Catheterization and Cardiovascular Interventions 83:190–191 (2014)
Editorial Comment Bleeding, A Call to Action Saurabh Gupta, MD, and Joaquin E. Cigarroa,* MD Knight Cardiovascular Institute, Oregon Health & Sciences University, Portland, Oregon
Although multiple definitions of bleeding post percutaneous coronary intervention (PCI) exist, the underlying message with regards to the impact of bleeding has been remarkably consistent: bleeding and blood transfusion are strongly associated with adverse outcomes. Patients who bleed after PCI have longer hospital lengths of stay and experience an increase in shortand long-term mortality. The dominant mode of bleeding is access site related. Nonaccess site-related bleeding, especially gastrointestinal (GI) bleeds remain important concerns (up to 40%) and are stronger correlates of mortality [1]. Several factors independently confer an increased risk: age, sex, body mass index, arterial hypertension, hypercholesterolemia, renal insufficiency, baseline platelet count, left ventricular ejection fraction, and presentation with an acute coronary syndrome. Although similar data trends have been observed across various age groups, specific knowledge with standardized bleeding definitions in the elderly has generally been lacking mostly due to inadequate sample size and underrepresentation of this age group in randomized clinical trials. In this issue of CCI, a post hoc analysis by Kastrati et al of seven randomized trials between 2000 and 2011 adds to the growing body of literature about the accentuated impact of post PCI bleeding in the elderly and its association with excess mortality (12.3 vs. 5.1%). The authors retrospectively applied a standardized Bleeding Academic Research Consortium (BARC) [2] definition of bleeding (the original trials all had varying criteria). Bleeding events (both access and nonaccess) were much more likely to have occurred in patients >75 years compared to younger patients confirming that increasing age translates to increase risk [1]. Patients who bled were more likely to be women, present with an acute coronary syndrome and have lower body mass index, creatinine clearance, and left ventricular ejection fraction. Bivalirudin was also noted to have a positive effect when compared with heparin (6 glycoprotein 2b 3a inhibitors). C 2014 Wiley Periodicals, Inc. V
Pharmacological therapies and procedural modifications are required to reduce this risk. Preprocedural recognition of patients with an increased bleeding risk allows selecting an appropriate strategy to reduce the bleeding risk. Routine use of bleeding risk calculators can help ensure a higher state of vigilance. Advances in our understanding of optimal periprocedural and post procedural antithrombotic and antiplatelet regimens in the elderly could translate into similar reductions for nonaccess-related bleeds. In this analysis, the access site was predominantly femoral and bivalarudin was effective in reducing risk but there is evidence to suggest that benefit of bivalirudin as an anticoagulant strategy persist regardless of access route [3]. Increased adoption of transradial approach can potentially have the biggest impact on access-related bleeding (which constitute a majority of bleeding related to PCI). In the elderly who are treated with antiplatelet therapy, several risk factors predispose to GI bleeding: history of prior GI bleed, concurrent use of anticoagulants, steroids, or non steroidal anti infammatory drugs; or Helicobacter pylori infection. The risk increases with a greater number of risk factors present. Given that increasing dosage of aspirin increases the risk of bleeding, the lowest effective dose should be utilized for maintenance therapy, 81 mg daily. Proton pump inhibitors (PPIs) are recommended to reduce GI bleeding. Evidence over the last several years has generally allayed concerns about the interactions between PPIs and thienopyridines and we feel comfortable with this strategy in our practice. With approval of prasugrel and ticagrelor, the arsenal of oral antiplatelet agents available to treat patients has expanded. It is important to note that prasugrel warrants extreme caution in the elderly. In TRITON-TIMI 38 [4] that compared prasugrel and clopidogrel, 13.2% of patients were 75 years (38.5% 65 years) of age. The risk of bleeding increased with advancing age in both Conflict of interest: Nothing to report. *Correspondence to: Dr. Joaquin Cigarroa; Oregon Health Science University Hospital, 3181 SW Sam Jackson Road, Portland, Oregon 97239-3098. E-mail: [email protected] Received 26 November 2013; Revision accepted 27 November 2013 DOI: 10.1002/ccd.25315 Published online 17 January 2014 in Wiley Online Library (wileyonlinelibrary.com)
