Balancing the risk of spontaneous ischemic and major bleeding events in acute coronary syndromes

Gregory Ducrocq, Phillip Schulte, Andrzej Budaj, Jan H. Cornel, Claes Held, Anders Himmelmann, Steen Husted, Robert F. Storey, Christopher P. Cannon, Richard C. Becker, Stefan K. James, Hugo A. Katus, Renato D. Lopes, Emmanuel Sorbets, Lars Wallentin, Philippe Gabriel Steg

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Abstract

Evaluation of antithrombotic treatments for acute coronary syndromes (ACS) requires balancing ischemic and bleeding risks to assess net benefit. We sought to compare the relative effects of ischemic and bleeding events on mortality. Methods In the PLATelet inhibition and patient Outcomes (PLATO) trial, we compared spontaneous ischemic events (myocardial infarction or stroke) with spontaneous major bleeding events (PLATO major, Thrombolysis In Myocardial Infarction [TIMI] major, Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries [GUSTO] severe) with respect to risk of mortality using time-dependent Cox proportional hazards models. The comparison was performed using ratio of hazard ratios for mortality increase after ischemic vs bleeding events. Results A total of 822 patients (4.4%) had ≥1 spontaneous ischemic event; 485 patients (2.6%), ≥1 spontaneous PLATO major bleed, 282 (1.5%), ≥1 spontaneous TIMI major bleed; and 207 (1.1%), ≥1 spontaneous severe GUSTO bleed. In patients who had both events, bleeding occurred first in most patients. Regardless of classification, major bleeding events were associated with increased short- and long-term mortality that were not significantly different from the increase associated with spontaneous ischemic events: ratio of hazard ratios (95% CIs) for short- and long-term mortality after spontaneous ischemic vs bleeding events: 1.46 (0.98-2.19) and 0.92 (0.52-1.62) (PLATO major); 1.26 (0.80-1.96) and 1.19 (0.58-2.24) (TIMI major), 0.72 (0.47-1.10) and 0.83 (0.38-1.79) (GUSTO severe) (all P > 0.05) Conclusions In patients with ACS on dual antiplatelet therapy, spontaneous major bleeding events seem “prognostically equivalent” to spontaneous ischemic complications. This result allows quantitative comparisons between both actual and predicted bleeding and ischemic risks. Our findings help to better define net clinical benefit of antithrombotic treatments and more accurately estimate mortality after ischemic and bleeding events in patients with ACS.

Original languageEnglish (US)
Pages (from-to)91-99
Number of pages9
JournalAmerican Heart Journal
Volume186
DOIs
StatePublished - Apr 1 2017

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Acute Coronary Syndrome
Hemorrhage
Mortality
Myocardial Infarction
Streptokinase
Tissue Plasminogen Activator
Proportional Hazards Models
Coronary Vessels
Therapeutics
Blood Platelets
Stroke
(1,2-diamino-4-nitrobenzene)dichloroplatinum(II)

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Balancing the risk of spontaneous ischemic and major bleeding events in acute coronary syndromes. / Ducrocq, Gregory; Schulte, Phillip; Budaj, Andrzej; Cornel, Jan H.; Held, Claes; Himmelmann, Anders; Husted, Steen; Storey, Robert F.; Cannon, Christopher P.; Becker, Richard C.; James, Stefan K.; Katus, Hugo A.; Lopes, Renato D.; Sorbets, Emmanuel; Wallentin, Lars; Steg, Philippe Gabriel.

In: American Heart Journal, Vol. 186, 01.04.2017, p. 91-99.

Research output: Contribution to journalArticle

Ducrocq, G, Schulte, P, Budaj, A, Cornel, JH, Held, C, Himmelmann, A, Husted, S, Storey, RF, Cannon, CP, Becker, RC, James, SK, Katus, HA, Lopes, RD, Sorbets, E, Wallentin, L & Steg, PG 2017, 'Balancing the risk of spontaneous ischemic and major bleeding events in acute coronary syndromes', American Heart Journal, vol. 186, pp. 91-99. https://doi.org/10.1016/j.ahj.2017.01.010
Ducrocq, Gregory ; Schulte, Phillip ; Budaj, Andrzej ; Cornel, Jan H. ; Held, Claes ; Himmelmann, Anders ; Husted, Steen ; Storey, Robert F. ; Cannon, Christopher P. ; Becker, Richard C. ; James, Stefan K. ; Katus, Hugo A. ; Lopes, Renato D. ; Sorbets, Emmanuel ; Wallentin, Lars ; Steg, Philippe Gabriel. / Balancing the risk of spontaneous ischemic and major bleeding events in acute coronary syndromes. In: American Heart Journal. 2017 ; Vol. 186. pp. 91-99.
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abstract = "Evaluation of antithrombotic treatments for acute coronary syndromes (ACS) requires balancing ischemic and bleeding risks to assess net benefit. We sought to compare the relative effects of ischemic and bleeding events on mortality. Methods In the PLATelet inhibition and patient Outcomes (PLATO) trial, we compared spontaneous ischemic events (myocardial infarction or stroke) with spontaneous major bleeding events (PLATO major, Thrombolysis In Myocardial Infarction [TIMI] major, Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries [GUSTO] severe) with respect to risk of mortality using time-dependent Cox proportional hazards models. The comparison was performed using ratio of hazard ratios for mortality increase after ischemic vs bleeding events. Results A total of 822 patients (4.4{\%}) had ≥1 spontaneous ischemic event; 485 patients (2.6{\%}), ≥1 spontaneous PLATO major bleed, 282 (1.5{\%}), ≥1 spontaneous TIMI major bleed; and 207 (1.1{\%}), ≥1 spontaneous severe GUSTO bleed. In patients who had both events, bleeding occurred first in most patients. Regardless of classification, major bleeding events were associated with increased short- and long-term mortality that were not significantly different from the increase associated with spontaneous ischemic events: ratio of hazard ratios (95{\%} CIs) for short- and long-term mortality after spontaneous ischemic vs bleeding events: 1.46 (0.98-2.19) and 0.92 (0.52-1.62) (PLATO major); 1.26 (0.80-1.96) and 1.19 (0.58-2.24) (TIMI major), 0.72 (0.47-1.10) and 0.83 (0.38-1.79) (GUSTO severe) (all P > 0.05) Conclusions In patients with ACS on dual antiplatelet therapy, spontaneous major bleeding events seem “prognostically equivalent” to spontaneous ischemic complications. This result allows quantitative comparisons between both actual and predicted bleeding and ischemic risks. Our findings help to better define net clinical benefit of antithrombotic treatments and more accurately estimate mortality after ischemic and bleeding events in patients with ACS.",
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AU - Ducrocq, Gregory

