Correspondence
We declare no competing interests.
*Jasmine Schulkind, Sarah Hurst, Rachael Biggart, Gemma Bowsher [email protected] Brighton and Sussex Medical School, Brighton, UK (JS, RB, SH); and Medicine, King’s College London, London, UK (GB) 1
2
3
4
5
6
Safeguarding Teenage Intimate Relationships (STIR). Briefing Paper 2: Incidence Rates and Impact of Experiencing Interpersonal Violence and Abuse in Young People’s Relationships. http://stiritup.eu/wp-content/uploads/2015/02/ STIR-Briefing-Paper-21.pdf (accessed May 7, 2015). Guasp A. The School Report: The experiences of gay young people in Britain’s schools in 2012. https://www.stonewall.org.uk/documents/ school_report_2012%282%29.pdf (accessed May 7, 2015). Public Health England. HIV in the United Kingdom: 2014 Report. https://www.gov.uk/ government/uploads/system/uploads/ attachment_data/file/401662/2014_PHE_ HIV_annual_report_draft_Final_07-01-2015. pdf (accessed May 7, 2015). House of Commons Education Committee. Life lessons: PSHE and SRE in schools. http://www.publications.parliament.uk/pa/ cm201415/cmselect/cmeduc/145/145.pdf (accessed May 7, 2015). The House of Lords. Children and Families Bill. http://www.publications.parliament.uk/pa/ ld201314/ldhansrd/text/140128-0002.htm (accessed May 7, 2015). The House of Commons. Personal, Social, Health and Economic Education (Statutory Requirement) Bill 2014–15. http://services. parliament.uk/bills/2014-15/ (accessed May 7, 2015).
Bivalirudin versus heparin use for patients undergoing PPCI We congratulate Adeel Shahzad and colleagues (Nov 22, p 1849)1 on their remarkable achievement of enrolling almost 2000 patients with ST-segment elevation myocardial infarction (STEMI) and undergoing primary percutaneous coronary intervention (PPCI) into their trial, with minimal exclusions. However, their results substantially differ to the previously reported EUROMAX trial. 2 In EUROMAX, 2 bivalirudin, compared with heparin with or without glycoprotein (GP) www.thelancet.com Vol 385 May 23, 2015
IIb/IIIa inhibitors, reduced the composite of death or major bleeding by 40%, at the expense of a 1% absolute increase in patients with acute stent thrombosis. By contrast, in HEAT-PPCI1 bivalirudin did not reduce bleeding, compared with heparin alone, and was associated with worse clinical outcomes—including an increased risk of acute stent thrombosis. The investigators1 and Comment authors (Peter B Bergeremail and James C Blankenship) 3 propose several possible explanations for this discrepancy. First, they suggest that previous trials used inappropriately high doses of heparin in the control arm, resulting in an artificially large incidence of bleeding. That hypothesis does not apply to EUROMAX,2 which used lower doses of unfractionated heparin (median dose of 61 U/kg [Q1–Q3: 56–71 U/kg] for patients given GP IIb/IIIa inhibitors, and 60 U/kg [Q1–Q3: 53–77 U/kg] for those not given these inhibitors) than in HEAT-PPCI (70 U/kg).1 Second, the authors1 postulated that the reported bleeding reduction with bivalirudin was associated with the systematic use of GP IIb/IIIa inhibitors in the control arm. However, in EUROMAX2 use of these inhibitors was by the investigators’ discretion, with 41·5% of patients in the control group being treated with heparin alone. A prespecified analysis4 of EUROMAX2 showed that bivalirudin, compared with heparin alone, reduced both the primary outcome (death or major bleeding; odds ratio [OR] 0·53, 95% CI 0·33–0·87) and major bleeding (0·44, 0·24–0·82). These results suggest that the bleeding reduction with bivalirudin cannot solely be attributed to the use of GP IIb/IIIa inhibitors in the control arm.2 Additional hypotheses suggested for the reduced incidence of bleeding complications with heparin in HEAT-PPCI1 include the frequent use of radial artery access and the fact that no heparin had been given before randomisation. In EUROMAX,2 about
