Effect of PCI-Related Bleeding on Mortality Risk Varies by Location

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Both access and non-access site bleeding occurring in the 30 days after percutaneous coronary intervention (PCI) heighten mortality risk at 1 year, according to a paper published online July 23, 2013, ahead of print in Circulation: Cardiovascular Interventions. However, non-access site bleeding carries greater impact, imparting a nearly threefold increase in risk.

Adnan Kastrati, MD, of Deutsches Herzzentrum (Munich, Germany), and colleagues pooled patient level-results from 7 randomized trials that enrolled a total of 14,180 patients between June 2000 and May 2011. The trials were designed to evaluate the effects of bivalirudin and abciximab as well as those of different heparin doses.

Patients’ CAD presentation varied, though all underwent PCI. Access and non-access site bleeding within 30 days of PCI were retrospectively assessed using Bleeding Academic Research Consortium (BARC) criteria.

Non-Access Events More Severe and Impactful

By 30 days, bleeding events had occurred in 1,510 patients (10.6%), of whom 905 had access site bleeding (6.4% of patients, 60% of events) and 605 had non-access site bleeding (4.2% of patients, 40% of events). Of the patients experiencing non-access site events, 120 also had access site bleeding.

Non-access site bleeding tended to be more severe, with 74.4% of those events ranked as BARC class 2 or higher compared with 47.3% of access site bleeds (P < 0.001). Patients with non-access site bleeding were older and more likely to have insulin-treated diabetes, ACS, elevated troponin or serum creatinine levels, normal cholesterol levels, and higher LVEF.

Kaplan-Meier curves showed that both types of bleeding increase 1-year mortality rates, though on multivariable analysis, the association between non-access site bleeding and mortality was much stronger (table 1). In addition, the discriminatory power of a multivariable model to predict 1-year mortality was enhanced by the inclusion of non-access bleeding but not access-site bleeding.

Table 1. Relationship Between 30-Day Bleeding and Estimated 1-Year Mortality

^a Compared with no bleeding.

Among patients who had events defined as BARC class 2 or greater, the 1-year mortality rate was nearly twice as high after non-access site compared with access site bleeding (12.2% vs. 6.5%; P = 0.004).

Multivariate predictors of access site bleeding were age, sex, BMI, arterial hypertension, and platelet count. Non-access site bleeding was predicted by the same factors as well as hypercholesterolemia, ACS presentation, and LVEF.

Patients randomized to bivalirudin had lower risk of access site bleeding than those assigned to heparin, regardless of whether the anticoagulant was given with or without abciximab. But for non-access site bleeding, bivalirudin was protective only when the comparison group received both heparin and abciximab (RR 0.58, 95% CI 0.48-0.78).

Several Factors Explain Added Risk

“Only non-access site bleeding seems to offer prognostic information that is independent of and supplementary to that provided by cardiovascular risk factors and clinical characteristics,” Dr. Kastrati and colleagues conclude.

The excess mortality may partly be explained by the fact that non-access site bleeding was more severe, they write, noting the “gradual increase in mortality with the increase in severity of bleeding as defined by BARC grading system.” Moreover, they continue, the “more adverse cardiovascular risk profile” of patients experiencing non-access vs. access site bleeding suggests that such events “could either be a sign of poorer health or it may be more devastating in these patients because of their compromised health at the time of the bleed.”

But in a telephone interview, Stephen Ramee, MD, of Ochsner Medical Center (New Orleans, LA), was quick to point out that the findings should be placed in context. Most of the included trials “were funded by drug companies trying to get their drug used, so they had a little bit of prejudice. Also, these [trials] were . . . all femoral access and no closure devices used.”

Furthermore, BARC class 1 represented the largest segment of bleeds—altogether 52.7% of access site and 25.6% of non-access site events. Such events “wouldn’t even be noticed [in real-world practice] unless you were really looking for them,” he noted.

Pulmonary and Intracranial Bleeds Stand Out

Dr. Ramee stressed that the consequences of non-access site events depended on their specific location, with “very high” mortality rates associated with pericardial (18.9%), pulmonary (45.5%), and intracranial bleeding (55.5%), all of which are relatively rare. Though pericardial bleeds usually mean that the operator perforated the heart during the procedure, pulmonary and intracranial bleeds tend to be spontaneous and result from “either a lesion or reaction to one of the drugs,” he explained. “They’re not predictable and not preventable. And it looks like they’re not very treatable either.”

The tight link between periprocedural non-access site bleeding and subsequent mortality is supported by the paper’s Kaplan-Meier analyses, he added, pointing out that the curves initially rise sharply after PCI but quickly plateau over the next year.

Dr. Kastrati agreed in an e-mail communication with TCTMD that some of the impact of non-access bleeding may relate to its occurrence in critical locations that compromise acute vital functions.

In terms of trying to prevent non-access bleeds as a whole, he suggested, “a feasible strategy is to avoid using the antithrombotic/anticoagulant regimens that are proven to increase the risk of bleeding (ie, the combination of glycoprotein IIb/IIIa inhibitors with unfractionated heparin), especially in patients with increased risk for bleeding.”

And while radial access may help reduce the risk of access site events, “reduction of a prognostically more relevant form of bleeding, non-access site bleeding, requires broader use of antithrombotic drugs with bleeding-saving properties such as bivalirudin,” Dr. Kastrati concluded. “Special medical attention should be reserved to certain categories of patients with excess risk of non-access site bleeding such as older patients, women, patients with small body mass index, and those with chronic kidney disease.”

Study Details

The included studies were: ISAR-REACT, ISAR-SWEET, ISAR-SMART-2, ISAR-REACT-2, ISAR-REACT-3, ISAR-REACT 3A, and ISAR-REACT-4.

Patients who did not experience bleeding were more likely to be smokers and to have previously undergone CABG but less likely to have multivessel disease or diabetes than those who had bleeding events within 30 days of PCI.

Source:

Ndrepepa G, Neumann F-J, Richardt G, et al. Prognostic value of access and non-access sites bleeding after percutaneous coronary intervention. Circ Cardiovasc Interv. 2013;Epub ahead of print.

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