correspondence
PARADIGM-HF started, cardiac resynchronization therapy was not indicated in most patients in the trial, who had New York Heart Association functional class II symptoms.2,3 Although ICDs were seldom used globally, such devices were implanted in 54% of patients in North America. The benefits of LCZ696 were consistent across geographic regions, and the hazard ratio for death from cardiovascular causes in the LCZ696 group, as compared with the enalapril group, was 0.76 (95% confidence interval [CI], 0.55 to 1.05) in patients with an ICD and 0.80 (95% CI, 0.71 to 0.90) in those without an ICD (P = 0.92 for the interaction between the baseline use of an ICD and the effect of LCZ696). Approximately half the patients were receiving 50% or more of the target dose of betablockers. The hazard ratio for the primary end point in the LCZ696 group versus the enalapril group was 0.79 (95% CI, 0.70 to 0.90) in the subgroup that received less than 50% of the target dose and 0.85 (95% CI, 0.74 to 0.97) in the subgroup that received 50% or more (P = 0.44 for the interaction between the baseline beta-blocker dose and the effect of LCZ696). Finally, in reply to Timmis: in the Supplementary Appendix of our article (available at NEJM .org), we reported daily doses of ACE inhibitors received at the screening visit. Enalapril was the most common ACE inhibitor received by patients before entering the study. The mean daily dose at the screening visit was 16.4 mg, and 93% of the patients received 20 mg or less at that visit. Overall, the mean daily dose of enalapril re-
ceived after randomization was 18.9 mg. Therefore, there was no decrease in intensity of renin– angiotensin system blockade in the enalapril group, and the lower blood pressure in the LCZ696 group reflected the addition of neprilysin inhibition. As we explained in our article, the benefit of LCZ696 over enalapril was not explained by the small difference in blood pressure. John J.V. McMurray, M.D. British Heart Foundation Cardiovascular Research Centre Glasgow, United Kingdom [email protected]
Milton Packer, M.D. University of Texas Southwestern Medical Center Dallas, TX
Scott D. Solomon, M.D. Brigham and Women’s Hospital Boston, MA Since publication of their article, the authors report no further potential conflict of interest. 1. Nalivaeva NN, Belyaev ND, Kerridge C, Turner AJ. Amyloid-
clearing proteins and their epigenetic regulation as a therapeutic target in Alzheimer’s disease. Front Aging Neurosci 2014;6:235. 2. Jessup M, Abraham WT, Casey DE, et al. 2009 Focused update: ACCF/AHA Guidelines for the Diagnosis and Management of Heart Failure in Adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: developed in collaboration with the International Society for Heart and Lung Transplantation. Circulation 2009;119:1977-2016. 3. Dickstein K, Cohen-Solal A, Filippatos G, et al. ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2008 of the European Society of Cardiology. Eur J Heart Fail 2008;10:933-89. [Errata, Eur Heart J Fail 2009;11:110; 2010;12:416.] DOI: 10.1056/NEJMc1412654
Prehospital Ticagrelor in ST-Segment Elevation Myocardial Infarction To the Editor: The negative results of the ATLANTIC (Administration of Ticagrelor in the Cath Lab or in the Ambulance for New ST Elevation Myocardial Infarction to Open the Coronary Artery) trial reported by Montalescot et al. (Sept. 11 issue)1 are not unexpected, since previous pharmacodynamic studies2,3 have shown that several hours are required to achieve effective platelet inhibition in patients with myocardial infarction who receive a standard loading dose of
ticagrelor. In the ATLANTIC trial, prehospital administration, as compared with in-hospital use, allowed a median time difference of only 31 minutes between the two loading doses. Thus, the time interval from administration of the loading doses to evaluation of the coprimary end points was too short for optimal absorption of ticagrelor and the onset of action, so that actually two placebo groups were compared. It has been reported that ticagrelor tablets
n engl j med 371;24 nejm.org december 11, 2014
The New England Journal of Medicine Downloaded from nejm.org on December 26, 2014. For personal use only. No other uses without permission. Copyright © 2014 Massachusetts Medical Society. All rights reserved.