Bleeding, A Call to Action
treatment groups although the relative risk of bleeding was similar across age groups. Patients 75 years of age that received prasugrel had an increased risk of fatal bleeding events (1.0%) compared to patients who received clopidogrel (0.1%). In PLATO trial for Ticagrelor [5], 43% of patients were >65 years of age and 15% were >75. The relative risk of bleeding was similar in both age groups. While in our practice, we have not transitioned to newer thienopyridines in the elderly, data would support the use of either clopidogrel or ticagrelor (compared to prasugrel). As the population ages: two trends are obvious – the proportion of elderly patients in cardiac catheterization laboratories will continue to increase and there will be higher prevalence of related comorbidities, some of which predispose to increased procedural-related bleeding. We now recognize that the most common complication in this patient population is bleeding and it, like stent thrombosis, is associated with significant morbidity and mortality. Given the strong correlation of post-PCI bleeding with mortality, it is paramount
191
that we routinely implement strategies in our clinical practices that mitigate this risk; we owe nothing less to our patients. REFERENCES 1. Ndrepepa G, Neumann FJ, Richardt G, et al. Prognostic value of access and nonaccess sites bleeding after percutaneous coronary intervention. Circu Cardiovasc Interv 2013;6:354–361. 2. Mehran R, Rao SV, Bhatt DL, et al. Standardized bleeding definitions for cardiovascular clinical trials: A consensus report from the bleeding academic research consortium. Circulation 2011; 123:2736–2747. 3. Baklanov DV, Kim S, Marso SP, et al. Comparison of bivalirudin and radial access across a spectrum of preprocedural risk of bleeding in percutaneous coronary intervention: Analysis from the national cardiovascular data registry. Circ Cardiovasc Interv 2013;6:347–353. 4. Wiviott SD, Braunwald E, McCabe CH, et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2007;357:2001–2015. 5. Wallentin L, Becker RC, Budaj A, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2009;361:1045–1057.
Catheterization and Cardiovascular Interventions DOI 10.1002/ccd. Published on behalf of The Society for Cardiovascular Angiography and Interventions (SCAI).
Editorial Comment Bleeding, A Call to Action Saurabh Gupta, MD, and Joaquin E. Cigarroa,* MD Knight Cardiovascular Institute, Oregon Health & Sciences University, Portland, Oregon
Although multiple definitions of bleeding post percutaneous coronary intervention (PCI) exist, the underlying message with regards to the impact of bleeding has been remarkably consistent: bleeding and blood transfusion are strongly associated with adverse outcomes. Patients who bleed after PCI have longer hospital lengths of stay and experience an increase in shortand long-term mortality. The dominant mode of bleeding is access site related. Nonaccess site-related bleeding, especially gastrointestinal (GI) bleeds remain important concerns (up to 40%) and are stronger correlates of mortality [1]. Several factors independently confer an increased risk: age, sex, body mass index, arterial hypertension, hypercholesterolemia, renal insufficiency, baseline platelet count, left ventricular ejection fraction, and presentation with an acute coronary syndrome. Although similar data trends have been observed across various age groups, specific knowledge with standardized bleeding definitions in the elderly has generally been lacking mostly due to inadequate sample size and underrepresentation of this age group in randomized clinical trials. In this issue of CCI, a post hoc analysis by Kastrati et al of seven randomized trials between 2000 and 2011 adds to the growing body of literature about the accentuated impact of post PCI bleeding in the elderly and its association with excess mortality (12.3 vs. 5.1%). The authors retrospectively applied a standardized Bleeding Academic Research Consortium (BARC) [2] definition of bleeding (the original trials all had varying criteria). Bleeding events (both access and nonaccess) were much more likely to have occurred in patients >75 years compared to younger patients confirming that increasing age translates to increase risk [1]. Patients who bled were more likely to be women, present with an acute coronary syndrome and have lower body mass index, creatinine clearance, and left ventricular ejection fraction. Bivalirudin was also noted to have a positive effect when compared with heparin (6 glycoprotein 2b 3a inhibitors). C 2014 Wiley Periodicals, Inc. V
