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Heparin Versus Bivalirudin in ST-Segment Elevation Myocardial Infarction: A SCAI-Based National Survey From US Interventional Cardiologists
Abstract: Background. The use of antithrombotic therapy (ATT) (bivalirudin or unfractionated heparin) is a class I recommendation for patients undergoing primary percutaneous coronary intervention (PPCI) for ST-segment elevation myocardial infarction (STEMI). This survey was conducted to better understand current United States (US) practices in terms of preferences regarding the selection of ATT in STEMI-PPCI, particularly in light of recent clinical trials. Methods. An electronic survey consisting of 9 focused questions was forwarded to 2676 US interventional cardiologists who were members of the Society for Cardiovascular Angiography and Interventions (SCAI). Results. Among 390 responders (14.5%), bivalirudin with bail-out glycoprotein IIb/IIIa inhibitor (GPI) was the predominant strategy for 53% of operators, whereas 32% preferred heparin with bail-out GPI and 15% preferred heparin with more routine GPI. The duration of bivalirudin infusion varied widely among operators, and significant variability existed in the bolus dose of heparin that was preferred by operators. About 49% of respondents stated that the choice of ATT was not affected by the bleeding risk of the patient, although access site did appear to affect the choice of ATT for some operators. Notably, 43% of operators reported to have changed their practice regarding ATT in light of recent trial results. Conclusion. There is marked variability in self-reported ATT use in STEMI-PPCI among US interventional cardiologists. Given the patient-related variability in bleeding risk and mixed clinical trial results between the two predominant ATT agents, bivalirudin and unfractionated heparin, more data are needed in order to further inform and potentially unify clinical practice in STEMI-PPCI.
J INVASIVE CARDIOL 2016;28(9):351-356
Key words: heparin, bivalirudin, STEMI, survey
The use of antithrombotic agents (ATTs) – typically either bivalirudin or unfractionated heparin – carries a class I recommendation in patients undergoing primary percutaneous coronary intervention (PPCI) for ST-segment elevation myocardial infarction (STEMI).1 The recent HEAT-PPCI, EUROMAX, BRIGHT, NAPLES-III, and MATRIX trials, as well as meta-analyses, have provided mixed results in terms of the optimal choice of ATT in STEMI patients undergoing PPCI.2-12 While the majority of trials have demonstrated bleeding reductions with a bivalirudin-based strategy compared with heparin (especially when heparin is used in conjunction with adjunctive glycoprotein IIb/IIIa inhibitor [GPI]), an increase in acute stent thrombosis has also been observed consistently with bivalirudin monotherapy in the STEMI setting, particularly when bivalirudin is stopped at the end of the PCI.5
Given the variability in the clinical trial data as well as polarized responses to these recent data that have been observed,13 we hypothesized that there would be significant variations in the choice, dosing, and other factors influencing the selection of ATT for STEMI-PPCI among United States (US) interventional cardiologists.
Methods
We constructed an electronic survey to investigate various factors that influence the choice and dose of ATTs employed in STEMI patients undergoing PPCI in current US practice. The electronic survey was sent to 2676 US interventional cardiologists who were members of the Society for Cardiovascular Angiography and Interventions (SCAI) in November 2014. Three reminders were sent at an interval of 2 weeks after the initial survey was submitted; thereafter, the survey was closed. The survey results were kept anonymous. The survey consisted of a set of 9 questions, as provided in Table 1.
Results
Of the 2676 US interventional cardiologists who were sent the survey, a total of 393 responses (14.3%) were received. A total of 49% of the respondents stated that they were private practitioners, 33% were in academic settings, and 19% were in semi-academic settings. Most respondents reported that they performed ≤50 STEMI interventions per year (41% performed 10-25 interventions annually; 40% performed 25-50 interventions annually). The choice of ATT per operator-reported STEMI interventions/year is shown in Table 2.
Regarding the ATT strategy, the majority of operators (53%) reported a preference for bivalirudin with bail-out GPI for STEMI-PPCI, 32% preferred unfractionated heparin with bail-out GPI, and the remaining 15% preferred unfractionated heparin with scheduled GPI as the regimen of choice during STEMI-PPCI (Figure 1).
