Mixing ‘apples and oranges’ in meta-analytic studies: dangerous or delicious?

Mixing ‘apples and oranges’ in meta-analytic studies: dangerous or delicious? European Journal of Cardio-Thoracic Surgery 53 (2018) 1294–1298 LETTERS TO THE EDITOR On the basis of these arguments, we do not believe that the results of the Mixing ‘apples and oranges’ in meta-analytic ATACAS study and other studies that randomized patients to either ASA or placebo on the day of surgery are appropriate in a meta-analysis aiming to studies: dangerous or delicious?† answer the question of whether to stop or continue ASA before CABG. From the perspective of recently published several clinical guidelines, this meta-ana- a,b, c a a Milan Milojevic *, Miguel Sousa-Uva , Andras P. Durko and Stuart J. Head lysis is confusing and may be potentially misleading due to its strong conclu- Department of Cardiothoracic Surgery, Erasmus University Medical Center, sions. On the basis of the risk–benefit ratio, we believe that ASA should be Rotterdam, Netherlands continued throughout the perioperative period in patients awaiting CABG Clinic for Anesthesiology and Intensive Care, “Dedinje” Cardiovascular who are not at a high bleeding risk. Institute, Belgrade, Serbia Department of Cardiac Surgery, Hospital de Santa Cruz, Carnaxide and the Faculdade de Medicina da Universidade do Porto, Porto, Portugal REFERENCES Received 14 November 2017; accepted 5 December 2017 [1] Sa MPBO, Soares AF, Miranda RGA, Araujo ML, Menezes AM, Silva FPV Keywords: Acetylsalicylic acid � Coronary artery bypass grafting � Stopping � et al. Stopping versus continuing acetylsalicylic acid before coronary artery bypass surgery: a systematic review and meta-analysis of 14 randomized Continuing controlled trials with 4499 patients. Eur J Cardiothorac Surg 2017;52:838–47. Sa et al. [1] observed no significant difference regarding the risk of periopera- [2] Hastings S, Myles P, McIlroy D. Aspirin and coronary artery surgery: a sys- tive myocardial infarction (MI) if the administration of acetylsalicylic acid tematic review and meta-analysis. Br J Anaesth 2015;115:376–85. (ASA) was stopped or continued in patients before undergoing coronary ar- [3] Myles PS, Smith JA, Forbes A, Silbert B, Jayarajah M, Painter T. Stopping vs. tery bypass graft (CABG) surgery. Compared with a similar meta-analysis re- continuing aspirin before coronary artery surgery. N Engl J Med ported by Hastings et al.[2] in 2015, only the results from the more recently 2016;374:728–37. released ATACAS trial were added to the analysis. [4] Zisman E, Erport A, Kohanovsky E, Ballagulah M, Cassel A, Quitt M et al. However, we have a major concern regarding the inclusion criteria of this Platelet function recovery after cessation of aspirin: preliminary study of meta-analysis. volunteers and surgical patients. Eur J Anaesthesiol 2010;27:617–23. First, the appropriateness for the inclusion criteria of a study is questionable. [5] Wright RS, Anderson JL, Adams CD, Bridges CR, Casey DE Jr, Ettinger SM The variation in design across studies is high, i.e. from the continuation of ASA et al. 2011 ACCF/AHA focused update of the guidelines for the manage- until the day of surgery to the initiation of ASA in naı ¨ve patients on the day of ment of patients with unstable angina/non-ST-elevation myocardial infarc- surgery. For example, in the aspirin and tranexamic acid for coronary artery tion (updating the 2007 guideline): a report of the American College of surgery (ATACAS) study [3], which consisted of approximately 50% of all pa- Cardiology Foundation/American Heart Association Task Force on practice tients included in this meta-analysis, patients were only eligible if they were guidelines. Circulation 2011;123:2022–60. not taking or stopped taking aspirin at least 4 days before surgery and were [6] Sousa-Uva M, Head SJ, Milojevic M, Collet J-P, Landoni G, Castella M et al. randomized to receive 100 mg of aspirin or placebo on the day of surgery. 