hours after administration of fibrinolysis.

Patient Traits Linked to Lytic Failure

Among fibrinolytic-treated patients, 2 baseline characteristics increased the odds of needing rescue PCI:

  • MI location (anterior vs inferior; OR 1.44; 95% CI 1.09-1.90; P = .038)
  • Increased body weight (OR 1.06; 95% CI 1.02-1.11; P = .009) 

Rates of postprocedural TIMI-3 flow were lower in patients who underwent either rescue or primary PCI than in those who had scheduled angiography. Interestingly, almost one-fifth of the latter group (18.6%) were managed with medical therapy alone, compared with 11.5% of rescue patients and 7.3% of those randomized to primary PCI. 

On baseline ECG, rescue patients had greater ST-elevation in their worst lead (P < .001), a greater sum of ST-segment deviation (P = .004), as well as a trend toward more Q-waves (P = .088) than did their counterparts undergoing scheduled angiography. Additionally, the more favorable ECG profile of the scheduled group was enhanced after angiography/PCI.

In adjusted 30-day clinical outcomes, rescue patients showed an almost 3-fold increase in the risk of the primary composite endpoint (all-cause death, cardiogenic shock, CHF, and reinfarction) compared with those undergoing scheduled angiography. They also had higher risk for the individual endpoints except reinfarction, which was similar between the groups (table 1).

Table 1. Risk of Clinical Outcomes for Rescue vs Scheduled Angiography

 

Adjusted RR (95% CI)

P Value

Death, Cardiogenic Shock, CHF, Reinfarction

2.92 (1.92-4.45)

< .001

Death

2.17 (1.07-4.41)

.033

Shock

3.32 (1.65-6.67)

.001

CHF

4.56 (2.38-8.71)

< .001

Reinfarction

1.00 (0.32-3.16)

.994

 

In addition, there was excess major nonintracranial bleeding in the rescue group compared with scheduled angiography group (9.5% vs 5.1%; P < .012). 

A subset of 32 patients with successful reperfusion nonetheless required urgent angiography a median of 3.5 hours after randomization due to evidence of ischemia. At 30 days, this group experienced no deaths, but their rate of the composite endpoint was 35.5%, driven largely by reinfarction (29.0%). 

In comparison, among primary PCI patients the incidence of the 30-day primary composite endpoint was 13.9%. One-year adjusted mortality rates were 5.5% for rescue patients, 6.9% for scheduled angiography patients, and 5.2% for primary PCI patients.

For each treatment group, patients with a worst lead residual ST elevation of at least 2 mm had the worst outcomes. 

In a telephone interview with TCTMD, Sorin J. Brener, MD, of Weill Cornell Medical College (New York, NY), applauded the authors for filling a 10-year gap in data on rescue PCI. The results, however, only reinforce earlier findings that rescue PCI provides marginal benefit, which is why it carries a Class II indication in the STEMI guidelines, he noted. “Once you fail fibrinolysis, there aren’t many good options,” he added. 

‘Successful Lysis’ a Misnomer?

Dr. Brener further suggested that calling lysis ‘successful’ is misleading.  In addition to the small percentage of reperfused patients who subsequently needed rescue PCI,  about one-quarter of the ‘successful lysis’ group had less than TIMI 3 flow in the infarct-related vessel, he explained, and many of those with TIMI 3 flow likely did not achieve microvascular perfusion. Thus, fibrinolysis is clearly a “suboptimal strategy” and should be used only as a stopgap until patients can be transported to a PCI-capable hospital, as the guidelines recommend, he asserted. 

The somewhat lower 30-day mortality in the successful fibrinolysis group vs the primary PCI group might suggest that the pharmacoinvasive strategy is acceptable, Dr. Brener said. But the fact that by 1 year there was no mortality difference “tells us that whatever appeared to be good about fibrinolysis probably doesn’t last,” he commented.

The paper’s analysis notwithstanding, it is difficult to predict accurately which patients are likely to fail fibrinolysis, Dr. Brener argued. Nonetheless, he said, after giving lytics, clinicians should at least advise the referred PCI facility that the patient has an anterior MI (or is overweight or had Q waves on his initial ECG) and so is less likely to be reperfused. 

Overall, it is difficult to know what to take away from the study except that the pharmacoinvasive strategy “has winners and losers,” said Timothy D. Henry, MD, of the Minneapolis Heart Institute Foundation (Minneapolis, MN). 

One important and controversial question, he told TCTMD in a telephone interview, is the timing of planned angiography following administration of lytics. An earlier trip to the cath lab might have improved outcomes for some of the 40% of patients who failed lysis, he suggested.

 


Source: Welsh RC, Van de Werf F, Westerhout CM, et al. Outcomes of a pharmacoinvasive strategy for successful versus failed fibrinolysis and primary percutaneous intervention in acute myocardial infarction (from the Strategic Reperfusion Early After Myocardial Infarction [STREAM] study). Am J Cardiol. 2014;Epub ahead of print.

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STREAM Substudy: Lytic Failure Means Worse Outcomes for Pharmacoinvasively Treated STEMI Patients

Disclosures
  • The STREAM trial was supported by Boehringer Ingelheim.
  • Dr. Armstrong makes no statement regarding conflicts of interest.
  • Drs. Brener and Henry report no relevant conflicts of interest.

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