Pharmacological therapies and procedural modifications are required to reduce this risk. Preprocedural recognition of patients with an increased bleeding risk allows selecting an appropriate strategy to reduce the bleeding risk. Routine use of bleeding risk calculators can help ensure a higher state of vigilance. Advances in our understanding of optimal periprocedural and post procedural antithrombotic and antiplatelet regimens in the elderly could translate into similar reductions for nonaccess-related bleeds. In this analysis, the access site was predominantly femoral and bivalarudin was effective in reducing risk but there is evidence to suggest that benefit of bivalirudin as an anticoagulant strategy persist regardless of access route [3]. Increased adoption of transradial approach can potentially have the biggest impact on access-related bleeding (which constitute a majority of bleeding related to PCI). In the elderly who are treated with antiplatelet therapy, several risk factors predispose to GI bleeding: history of prior GI bleed, concurrent use of anticoagulants, steroids, or non steroidal anti infammatory drugs; or Helicobacter pylori infection. The risk increases with a greater number of risk factors present. Given that increasing dosage of aspirin increases the risk of bleeding, the lowest effective dose should be utilized for maintenance therapy, 81 mg daily. Proton pump inhibitors (PPIs) are recommended to reduce GI bleeding. Evidence over the last several years has generally allayed concerns about the interactions between PPIs and thienopyridines and we feel comfortable with this strategy in our practice. With approval of prasugrel and ticagrelor, the arsenal of oral antiplatelet agents available to treat patients has expanded. It is important to note that prasugrel warrants extreme caution in the elderly. In TRITON-TIMI 38 [4] that compared prasugrel and clopidogrel, 13.2% of patients were 75 years (38.5% 65 years) of age. The risk of bleeding increased with advancing age in both Conflict of interest: Nothing to report. *Correspondence to: Dr. Joaquin Cigarroa; Oregon Health Science University Hospital, 3181 SW Sam Jackson Road, Portland, Oregon 97239-3098. E-mail: [email protected] Received 26 November 2013; Revision accepted 27 November 2013 DOI: 10.1002/ccd.25315 Published online 17 January 2014 in Wiley Online Library (wileyonlinelibrary.com)
Bleeding, A Call to Action
treatment groups although the relative risk of bleeding was similar across age groups. Patients 75 years of age that received prasugrel had an increased risk of fatal bleeding events (1.0%) compared to patients who received clopidogrel (0.1%). In PLATO trial for Ticagrelor [5], 43% of patients were >65 years of age and 15% were >75. The relative risk of bleeding was similar in both age groups. While in our practice, we have not transitioned to newer thienopyridines in the elderly, data would support the use of either clopidogrel or ticagrelor (compared to prasugrel). As the population ages: two trends are obvious – the proportion of elderly patients in cardiac catheterization laboratories will continue to increase and there will be higher prevalence of related comorbidities, some of which predispose to increased procedural-related bleeding. We now recognize that the most common complication in this patient population is bleeding and it, like stent thrombosis, is associated with significant morbidity and mortality. Given the strong correlation of post-PCI bleeding with mortality, it is paramount
191
that we routinely implement strategies in our clinical practices that mitigate this risk; we owe nothing less to our patients. REFERENCES 1. Ndrepepa G, Neumann FJ, Richardt G, et al. Prognostic value of access and nonaccess sites bleeding after percutaneous coronary intervention. Circu Cardiovasc Interv 2013;6:354–361. 2. Mehran R, Rao SV, Bhatt DL, et al. Standardized bleeding definitions for cardiovascular clinical trials: A consensus report from the bleeding academic research consortium. Circulation 2011; 123:2736–2747. 3. Baklanov DV, Kim S, Marso SP, et al. Comparison of bivalirudin and radial access across a spectrum of preprocedural risk of bleeding in percutaneous coronary intervention: Analysis from the national cardiovascular data registry. Circ Cardiovasc Interv 2013;6:347–353. 4. Wiviott SD, Braunwald E, McCabe CH, et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2007;357:2001–2015. 5. Wallentin L, Becker RC, Budaj A, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2009;361:1045–1057.
Catheterization and Cardiovascular Interventions DOI 10.1002/ccd. Published on behalf of The Society for Cardiovascular Angiography and Interventions (SCAI).
