L E TT E R
Bivalirudin: Treatment Effect Versus Side Effect Bartosz Hudzik, Jaroslaw Gorol, Janusz Szkodzinski, Andrzej Lekston & Lech Polonski Third Department of Cardiology, Silesian Center for Heart Disease, Medical University of Silesia, Zabrze, Poland
Correspondence Dr. Bartosz Hudzik M.D., Ph.D., Third Department of Cardiology, Silesian Center for Heart Disease, Medical University of Silesia, Curie-Sklodowska 9, 41-800 Zabrze, Poland. Tel.: +48-323733788; Fax: +48-322732679; E-mail: [email protected]
doi: 10.1111/1755-5922.12071
Alexopoulos et al. [1] presented interesting data showing that in “real-life” scenario, there are no differences in one-month outcome between bivalirudin- and no bivalirudin-treated patients. When talking about bivalirudin efficacy, we have to consider two distinct features: treatment effect (antithrombotic action) and side effect (bleeding events). In HORIZONS-AMI trial, there was a reduction in cardiac mortality in the bivalirudin group that can only partly be attributed to prevention of bleeding [2]. Notwithstanding, in EUROMAX trial, there was a substantial decline in bleeding events which did not transfer into survival benefit [3]. Repeatedly, however, there was a higher incidence of stent thrombosis and a trend toward a higher incidence of myocardial infarction [3,4], despite investigators’ attempts to prevent it by prolonging bivalirudin infusion to 4 h following PCI. So actually, in terms of treatment effect, the study proved the drug not to be so efficacious.
References 1. Alexopoulos D, Xanthopoulou I, Deftereos S, et al. Bivalirudin use and one-month outcome in
Bleeding events are independently associated with a worse long-term prognosis across a wide spectrum of patients with coronary artery disease and the risk of death progresses with increasing severity of bleeding [5,6]. However, in this instance, it would seem that we have decreased the risk of side effects (excellent safety profile) at the trade-off of increasing the risk of thrombotic events – events that, one would expect, should decline using antithrombotic agent [7]. In addition, the cost of bivalirudin far exceeds that of standard treatment, thereby calling into question the ancillary benefits of the drug that would justify its use in place of the conventional regimen. Accordingly, we emphasize caution when talking about therapeutic effect. Until then, findings should be considered signals warranting further investigation.
Conflict of Interest The authors declare no conflict of interest.
Revascularization and Stents in Acute Myocardial
with coronary artery disease undergoing
Infarction). J Am Coll Cardiol 2014;63:15–20.
percutaneous coronary intervention. Circulation
3. Steg PG, van’t Hof A, Hamm CW, et al. Bivalirudin started during emergency transport
2012;125:1424–1431. 6. Eikelboom JW, Mehta SR, Anand SS, Xie C,
the context of contemporary antiplatelet
for primary PCI. N Engl J Med 2013;369:2207–
Fox KA, Yusuf S. Adverse impact of bleeding on
treatment: Insights from the Greek Antiplatelet
2217.
prognosis in patients with acute coronary
Registry. Cardiovasc Ther 2014;32:120–126. 2. Stone GW, Clayton T, Deliargyris EN, Prats J, Mehran R, Pocock SJ. Reduction in cardiac mortality with bivalirudin in patients with and
4. Stone GW, Witzenbichler B, Guagliumi G, et al. Bivalirudin during primary PCI in acute myocardial infarction. N Engl J Med 2008;358:2218–2230. 5. Ndrepepa G, Schuster T, Hadamitzky M, et al.
without major bleeding: The HORIZONS-AMI
Validation of the Bleeding Academic Research
trial (Harmonizing Outcomes with
Consortium definition of bleeding in patients
ª 2014 John Wiley & Sons Ltd
syndromes. Circulation 2006;114:774–782. 7. Iakovou I, Schmidt T, Bonizzoni E, et al. Incidence, predictors, and outcome of thrombosis after successful implantation of drug-eluting stents. JAMA 2005;293:2126–2130.