2017 EACTS Guidelines on perioperative medication in adult cardiac sur- Therefore, patients who continued aspirin were not included in the trial, gery. Eur J Cardiothorac Surg 2018;53:5–33. which is highly misleading with regard to the title of the article. Moreover, if we wanted to test whether a single dose of aspirin on the day of surgery would reduce ischaemic events in patients who discontinued as- *Corresponding author. Department of Cardiothoracic Surgery, Erasmus pirin for at least 4 days before surgery, the given 100 mg dose would only re- University Medical Center’s Gravendijkwal 230, 3015 CE Rotterdam, sult in partial platelet inhibition. When stopping the administration of aspirin, Netherlands. Tel: +31-1-07034375; fax: +31-1-7032358; e-mail: mln.milojevic@ full platelet function recovery is observed after 96 h [4], and a (re)loading dose gmail.com of at least 160 mg would be required to sufficiently inhibit platelet function [5]. †The corresponding author of the original article [1] was invited to reply but did Second, since other included studies fulfilled the criteria of full platelet in- not respond. hibition based on the dose of administered ASA, this meta-analysis mixes the results of patients with total and partial platelet inhibition, with potentially doi:10.1093/ejcts/ezx471 misleading consequences. The authors also performed a sensitivity analysis Advance Access publication 26 December 2017 excluding the ATACAS study: the reported finding was still non-significant about the effect of continued ASA on the reduction in perioperative MI (risk ratio 0.62, 95% confidence interval 0.37–1.05; P = 0.074). This is particularly interesting in the light of a recent meta-analysis published by Hastings and colleagues from Melbourne [2]. This study—neither cited nor discussed by the authors—demonstrated a significant reduction in perioperative MI with con- Clarifying the doubly committed and tinued ASA (odds ratio 0.56, 95% confidence interval 0.33–0.96; P = 0.03)—with the exact same studies included as in the sensitivity analysis performed by Sa juxta-arterial ventricular septal defect† et al. [1]. These results seem to depend on the effect measure that is chosen a, b and that by itself introduces a dilemma on how strong the evidence is. Justin T. Tretter * and Robert H. Anderson However, borderline P-values cannot be considered as a strong argument ei- The Heart Institute, Cincinnati Children’s Hospital Medical Center, ther for or against an intervention, and the risk–benefit ratio of thrombotic Cincinnati, OH, USA risk versus bleeding risk should be considered in treatment decision-making. Institute of Genetic Medicine, Newcastle University, Newcastle-upon-Tyne, The recently published EACTS Guidelines on perioperative medication in UK adult cardiac surgery recommends that ‘in patients on ASA who need to Received 14 November 2017; accepted 6 December 2017 undergo CABG surgery, continuing ASA throughout the preoperative period should be considered (Class IIa, Level of Evidence C)’ [6]. This is mainly based Keywords: Ventricular septal defect � Doubly committed ventricular septal on the meta-analysis by Hasting et al. [2], where the use of ASA resulted in a defect � Perventricular device closure � Device closure of ventricular septal 44% reduction in perioperative MI with an acceptable increase in the total chest blood drainage (mean + 168 ml). defect The Author(s) 2017/2018. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved. Downloaded from https://academic.oup.com/ejcts/article-abstract/53/6/1294/4775058 by Ed 'DeepDyve' Gillespie user on 20 June 2018 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png European Journal of Cardio-Thoracic Surgery Oxford University Press