half of patients were treated with radial access; furthermore, the benefits of bivalirudin on the primary outcome were consistent, irrespective of whether arterial access was via radial (relative risk 0·60, 95% CI 0·35–1·03) or femoral (0·61, 0·40–0·94, p interaction=0·94) arteries. No anticoagulation was given to patients before their random allocation to a treatment group,2 allowing for so-called pure comparisons between bivalirudin and heparins with or without GP IIb/IIIa inhibitors. We suggest that the benefits of bivalirudin in EUROMAX2 and HORIZONS-AMI5 might be associated with careful dosing and with the short half-life of bivalirudin, which minimises the risks and consequences of bleeding. However, because oral antiplatelet drugs take several hours to become active in PPCI for STEMI, patients are susceptible to stent thrombosis in the first few hours after PPCI when anticoagulation might no longer be present, but the antiplatelet drugs are not yet effective. In both trials,1,2 almost all acute stent thromboses happened during the first 4 h after PPCI.5 Discontinuation of bivalirudin immediately after the PPCI procedure (as was done in HEAT-PPCI1) might therefore leave patients treated with this drug without adequate antithrombotic protection against early stent thrombosis in these first hours. By contrast, patients receiving longer-acting drugs (such as unfractionated heparin, enoxaparin, or GP IIb/IIIa inhibitors) might be protected. This asymmetry in protection is even more true if anticoagulants are readministered during the procedure in an unbalanced way, such as in HEAT-PPCI 1 (supplemental bolus doses were given to 35·2% of patients in the heparin group vs 12·7% in the bivalirudin group). A post-hoc analysis6 of EUROMAX showed that patients treated with bivalirudin with an extended infusion after percutaneous coronary intervention (at a dose of 1·75 mg/kg per h for more than 2 h) had low rates of stent thrombosis without
Molekuul/Science Photo Library
The new government should act now or fail another generation of young people.
2043
Correspondence
increased bleeding rates. This dosing regimen could be crucial to obtain the clinical benefits associated with use of short-acting anticoagulants, such as bivalirudin, at low doses. PGS reports personal fees from Amarin, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, GlaxoSmithKline, Eli Lilly, Merck Sharp & Dohme, Novartis, Otsuka, Pfizer, Roche, Sanofi, Servier, The Medicines Company, and Vivus. PGS reports grants from Sanofi and Servier. AWvH reports grant and non-financial support from The Medicines Company; and grant support from Correvio, AstraZeneca, Eli Lilly, and Medtronic. UZ reports grant support and personal fees from Daiichi Sankyo, Eli Lilly, Novartis, and Sanofi; and reports personal fees from AstraZeneca, Bayer Healthcare, Boehringer Ingelheim, Merck Sharp & Dohme, and The Medicines Company. PG reports personal fees from AstraZeneca, Bayer, Eli Lilly, Pfizer, Boehringer Ingelheim, Daiichi Sankyo, The Medicines Company, and Brahms.
*Philippe Gabriel Steg, Arnoud W van’t Hof, Uwe Zeymer, Patrick Goldstein [email protected] Université Paris-Diderot, Sorbonne Paris-Cité, Hôpital Bichat, Paris, 75018, France (PGS); National Heart and Lung Institute, Imperial College, Royal Brompton Hospital, London, UK (PGS); Isala, Department of Cardiology, Zwolle, Netherlands (AWvH); Klinikum Ludwigshafen and Institut für Herzinfarktforschung, Ludwigshafen, Germany (UZ); and Emergency Department and SAMU, Lille University Hospital, Lille, France (PG) 1
2
3
4
5
6
2044
Shahzad A, Kemp I, Mars C, 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. Steg PG, van‘t Hof A, Hamm CW, et al, and the EUROMAX Investigators. Bivalirudin started during emergency transport for primary PCI. N Engl J Med 2013; 369: 2207–17. Berger PB, Blankenship JC. Is the heat on HEAT-PPCI appropriate? Lancet 2014; 384: 1824–26. Zeymer U, van‘t Hof A, Adgey J, et al. Bivalirudin is superior to heparins alone with bailout GP IIb/ IIIa inhibitors in patients with ST-segment elevation myocardial infarction transported emergently for primary percutaneous coronary intervention: a pre-specified analysis from the EUROMAX trial. Eur Heart J 2014; 35: 2460–67. Steg PG, Mehran R, Goldstein P, et al. Bivalirudin versus heparin with or without glycoprotein IIb/ IIIa inhibitors in STEMI patients undergoing primary PCI: a pooled analysis of patient-level data from the HORIZONS-AMI and EUROMAX trials. J Am Coll Cardiol 2014; 63 (suppl 1): A34. Clemmensen P, Wiberg S, van’t Hof A, et al. Acute stent thrombosis after primary percutaneous coronary intervention: insights from the EUROMAX trial (European Ambulance Acute Coronary Syndrome Angiography). JACC Cardiovasc Interv 2015; 8: 214–20.