2337
The
n e w e ng l a n d j o u r na l
could be easily crushed to deliver the full dose of the original tablet4 and theoretically allow faster absorption of the drug. Recently, the new opportunity to anticipate the onset of action of the antiplatelet effect of ticagrelor with the use of crushed rather than whole tablets of an equal dose has been proposed for patients with myocardial infarction.5 Data are lacking on the combination of the early use of ticagrelor (at the first medical contact) and administration of the crushed form of the drug. Guido Parodi, M.D. Careggi University Hospital Florence, Italy [email protected]
m e dic i n e
hospital group, P = 0.04 by Fisher’s exact test) (see Table S4 in the Supplementary Appendix, available with the full text of the article at NEJM .org). In our opinion, the conclusion that “prehospital administration of ticagrelor in patients with acute STEMI [ST-segment elevation myocardial infarction] appeared to be safe” should not be drawn. Do the authors have a possible explanation for the significantly higher rate of early death? Stefan Toggweiler, M.D. Zaid Sabti, M.D. Florim Cuculi, M.D. Luzerner Kantonsspital Lucerne, Switzerland [email protected]
Dimitrios Alexopoulos, M.D. Patras University Hospital Patras, Greece Dr. Parodi reports receiving consulting fees from Daiichi Sankyo and Eli Lilly, AstraZeneca, Bayer, and the Medicines Company and lecture fees from Daiichi Sankyo and Eli Lilly and AstraZeneca; and Dr. Alexopoulos, lecture fees from AstraZeneca. No other potential conflict of interest relevant to this letter was reported. 1. Montalescot G, van ’t Hof AW, Lapostolle F, et al. Prehospital
ticagrelor in ST-segment elevation myocardial infarction. N Engl J Med 2014;371:1016-27. 2. Alexopoulos D, Xanthopoulou I, Gkizas V, et al. Randomized assessment of ticagrelor versus prasugrel antiplatelet effects in patients with ST-segment-elevation myocardial infarction. Circ Cardiovasc Interv 2012;5:797-804. 3. Parodi G, Valenti R, Bellandi B, et al. Comparison of prasugrel and ticagrelor loading doses in ST-segment elevation myocardial infarction patients: RAPID (Rapid Activity of Platelet Inhibitor Drugs) primary PCI study. J Am Coll Cardiol 2013;61: 1601-6. 4. Crean B, Finnie C, Crosby A. Evaluation of crushed ticagrelor tablet doses: recovery following crushing and naso-gastric tube passage ex vivo. Drugs R D 2013;13:153-7. 5. Parodi G, Xanthopoulou I, Bellandi B, et al. Ticagrelor crushed tablets administration in STEMI patients: the Mashed Or Just Integral Tablets of ticagrelOr (MOJITO) study. J Am Coll Cardiol (in press). DOI: 10.1056/NEJMoa1412729
To the Editor: Montalescot et al. report that during the first 24 hours after the index percutaneous coronary intervention (PCI), definite stent thrombosis occurred less frequently in patients who received prehospital treatment with ticagrelor.1 Despite the lower rate of definite stent thrombosis, more patients died during the first 24 hours after early administration of ticagrelor (12 of 906 patients [1.3%] in the prehospital group vs. 4 of 952 patients [0.4%] in the in-
2338
of
Dr. Toggweiler reports receiving lecture fees from Edwards Lifesciences and Medtronic; and Dr. Cuculi, lecture fees from AstraZeneca and Eli Lilly. No other potential conflict of interest relevant to this letter was reported. DOI: 10.1056/NEJMoa1412729
To the Editor: Montalescot et al. describe the timing of administration of ticagrelor in patients with STEMI who were undergoing primary PCI. The authors did not find differences in pre-PCI reperfusion, defined as 70% or greater resolution of ST-segment elevation or Thrombolysis in Myocardial Infarction (TIMI) flow grade 3, between patients receiving prehospital treatment and those receiving in-hospital treatment with ticagrelor. However, the rates of definite stent thrombosis were lower in the prehospital group than in the in-hospital group both at 24 hours and at 30 days, so the authors concluded that prehospital administration of ticagrelor may prevent acute stent thrombosis. Besides antiplatelet therapy, the authors did not consider important angiographic predictors of acute stent thrombosis such as coronary-stent undersizing, which is particularly frequent in patients with STEMI because of high thrombotic burden and subsequent vasoconstriction, and coronary atherosclerosis burden (in particular, the presence of intermediate lesions proximal and distal to the culprit site).1,2 Can the authors provide details about baseline and post-PCI angiographic analysis to clarify the role of prehospital administration of ticagrelor in the prevention of acute stent thrombosis?