Mixing ‘apples and oranges’ in meta-analytic studies: dangerous or delicious?

Free
1 page

Loading next page...
1 Page
 
/lp/ou_press/mixing-apples-and-oranges-in-meta-analytic-studies-dangerous-or-r0yTb2R2rL
Publisher
Oxford University Press
Copyright
© The Author(s) 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
ISSN
1010-7940
eISSN
1873-734X
D.O.I.
10.1093/ejcts/ezx471
Publisher site
See Article on Publisher Site

Abstract

European Journal of Cardio-Thoracic Surgery 53 (2018) 1294–1298 LETTERS TO THE EDITOR On the basis of these arguments, we do not believe that the results of the Mixing ‘apples and oranges’ in meta-analytic ATACAS study and other studies that randomized patients to either ASA or placebo on the day of surgery are appropriate in a meta-analysis aiming to studies: dangerous or delicious?† answer the question of whether to stop or continue ASA before CABG. From the perspective of recently published several clinical guidelines, this meta-ana- a,b, c a a Milan Milojevic *, Miguel Sousa-Uva , Andras P. Durko and Stuart J. Head lysis is confusing and may be potentially misleading due to its strong conclu- Department of Cardiothoracic Surgery, Erasmus University Medical Center, sions. On the basis of the risk–benefit ratio, we believe that ASA should be Rotterdam, Netherlands continued throughout the perioperative period in patients awaiting CABG Clinic for Anesthesiology and Intensive Care, “Dedinje” Cardiovascular who are not at a high bleeding risk. Institute, Belgrade, Serbia Department of Cardiac Surgery, Hospital de Santa Cruz, Carnaxide and the Faculdade de Medicina da Universidade do Porto, Porto, Portugal REFERENCES Received 14 November 2017; accepted 5 December 2017 [1] Sa MPBO, Soares AF, Miranda RGA, Araujo ML, Menezes AM, Silva FPV Keywords: Acetylsalicylic acid � Coronary artery bypass grafting � Stopping � et al. Stopping versus continuing acetylsalicylic acid before coronary artery bypass surgery: a systematic review and meta-analysis of 14 randomized Continuing controlled trials with 4499 patients. Eur J Cardiothorac Surg 2017;52:838–47. Sa et al. [1] observed no significant difference regarding the risk of periopera- [2] Hastings S, Myles P, McIlroy D. Aspirin and coronary artery surgery: a sys- tive myocardial infarction (MI) if the administration of acetylsalicylic acid tematic review and meta-analysis. Br J Anaesth 2015;115:376–85. (ASA) was stopped or continued in patients before undergoing coronary ar- [3] Myles PS, Smith JA, Forbes A, Silbert B, Jayarajah M, Painter T. Stopping vs. tery bypass graft (CABG) surgery. Compared with a similar meta-analysis re- continuing aspirin before coronary artery surgery. N Engl J Med ported by Hastings et al.[2] in 2015, only the results from the more recently 2016;374:728–37. released ATACAS trial were added to the analysis. [4] Zisman E, Erport A, Kohanovsky E, Ballagulah M, Cassel A, Quitt M et al. However, we have a major concern regarding the inclusion criteria of this Platelet function recovery after cessation of aspirin: preliminary study of meta-analysis. volunteers and surgical patients. Eur J Anaesthesiol 2010;27:617–23. First, the appropriateness for the inclusion criteria of a study is questionable. [5] Wright RS, Anderson JL, Adams CD, Bridges CR, Casey DE Jr, Ettinger SM The variation in design across studies is high, i.e. from the continuation of ASA et al. 2011 ACCF/AHA focused update of the guidelines for the manage- until the day of surgery to the initiation of ASA in naı ¨ve patients on the day of ment of patients with unstable angina/non-ST-elevation myocardial infarc- surgery. For example, in the aspirin and tranexamic acid for coronary artery tion (updating the 2007 guideline): a report of the American College of surgery (ATACAS) study [3], which consisted of approximately 50% of all pa- Cardiology Foundation/American Heart Association Task Force on practice tients included in this meta-analysis, patients were only eligible if they were guidelines. Circulation 2011;123:2022–60. not taking or stopped taking aspirin at least 4 days before surgery and were [6] Sousa-Uva M, Head SJ, Milojevic M, Collet J-P, Landoni G, Castella M et al. randomized to receive 100 mg of aspirin or placebo on the day of surgery. 2017 EACTS Guidelines on perioperative medication in adult cardiac sur- Therefore, patients who continued aspirin were not included in the trial, gery. Eur J Cardiothorac Surg 2018;53:5–33. which is highly misleading with regard to the title of the article. Moreover, if we wanted to test whether a single dose of aspirin on the day of surgery would reduce ischaemic events in patients who discontinued as- *Corresponding author. Department of Cardiothoracic Surgery, Erasmus pirin for at least 4 days before surgery, the given 100 mg dose would only re- University Medical Center’s Gravendijkwal 230, 3015 CE Rotterdam, sult in partial platelet inhibition. When stopping the administration of aspirin, Netherlands. Tel: +31-1-07034375; fax: +31-1-7032358; e-mail: mln.milojevic@ full platelet function recovery is observed after 96 h [4], and a (re)loading dose gmail.com of at least 160 mg would be required to sufficiently inhibit platelet function [5]. †The corresponding author of the original article [1] was invited to reply but did Second, since other included studies fulfilled the criteria of full platelet in- not respond. hibition based on the dose of administered ASA, this meta-analysis mixes the results of patients with total and partial platelet inhibition, with potentially doi:10.1093/ejcts/ezx471 misleading consequences. The authors also performed a sensitivity analysis Advance Access publication 26 December 2017 excluding the ATACAS study: the reported finding was still non-significant about the effect of continued ASA on the reduction in perioperative MI (risk ratio 0.62, 95% confidence interval 0.37–1.05; P = 0.074). This is particularly interesting in the light of a recent meta-analysis published by Hastings and colleagues from Melbourne [2]. This study—neither cited nor discussed by the authors—demonstrated a significant reduction in perioperative MI with con- Clarifying the doubly committed and tinued ASA (odds ratio 0.56, 95% confidence interval 0.33–0.96; P = 0.03)—with the exact same studies included as in the sensitivity analysis performed by Sa juxta-arterial ventricular septal defect† et al. [1]. These results seem to depend on the effect measure that is chosen a, b and that by itself introduces a dilemma on how strong the evidence is. Justin T. Tretter * and Robert H. