Dialysis Patients Undergoing PCI Often Get Wrong Antithrombotics

A new study found that more than one-fifth of dialysis patients received a contraindicated antithrombotic medication when they underwent percutaneous coronary intervention (PCI), raising their risk of adverse outcomes….

“The results of this study illustrate the problem of medication errors in the U.S., as well as the need to make patient safety a priority on the healthcare agenda,” the investigators wrote.

According to Thomas T. Tsai, MD, of the Denver VA Medical Center, CO, patients who received the antiplatelet agent eptifibatide or the anticoagulant enoxaparin, which are renally cleared and therefore not recommended for dialysis patients, had higher unadjusted rates of in-hospital bleeding (5.6% versus 2.9%, OR 1.93, 95% CI 1.66 to 2.23) than patients who received recommended antithrombotics.

Patients who were given these drugs also had higher rates of all-cause in hospital death (6.5% versus 3.9%, OR 1.68, 95% CI 1.46 to 1.95), the investigators reported.

It has been unclear to what extent clinicians follow FDA recommendations against use of renally cleared medications in dialysis patients, so Tsai and colleagues analyzed data from the National Cardiovascular Data CathPCI registry, which collects information on patients and outcomes for PCI procedures from more than 800 hospital sites.

They found that among 22,778 dialysis patients who underwent PCI between January 2004 and August 2008, 5,084 patients (22.3%) received a contraindicated antithrombotic.

A total of 2,375 (46.7%) were given enoxaparin, 3,261 (64.1%) received eptifibatide, and 552 (10.9%) were given both.

The gastrointestinal tract was the most common site of bleeding in patients given a contraindicated antithrombotic, while the percutaneous entry site was the most common site of bleeding in those who did not receive a contraindicated agent.

Most of the deaths (64.5%) were from cardiac causes.

In multivariable regression analysis, the significant association with a contraindicated antithrombotic remained for both major bleeding (adjusted OR 1.66, 95% CI 1.43 to 1.92) and death (adjusted OR 1.24, 95% CI 1.04 to 1.48).

A propensity analysis involving 5,079 matched pairs also found a significant association with inhospital major bleeding (OR 1.63, 95% CI 1.35 to 1.98), although not with death (OR 1.15, 95% CI 0.97 to 1.36).

Secondary analyses within antiplatelet and anticoagulant classes showed that rates of adverse outcomes were higher in patients receiving the contraindicated agents compared with those who received the approved medications, unfractionated heparin or bivalirudin:

• Bleeding, 5% versus 3.9% versus 3%, P<0.001
• Death, 6% versus 5.4% versus 3%, P<0.001

In an additional secondary analysis, when patients were stratified according to whether or not the PCI took place in the setting of acute coronary syndrome, the use of any contraindicated antithrombotic again was associated with an elevated risk of bleeding (adjusted OR 1.82, 95% CI 1.52 to 2.17) and death (adjusted OR 1.20, 95% CI 1 to 1.46).

There are several reasons why these medications continue to be used despite FDA-directed labeling, such as ease of use with enoxaparin compared with unfractionated heparin.

Enoxaparin can be given as an intravenous bolus or a subcutaneous injection, which simplifies emergency management and transfer protocols and accordingly is commonly cited in preprinted order sets for the management of acute coronary syndrome, the authors noted.

Another reason is that eptifibatide is less costly and more widely available than abciximab, a preferred alternative. Nonetheless, the data support the avoidance of enoxaparin and eptifibatide in dialysis patients undergoing PCI, according to the authors.

“Educational efforts targeting clinicians who prescribe these medications and quality improvement interventions, such as amending clinical pathway order sets to include consideration of renal function, are urgently needed,” they concluded.

The investigators noted that their findings may underestimate the true incidence of the use of contraindicated drugs, because hospitals enrolled in registries may be more committed to quality assurance than hospitals that are not enrolled.

“The study tells us that one out of every five dialysis patients undergoing PCI is being given a contraindicated antithrombotic drug,” said Issam Moussa, MD, of Weill Medical College of Cornell University, NY, and a member of the Society for Coronary Angiography and Intervention.

“The other interesting finding in this study was that interventionists in low-volume centers were more likely to give more of the contraindicated drugs, which is consistent with what we know about interventional practice in general in low-volume centers,” said Moussa, who was not involved in the study.

“Although the relationship between procedural volume and quality of care remains a topic of intense debate, this study brings this topic into focus and presents a call to action. Deficiencies in adherence to standards of practice, particularly in low-volume centers, should be addressed by continuing medical education, through national medical societies, and by setting up specific local standards that ensure our patients are getting the best possible care,” he wrote.

Tsai T, et al “Contraindicated medication use in dialysis patients undergoing percutaneous coronary intervention” JAMA 2009; 302: 2458- 64.