BMJ 2015;350:h1395 doi: 10.1136/bmj.h1395 (Published 24 March 2015)
Page 1 of 2
Editorials
EDITORIALS Minimising bleeding during percutaneous coronary intervention Identify high risk patients likely to benefit from bleeding avoidance strategies Gjin Ndrepepa senior research scientist, Adnan Kastrati professor of cardiology German Heart Centre, Technical University of Munich, Germany
In 2013 more than 92 500 percutaneous coronary intervention (PCI) procedures were performed in the United Kingdom alone.1 Bleeding events are among the most common complications; reported incidences vary between 2.2% and 14%.2 Peri-procedural bleeding has a negative effect on patients’ outcomes—as indicated by higher mortality and morbidity and diminished quality of life—and on metrics of healthcare provision such as length of stay and associated costs.3 Large registries of US patients undergoing PCI have shown that 12.1% of in-hospital mortality is attributable to post-procedural bleeding and suggest a significant association between major bleeding and in-hospital mortality across all strata of bleeding risk.4 The 2011 American Heart Association guidelines state that all patients should be evaluated for risk of bleeding before PCI (class of recommendation 1, level of evidence C).5 In a linked paper (doi:10.1136/bmj.h1302), Spertus and colleagues report findings from a prospective cohort study designed to investigate whether prospective assessment of bleeding risk has any effect on use of bleeding avoidance strategies or subsequent bleeding rates in patients undergoing PCI.6 Bleeding avoidance strategies investigated in this study include a radial approach to vascular access, use of bivalirudin—a direct thrombin inhibitor—as an anticoagulant with favourable bleeding profile, and vascular closure devices.3
Spertus and colleagues hypothesised that prospective risk stratification could improve the uptake of bleeding avoidance strategies in higher risk patients undergoing PCI and reduce overall risk of bleeding. Their study supports their hypothesis. Pre-procedural risk stratification was associated with an increase in the use of such strategies and a reduction in rates of bleeding, particularly among high risk patients. They also observed substantial variability in use of bleeding avoidance strategies across participating sites and doctors. Using bleeding avoidance strategies according to the degree of risk for peri-procedural bleeding is an example of evidence based personalised medicine with the potential to improve the efficacy and safety of PCI. Arguably, the key finding is that even a modest increase in the use of such strategies in high risk patients was associated with a significant reduction in bleeding
rates after the procedure. Given the close association between bleeding and outcome, this finding may have important clinical implications.
Although the study findings are generally robust, some caveats should be mentioned. Firstly, the study was not randomised; although the authors used several strategies and statistical tools to overcome this limitation (multiple adjustment and matching to correct for contemporary trends in the use of bleeding avoidance strategies), potentially important bias and confounders remain. Despite considerable efforts to provide information on use of bleeding avoidance strategies, the increase in use was marginal and patchy. Use of the radial artery for access was increased, but not according to risk categories for bleeding, and use of bivalirudin was increased in high risk patients only. Secondly, bleeding events were not independently adjudicated, which introduces some uncertainty about the true rates of bleeding. Thirdly, a reduction in bleeding was not associated with a reduction in in-hospital mortality. This seems counterintuitive, given the strong association between bleeding and mortality.4 7 However, bivalirudin was the most frequently used strategy, and most randomised trials of bivalirudin have failed to show a reduction in mortality despite a significant reduction in rates of bleeding.8
The variation in practice among doctors and hospitals in this study is an important finding. The true potential of routine use of bleeding avoidance strategies remains unclear. We still do not know the sources of heterogeneity in Spertus and colleagues’ study, although doctors’ personal experience, immaturity of some components of bleeding avoidance strategies, and the extra costs associated with these strategies may be relevant considerations. Despite previous research indicating that patients at the highest risk of bleeding gain the greatest benefit from transradial vascular access during PCI,9 this approach continues to be less popular in the United States than in Europe. The effectiveness of closure devices in reducing vascular complications and bleeding at the access site remains disputed,5 and bivalirudin did not reduce risk of bleeding compared with unfractionated heparin in one recent trial.10 It is too early to assess the impact
Correspondence to: G Ndrepepa, Deutsches Herzzentrum München, Lazarettstrasse 36, 80636 München, Germany [email protected] For personal use only: See rights and reprints http://www.bmj.com/permissions
Subscribe: http://www.bmj.com/subscribe
BMJ 2015;350:h1395 doi: 10.1136/bmj.h1395 (Published 24 March 2015)
Page 2 of 2
EDITORIALS
of that trial on clinical practice. Bleeding avoidance strategies may also increase hospital costs associated with PCI. Cost effectiveness may become particularly important if these strategies are widely adopted or used indiscriminately. Even so, bleeding avoidance strategies are likely to be cost effective in many healthcare settings owing to the substantial costs of peri-procedural bleeding, particularly if use is tailored to each patient’s baseline risk.3 Finally, debate continues as to whether bleeding events should be incorporated into composite endpoints used in clinical trials testing drugs or interventions in patients undergoing PCI. Sceptics argue against combining endpoints such as bleeding and ischaemia, which are influenced in opposite directions by antithrombotic drugs. Protagonists argue that combining ischaemic and bleeding events in composite endpoints captures the net clinical effects of a given drug or intervention more comprehensively. Moreover, both types of events have an important and comparable effect on mortality.