There was substantial reported variability in dosing for both unfractionated heparin and bivalirudin during STEMI-PPCI. For unfractionated heparin, over one-half of the operators (58%) preferred a dose of 70 U/kg with subsequent boluses based on activated clotting time (ACT), whereas 18% preferred the dose between 70-100 U/kg with subsequent boluses based on the ACT (Figure 2). For bivalirudin, the variation was even more marked. After administration of a standard bolus dose of 0.75 mg/kg followed by 1.75 mg/kg/hr infusion, 36% of operators reported a preference to stop the bivalirudin infusion at the end of the procedure, 34% continued the infusion until the completion of the infusion bag, and 21% preferred to continue the bivalirudin infusion for 2 hours after the completion of the procedure (Figure 3).
When considering factors that could influence the choice of ATT during STEMI-PPCI, 49% of operators reported that the patient’s bleeding risk did not affect their strategy, whereas 42% of operators reported a preference for bivalirudin in patients at high bleeding risk (Figure 4). The preferred choice of anticoagulation also varied somewhat based on access site; 48% reported a preference for bivalirudin for both radial and femoral accesses, 36% favored unfractionated heparin for both radial and femoral access, and 15% preferred heparin for radial access and bivalirudin for femoral access (Figure 5).
Notably, the cost of ATT affected the choice of ATT in a minority of operators (39%) (Figure 6). In addition, recent clinical trial data appeared to have influenced 43% of respondents, who reported to have shifted their anticoagulation strategy in light of recent trial data (Figure 7).
Discussion
In this survey-based study of US interventional cardiologists, we identified significant variability in the choice and dosing of ATT in STEMI-PPCI. Specific factors influencing these choices are related to recent clinical trial data in addition to perceptions of cost, access site, and bleeding risk.
Our study has several clinical implications. With mixed data from clinical trials in regard to optimal choice of ATT during STEMI-PPCI,2-4,12 our survey provides insights into the contemporary preference as well as factors perceived while selecting ATT during STEMI-PPCI by US interventional cardiologists. In this survey, in which 80% of operators who reported performing between 10-50 STEMI-PPCIs annually, the preferential choice of ATT was bivalirudin with bail-out GPI for 53% of operators, whereas the remaining 47% preferred unfractionated heparin with or without use of GPI. Selection/reporting bias may have influenced these findings, as these reports are not entirely consistent with those from the CathPCI National Cardiovascular Database Registry (NCDR), which reported the use of unfractionated heparin in 66% of STEMI-PPCIs and bivalirudin use in 20% of cases (concomitant GPI was used in approximately 79% of patients receiving unfractionated heparin and 45% of patients receiving bivalirudin).14 Additional hypotheses regarding these differences may also relate to the timing of published reports from CathPCI, which are less contemporary than the present survey. With the results of the HORIZONS-AMI and ACUITY trials, the use of bivalirudin rose, but with the recent data from the EUROMAX and HEAT-PPCI trials, variability and ambiguity in the choice of ATT exist in contemporary practice.2,4,7,12
Another important finding of our survey involves the variability in the dosing of ATT during STEMI-PPCI. Thus far, different clinical trials have used different dosing strategies for unfractionated heparin during PCI for acute coronary syndromes, ranging from 60 U/kg in trials with scheduled GPI use, to 100 U/kg in trials with bail-out GPI use.2,4,8,12,15 The ACC/AHA guidelines do not recommend a single dosing strategy, but rather recommend the use of unfractionated heparin at a weight-adjusted dose range of 70-100 U/kg for STEMI-PPCI.1 Our survey demonstrates that over one-half of the surveyed operators stated their preference for the dose of 70 U/kg bolus of unfractionated heparin, whereas 18% preferred higher doses of 70-100 U/kg with subsequent boluses based on ACT. The variability in the dosing of unfractionated heparin can be explained by multiple factors including operator preference, access site (radial vs femoral), intracoronary thrombus burden, patient bleeding risk, as well as risk of ischemic complications with abrupt vessel closure with lower levels of anticoagulation. The ideal unfractionated heparin dosing for STEMI-PPCI that would optimally balance bleeding risks with ischemic complications in this era of newer antiplatelet therapy remains a matter of debate and