n engl j med 371;24 nejm.org december 11, 2014
The New England Journal of Medicine Downloaded from nejm.org on December 26, 2014. For personal use only. No other uses without permission. Copyright © 2014 Massachusetts Medical Society. All rights reserved.
correspondence
Rocco A. Montone, M.D. Stephen P. Hoole, M.D. Nick E.J. West, M.D. Papworth Hospital NHS Foundation Trust Cambridge, United Kingdom [email protected] No potential conflict of interest relevant to this letter was reported. 1. Aoki J, Lansky AJ, Mehran R, et al. Early stent thrombosis in
patients with acute coronary syndromes treated with drug-eluting and bare metal stents: the Acute Catheterization and Urgent Intervention Triage Strategy trial. Circulation 2009;119:687-98. 2. van Werkum JW, Heestermans AA, Zomer AC, et al. Predictors of coronary stent thrombosis: the Dutch Stent Thrombosis Registry. J Am Coll Cardiol 2009;53:1399-409. DOI: 10.1056/NEJMoa1412729
sis at both 24 hours (P = 0.008) and 30 days (P = 0.02). We believe that the numerical difference in overall mortality may be partly explained by the fact that higher-risk patients (i.e., patients with a TIMI risk score >6) were recruited into the prehospital group (Table 1 of the article). The causes of death were mostly related to cardiogenic shock, cardiac arrest, or cardiac rupture rather than to bleeding or ischemic events (Table S4 in the Supplementary Appendix of the article). The same treatment was used in both groups, and the delay between loading doses was only 31 minutes. Therefore, a causality relationship between death at 30 days and the time to drug administration is unlikely and difficult to explain on a rational basis. The play of chance is a more likely explanation. We understand the concern about the risk factors for stent thrombosis mentioned by Montone et al. However, stent thrombosis is a multifactorial complication, and there are even stronger risk factors such as diabetes, reduced left ventricular function, complex lesions, and certain genotypes.3 Moreover, there is no reason to believe that risk factors would be represented differently in the two groups of this randomized study. The history of cardiovascular events was well balanced between the treatment groups (Table S2 in the Supplementary Appendix of the article), and there were no differences in terms of the culprit vessel, type of lesion, TIMI flow grade, or myocardial perfusion grade before or after PCI. Gilles Montalescot, M.D., Ph.D.