In the end, increased recognition of the clinical importance of bleeding events after PCI has been an important development. Bleeding increases patients’ suffering and places them at higher risk of death. The tailored delivery of bleeding avoidance strategies according to the bleeding risk has the potential to reduce bleeding events, prevent suffering, and improve quality of life for patients undergoing PCI. The cardiology community should strive to ensure that the individualised implementation of these strategies becomes a central component of our practice in the coming years.
Competing interests: We have read and understood the BMJ policy on declaration of interests and declare the following interests: none. Provenance: Commissioned; not externally peer reviewed. 1 2 3 4 5
6
7
8 9 10
National Institute for Cardiovascular Outcomes Research. National audit of percutaneous coronary interventions (NAPCI) 2014 annual public report. www.ucl.ac.uk/nicor/nicornews-publication/PCI_2014_report_annual. Kinnaird T, Anderson R, Hill J, Thomas M. Bleeding during percutaneous intervention: tailoring the approach to minimise risk. Heart 2009;95:15-9. Dauerman HL, Rao SV, Resnic FS, Applegate RJ. Bleeding avoidance strategies: consensus and controversy. J Am Coll Cardiol 2011;58:1-10. Chhatriwalla AK, Amin AP, Kennedy KF, House JA, Cohen DJ, Rao SV, et al. Association between bleeding events and in-hospital mortality after percutaneous coronary intervention. JAMA 2013;309:1022-9. Levine GN, Bates ER, Blankenship JC, Bailey SR, Bittl JA, Cercek B, et al. 2011 ACCF/AHA/SCAI guideline for percutaneous coronary intervention: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions. Circulation 2011;124:e574-651. Spertus JA, Decker C, Gialde E, Jones PG, McNulty EJ, Bach R, et al. Precision medicine to improve use of bleeding avoidance strategies and reduce bleeding in patients undergoing percutaneous coronary intervention: prospective cohort study before and after implementation of personalized bleeding risks. BMJ 2015;350:h1302. Ndrepepa G, Berger PB, Mehilli J, Seyfarth M, Neumann FJ, Schomig A, et al. Periprocedural bleeding and 1-year outcome after percutaneous coronary interventions: appropriateness of including bleeding as a component of a quadruple end point. J Am Coll Cardiol 2008;51:690-7. Cavender MA, Sabatine MS. Bivalirudin versus heparin in patients planned for percutaneous coronary intervention: a meta-analysis of randomised controlled trials. Lancet . 2014;384:599-606. Mamas MA, Anderson SG, Carr M, Ratib K, Buchan I, Sirker A, et al. Baseline bleeding risk and arterial access site practice in relation to procedural outcomes after percutaneous coronary intervention. J Am Coll Cardiol 2014;64:1554-64. Shahzad A, Kemp I, Mars C, Wilson K, Roome C, Cooper R, et al, for the HEAT-PPCI Trial Investigators. Unfractionated heparin versus bivalirudin in primary percutaneous coronary intervention (HEAT-PPCI): an open-label, single centre, randomised controlled trial. Lancet 2014;384:1849-58.
