2266
JACC VOL. 66, NO. 20, 2015
Letters
NOVEMBER 17/24, 2015:2263–8
2. Mahajan R, Lau DH, Brooks AG, et al. Electrophysiological, electroanatomical, and structural remodeling of the atria as consequences of sustained obesity. J Am Coll Cardiol 2015;66:1–11. 3. Pathak RK, Middeldorp ME, Lau DH, et al. Aggressive risk factor reduction study for atrial fibrillation and implications for the outcome of ablation: the ARREST-AF cohort study. J Am Coll Cardiol 2014;64: 2222–31.
*Ramez Nairooz, MD Karam Ayoub, MD David Shavelle, MD *Division of Cardiology University of Arkansas for Medical Sciences 4301 West Markham, Slot 532
4. Pathak RK, Elliott A, Middeldorp ME, et al. Impact of CARDIOrespiratory FITness on arrhythmia recurrence in obese individuals with atrial fibrillation: the CARDIO-FIT study. J Am Coll Cardiol 2015;66:985–96.
Little Rock, Arkansas 72205-7199 E-mail: [email protected] http://dx.doi.org/10.1016/j.jacc.2015.07.085 Please note: Dr. Shavelle has received research grants from Zoll Medical, Abbott Vascular, St. Jude Medical, and Neostem; and is on the speakers bureau of Maquet, Medtronic, and St. Jude Medical. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
Duration of Triple Therapy A Clinical Question Yet to Be Answered
We commend the authors of the recently pub-
REFERENCE
lished ISAR-TRIPLE (Duration of Triple Therapy in
1. Fiedler KA, Maeng M, Mehilli J, et al. Duration of Triple Therapy in Patients
Patients Requiring Oral Anticoagulation After Drug
Requiring Oral Anticoagulation After Drug-Eluting Stent Implantation: the ISAR-TRIPLE trial. J Am Coll Cardiol 2015;65:1619–29.
Eluting Stent Implantation) clinical trial on their efforts (1). The trial adds valuable information to
the
ongoing
debate
of
antiplatelet
REPLY: Duration of Triple Therapy
and
anticoagulation management in patients on chronic oral anticoagulation who undergo coronary artery stenting; however, we would like to address several important points:
A Clinical Question Yet to Be Answered
We thank Dr. Nairooz and colleagues for the comments regarding the results of our ISAR TRIPLE trial (Duration of Triple Therapy in Patients Requiring Oral
1. The authors mention that the clopidogrel loading
Anticoagulation After Drug Eluting Stent Implanta-
dose was 300 mg to 600 mg, but they do not
tion) (1) and are happy to provide our answers to his
mention specific data about the loading dose in
3 questions:
each of the treatment arms. Given the numerically higher periprocedural myocardial infarctions observed in the 6-weeks group, could a preferential
lower
clopidogrel
loading
dose
have
affected this outcome? It would be interesting to know such data, as well as the repeat revascularization data. 2. There are no data about the prevalence of chronic kidney disease in each of the 2 treatment arms. Chronic kidney disease patients are prone to a higher risk of bleeding, and thus it is important to know whether such data could have affected the results. 3. The decision to present 9-month data as opposed to longer follow-up, especially with the relatively small sample, raises questions about the power of the study to depict differences in ischemic outcomes. In conclusion, the optimal duration of triple therapy is a question that remains unanswered, and for
1. Only 5% of the patients (n ¼ 30) in the ISAR TRIPLE trial were loaded with 300-mg clopidogrel, and they were evenly distributed in the 2 study arms. Interestingly, all patients who developed myocardial infarction had a loading dose of 600-mg clopidogrel. 2. The lack of treatment effect regarding the primary combined endpoint was consistent in the prespecified subgroup analysis according to renal function and this, as well as the prevalence of reduced renal function, was already shown in Online Figure 2. Dr. Nairooz and colleagues are concerned that patients with chronic kidney disease may have experienced higher bleeding rates; however, there was also no association with renal function and the occurrence of the secondary endpoint Thrombolysis In Myocardial Infarction major bleeding (p for interaction ¼ 0.89) or any bleeding according to Bleeding Academic Research Consortium (p for interaction ¼ 0.70).
now, mostly relies on physicians weighing the
3. A longer follow-up period for the evaluation of
ischemic versus bleeding risk with short compared to
treatment effect would have been inappropriate
extended duration of therapy. A large, randomized
because the protocol did not define differences in
trial comparing these various treatment options is
antiplatelet therapy after 6 months in the 2 study
needed.
arms. Thus, ischemic complications occurring after
JACC VOL. 66, NO. 20, 2015
Letters
NOVEMBER 17/24, 2015:2263–8
this time point may not be attributed to duration of
stress echocardiography emerged as the ultimate
clopidogrel therapy.
