From SCAI 2012: Fast-PCI Moves Up the Clock

Las Vegas—Each year in the United States, approximately 400,000 people suffer a STEMI with an approximate in-hospital mortality of 8%. Although STEMI guidelines recommend PCI as the preferred strategy, it is not always feasible. 

One alternative approach, “facilitated PCI” using full-dose fibrinolytics, has not been useful and, indeed, appeared to have increased risk. Smalling and colleagues at the University of Texas Medical School have shown that pre-hospital reduced dose fibrinolytic administration followed by urgent PCI reduced mortality and the combined endpoint of death, reinfarction, and stroke among STEMI patients, without increasing the risk of stroke or bleeding, compared to primary PCI alone.1 Fibrinolysis before hospital admission also increased the initial infarct-related artery patency and decreased the likelihood of shock at presentation.

Two studies presented at SCAI from the UT Medical team revisited this strategy of FAST-PCI.

In-Hospital Outcomes

One study compared in-hospital outcomes of 253 STEMI patients treated with a single 10 unit dose of reteplase prior to urgent PCI between 2003 and 2009. The primary PCI group consisted of 124 STEMI patients treated with primary PCI alone between 2009 and 2011 following an interruption in the national reteplase supply. 

According to Prakash Balan, MD, JD, as a result of the shortage, they have two groups representative of the center’s standard STEMI population. Thus, while not randomized, he said they are roughly comparable groups and using that population set they’ve been able to compare fast PCI to primary PCI.

There was no significant difference between the two groups in rates of reinfarction and—importantly—no significant difference in the rates for stroke and GUSTO major bleeding, which were increased in earlier studies of facilitated PCI (see Table). In-hospital mortality was considerably lower with FAST PCI (2.77% vs. 10.48%; p = 0.0017).  Patients receiving pre-hospital reduced-dose fibrinolytic also were less likely to arrive at the hospital with Killip class IV shock (2.5% vs. 20.96%; p < 0.0001) and much less likely to have TIMI 0 flow in the infarct-related artery at the start of PCI (20.11% vs. 56.56%; p < 0.0001).

 

FAST-PCI
  n = 253

Primary PCI
n = 124

p Value

Mortality

2.77%

10.48%

0.0017

Stroke

0.79%

3.22%

0.094

Bleeding (GUSTO Major)

1.98%

0%

0.176

Reinfarction

0.39%

1.61%

0.253

Killip class IV shock at arrival

2.5%

20.96%

0.0001

TIMI 0 flow of the IRA at time of PCI

20.11%

56.56%

0.0001

Table.   

 

Effect on Infarct Size

Total ischemic time (IT), scar size, transmural infarcts, and microvascular obstruction are all strong prognostic factors of adverse events. The second study involved 262 patients with STEMI who were treated with either FAST-PCI (n = 174) or primary PCI (n = 88). The study group all underwent delayed hyperenhancement cardiac magnetic resonance imaging on day 3-5 to measure scar and microvascular obstruction volumes.

Total ischemic times (defined as symptom onset to TIMI 2-3 flow) were recorded and correlated with infarct size measurements. Patients were divided into groups according to ischemic time (<120, 120-239, >240 min).

The FAST-PCI strategy for STEMI reduced infarct size by 34% if total IT was <120 min (p = 0.04) compared to primary PCI, and the patients who received reduced-dose fibrinolytic were five times less likely to have TIMI 0 flow on initial angiogram (14% vs. 70%; p = 0.0001).

Congruent Data

Median door-to-balloon (D2B) times for patients undergoing PCI following an acute MI have declined 30% in the last few years. The percent of patients with D2B times <90 minutes increased from 44.2% to 91.4% from 2005 to 2010, as did the percent of patients with D2B times <75 minutes (23.3% to 70.4%).

Manuel M. Reyes, MD, first author of the infarct size study told CSWN, &ldquo;We&rsquo;ve done really well and we&rsquo;ve decreased [D2B] pretty significantly, but we&rsquo;ve started to realize that&rsquo;s not the entire picture. When we focus on that alone we exclude the pre-hospital period, which is crucial to the total ischemic time.&rdquo;
In their study, FAST-PCI had its best benefit if the total ischemic time was less than 120 minutes. After 120 minutes, the difference &ldquo;is a wash.&rdquo; Said Dr. Reyes, &ldquo;It doesn&rsquo;t necessarily matter what we throw at it (after 120 minutes); the result will be larger infarcts which we&rsquo;ve been measuring by MRI.&rdquo;

How do the results square with the 2008 FINESSE trial? Patients with STEMI were randomized to abciximab with half-dose reteplase (n = 828), abciximab alone (n = 818), or placebo (n = 806). There was no difference in the frequency of death or complications of MI by 90 days when comparing the three approaches. However, both facilitated PCI strategies were associated with an increased risk of bleeding.

&ldquo;If you go back to the original data of FINESSE,&rdquo; Dr. Reyes explained, &ldquo;all these big thrombolytic trials, you notice that their average ischemic time actually extended beyond 120 minutes so it made sense. These data do not conflict. They actually are congruent. The total ischemic time was larger in that data and it makes sense that when we have ischemic times that are less, we do provide that extra benefit so in our data, our population, we said that fast PCI, when it is performed with ischemic times of less than 120 minutes, does provide a benefit. After that, the benefit is not so much.&rdquo;

Added Dr. Balan: &ldquo;We&rsquo;ve been using a single fixed dose of reteplase, 10 units administered upon recognition of STEMI and, as quickly as possible, get the patient to the cath lab before emerging PCI. The idea here is to use the fibrinolytic to get the flow down the artery that reduces the ultimate infarct size, which is what Manny has shown with his MRI study, [but] just restoring flow is not by itself enough. There is a ruptured plaque there that has to be treated and we get that treated as quickly as possible with PCI.&rdquo;

Richard W. Smalling, MD, PhD, oversaw these and earlier studies. He wrote a commentary for JACC on the critical importance of ischemic time in the management of STEMI patients.3 To watch an interview with his colleagues Drs. Balan and Reyes, visit youtube.cswnews.org.

References
  1. Denktas AE, Athar H, Henry TD, et al. JACC Cardiovasc Interv. 2008;1:504-10.
  2. Ellis SG, Tendera M, de Belder MA, et al. N Engl J Med. 2008;358:2205-17.
  3. Smalling RW. J Am Coll Cardiol. 2009;54:2154-6.

 

Clinical Topics: Clinical Topic Collection: Dyslipidemia, Noninvasive Imaging, Lipid Metabolism, Magnetic Resonance Imaging

Keywords: Thrombolytic Therapy, Stroke, Hospital Mortality, Cicatrix, Fibrinolysis, Immunoglobulin Fab Fragments, Tissue Plasminogen Activator, Toluidines, Magnetic Resonance Imaging, United States


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