Cite this as: BMJ 2015;350:h1395 © BMJ Publishing Group Ltd 2015
For personal use only: See rights and reprints http://www.bmj.com/permissions
Subscribe: http://www.bmj.com/subscribe
Page 1 of 2
Editorials
EDITORIALS Minimising bleeding during percutaneous coronary intervention Identify high risk patients likely to benefit from bleeding avoidance strategies Gjin Ndrepepa senior research scientist, Adnan Kastrati professor of cardiology German Heart Centre, Technical University of Munich, Germany
In 2013 more than 92 500 percutaneous coronary intervention (PCI) procedures were performed in the United Kingdom alone.1 Bleeding events are among the most common complications; reported incidences vary between 2.2% and 14%.2 Peri-procedural bleeding has a negative effect on patients’ outcomes—as indicated by higher mortality and morbidity and diminished quality of life—and on metrics of healthcare provision such as length of stay and associated costs.3 Large registries of US patients undergoing PCI have shown that 12.1% of in-hospital mortality is attributable to post-procedural bleeding and suggest a significant association between major bleeding and in-hospital mortality across all strata of bleeding risk.4 The 2011 American Heart Association guidelines state that all patients should be evaluated for risk of bleeding before PCI (class of recommendation 1, level of evidence C).5 In a linked paper (doi:10.1136/bmj.h1302), Spertus and colleagues report findings from a prospective cohort study designed to investigate whether prospective assessment of bleeding risk has any effect on use of bleeding avoidance strategies or subsequent bleeding rates in patients undergoing PCI.6 Bleeding avoidance strategies investigated in this study include a radial approach to vascular access, use of bivalirudin—a direct thrombin inhibitor—as an anticoagulant with favourable bleeding profile, and vascular closure devices.3
Spertus and colleagues hypothesised that prospective risk stratification could improve the uptake of bleeding avoidance strategies in higher risk patients undergoing PCI and reduce overall risk of bleeding. Their study supports their hypothesis. Pre-procedural risk stratification was associated with an increase in the use of such strategies and a reduction in rates of bleeding, particularly among high risk patients. They also observed substantial variability in use of bleeding avoidance strategies across participating sites and doctors. Using bleeding avoidance strategies according to the degree of risk for peri-procedural bleeding is an example of evidence based personalised medicine with the potential to improve the efficacy and safety of PCI. Arguably, the key finding is that even a modest increase in the use of such strategies in high risk patients was associated with a significant reduction in bleeding
rates after the procedure. Given the close association between bleeding and outcome, this finding may have important clinical implications.
Although the study findings are generally robust, some caveats should be mentioned. Firstly, the study was not randomised; although the authors used several strategies and statistical tools to overcome this limitation (multiple adjustment and matching to correct for contemporary trends in the use of bleeding avoidance strategies), potentially important bias and confounders remain. Despite considerable efforts to provide information on use of bleeding avoidance strategies, the increase in use was marginal and patchy. Use of the radial artery for access was increased, but not according to risk categories for bleeding, and use of bivalirudin was increased in high risk patients only. Secondly, bleeding events were not independently adjudicated, which introduces some uncertainty about the true rates of bleeding. Thirdly, a reduction in bleeding was not associated with a reduction in in-hospital mortality. This seems counterintuitive, given the strong association between bleeding and mortality.4 7 However, bivalirudin was the most frequently used strategy, and most randomised trials of bivalirudin have failed to show a reduction in mortality despite a significant reduction in rates of bleeding.8
The variation in practice among doctors and hospitals in this study is an important finding. The true potential of routine use of bleeding avoidance strategies remains unclear. We still do not know the sources of heterogeneity in Spertus and colleagues’ study, although doctors’ personal experience, immaturity of some components of bleeding avoidance strategies, and the extra costs associated with these strategies may be relevant considerations. Despite previous research indicating that patients at the highest risk of bleeding gain the greatest benefit from transradial vascular access during PCI,9 this approach continues to be less popular in the United States than in Europe. The effectiveness of closure devices in reducing vascular complications and bleeding at the access site remains disputed,5 and bivalirudin did not reduce risk of bleeding compared with unfractionated heparin in one recent trial.10 It is too early to assess the impact
Correspondence to: G Ndrepepa, Deutsches Herzzentrum München, Lazarettstrasse 36, 80636 München, Germany [email protected] For personal use only: See rights and reprints http://www.bmj.com/permissions
Subscribe: http://www.bmj.com/subscribe
BMJ 2015;350:h1395 doi: 10.1136/bmj.h1395 (Published 24 March 2015)
Page 2 of 2
EDITORIALS
of that trial on clinical practice. Bleeding avoidance strategies may also increase hospital costs associated with PCI. Cost effectiveness may become particularly important if these strategies are widely adopted or used indiscriminately. Even so, bleeding avoidance strategies are likely to be cost effective in many healthcare settings owing to the substantial costs of peri-procedural bleeding, particularly if use is tailored to each patient’s baseline risk.3 Finally, debate continues as to whether bleeding events should be incorporated into composite endpoints used in clinical trials testing drugs or interventions in patients undergoing PCI. Sceptics argue against combining endpoints such as bleeding and ischaemia, which are influenced in opposite directions by antithrombotic drugs. Protagonists argue that combining ischaemic and bleeding events in composite endpoints captures the net clinical effects of a given drug or intervention more comprehensively. Moreover, both types of events have an important and comparable effect on mortality.