Cardiovascular Therapeutics 32 (2014) 127
127
Bivalirudin: Treatment Effect Versus Side Effect Bartosz Hudzik, Jaroslaw Gorol, Janusz Szkodzinski, Andrzej Lekston & Lech Polonski Third Department of Cardiology, Silesian Center for Heart Disease, Medical University of Silesia, Zabrze, Poland
Correspondence Dr. Bartosz Hudzik M.D., Ph.D., Third Department of Cardiology, Silesian Center for Heart Disease, Medical University of Silesia, Curie-Sklodowska 9, 41-800 Zabrze, Poland. Tel.: +48-323733788; Fax: +48-322732679; E-mail: [email protected]
doi: 10.1111/1755-5922.12071
Alexopoulos et al. [1] presented interesting data showing that in “real-life” scenario, there are no differences in one-month outcome between bivalirudin- and no bivalirudin-treated patients. When talking about bivalirudin efficacy, we have to consider two distinct features: treatment effect (antithrombotic action) and side effect (bleeding events). In HORIZONS-AMI trial, there was a reduction in cardiac mortality in the bivalirudin group that can only partly be attributed to prevention of bleeding [2]. Notwithstanding, in EUROMAX trial, there was a substantial decline in bleeding events which did not transfer into survival benefit [3]. Repeatedly, however, there was a higher incidence of stent thrombosis and a trend toward a higher incidence of myocardial infarction [3,4], despite investigators’ attempts to prevent it by prolonging bivalirudin infusion to 4 h following PCI. So actually, in terms of treatment effect, the study proved the drug not to be so efficacious.
References 1. Alexopoulos D, Xanthopoulou I, Deftereos S, et al. Bivalirudin use and one-month outcome in
Bleeding events are independently associated with a worse long-term prognosis across a wide spectrum of patients with coronary artery disease and the risk of death progresses with increasing severity of bleeding [5,6]. However, in this instance, it would seem that we have decreased the risk of side effects (excellent safety profile) at the trade-off of increasing the risk of thrombotic events – events that, one would expect, should decline using antithrombotic agent [7]. In addition, the cost of bivalirudin far exceeds that of standard treatment, thereby calling into question the ancillary benefits of the drug that would justify its use in place of the conventional regimen. Accordingly, we emphasize caution when talking about therapeutic effect. Until then, findings should be considered signals warranting further investigation.
Conflict of Interest The authors declare no conflict of interest.
Revascularization and Stents in Acute Myocardial
with coronary artery disease undergoing
Infarction). J Am Coll Cardiol 2014;63:15–20.
percutaneous coronary intervention. Circulation
3. Steg PG, van’t Hof A, Hamm CW, et al. Bivalirudin started during emergency transport
2012;125:1424–1431. 6. Eikelboom JW, Mehta SR, Anand SS, Xie C,
the context of contemporary antiplatelet
for primary PCI. N Engl J Med 2013;369:2207–
Fox KA, Yusuf S. Adverse impact of bleeding on
treatment: Insights from the Greek Antiplatelet
2217.
prognosis in patients with acute coronary
Registry. Cardiovasc Ther 2014;32:120–126. 2. Stone GW, Clayton T, Deliargyris EN, Prats J, Mehran R, Pocock SJ. Reduction in cardiac mortality with bivalirudin in patients with and
4. Stone GW, Witzenbichler B, Guagliumi G, et al. Bivalirudin during primary PCI in acute myocardial infarction. N Engl J Med 2008;358:2218–2230. 5. Ndrepepa G, Schuster T, Hadamitzky M, et al.
without major bleeding: The HORIZONS-AMI
Validation of the Bleeding Academic Research
trial (Harmonizing Outcomes with
Consortium definition of bleeding in patients
ª 2014 John Wiley & Sons Ltd
syndromes. Circulation 2006;114:774–782. 7. Iakovou I, Schmidt T, Bonizzoni E, et al. Incidence, predictors, and outcome of thrombosis after successful implantation of drug-eluting stents. JAMA 2005;293:2126–2130.
Cardiovascular Therapeutics 32 (2014) 127
127