“winner.” It is well known that the negative predictive value of
*Nikolaus Sarafoff, MD Robert A. Byrne, MB, BCH, PhD Julinda Mehilli, MD Dirk Sibbing, MD Steen D. Kristensen, MD Karl-Ludwig Laugwitz, MD Michael Maeng, MD Adnan Kastrati, MD *Klinikum der Universität München Ludwig-Maximilians Universität Medizinische Klinik und Poliklinik I Marchioninistrasse 15 Munich 81377 Germany E-mail: [email protected] http://dx.doi.org/10.1016/j.jacc.2015.08.886 Please note: Dr. Sarafoff has received fees for lectures or traveling from Lilly/ Daiichi-Sankyo, Boehringer Ingelheim, AstraZeneca, Bayer Healthcare, Boston Scientific, Biotronik, and Medtronic. Dr. Byrne has received lecture fees from B. Braun and Biotronik; and has received fees for lectures, advisory board service, or traveling from Abbott Vascular and Medtronic. Dr. Mehilli has received fees for lectures and advisory board service from Abbot Vascular, Terumo, and Lilly/Daiichi-Sankyo. Dr. Sibbing has received speaker fees and honoraria for consulting from Eli Lilly, Daiichi-Sankyo, Bayer Vital, AstraZeneca, Verum Diagnostica, and Roche Diagnostics; and has received research grants from Roche Diagnostics. Dr. Kristensen has received lecture fees from AstraZeneca, Eli Lilly, Sanofi, and The Medicines Company. Dr. Kastrati has received payments for lectures or event adjudication activity from Abbott, AstraZeneca, Biosensors, Biotronik, Daiichi-Sankyo, MSD, and The Medicines Company; and holds patents related to stent technology. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
REFERENCE 1. Fiedler KA, Maeng M, Mehilli J, et al. Duration of Triple Therapy in Patients Requiring Oral Anticoagulation After Drug-Eluting Stent Implantation: the ISAR-TRIPLE trial. J Am Coll Cardiol 2015;65:1619–29.
CCTA
for
coronary
disease
in
low-
and
low-
intermediate-risk patients is high. But the clinically meaningful outcome benefit of CCTA versus physiological modalities has not yet been convincingly demonstrated. On the other hand, CCTA is associated with contrast and radiation exposure in these younger patients. Low-dose radiation–related risks have been recently confirmed by both a longitudinal study and protein and genetic biomarker changes (2). Stress echocardiography is efficient, inexpensive, and safe. In the PROMISE trial, the cumulative radiation exposure up to 90 days after randomization was markedly lower among patients undergoing stress echocardiography as compared with CCTA (1.3 vs. 12.6 mSv; p < 0.001) (1,3). Moreover, in younger patients, noncoronary causes of chest symptoms (such as hypertrophic cardiomyopathy with latent obstruction, valve disease, and pulmonary hypertension) are relatively common, and these can be properly
evaluated
by
stress
echocardiography.
Finally, incidental noncardiac findings on CCTA may provoke unnecessary anxiety and lead to further testing. In high-risk (older) patients with a higher prevalence of coronary disease, CCTA results in “incidental” coronary findings, as described by Marwick et al. (1). The main advantage of stress echocardiography in
these
settings
is
correlation
of
stress
test
findings with patient symptoms, because routine revascularization in stable coronary disease offers no outcome benefit. A prior finding of higher revascularization rates with CCTA compared with
Living Up to the PROMISE
patients
undergoing
Is There an Ultimate Winner?
90 days; p < 0.001) (4).
physiological
testing
was
confirmed in the PROMISE trial (6.2% vs. 3.2% within In the current stage, with rapidly increasing options for noninvasive imaging, one should make
We read with great interest the review by Marwick
an argument that a modality with the best balance
et al. (1) discussing the potential role of coronary
of versatility, accuracy, safety, and cost effectiveness
computed tomography angiography (CCTA) in the
should prevail. The accumulating evidence so far
current paradigm of chest pain evaluation following
argues in favor of stress echocardiography.
the PROMISE (Prospective Multicenter Imaging Study the existing evidence, the authors argue that CCTA
*Vikram Agarwal, MD, MPH Edgar Argulian, MD, MPH
can serve as an effective gatekeeper to invasive
*Division of Cardiology
angiography. The PROMISE trial is interpreted by
Shapiro Cardiovascular Center
for Evaluation of Chest Pain) trial. On the basis of
many as an “equivocal” study without any obvious
Brigham and Women’s Hospital
“winner” because neither of the testing strategies
75 Francis Street
(anatomic vs. physiological) resulted in improved
Boston, Massachusetts 02115
outcome. But are there any advantages that would
E-mail: [email protected]
favor any particular modality? We strongly argue that
http://dx.doi.org/10.1016/j.jacc.2015.08.887
2267
JACC VOL. 66, NO. 20, 2015
Letters
NOVEMBER 17/24, 2015:2263–8
2. Mahajan R, Lau DH, Brooks AG, et al. Electrophysiological, electroanatomical, and structural remodeling of the atria as consequences of sustained obesity. J Am Coll Cardiol 2015;66:1–11. 3. Pathak RK, Middeldorp ME, Lau DH, et al. Aggressive risk factor reduction study for atrial fibrillation and implications for the outcome of ablation: the ARREST-AF cohort study. J Am Coll Cardiol 2014;64: 2222–31.
*Ramez Nairooz, MD Karam Ayoub, MD David Shavelle, MD *Division of Cardiology University of Arkansas for Medical Sciences 4301 West Markham, Slot 532
4. Pathak RK, Elliott A, Middeldorp ME, et al. Impact of CARDIOrespiratory FITness on arrhythmia recurrence in obese individuals with atrial fibrillation: the CARDIO-FIT study. J Am Coll Cardiol 2015;66:985–96.
Little Rock, Arkansas 72205-7199 E-mail: [email protected] http://dx.doi.org/10.1016/j.jacc.2015.07.085 Please note: Dr. Shavelle has received research grants from Zoll Medical, Abbott Vascular, St. Jude Medical, and Neostem; and is on the speakers bureau of Maquet, Medtronic, and St. Jude Medical. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
Duration of Triple Therapy A Clinical Question Yet to Be Answered
We commend the authors of the recently pub-
REFERENCE
lished ISAR-TRIPLE (Duration of Triple Therapy in
1. Fiedler KA, Maeng M, Mehilli J, et al. Duration of Triple Therapy in Patients
Patients Requiring Oral Anticoagulation After Drug
Requiring Oral Anticoagulation After Drug-Eluting Stent Implantation: the ISAR-TRIPLE trial. J Am Coll Cardiol 2015;65:1619–29.
Eluting Stent Implantation) clinical trial on their efforts (1). The trial adds valuable information to
the
ongoing
debate
of
antiplatelet
REPLY: Duration of Triple Therapy
and
anticoagulation management in patients on chronic oral anticoagulation who undergo coronary artery stenting; however, we would like to address several important points:
A Clinical Question Yet to Be Answered
We thank Dr. Nairooz and colleagues for the comments regarding the results of our ISAR TRIPLE trial (Duration of Triple Therapy in Patients Requiring Oral
1. The authors mention that the clopidogrel loading
Anticoagulation After Drug Eluting Stent Implanta-
dose was 300 mg to 600 mg, but they do not
tion) (1) and are happy to provide our answers to his
mention specific data about the loading dose in
3 questions:
each of the treatment arms. Given the numerically higher periprocedural myocardial infarctions observed in the 6-weeks group, could a preferential
lower
clopidogrel
loading
dose
have
affected this outcome? It would be interesting to know such data, as well as the repeat revascularization data. 2. There are no data about the prevalence of chronic kidney disease in each of the 2 treatment arms. Chronic kidney disease patients are prone to a higher risk of bleeding, and thus it is important to know whether such data could have affected the results. 3. The decision to present 9-month data as opposed to longer follow-up, especially with the relatively small sample, raises questions about the power of the study to depict differences in ischemic outcomes. In conclusion, the optimal duration of triple therapy is a question that remains unanswered, and for
1. Only 5% of the patients (n ¼ 30) in the ISAR TRIPLE trial were loaded with 300-mg clopidogrel, and they were evenly distributed in the 2 study arms. Interestingly, all patients who developed myocardial infarction had a loading dose of 600-mg clopidogrel. 2. The lack of treatment effect regarding the primary combined endpoint was consistent in the prespecified subgroup analysis according to renal function and this, as well as the prevalence of reduced renal function, was already shown in Online Figure 2. Dr. Nairooz and colleagues are concerned that patients with chronic kidney disease may have experienced higher bleeding rates; however, there was also no association with renal function and the occurrence of the secondary endpoint Thrombolysis In Myocardial Infarction major bleeding (p for interaction ¼ 0.89) or any bleeding according to Bleeding Academic Research Consortium (p for interaction ¼ 0.70).
now, mostly relies on physicians weighing the
3. A longer follow-up period for the evaluation of
ischemic versus bleeding risk with short compared to
treatment effect would have been inappropriate
extended duration of therapy. A large, randomized
because the protocol did not define differences in
trial comparing these various treatment options is
antiplatelet therapy after 6 months in the 2 study
needed.
arms. Thus, ischemic complications occurring after
JACC VOL. 66, NO. 20, 2015
Letters
NOVEMBER 17/24, 2015:2263–8
this time point may not be attributed to duration of
stress echocardiography emerged as the ultimate
clopidogrel therapy.