The Authors Reply: In response to Parodi and Alexopoulos: we suggest caution before stating that several hours are needed for oral ticagrelor to take effect. The results of our platelet-function substudy showed a global, significant early decrease in platelet reactivity and suggested a differential effect between the two groups immediately after the end of PCI, at 1 hours 17 minutes after the first loading dose (Fig. S2 in the Supplementary Appendix of our article). These data are consistent with the substudy that was performed to evaluate the effect of prasugrel on the inhibition of platelet aggregation in the ACCOAST (Comparison of Prasugrel at the Time of Percutaneous Coronary Intervention (PCI) or as Pretreatment at the Time of Diagnosis in Patients with Non-ST Elevation Myocardial Infarction) trial.1 In our study, a benefit was observed with prehospital administration of ticagrelor in terms of resolution of ST-segment elevation after PCI Pitié–Salpêtrière Hospital (P = 0.05) (Table 2 of the article) and in patients Paris, France who did not receive morphine before PCI (P = 0.005 [email protected] for interaction) (Fig. S4 in the Supplementary Ap- Arnoud W. van ‘t Hof, M.D., Ph.D. Clinics pendix of the article). Whether crushed ticagrelor Isala Zwolle, the Netherlands is more effective for reperfusion or the clinical Since publication of their article, the authors report no furoutcome is unknown.2 ther potential conflict of interest. In response to Toggweiler et al.: we described 1. Montalescot G, Bolognese L, Dudek D, et al. Pretreatment the difference in the number of deaths between with prasugrel in non–ST-segment elevation acute coronary synthe groups. However, the numerical difference in dromes. N Engl J Med 2013;369:999-1010. Parodi G, Xanthopoulou I, Bellandi B, et al. Ticagrelor overall mortality between the groups at 30 days 2. Crushed Tablets Administration in STEMI patients: The Mashed was not significant (30 patients [3.3%] in the pre- Or Just Integral Tablets of ticagrel Or (MOJITO) study. J Am Coll hospital group vs. 19 patients [2.0%] in the in- Cardiol (in press). Cayla G, Hulot J-S, O’Connor SA, et al. Clinical, angiographhospital group; P = 0.08), whereas there was a 3. ic, and genetic factors associated with early coronary stent statistically significant between-group differ- thrombosis. JAMA 2011;306:1765-74. ence in the reduction in definite stent thrombo- DOI: 10.1056/NEJMoa1412729
n engl j med 371;24 nejm.org december 11, 2014
The New England Journal of Medicine Downloaded from nejm.org on December 26, 2014. For personal use only. No other uses without permission. Copyright © 2014 Massachusetts Medical Society. All rights reserved.
2339
PARADIGM-HF started, cardiac resynchronization therapy was not indicated in most patients in the trial, who had New York Heart Association functional class II symptoms.2,3 Although ICDs were seldom used globally, such devices were implanted in 54% of patients in North America. The benefits of LCZ696 were consistent across geographic regions, and the hazard ratio for death from cardiovascular causes in the LCZ696 group, as compared with the enalapril group, was 0.76 (95% confidence interval [CI], 0.55 to 1.05) in patients with an ICD and 0.80 (95% CI, 0.71 to 0.90) in those without an ICD (P = 0.92 for the interaction between the baseline use of an ICD and the effect of LCZ696). Approximately half the patients were receiving 50% or more of the target dose of betablockers. The hazard ratio for the primary end point in the LCZ696 group versus the enalapril group was 0.79 (95% CI, 0.70 to 0.90) in the subgroup that received less than 50% of the target dose and 0.85 (95% CI, 0.74 to 0.97) in the subgroup that received 50% or more (P = 0.44 for the interaction between the baseline beta-blocker dose and the effect of LCZ696). Finally, in reply to Timmis: in the Supplementary Appendix of our article (available at NEJM .org), we reported daily doses of ACE inhibitors received at the screening visit. Enalapril was the most common ACE inhibitor received by patients before entering the study. The mean daily dose at the screening visit was 16.4 mg, and 93% of the patients received 20 mg or less at that visit. Overall, the mean daily dose of enalapril re-
