STEMI Patients Benefit From Clopidogrel Given Prior to PCI Center

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In patients with ST-segment elevation myocardial infarction (STEMI), administering clopidogrel prior to their arrival at the facility where they will receive percutaneous coronary intervention (PCI) can reduce in-hospital mortality. The results from a multicenter Austrian registry were published online September 14, 2011, ahead of print in the European Heart Journal.

Franz Weidinger, MD, of Hospital Rudolfstiftung (Vienna, Austria), and colleagues prospectively enrolled 5,955 patients who underwent primary PCI for STEMI between 2005 and 2009. Among them, 27.5% received clopidogrel before arrival at the PCI center (in the ambulance or at the referral hospital) and the remaining 72.5% were given the drug at the PCI center (just before cath lab arrival, at the cath lab, or shortly after PCI). Because of the study’s observational design, many baseline patient and procedure characteristics varied between the pretreatment and peri-interventional groups.

Univariate analysis found pretreated patients had better in-hospital outcomes for mortality, reinfarction, and stroke. Major bleeding and elective use of repeat revascularization, however, were equivalent between the 2 groups (table 1).

Table 1. In-Hospital Outcomes by Clopidogrel Use

Adverse outcomes progressively increased the later patients received clopidogrel. The highest risk occurred in those given the drug either at the cath lab or after PCI, with mortality, reinfarction, and stroke rates of 10.2%, 2.1%, and 2.4%, respectively.

Multiple logistic regression analysis that accounted for possible cofounders also demonstrated a link between pretreatment and in-hospital mortality (OR 0.60; 95% CI 0.35-0.99; P = 0.048). This relationship was particularly strong in patients who also received glycoprotein IIb/IIIa inhibitors (GPIs) in the cath lab (OR 0.40; 95% CI 0.29-0.83; P = 0.01) but was not seen in those not given GPIs (OR 0.88; 95% CI 0.39-1.95; P = 0.75).

“Sufficient platelet inhibition is achieved 1 to 2 hours after a loading dose of 600-mg clopidogrel. Thus, clopidogrel pretreatment before arrival at the PCI center may lead to better primary PCI results,” Dr. Weidinger and colleagues note. The current findings are in line with American College of Cardiology/American Heart Association and European Society of Cardiology guidelines that advocate an “as soon as possible” approach to clopidogrel use in STEMI patients, they add.

Reiterating the Gold Standard

In a telephone interview, Shamir R. Mehta, MD, of McMaster University (Hamilton, Canada), told TCTMD that the most valuable message to come from the paper is that it confirms common practices and guideline-recommended care.

Clopidogrel pretreatment is fairly standard right now, he observed, though there are variations in how this is achieved. “In some places in North America, they’re giving it in the ambulance, but largely it’s at the referral hospital or in the emergency room prior to transfer to the cath lab,” he said, adding that in-ambulance clopidogrel is routine in Europe.

According to Dr. Mehta, very little stands in the way of early clopidogrel. “We’ve known pretreatment works in acute coronary syndromes for about 10 years now, so it’s really been widely adopted,” he noted, adding that previous studies have mainly shown reductions in reinfarction. “It’s the standard of care, essentially, in patients with STEMI.”

Sunil V. Rao, MD, of Duke University Medical Center (Durham, NC), however, described practices as more varied. “This is a European study. We know that the systems of care are different. The fundamental goal—to get that artery open—is still the same, but how that happens is not only different between Europe and North America but also within Europe,” he told TCTMD in a telephone interview. In the United States, most patients receive clopidogrel before they arrive at the cath lab, Dr. Rao confirmed, but many may not be given the drug prior to the PCI center.

The message of the study is universal, Dr. Rao stressed: “[E]arly implementation of evidence-based therapy is important for outcomes.”

Still, Dr. Rao also emphasized that late clopidogrel is better than none at all. “This is an important clinical question that PCI centers ask. They say, ‘In our system of care, we’re not able to give clopidogrel early for whatever reason. . . . Is it such a terrible thing that I give it on the table?’” he reported. “I can’t tell you [how bad it is] to give it afterward, but I can tell you that not giving it at all is a terrible thing.”

Both Drs. Mehta and Rao agreed that the study was well conducted, but they highlighted the limitation of its observational design. Given the possibility of confounders, Dr. Mehta was not convinced that the real mortality benefit was as high as observed, while Dr. Rao noted, “In-hospital mortality is relatively low these days, so some of the difference may be driven by the fact that sicker patients just simply didn’t get clopidogrel until later.”

One red flag pointed out by Dr. Rao is that every enrolled patient received clopidogrel; however, this is not always the case in actual practice. “It’s unclear how representative the registry is,” he said. It also would be informative to know whether the patients who did not ultimately undergo PCI in the study (12.5% had CABG or conservative treatment) experienced any delays before surgery, Dr. Rao added, since in the United States there is still a reluctance to administer early clopidogrel in cases where CABG may be required.

Study Details

Pretreated patients were more likely to be men and have a history of MI or PCI. Conversely, they were less likely than those who received clopidogrel at the PCI center to present with cardiogenic shock or resuscitation. Aspirin and heparin use were more common in conjunction with clopidogrel pretreatment, while the pre-cath lab GPI use was less frequent. Rates of thrombus aspiration as well as a preference for PCI rather than CABG were slightly but significantly elevated among pretreated patients, as was postprocedural TIMI 3 flow.

 

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Source:
Dörler J, Edlinger M, Alber HF, et al. Clopidogrel pre-treatment is associated with reduced in-hospital mortality in primary percutaneous coronary intervention for acute ST-elevation myocardial infarction. Eur Heart J. 2011;Epub ahead of print.

 

 

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