Although randomised clinical trials are the gold standard used to define treatment recommendations, beneficial effects of a drug for treatment might be obscured because of the effect of adjunctive treatment on patient outcomes. The GUSTO trial investigators 1 reported that treatment of ST-segment elevation myocardial infarction (STEMI) with tissue plasminogen activator reduced mortality compared with the use of streptokinase. To show this benefit, effective adjunctive treatment with intravenous heparin was necessary. The heparin versus bivalirudin in primary percutaneous coronary intervention trial (HEAT-PPCI) 2 compared unfractionated heparin with bivalirudin for treatment of STEMI. Greater efficacy was reported with unfractionated heparin than with bivalirudin, and was mostly driven by acute stent thrombosis. An increased risk of early stent thrombosis with bivalirudin was also reported in the HORIZONS-AMI3 and the EUROMAX4 trials. Bivalirudin is a direct-acting inhibitor of thrombin. 5 Because bivalirudin is a substrate for thrombin it has a short half-life of about 25 min. This short half-life could be a double-edged sword, contributing to a reduced risk of bleeding but necessitating the use of an effective adjunctive strategy in patients with STEMI who are prothrombotic. Potentially advantageous features of bivalirudin—such as not being dependent on an endogenous cofactor, its consistent anticoagulant effect, and its ability to inhibit clot-bound thrombin—cannot be accurately assessed until a treatment strategy that prevents acute stent thrombosis is defined. Lessons learned during the early development of reperfusion strategies for patients with STEMI should be regarded in the interpretation of HEAT-PPCI. 2 A treatment strategy that prevents acute stent thrombosis will be needed to clearly define the potential clinical
benefits associated with the use of bivalirudin for primary percutaneous coronary intervention in STEMI. I report grants and personal fees from The Medicines Company and AstraZeneca.
David J Schneider [email protected] University of Vermont, Colchester, VT 05446, USA 1
2
3
4
5
The GUSTO investigators. An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction. N Engl J Med 1993; 329: 673–82. Shahzad A, Kemp I, Mars C, et al, for the HEAT-PPCI 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. Stone GW, Witzenbichler B, Guagliumi G, et al, for the HORIZONS-AMI Trial Investigators. Bivalirudin during primary PCI in acute myocardial infarction. N Engl J Med 2008; 358: 2218–30. Steg PG, van‘t Hof A, Hamm CW, et al, for the EUROMAX Investigators. Bivalirudin started during emergency transport for primary PCI. N Engl J Med 2013; 369: 2207–17. Arsenault KA, Hirsh J, Whitlock RP, Eikelboom JW. Direct thrombin inhibitors in cardiovascular disease. Nat Rev Cardiol 2012; 9: 402–14.
Adeel Shahzad and colleagues1 showed that the use of heparin, compared with bivalirudin, substantially reduces the incidence of major adverse events (principally acute stent thrombosis) in patients, with no differences between the two drugs in bleeding complications. The rates of acute stent thrombosis were 3·4% in the bivalirudin group and 0·9% in the heparin group. These results should urge health-care providers to refrain from using bivalirudin in the setting of primary percutaneous coronary intervention, especially for patients with risk factors of acute stent thrombosis. In this study1 the absolute rates of acute stent thrombosis were higher than reported in the HORIZONS-AMI trial.2 Patients’ backgrounds might have differed between the two studies; however, the risk factors of patients who developed stent thrombosis were not shown. Risk factors for acute stent thrombosis included stent length, congestive heart failure, and a www.thelancet.com Vol 385 May 23, 2015
We declare no competing interests.