ceived after randomization was 18.9 mg. Therefore, there was no decrease in intensity of renin– angiotensin system blockade in the enalapril group, and the lower blood pressure in the LCZ696 group reflected the addition of neprilysin inhibition. As we explained in our article, the benefit of LCZ696 over enalapril was not explained by the small difference in blood pressure. John J.V. McMurray, M.D. British Heart Foundation Cardiovascular Research Centre Glasgow, United Kingdom [email protected]
Milton Packer, M.D. University of Texas Southwestern Medical Center Dallas, TX
Scott D. Solomon, M.D. Brigham and Women’s Hospital Boston, MA Since publication of their article, the authors report no further potential conflict of interest. 1. Nalivaeva NN, Belyaev ND, Kerridge C, Turner AJ. Amyloid-
clearing proteins and their epigenetic regulation as a therapeutic target in Alzheimer’s disease. Front Aging Neurosci 2014;6:235. 2. Jessup M, Abraham WT, Casey DE, et al. 2009 Focused update: ACCF/AHA Guidelines for the Diagnosis and Management of Heart Failure in Adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: developed in collaboration with the International Society for Heart and Lung Transplantation. Circulation 2009;119:1977-2016. 3. Dickstein K, Cohen-Solal A, Filippatos G, et al. ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2008 of the European Society of Cardiology. Eur J Heart Fail 2008;10:933-89. [Errata, Eur Heart J Fail 2009;11:110; 2010;12:416.] DOI: 10.1056/NEJMc1412654
Prehospital Ticagrelor in ST-Segment Elevation Myocardial Infarction To the Editor: The negative results of the ATLANTIC (Administration of Ticagrelor in the Cath Lab or in the Ambulance for New ST Elevation Myocardial Infarction to Open the Coronary Artery) trial reported by Montalescot et al. (Sept. 11 issue)1 are not unexpected, since previous pharmacodynamic studies2,3 have shown that several hours are required to achieve effective platelet inhibition in patients with myocardial infarction who receive a standard loading dose of
ticagrelor. In the ATLANTIC trial, prehospital administration, as compared with in-hospital use, allowed a median time difference of only 31 minutes between the two loading doses. Thus, the time interval from administration of the loading doses to evaluation of the coprimary end points was too short for optimal absorption of ticagrelor and the onset of action, so that actually two placebo groups were compared. It has been reported that ticagrelor tablets
n engl j med 371;24 nejm.org december 11, 2014
The New England Journal of Medicine Downloaded from nejm.org on December 26, 2014. For personal use only. No other uses without permission. Copyright © 2014 Massachusetts Medical Society. All rights reserved.
2337
The
n e w e ng l a n d j o u r na l
could be easily crushed to deliver the full dose of the original tablet4 and theoretically allow faster absorption of the drug. Recently, the new opportunity to anticipate the onset of action of the antiplatelet effect of ticagrelor with the use of crushed rather than whole tablets of an equal dose has been proposed for patients with myocardial infarction.5 Data are lacking on the combination of the early use of ticagrelor (at the first medical contact) and administration of the crushed form of the drug. Guido Parodi, M.D. Careggi University Hospital Florence, Italy [email protected]
m e dic i n e
hospital group, P = 0.04 by Fisher’s exact test) (see Table S4 in the Supplementary Appendix, available with the full text of the article at NEJM .org). In our opinion, the conclusion that “prehospital administration of ticagrelor in patients with acute STEMI [ST-segment elevation myocardial infarction] appeared to be safe” should not be drawn. Do the authors have a possible explanation for the significantly higher rate of early death? Stefan Toggweiler, M.D. Zaid Sabti, M.D. Florim Cuculi, M.D. Luzerner Kantonsspital Lucerne, Switzerland [email protected]