AU - Schulte, Phillip

AU - Budaj, Andrzej

AU - Cornel, Jan H.

AU - Held, Claes

AU - Himmelmann, Anders

AU - Husted, Steen

AU - Storey, Robert F.

AU - Cannon, Christopher P.

AU - Becker, Richard C.

AU - James, Stefan K.

AU - Katus, Hugo A.

AU - Lopes, Renato D.

AU - Sorbets, Emmanuel

AU - Wallentin, Lars

AU - Steg, Philippe Gabriel

PY - 2017/4/1

Y1 - 2017/4/1

N2 - Evaluation of antithrombotic treatments for acute coronary syndromes (ACS) requires balancing ischemic and bleeding risks to assess net benefit. We sought to compare the relative effects of ischemic and bleeding events on mortality. Methods In the PLATelet inhibition and patient Outcomes (PLATO) trial, we compared spontaneous ischemic events (myocardial infarction or stroke) with spontaneous major bleeding events (PLATO major, Thrombolysis In Myocardial Infarction [TIMI] major, Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries [GUSTO] severe) with respect to risk of mortality using time-dependent Cox proportional hazards models. The comparison was performed using ratio of hazard ratios for mortality increase after ischemic vs bleeding events. Results A total of 822 patients (4.4%) had ≥1 spontaneous ischemic event; 485 patients (2.6%), ≥1 spontaneous PLATO major bleed, 282 (1.5%), ≥1 spontaneous TIMI major bleed; and 207 (1.1%), ≥1 spontaneous severe GUSTO bleed. In patients who had both events, bleeding occurred first in most patients. Regardless of classification, major bleeding events were associated with increased short- and long-term mortality that were not significantly different from the increase associated with spontaneous ischemic events: ratio of hazard ratios (95% CIs) for short- and long-term mortality after spontaneous ischemic vs bleeding events: 1.46 (0.98-2.19) and 0.92 (0.52-1.62) (PLATO major); 1.26 (0.80-1.96) and 1.19 (0.58-2.24) (TIMI major), 0.72 (0.47-1.10) and 0.83 (0.38-1.79) (GUSTO severe) (all P > 0.05) Conclusions In patients with ACS on dual antiplatelet therapy, spontaneous major bleeding events seem “prognostically equivalent” to spontaneous ischemic complications. This result allows quantitative comparisons between both actual and predicted bleeding and ischemic risks. Our findings help to better define net clinical benefit of antithrombotic treatments and more accurately estimate mortality after ischemic and bleeding events in patients with ACS.

AB - Evaluation of antithrombotic treatments for acute coronary syndromes (ACS) requires balancing ischemic and bleeding risks to assess net benefit. We sought to compare the relative effects of ischemic and bleeding events on mortality. Methods In the PLATelet inhibition and patient Outcomes (PLATO) trial, we compared spontaneous ischemic events (myocardial infarction or stroke) with spontaneous major bleeding events (PLATO major, Thrombolysis In Myocardial Infarction [TIMI] major, Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries [GUSTO] severe) with respect to risk of mortality using time-dependent Cox proportional hazards models. The comparison was performed using ratio of hazard ratios for mortality increase after ischemic vs bleeding events. Results A total of 822 patients (4.4%) had ≥1 spontaneous ischemic event; 485 patients (2.6%), ≥1 spontaneous PLATO major bleed, 282 (1.5%), ≥1 spontaneous TIMI major bleed; and 207 (1.1%), ≥1 spontaneous severe GUSTO bleed. In patients who had both events, bleeding occurred first in most patients. Regardless of classification, major bleeding events were associated with increased short- and long-term mortality that were not significantly different from the increase associated with spontaneous ischemic events: ratio of hazard ratios (95% CIs) for short- and long-term mortality after spontaneous ischemic vs bleeding events: 1.46 (0.98-2.19) and 0.92 (0.52-1.62) (PLATO major); 1.26 (0.80-1.96) and 1.19 (0.58-2.24) (TIMI major), 0.72 (0.47-1.10) and 0.83 (0.38-1.79) (GUSTO severe) (all P > 0.05) Conclusions In patients with ACS on dual antiplatelet therapy, spontaneous major bleeding events seem “prognostically equivalent” to spontaneous ischemic complications. This result allows quantitative comparisons between both actual and predicted bleeding and ischemic risks. Our findings help to better define net clinical benefit of antithrombotic treatments and more accurately estimate mortality after ischemic and bleeding events in patients with ACS.

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