*Jasmine Schulkind, Sarah Hurst, Rachael Biggart, Gemma Bowsher [email protected] Brighton and Sussex Medical School, Brighton, UK (JS, RB, SH); and Medicine, King’s College London, London, UK (GB) 1
2
3
4
5
6
Safeguarding Teenage Intimate Relationships (STIR). Briefing Paper 2: Incidence Rates and Impact of Experiencing Interpersonal Violence and Abuse in Young People’s Relationships. http://stiritup.eu/wp-content/uploads/2015/02/ STIR-Briefing-Paper-21.pdf (accessed May 7, 2015). Guasp A. The School Report: The experiences of gay young people in Britain’s schools in 2012. https://www.stonewall.org.uk/documents/ school_report_2012%282%29.pdf (accessed May 7, 2015). Public Health England. HIV in the United Kingdom: 2014 Report. https://www.gov.uk/ government/uploads/system/uploads/ attachment_data/file/401662/2014_PHE_ HIV_annual_report_draft_Final_07-01-2015. pdf (accessed May 7, 2015). House of Commons Education Committee. Life lessons: PSHE and SRE in schools. http://www.publications.parliament.uk/pa/ cm201415/cmselect/cmeduc/145/145.pdf (accessed May 7, 2015). The House of Lords. Children and Families Bill. http://www.publications.parliament.uk/pa/ ld201314/ldhansrd/text/140128-0002.htm (accessed May 7, 2015). The House of Commons. Personal, Social, Health and Economic Education (Statutory Requirement) Bill 2014–15. http://services. parliament.uk/bills/2014-15/ (accessed May 7, 2015).
Bivalirudin versus heparin use for patients undergoing PPCI We congratulate Adeel Shahzad and colleagues (Nov 22, p 1849)1 on their remarkable achievement of enrolling almost 2000 patients with ST-segment elevation myocardial infarction (STEMI) and undergoing primary percutaneous coronary intervention (PPCI) into their trial, with minimal exclusions. However, their results substantially differ to the previously reported EUROMAX trial. 2 In EUROMAX, 2 bivalirudin, compared with heparin with or without glycoprotein (GP) www.thelancet.com Vol 385 May 23, 2015
IIb/IIIa inhibitors, reduced the composite of death or major bleeding by 40%, at the expense of a 1% absolute increase in patients with acute stent thrombosis. By contrast, in HEAT-PPCI1 bivalirudin did not reduce bleeding, compared with heparin alone, and was associated with worse clinical outcomes—including an increased risk of acute stent thrombosis. The investigators1 and Comment authors (Peter B Bergeremail and James C Blankenship) 3 propose several possible explanations for this discrepancy. First, they suggest that previous trials used inappropriately high doses of heparin in the control arm, resulting in an artificially large incidence of bleeding. That hypothesis does not apply to EUROMAX,2 which used lower doses of unfractionated heparin (median dose of 61 U/kg [Q1–Q3: 56–71 U/kg] for patients given GP IIb/IIIa inhibitors, and 60 U/kg [Q1–Q3: 53–77 U/kg] for those not given these inhibitors) than in HEAT-PPCI (70 U/kg).1 Second, the authors1 postulated that the reported bleeding reduction with bivalirudin was associated with the systematic use of GP IIb/IIIa inhibitors in the control arm. However, in EUROMAX2 use of these inhibitors was by the investigators’ discretion, with 41·5% of patients in the control group being treated with heparin alone. A prespecified analysis4 of EUROMAX2 showed that bivalirudin, compared with heparin alone, reduced both the primary outcome (death or major bleeding; odds ratio [OR] 0·53, 95% CI 0·33–0·87) and major bleeding (0·44, 0·24–0·82). These results suggest that the bleeding reduction with bivalirudin cannot solely be attributed to the use of GP IIb/IIIa inhibitors in the control arm.2 Additional hypotheses suggested for the reduced incidence of bleeding complications with heparin in HEAT-PPCI1 include the frequent use of radial artery access and the fact that no heparin had been given before randomisation. In EUROMAX,2 about
half of patients were treated with radial access; furthermore, the benefits of bivalirudin on the primary outcome were consistent, irrespective of whether arterial access was via radial (relative risk 0·60, 95% CI 0·35–1·03) or femoral (0·61, 0·40–0·94, p interaction=0·94) arteries. No anticoagulation was given to patients before their random allocation to a treatment group,2 allowing for so-called pure comparisons between bivalirudin and heparins with or without GP IIb/IIIa inhibitors. We suggest that the benefits of bivalirudin in EUROMAX2 and HORIZONS-AMI5 might be associated with careful dosing and with the short half-life of bivalirudin, which minimises the risks and consequences of bleeding. However, because oral antiplatelet drugs take several hours to become active in PPCI for STEMI, patients are susceptible to stent thrombosis in the first few hours after PPCI when anticoagulation might no longer be present, but the antiplatelet drugs are not yet effective. In both trials,1,2 almost all acute stent thromboses happened during the first 4 h after PPCI.5 Discontinuation of bivalirudin immediately after the PPCI procedure (as was done in HEAT-PPCI1) might therefore leave patients treated with this drug without adequate antithrombotic protection against early stent thrombosis in these first hours. By contrast, patients receiving longer-acting drugs (such as unfractionated heparin, enoxaparin, or GP IIb/IIIa inhibitors) might be protected. This asymmetry in protection is even more true if anticoagulants are readministered during the procedure in an unbalanced way, such as in HEAT-PPCI 1 (supplemental bolus doses were given to 35·2% of patients in the heparin group vs 12·7% in the bivalirudin group). A post-hoc analysis6 of EUROMAX showed that patients treated with bivalirudin with an extended infusion after percutaneous coronary intervention (at a dose of 1·75 mg/kg per h for more than 2 h) had low rates of stent thrombosis without
Molekuul/Science Photo Library
The new government should act now or fail another generation of young people.
2043
Correspondence
increased bleeding rates. This dosing regimen could be crucial to obtain the clinical benefits associated with use of short-acting anticoagulants, such as bivalirudin, at low doses. PGS reports personal fees from Amarin, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, GlaxoSmithKline, Eli Lilly, Merck Sharp & Dohme, Novartis, Otsuka, Pfizer, Roche, Sanofi, Servier, The Medicines Company, and Vivus. PGS reports grants from Sanofi and Servier. AWvH reports grant and non-financial support from The Medicines Company; and grant support from Correvio, AstraZeneca, Eli Lilly, and Medtronic. UZ reports grant support and personal fees from Daiichi Sankyo, Eli Lilly, Novartis, and Sanofi; and reports personal fees from AstraZeneca, Bayer Healthcare, Boehringer Ingelheim, Merck Sharp & Dohme, and The Medicines Company. PG reports personal fees from AstraZeneca, Bayer, Eli Lilly, Pfizer, Boehringer Ingelheim, Daiichi Sankyo, The Medicines Company, and Brahms.
*Philippe Gabriel Steg, Arnoud W van’t Hof, Uwe Zeymer, Patrick Goldstein [email protected] Université Paris-Diderot, Sorbonne Paris-Cité, Hôpital Bichat, Paris, 75018, France (PGS); National Heart and Lung Institute, Imperial College, Royal Brompton Hospital, London, UK (PGS); Isala, Department of Cardiology, Zwolle, Netherlands (AWvH); Klinikum Ludwigshafen and Institut für Herzinfarktforschung, Ludwigshafen, Germany (UZ); and Emergency Department and SAMU, Lille University Hospital, Lille, France (PG) 1
2
3
4
5
6
2044
Shahzad A, Kemp I, Mars C, 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. Steg PG, van‘t Hof A, Hamm CW, et al, and the EUROMAX Investigators. Bivalirudin started during emergency transport for primary PCI. N Engl J Med 2013; 369: 2207–17. Berger PB, Blankenship JC. Is the heat on HEAT-PPCI appropriate? Lancet 2014; 384: 1824–26. Zeymer U, van‘t Hof A, Adgey J, et al. Bivalirudin is superior to heparins alone with bailout GP IIb/ IIIa inhibitors in patients with ST-segment elevation myocardial infarction transported emergently for primary percutaneous coronary intervention: a pre-specified analysis from the EUROMAX trial. Eur Heart J 2014; 35: 2460–67. Steg PG, Mehran R, Goldstein P, et al. Bivalirudin versus heparin with or without glycoprotein IIb/ IIIa inhibitors in STEMI patients undergoing primary PCI: a pooled analysis of patient-level data from the HORIZONS-AMI and EUROMAX trials. J Am Coll Cardiol 2014; 63 (suppl 1): A34. Clemmensen P, Wiberg S, van’t Hof A, et al. Acute stent thrombosis after primary percutaneous coronary intervention: insights from the EUROMAX trial (European Ambulance Acute Coronary Syndrome Angiography). JACC Cardiovasc Interv 2015; 8: 214–20.
Although randomised clinical trials are the gold standard used to define treatment recommendations, beneficial effects of a drug for treatment might be obscured because of the effect of adjunctive treatment on patient outcomes. The GUSTO trial investigators 1 reported that treatment of ST-segment elevation myocardial infarction (STEMI) with tissue plasminogen activator reduced mortality compared with the use of streptokinase. To show this benefit, effective adjunctive treatment with intravenous heparin was necessary. The heparin versus bivalirudin in primary percutaneous coronary intervention trial (HEAT-PPCI) 2 compared unfractionated heparin with bivalirudin for treatment of STEMI. Greater efficacy was reported with unfractionated heparin than with bivalirudin, and was mostly driven by acute stent thrombosis. An increased risk of early stent thrombosis with bivalirudin was also reported in the HORIZONS-AMI3 and the EUROMAX4 trials. Bivalirudin is a direct-acting inhibitor of thrombin. 5 Because bivalirudin is a substrate for thrombin it has a short half-life of about 25 min. This short half-life could be a double-edged sword, contributing to a reduced risk of bleeding but necessitating the use of an effective adjunctive strategy in patients with STEMI who are prothrombotic. Potentially advantageous features of bivalirudin—such as not being dependent on an endogenous cofactor, its consistent anticoagulant effect, and its ability to inhibit clot-bound thrombin—cannot be accurately assessed until a treatment strategy that prevents acute stent thrombosis is defined. Lessons learned during the early development of reperfusion strategies for patients with STEMI should be regarded in the interpretation of HEAT-PPCI. 2 A treatment strategy that prevents acute stent thrombosis will be needed to clearly define the potential clinical
benefits associated with the use of bivalirudin for primary percutaneous coronary intervention in STEMI. I report grants and personal fees from The Medicines Company and AstraZeneca.
David J Schneider [email protected] University of Vermont, Colchester, VT 05446, USA 1
2
3
4
5
The GUSTO investigators. An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction. N Engl J Med 1993; 329: 673–82. Shahzad A, Kemp I, Mars C, et al, for the HEAT-PPCI 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. Stone GW, Witzenbichler B, Guagliumi G, et al, for the HORIZONS-AMI Trial Investigators. Bivalirudin during primary PCI in acute myocardial infarction. N Engl J Med 2008; 358: 2218–30. Steg PG, van‘t Hof A, Hamm CW, et al, for the EUROMAX Investigators. Bivalirudin started during emergency transport for primary PCI. N Engl J Med 2013; 369: 2207–17. Arsenault KA, Hirsh J, Whitlock RP, Eikelboom JW. Direct thrombin inhibitors in cardiovascular disease. Nat Rev Cardiol 2012; 9: 402–14.
Adeel Shahzad and colleagues1 showed that the use of heparin, compared with bivalirudin, substantially reduces the incidence of major adverse events (principally acute stent thrombosis) in patients, with no differences between the two drugs in bleeding complications. The rates of acute stent thrombosis were 3·4% in the bivalirudin group and 0·9% in the heparin group. These results should urge health-care providers to refrain from using bivalirudin in the setting of primary percutaneous coronary intervention, especially for patients with risk factors of acute stent thrombosis. In this study1 the absolute rates of acute stent thrombosis were higher than reported in the HORIZONS-AMI trial.2 Patients’ backgrounds might have differed between the two studies; however, the risk factors of patients who developed stent thrombosis were not shown. Risk factors for acute stent thrombosis included stent length, congestive heart failure, and a www.thelancet.com Vol 385 May 23, 2015