Dimitrios Alexopoulos, M.D. Patras University Hospital Patras, Greece Dr. Parodi reports receiving consulting fees from Daiichi Sankyo and Eli Lilly, AstraZeneca, Bayer, and the Medicines Company and lecture fees from Daiichi Sankyo and Eli Lilly and AstraZeneca; and Dr. Alexopoulos, lecture fees from AstraZeneca. No other potential conflict of interest relevant to this letter was reported. 1. Montalescot G, van ’t Hof AW, Lapostolle F, et al. Prehospital
ticagrelor in ST-segment elevation myocardial infarction. N Engl J Med 2014;371:1016-27. 2. Alexopoulos D, Xanthopoulou I, Gkizas V, et al. Randomized assessment of ticagrelor versus prasugrel antiplatelet effects in patients with ST-segment-elevation myocardial infarction. Circ Cardiovasc Interv 2012;5:797-804. 3. Parodi G, Valenti R, Bellandi B, et al. Comparison of prasugrel and ticagrelor loading doses in ST-segment elevation myocardial infarction patients: RAPID (Rapid Activity of Platelet Inhibitor Drugs) primary PCI study. J Am Coll Cardiol 2013;61: 1601-6. 4. Crean B, Finnie C, Crosby A. Evaluation of crushed ticagrelor tablet doses: recovery following crushing and naso-gastric tube passage ex vivo. Drugs R D 2013;13:153-7. 5. Parodi G, Xanthopoulou I, Bellandi B, et al. Ticagrelor crushed tablets administration in STEMI patients: the Mashed Or Just Integral Tablets of ticagrelOr (MOJITO) study. J Am Coll Cardiol (in press). DOI: 10.1056/NEJMoa1412729
To the Editor: Montalescot et al. report that during the first 24 hours after the index percutaneous coronary intervention (PCI), definite stent thrombosis occurred less frequently in patients who received prehospital treatment with ticagrelor.1 Despite the lower rate of definite stent thrombosis, more patients died during the first 24 hours after early administration of ticagrelor (12 of 906 patients [1.3%] in the prehospital group vs. 4 of 952 patients [0.4%] in the in-
2338
of
Dr. Toggweiler reports receiving lecture fees from Edwards Lifesciences and Medtronic; and Dr. Cuculi, lecture fees from AstraZeneca and Eli Lilly. No other potential conflict of interest relevant to this letter was reported. DOI: 10.1056/NEJMoa1412729
To the Editor: Montalescot et al. describe the timing of administration of ticagrelor in patients with STEMI who were undergoing primary PCI. The authors did not find differences in pre-PCI reperfusion, defined as 70% or greater resolution of ST-segment elevation or Thrombolysis in Myocardial Infarction (TIMI) flow grade 3, between patients receiving prehospital treatment and those receiving in-hospital treatment with ticagrelor. However, the rates of definite stent thrombosis were lower in the prehospital group than in the in-hospital group both at 24 hours and at 30 days, so the authors concluded that prehospital administration of ticagrelor may prevent acute stent thrombosis. Besides antiplatelet therapy, the authors did not consider important angiographic predictors of acute stent thrombosis such as coronary-stent undersizing, which is particularly frequent in patients with STEMI because of high thrombotic burden and subsequent vasoconstriction, and coronary atherosclerosis burden (in particular, the presence of intermediate lesions proximal and distal to the culprit site).1,2 Can the authors provide details about baseline and post-PCI angiographic analysis to clarify the role of prehospital administration of ticagrelor in the prevention of acute stent thrombosis?
n engl j med 371;24 nejm.org december 11, 2014
The New England Journal of Medicine Downloaded from nejm.org on December 26, 2014. For personal use only. No other uses without permission. Copyright © 2014 Massachusetts Medical Society. All rights reserved.
