- Email: [email protected]
Aspirin for the Prevention of Infective Endocarditis?
1104
JACC VOL. 70, NO. 8, 2017
Letters
AUGUST 22, 2017:1099–105
disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol 2017;70:252–89. 5. Vahanian A, Alfieri O, Andreotti F, et al. Guidelines on the management of valvular heart disease (version 2012). Eur Heart J 2012;33:2451–96.
REFERENCES 1. Yan AT, Koh M, Chan KK, et al. Association between cardiovascular risk factors and aortic stenosis: the CANHEART aortic stenosis study. J Am Coll Cardiol 2017;69:1523–32. 2. Nishimura RA, Otto CM, Bonow RO, et al. 2014 AHA/ACC guideline for the management of patients with valvular heart disease: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2014;63: 2438–88.
REPLY: Coronary Artery Disease Affects Symptomatology of Aortic Valve Stenosis We appreciate the insights and interest raised by Dr. Boekholdt and colleagues. In our study, we followed more than 1 million older individuals in Ontario, Canada, for a median of 13 years and found significant independent
associations
between
hypertension,
diabetes, and dyslipidemia, and incident aortic stenosis (AS) (1). We defined incident AS as hospitalization
for
AS
or
aortic
valve
interventions. Dr.
Boekholdt and colleagues correctly point out that some patients who had combined coronary artery bypass surgery (CABG) and aortic valve replacement (AVR) might actually have moderate AS. This is because practice guidelines endorse concomitant AVR for patients who have moderate AS when cardiac surgery is required (2). In the 20,995 patients who had incident AS in our study, 8,233 patients received AVR, and among them, 47.4% had concomitant CABG and 52.5% had isolated AVR procedures. We were unable to determine the proportion of patients who had moderate AS because we lacked echocardiography data on their aortic valve gradient. Instead, we performed an additional analysis by censoring patients who had combined CABG and AVR. Using causespecific hazard models, we found that hypertension (adjusted hazard ratio [HR]: 1.73; 95% confidence interval [CI]: 1.68 to 1.79), diabetes (HR: 1.46; 95% CI: 1.41 to 1.52), and dyslipidemia (HR: 1.13; 95% CI: 1.09 to 1.18) maintained a significant association with increased risk of developing incident AS (all p < 0.001). These estimates were similar to our original results. Accordingly, we believe that cardiac risk factors
have
independent
Aspirin for the Prevention of Infective Endocarditis?
associations
with
AS
beyond the potential influence of coronary artery disease. Andrew T. Yan, MD Maria Koh, MSc *Dennis T. Ko, MD, MSc *Institute for Clinical Evaluative Sciences (ICES) G106-2075 Bayview Avenue
I enjoyed reading the review on infective endocarditis (IE) by Cahill et al. (1). I was intrigued by the description of the 3 stages via which IE develops, particularly the 2nd stage, in which bacteria adhere to abnormal or damaged endothelium, effected by the interaction of the microorganisms’ surface adhesins with the host’s extracellular matrix proteins, in a process “facilitated by fibrin and platelet microthrombi” (1). One wonders whether antiplatelet agents, primarily aspirin (ASA), could potentially have a preventive role in IE by counteracting such facilitation. Accordingly, patients at risk for IE will receive antibiotic prophylaxis (not always preventive of IE) and 325 mg of plain ASA (2) 1 h before procedures. Because patients are also believed to be at risk for IE via “tooth brushing, chewing, and inadequate dental hygiene” or in the setting of “hemodialysis, cancer, diabetes mellitus, and the presence of cardiac implantable electronic devices” (1), daily taking of 81 mg of ASA may potentially be justified. A previous randomized trial of patients with IE has found ASA to be ineffective, but it focused on prevention of stroke events in already established IE (3). However, there is prior animal work revealing a preventive effect of ASA administered before inoculation, on the emergence of IE (4,5). Existing databases and registries could be explored regarding the daily use of ASA, for whatever indication, and a possible protective role in preventing IE. For such inquiry, we could probably focus on the databases listed in Table 1 (1), dealing with the prevalence of IE following the recent
changes
in
the
*John E. Madias, MD
Toronto, Ontario
*Division of Cardiology
Canada M4N 3M5
Elmhurst Hospital Center
E-mail: [email protected]
79-01 Broadway
http://dx.doi.org/10.1016/j.jacc.2017.05.070
Elmhurst, New York 11373
Please note: The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
guidelines
prophylaxis for IE.
E-mail: [email protected] http://dx.doi.org/10.1016/j.jacc.2017.04.073
of
antibiotic
JACC VOL. 70, NO. 8, 2017
Letters
AUGUST 22, 2017:1099–105
Please note: Dr. Madias has reported that he has no relationships relevant to the contents of this paper to disclose.
antiplatelet inhibition with both aspirin and ticlopidine; either drug alone had no significant effect. Clinical data to support aspirin for prophylaxis of
REFERENCES 1. Cahill TJ, Baddour LM, Habib G, et al. Challenges in infective endocarditis. J Am Coll Cardiol 2017;69:325–44. 2. Patrono C, Rocca B. Type 2 diabetes, obesity, and aspirin responsiveness. J Am Coll Cardiol 2017;69:613–5. 3. Chan KL, Dumesnil JG, Cujec B, et al., Investigators of the Multicenter Aspirin Study in Infective Endocarditis. A randomized trial of aspirin on the risk of embolic events in patients with infective endocarditis. J Am Coll Cardiol 2003;42:775–80. 4. Veloso TR, Oechslin F, Que YA, Moreillon P, Entenza JM, Mancini S. Aspirin plus ticlopidine prevented experimental endocarditis due to Enterococcus faecalis and Streptococcus gallolyticus. Pathog Dis 2015;73:ftv060.
IE are currently lacking. Given the scale and cost of conducting a randomized controlled trial, we agree that analysis of existing cohorts of “at-risk” groups would be valuable and might provide supportive evidence. In fact, a prospective series addressing precisely this question in patients with bioprosthetic heart valves has recently been proposed (4). Finally, the risks of aspirin prophylaxis need to be taken into account, and depending on the population, dose and nature of the dental/surgical intervention,
5. Veloso TR, Que YA, Chaouch A, et al. Prophylaxis of experimental endo-
might be associated with an increase in bleeding
carditis with antiplatelet and antithrombin agents: a role for long-term prevention of infective endocarditis in humans? J Infect Dis 2015;211:72–9.
complications. Thomas J. Cahill, MBBS *Bernard D. Prendergast, DM
REPLY: Aspirin for the Prevention of
*Department of Cardiology
Infective Endocarditis?
St. Thomas’ Hospital
Dr. Madias proposes a potential role for aspirin in the prevention of infective endocarditis (IE). The role of platelets in the pathogenesis of IE is established: in addition to enabling bacterial adhesion, activated platelets lead to formation of neutrophil extracellular traps, which enmesh platelet-bacterial
Westminster Bridge Road London, SE17EH United Kingdom E-mail: [email protected] http://dx.doi.org/10.1016/j.jacc.2017.05.071 © 2017 by the American College of Cardiology Foundation. Published by Elsevier. All rights reserved.
aggregates together to facilitate vegetation formation (1). Furthermore, platelets contribute to the
Please note: The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
formation of multilayered biofilms. However, platelets also have protective effects through release of platelet microbicidal proteins and activation of the immune response. Findings in preclinical models reflect these dual functions. In a rabbit model of experimental streptococcal IE, platelets have been shown to restrain development of early IE (2). In a rat model of staphylococcal and streptotoccal IE, Veloso et al. (3) demonstrated
that
platelet
inhibition
using
aspirin and ticlopidine could prevent formation of vegetations.
Notably,
this
required
dual
agent
REFERENCES 1. Jung C-J, Yeh C-Y, Shun C-T, et al. Platelets enhance biofilm formation and resistance of endocarditis-inducing streptococci on the injured heart valve. J Infect Dis 2012;205:1066–75. 2. Sullam PM, Frank U, Yeaman MR, Tauber MG, Bayer AS, Chambers HF. Effect of thrombocytopenia on the early course of streptococcal endocarditis. J Infect Dis 1993;168:910–4. 3. Veloso TR, Que Y-A, Chaouch A, et al. Prophylaxis of experimental endocarditis with antiplatelet and antithrombin agents: a role for long-term prevention of infective endocarditis in humans? J Infect Dis 2015;211:72–9. 4. Veloso TR, Que Y-A, Moreillon P, Entenza JM. Reply to Eisen and McBryde. J Infect Dis 2015;212:674–5.