requires further study. In terms of bivalirudin dosing, the variability was even greater, with 36% of operators stopping the bivalirudin infusion at the completion of the procedure, 34% continuing the infusion until the completion of the bag, and 21% continuing the infusion for 2 hours post procedure. The reasons for this variability in dosing can be partly explained by the results from multiple prior clinical trials that demonstrated increased risk of acute stent thrombosis in patients randomized to bivalirudin treatment arm for STEMI-PPCI, presumed to be due to the shorter half-life of bivalirudin as compared with unfractionated heparin.2,4,12 It is thus not unreasonable for operators to either continue the infusion for 2 hours post procedure or until the completion of the bag to reach an “antithrombotic sweet spot” where antiplatelet effects are achieved as the effect of anticoagulation is wearing off. This would theoretically prevent ischemic complications and at the same time reduce the risk of bleeding. Data from the BRIGHT and EUROMAX trials do support the value of high-dose bivalirudin in mitigating the risk of acute stent thrombosis with bivalirudin; however, in the MATRIX trial, a prolonged infusion of bivalirudin at a lower dose did not reduce the incidence of stent thrombosis in the bivalirudin arm.3,4,9,11
Access site and bleeding risk also affected the choice of ATT in our survey, despite data that demonstrate reductions in both access site as well as non-access site bleeding with bivalirudin.16 Whether a strategy of tailoring bivalirudin usage to patients at the highest risk of bleeding is effective remains to be determined. It is notable that cost considerations influenced the choice of ATT in a significant minority of respondents (39%). This suggests that a significant proportion of US operators are sensitive to differences in cost between agents, particularly when the clinical data are less definitive regarding the relative risks/benefits of that agent.
Notably, almost one-half of operators (43%) reported changing their practice regarding the ATT of choice during STEMI-PPCI. Whether these changes in practice are the “right” or “wrong” answer is unclear. The contradictory results of various trials in the recent era (HEAT-PPCI, EUROMAX, BRIGHT, MATRIX) can be attributed to different population inclusion criteria, differences in dosing strategy between heparin and bivalirudin arms, different concomitant antiplatelet regimens used, etc. Nonetheless, the change in practice in this area in particular stands in contrast to historical standards of the way clinicians traditionally react to clinical trial data.17
Study limitations. Limitations to our study include those inherent in any type of survey, including response rate, which limits the generalizability of our results. The small sample size with limited response rate also introduces potential for selection bias. Nonetheless, our study is similar to other published survey studies, with response rates of 10%-15%. In addition, although we attempted to capture operator preferences based upon generalized clinical scenarios, it is clear that individual patient variability due to the type of presentation, co-morbid conditions, and other geographic and hospital-level considerations could potentially affect the choice of ATT by individual operators, and were not captured by our survey.
Conclusion
There is marked variability in self-reported ATT use in STEMI-PPCI among US interventional cardiologists. Given the patient-related variability in bleeding risk, mixed clinical trial results, and (evolving) cost differences between the two predominant ATTs, more data are needed in order to further inform and potentially unify clinical practice in STEMI-PPCI.
References
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From the 1University of Louisville School of Medicine, Louisville, Kentucky; 2University of Texas Southwestern Medical Center, Dallas, Texas; and 3Columbia University Medical Center/New York Presbyterian Hospital, New York, New York.
Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Kirtane reports research grants to his institution from Medtronic, Boston Scientific, Vascular Dynamics, St. Jude Medical, Abiomed, Abbott Vascular, and Eli Lilly. The remaining authors report no conflicts of interest regarding the content herein.
Manuscript submitted April 29, 2016, provisional acceptance given May 3, 2016, final version accepted May 11, 2016.
Address for correspondence: Ajay J. Kirtane, MD, SM, Center for Interventional Vascular Therapy, Columbia University Medical Center/New York Presbyterian Hospital, 161 Fort Washington Ave, 6th Floor, New York, NY 10032. Email: akirtane@columbia.edu
