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Contraindicated Medications Increase Risk of PCI in Dialysis Patients
Abstract & Commentary
By Andrew J. Boyle, MBBS, PhD Assistant Professor of Medicine, Interventional Cardiology, University of California, San Francisco Dr. Boyle reports no financial relationships relevant to this field of study.
Source: Tsai TT, et al. Contraindicated medication use in dialysis patients undergoing percutaneous coronary intervention. JAMA. 2009;302(22):2458-2464
Anticoagulation during percutaneous coronary intervention (PCI), although necessary to prevent thrombus formation on the interventional equipment, can lead to significant morbidity from bleeding complications, particularly if the dosage is excessive. Several antithrombins are approved for use, including unfractionated heparin, enoxaparin, bivalirudin, and fondaparinux. In addition to antithrombins, glycoprotein IIb/IIIa inhibitors, such as eptifibatide, abciximab, or tirofiban, are often used during PCI. Due to their renal clearance, enoxaparin and eptifibatide are contraindicated in patients with end-stage renal failure on hemodialysis. Tsai et al utilized the National Cardiovascular Data Registry (NCDR) to examine the use of these agents in dialysis patients undergoing PCI. Between January 2004 and August 2008, data from over 1.3 million PCI procedures in 829 hospitals were entered into the NCDR database; among these, 24,656 (1.8%) were performed on patients receiving hemodialysis. After excluding patients who were taking warfarin or had received fibrinolytics, as well as those who received infrequently used antithrombotics such as tirofiban, argatroban, lepirudin, dalteparin, or nadroparin, 22,778 patients were included in the analysis.
Results: Of these 22,778 dialysis patients undergoing PCI, 5,084 (22.3%) received a contraindicated antithrombotic medication. Enoxaparin was used in 2,375 (47%), eptifibatide was used in 3,261 (64%) and both were used in 552 cases (11%); their use was associated with higher in-hospital bleeding and mortality. Tsai et al performed multivariable analysis to account for factors associated with increased risk of in-hospital mortality (including cardiogenic shock, age, salvage, urgent, or emergent PCI, pre-procedure intra-aortic balloon pump insertion, decreased left ventricular ejection fraction, presentation with acute MI, diabetes, chronic lung disease; treatment approaches including non-stent devices; and lesion characteristics including left main and proximal left anterior descending disease) and in-hospital bleeding (age, gender, previous heart failure, peripheral vascular disease, no previous PCI, New York Heart Association/Canadian Cardiovascular Society Functional Classification class IV heart failure, myocardial infarction, and cardiogenic shock). After multivariable analysis, patients receiving contraindicated antithrombotic mediations had a 66% increased risk of major bleeding and a 24% higher in-hospital mortality. To further analyze the relationship between the use of contraindicated anti-thrombotic medication, Tsai et al performed a propensity matching, and identified 5,079 pairs. Using this model, there was a 63% increase in major bleeding, but the increase in mortality was no longer statistically significant.
Secondary endpoints were the rates of major bleeding and death with each individual agent. Major bleeding rates were higher with enoxaparin than unfractionated heparin or bivalirudin (5.0% vs. 3.9% vs. 3.0%, respectively; p < 0.001) in dialysis patients undergoing PCI. Similarly, rates of in-hospital death were also higher (6.0% vs. 5.4% vs. 3.0%, respectively; p < 0.001). The use of eptifibatide was not significantly associated with bleeding or mortality. The association between the use of contraindicated antithrombotics and bleeding and mortality appeared to be strongest in patients presenting with acute coronary syndromes. Tsai et al conclude that in a sample of dialysis patients undergoing PCI, 22.3% received a contraindicated antithrombotic medication, which was associated with a significantly increased risk of in-hospital major bleeding.
This study is disturbing for the fact that many physicians are inappropriately prescribing contraindicated medications and may, thereby, be harming their patients. Whether this staggeringly high rate of inappropriate prescribing is through lack of knowledge of the contraindications to the use of these agents or due to disregard of the medication labeling is unknown. Patients with renal failure are already at higher risk of complications from PCI. Tsai et al show us that administering inappropriate antithrombotics can further increase their peri-procedural risk of bleeding and death. Fortunately, this is an area of medicine that can be improved by education of physicians and by putting systems in place to prevent medication errors, such as electronic medication alerts.
Although this is a retrospective registry study, not a prospective study, the findings are strengthened by the large number of patients included in the analysis. This study underscores the importance of real-world registries in the medical literature. Although randomized, controlled trials are necessary in assessing new therapies, only registries like this can monitor day-to-day clinical practice for areas where improvement is needed. This study is a wake-up call for interventional cardiologists it behooves us all to know, and follow, the labeling for antithrombotic agents when treating patients on dialysis.