1105
JACC VOL. 70, NO. 8, 2017
Letters
AUGUST 22, 2017:1099–105
disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol 2017;70:252–89. 5. Vahanian A, Alfieri O, Andreotti F, et al. Guidelines on the management of valvular heart disease (version 2012). Eur Heart J 2012;33:2451–96.
REFERENCES 1. Yan AT, Koh M, Chan KK, et al. Association between cardiovascular risk factors and aortic stenosis: the CANHEART aortic stenosis study. J Am Coll Cardiol 2017;69:1523–32. 2. Nishimura RA, Otto CM, Bonow RO, et al. 2014 AHA/ACC guideline for the management of patients with valvular heart disease: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2014;63: 2438–88.
REPLY: Coronary Artery Disease Affects Symptomatology of Aortic Valve Stenosis We appreciate the insights and interest raised by Dr. Boekholdt and colleagues. In our study, we followed more than 1 million older individuals in Ontario, Canada, for a median of 13 years and found significant independent
associations
between
hypertension,
diabetes, and dyslipidemia, and incident aortic stenosis (AS) (1). We defined incident AS as hospitalization
for
AS
or
aortic
valve
interventions. Dr.
Boekholdt and colleagues correctly point out that some patients who had combined coronary artery bypass surgery (CABG) and aortic valve replacement (AVR) might actually have moderate AS. This is because practice guidelines endorse concomitant AVR for patients who have moderate AS when cardiac surgery is required (2). In the 20,995 patients who had incident AS in our study, 8,233 patients received AVR, and among them, 47.4% had concomitant CABG and 52.5% had isolated AVR procedures. We were unable to determine the proportion of patients who had moderate AS because we lacked echocardiography data on their aortic valve gradient. Instead, we performed an additional analysis by censoring patients who had combined CABG and AVR. Using causespecific hazard models, we found that hypertension (adjusted hazard ratio [HR]: 1.73; 95% confidence interval [CI]: 1.68 to 1.79), diabetes (HR: 1.46; 95% CI: 1.41 to 1.52), and dyslipidemia (HR: 1.13; 95% CI: 1.09 to 1.18) maintained a significant association with increased risk of developing incident AS (all p < 0.001). These estimates were similar to our original results. Accordingly, we believe that cardiac risk factors
have
independent
Aspirin for the Prevention of Infective Endocarditis?
associations
with
AS
beyond the potential influence of coronary artery disease. Andrew T. Yan, MD Maria Koh, MSc *Dennis T. Ko, MD, MSc *Institute for Clinical Evaluative Sciences (ICES) G106-2075 Bayview Avenue
I enjoyed reading the review on infective endocarditis (IE) by Cahill et al. (1). I was intrigued by the description of the 3 stages via which IE develops, particularly the 2nd stage, in which bacteria adhere to abnormal or damaged endothelium, effected by the interaction of the microorganisms’ surface adhesins with the host’s extracellular matrix proteins, in a process “facilitated by fibrin and platelet microthrombi” (1). One wonders whether antiplatelet agents, primarily aspirin (ASA), could potentially have a preventive role in IE by counteracting such facilitation. Accordingly, patients at risk for IE will receive antibiotic prophylaxis (not always preventive of IE) and 325 mg of plain ASA (2) 1 h before procedures. Because patients are also believed to be at risk for IE via “tooth brushing, chewing, and inadequate dental hygiene” or in the setting of “hemodialysis, cancer, diabetes mellitus, and the presence of cardiac implantable electronic devices” (1), daily taking of 81 mg of ASA may potentially be justified. A previous randomized trial of patients with IE has found ASA to be ineffective, but it focused on prevention of stroke events in already established IE (3). However, there is prior animal work revealing a preventive effect of ASA administered before inoculation, on the emergence of IE (4,5). Existing databases and registries could be explored regarding the daily use of ASA, for whatever indication, and a possible protective role in preventing IE. For such inquiry, we could probably focus on the databases listed in Table 1 (1), dealing with the prevalence of IE following the recent
changes
in
the
*John E. Madias, MD
Toronto, Ontario
*Division of Cardiology
Canada M4N 3M5
Elmhurst Hospital Center
E-mail: [email protected]
79-01 Broadway
http://dx.doi.org/10.1016/j.jacc.2017.05.070
Elmhurst, New York 11373
Please note: The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
guidelines
prophylaxis for IE.