In the end, increased recognition of the clinical importance of bleeding events after PCI has been an important development. Bleeding increases patients’ suffering and places them at higher risk of death. The tailored delivery of bleeding avoidance strategies according to the bleeding risk has the potential to reduce bleeding events, prevent suffering, and improve quality of life for patients undergoing PCI. The cardiology community should strive to ensure that the individualised implementation of these strategies becomes a central component of our practice in the coming years.
Competing interests: We have read and understood the BMJ policy on declaration of interests and declare the following interests: none. Provenance: Commissioned; not externally peer reviewed. 1 2 3 4 5
6
7
8 9 10
National Institute for Cardiovascular Outcomes Research. National audit of percutaneous coronary interventions (NAPCI) 2014 annual public report. www.ucl.ac.uk/nicor/nicornews-publication/PCI_2014_report_annual. Kinnaird T, Anderson R, Hill J, Thomas M. Bleeding during percutaneous intervention: tailoring the approach to minimise risk. Heart 2009;95:15-9. Dauerman HL, Rao SV, Resnic FS, Applegate RJ. Bleeding avoidance strategies: consensus and controversy. J Am Coll Cardiol 2011;58:1-10. Chhatriwalla AK, Amin AP, Kennedy KF, House JA, Cohen DJ, Rao SV, et al. Association between bleeding events and in-hospital mortality after percutaneous coronary intervention. JAMA 2013;309:1022-9. Levine GN, Bates ER, Blankenship JC, Bailey SR, Bittl JA, Cercek B, et al. 2011 ACCF/AHA/SCAI guideline for percutaneous coronary intervention: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions. Circulation 2011;124:e574-651. Spertus JA, Decker C, Gialde E, Jones PG, McNulty EJ, Bach R, et al. Precision medicine to improve use of bleeding avoidance strategies and reduce bleeding in patients undergoing percutaneous coronary intervention: prospective cohort study before and after implementation of personalized bleeding risks. BMJ 2015;350:h1302. Ndrepepa G, Berger PB, Mehilli J, Seyfarth M, Neumann FJ, Schomig A, et al. Periprocedural bleeding and 1-year outcome after percutaneous coronary interventions: appropriateness of including bleeding as a component of a quadruple end point. J Am Coll Cardiol 2008;51:690-7. Cavender MA, Sabatine MS. Bivalirudin versus heparin in patients planned for percutaneous coronary intervention: a meta-analysis of randomised controlled trials. Lancet . 2014;384:599-606. Mamas MA, Anderson SG, Carr M, Ratib K, Buchan I, Sirker A, et al. Baseline bleeding risk and arterial access site practice in relation to procedural outcomes after percutaneous coronary intervention. J Am Coll Cardiol 2014;64:1554-64. Shahzad A, Kemp I, Mars C, Wilson K, Roome C, Cooper R, et al, for the HEAT-PPCI Trial Investigators. Unfractionated heparin versus bivalirudin in primary percutaneous coronary intervention (HEAT-PPCI): an open-label, single centre, randomised controlled trial. Lancet 2014;384:1849-58.
Cite this as: BMJ 2015;350:h1395 © BMJ Publishing Group Ltd 2015
For personal use only: See rights and reprints http://www.bmj.com/permissions
Subscribe: http://www.bmj.com/subscribe