“winner.” It is well known that the negative predictive value of
*Nikolaus Sarafoff, MD Robert A. Byrne, MB, BCH, PhD Julinda Mehilli, MD Dirk Sibbing, MD Steen D. Kristensen, MD Karl-Ludwig Laugwitz, MD Michael Maeng, MD Adnan Kastrati, MD *Klinikum der Universität München Ludwig-Maximilians Universität Medizinische Klinik und Poliklinik I Marchioninistrasse 15 Munich 81377 Germany E-mail: [email protected] http://dx.doi.org/10.1016/j.jacc.2015.08.886 Please note: Dr. Sarafoff has received fees for lectures or traveling from Lilly/ Daiichi-Sankyo, Boehringer Ingelheim, AstraZeneca, Bayer Healthcare, Boston Scientific, Biotronik, and Medtronic. Dr. Byrne has received lecture fees from B. Braun and Biotronik; and has received fees for lectures, advisory board service, or traveling from Abbott Vascular and Medtronic. Dr. Mehilli has received fees for lectures and advisory board service from Abbot Vascular, Terumo, and Lilly/Daiichi-Sankyo. Dr. Sibbing has received speaker fees and honoraria for consulting from Eli Lilly, Daiichi-Sankyo, Bayer Vital, AstraZeneca, Verum Diagnostica, and Roche Diagnostics; and has received research grants from Roche Diagnostics. Dr. Kristensen has received lecture fees from AstraZeneca, Eli Lilly, Sanofi, and The Medicines Company. Dr. Kastrati has received payments for lectures or event adjudication activity from Abbott, AstraZeneca, Biosensors, Biotronik, Daiichi-Sankyo, MSD, and The Medicines Company; and holds patents related to stent technology. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
REFERENCE 1. Fiedler KA, Maeng M, Mehilli J, et al. Duration of Triple Therapy in Patients Requiring Oral Anticoagulation After Drug-Eluting Stent Implantation: the ISAR-TRIPLE trial. J Am Coll Cardiol 2015;65:1619–29.
CCTA
for
coronary
disease
in
low-
and
low-
intermediate-risk patients is high. But the clinically meaningful outcome benefit of CCTA versus physiological modalities has not yet been convincingly demonstrated. On the other hand, CCTA is associated with contrast and radiation exposure in these younger patients. Low-dose radiation–related risks have been recently confirmed by both a longitudinal study and protein and genetic biomarker changes (2). Stress echocardiography is efficient, inexpensive, and safe. In the PROMISE trial, the cumulative radiation exposure up to 90 days after randomization was markedly lower among patients undergoing stress echocardiography as compared with CCTA (1.3 vs. 12.6 mSv; p < 0.001) (1,3). Moreover, in younger patients, noncoronary causes of chest symptoms (such as hypertrophic cardiomyopathy with latent obstruction, valve disease, and pulmonary hypertension) are relatively common, and these can be properly
evaluated
by
stress
echocardiography.
Finally, incidental noncardiac findings on CCTA may provoke unnecessary anxiety and lead to further testing. In high-risk (older) patients with a higher prevalence of coronary disease, CCTA results in “incidental” coronary findings, as described by Marwick et al. (1). The main advantage of stress echocardiography in
these
settings
is
correlation
of
stress
test
findings with patient symptoms, because routine revascularization in stable coronary disease offers no outcome benefit. A prior finding of higher revascularization rates with CCTA compared with
Living Up to the PROMISE
patients
undergoing
Is There an Ultimate Winner?
90 days; p < 0.001) (4).
physiological
testing
was
confirmed in the PROMISE trial (6.2% vs. 3.2% within In the current stage, with rapidly increasing options for noninvasive imaging, one should make
We read with great interest the review by Marwick
an argument that a modality with the best balance
et al. (1) discussing the potential role of coronary
of versatility, accuracy, safety, and cost effectiveness
computed tomography angiography (CCTA) in the
should prevail. The accumulating evidence so far
current paradigm of chest pain evaluation following
argues in favor of stress echocardiography.
the PROMISE (Prospective Multicenter Imaging Study the existing evidence, the authors argue that CCTA
*Vikram Agarwal, MD, MPH Edgar Argulian, MD, MPH
can serve as an effective gatekeeper to invasive
*Division of Cardiology
angiography. The PROMISE trial is interpreted by
Shapiro Cardiovascular Center
for Evaluation of Chest Pain) trial. On the basis of
many as an “equivocal” study without any obvious
Brigham and Women’s Hospital
“winner” because neither of the testing strategies
75 Francis Street
(anatomic vs. physiological) resulted in improved
Boston, Massachusetts 02115
outcome. But are there any advantages that would
E-mail: [email protected]
favor any particular modality? We strongly argue that
http://dx.doi.org/10.1016/j.jacc.2015.08.887
2267