E-mail: [email protected] http://dx.doi.org/10.1016/j.jacc.2017.04.073
of
antibiotic
JACC VOL. 70, NO. 8, 2017
Letters
AUGUST 22, 2017:1099–105
Please note: Dr. Madias has reported that he has no relationships relevant to the contents of this paper to disclose.
antiplatelet inhibition with both aspirin and ticlopidine; either drug alone had no significant effect. Clinical data to support aspirin for prophylaxis of
REFERENCES 1. Cahill TJ, Baddour LM, Habib G, et al. Challenges in infective endocarditis. J Am Coll Cardiol 2017;69:325–44. 2. Patrono C, Rocca B. Type 2 diabetes, obesity, and aspirin responsiveness. J Am Coll Cardiol 2017;69:613–5. 3. Chan KL, Dumesnil JG, Cujec B, et al., Investigators of the Multicenter Aspirin Study in Infective Endocarditis. A randomized trial of aspirin on the risk of embolic events in patients with infective endocarditis. J Am Coll Cardiol 2003;42:775–80. 4. Veloso TR, Oechslin F, Que YA, Moreillon P, Entenza JM, Mancini S. Aspirin plus ticlopidine prevented experimental endocarditis due to Enterococcus faecalis and Streptococcus gallolyticus. Pathog Dis 2015;73:ftv060.
IE are currently lacking. Given the scale and cost of conducting a randomized controlled trial, we agree that analysis of existing cohorts of “at-risk” groups would be valuable and might provide supportive evidence. In fact, a prospective series addressing precisely this question in patients with bioprosthetic heart valves has recently been proposed (4). Finally, the risks of aspirin prophylaxis need to be taken into account, and depending on the population, dose and nature of the dental/surgical intervention,
5. Veloso TR, Que YA, Chaouch A, et al. Prophylaxis of experimental endo-
might be associated with an increase in bleeding
carditis with antiplatelet and antithrombin agents: a role for long-term prevention of infective endocarditis in humans? J Infect Dis 2015;211:72–9.
complications. Thomas J. Cahill, MBBS *Bernard D. Prendergast, DM
REPLY: Aspirin for the Prevention of
*Department of Cardiology
Infective Endocarditis?
St. Thomas’ Hospital
Dr. Madias proposes a potential role for aspirin in the prevention of infective endocarditis (IE). The role of platelets in the pathogenesis of IE is established: in addition to enabling bacterial adhesion, activated platelets lead to formation of neutrophil extracellular traps, which enmesh platelet-bacterial
Westminster Bridge Road London, SE17EH United Kingdom E-mail: [email protected] http://dx.doi.org/10.1016/j.jacc.2017.05.071 © 2017 by the American College of Cardiology Foundation. Published by Elsevier. All rights reserved.
aggregates together to facilitate vegetation formation (1). Furthermore, platelets contribute to the
Please note: The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
formation of multilayered biofilms. However, platelets also have protective effects through release of platelet microbicidal proteins and activation of the immune response. Findings in preclinical models reflect these dual functions. In a rabbit model of experimental streptococcal IE, platelets have been shown to restrain development of early IE (2). In a rat model of staphylococcal and streptotoccal IE, Veloso et al. (3) demonstrated
that
platelet
inhibition
using
aspirin and ticlopidine could prevent formation of vegetations.
Notably,
this
required
dual
agent
REFERENCES 1. Jung C-J, Yeh C-Y, Shun C-T, et al. Platelets enhance biofilm formation and resistance of endocarditis-inducing streptococci on the injured heart valve. J Infect Dis 2012;205:1066–75. 2. Sullam PM, Frank U, Yeaman MR, Tauber MG, Bayer AS, Chambers HF. Effect of thrombocytopenia on the early course of streptococcal endocarditis. J Infect Dis 1993;168:910–4. 3. Veloso TR, Que Y-A, Chaouch A, et al. Prophylaxis of experimental endocarditis with antiplatelet and antithrombin agents: a role for long-term prevention of infective endocarditis in humans? J Infect Dis 2015;211:72–9. 4. Veloso TR, Que Y-A, Moreillon P, Entenza JM. Reply to Eisen and McBryde. J Infect Dis 2015;212:674–5.
1105