correspondence
Rocco A. Montone, M.D. Stephen P. Hoole, M.D. Nick E.J. West, M.D. Papworth Hospital NHS Foundation Trust Cambridge, United Kingdom [email protected] No potential conflict of interest relevant to this letter was reported. 1. Aoki J, Lansky AJ, Mehran R, et al. Early stent thrombosis in
patients with acute coronary syndromes treated with drug-eluting and bare metal stents: the Acute Catheterization and Urgent Intervention Triage Strategy trial. Circulation 2009;119:687-98. 2. van Werkum JW, Heestermans AA, Zomer AC, et al. Predictors of coronary stent thrombosis: the Dutch Stent Thrombosis Registry. J Am Coll Cardiol 2009;53:1399-409. DOI: 10.1056/NEJMoa1412729
sis at both 24 hours (P = 0.008) and 30 days (P = 0.02). We believe that the numerical difference in overall mortality may be partly explained by the fact that higher-risk patients (i.e., patients with a TIMI risk score >6) were recruited into the prehospital group (Table 1 of the article). The causes of death were mostly related to cardiogenic shock, cardiac arrest, or cardiac rupture rather than to bleeding or ischemic events (Table S4 in the Supplementary Appendix of the article). The same treatment was used in both groups, and the delay between loading doses was only 31 minutes. Therefore, a causality relationship between death at 30 days and the time to drug administration is unlikely and difficult to explain on a rational basis. The play of chance is a more likely explanation. We understand the concern about the risk factors for stent thrombosis mentioned by Montone et al. However, stent thrombosis is a multifactorial complication, and there are even stronger risk factors such as diabetes, reduced left ventricular function, complex lesions, and certain genotypes.3 Moreover, there is no reason to believe that risk factors would be represented differently in the two groups of this randomized study. The history of cardiovascular events was well balanced between the treatment groups (Table S2 in the Supplementary Appendix of the article), and there were no differences in terms of the culprit vessel, type of lesion, TIMI flow grade, or myocardial perfusion grade before or after PCI. Gilles Montalescot, M.D., Ph.D.
The Authors Reply: In response to Parodi and Alexopoulos: we suggest caution before stating that several hours are needed for oral ticagrelor to take effect. The results of our platelet-function substudy showed a global, significant early decrease in platelet reactivity and suggested a differential effect between the two groups immediately after the end of PCI, at 1 hours 17 minutes after the first loading dose (Fig. S2 in the Supplementary Appendix of our article). These data are consistent with the substudy that was performed to evaluate the effect of prasugrel on the inhibition of platelet aggregation in the ACCOAST (Comparison of Prasugrel at the Time of Percutaneous Coronary Intervention (PCI) or as Pretreatment at the Time of Diagnosis in Patients with Non-ST Elevation Myocardial Infarction) trial.1 In our study, a benefit was observed with prehospital administration of ticagrelor in terms of resolution of ST-segment elevation after PCI Pitié–Salpêtrière Hospital (P = 0.05) (Table 2 of the article) and in patients Paris, France who did not receive morphine before PCI (P = 0.005 [email protected] for interaction) (Fig. S4 in the Supplementary Ap- Arnoud W. van ‘t Hof, M.D., Ph.D. Clinics pendix of the article). Whether crushed ticagrelor Isala Zwolle, the Netherlands is more effective for reperfusion or the clinical Since publication of their article, the authors report no furoutcome is unknown.2 ther potential conflict of interest. In response to Toggweiler et al.: we described 1. Montalescot G, Bolognese L, Dudek D, et al. Pretreatment the difference in the number of deaths between with prasugrel in non–ST-segment elevation acute coronary synthe groups. However, the numerical difference in dromes. N Engl J Med 2013;369:999-1010. Parodi G, Xanthopoulou I, Bellandi B, et al. Ticagrelor overall mortality between the groups at 30 days 2. Crushed Tablets Administration in STEMI patients: The Mashed was not significant (30 patients [3.3%] in the pre- Or Just Integral Tablets of ticagrel Or (MOJITO) study. J Am Coll hospital group vs. 19 patients [2.0%] in the in- Cardiol (in press). Cayla G, Hulot J-S, O’Connor SA, et al. Clinical, angiographhospital group; P = 0.08), whereas there was a 3. ic, and genetic factors associated with early coronary stent statistically significant between-group differ- thrombosis. JAMA 2011;306:1765-74. ence in the reduction in definite stent thrombo- DOI: 10.1056/NEJMoa1412729
n engl j med 371;24 nejm.org december 11, 2014
The New England Journal of Medicine Downloaded from nejm.org on December 26, 2014. For personal use only. No other uses without permission. Copyright © 2014 Massachusetts Medical Society. All rights reserved.
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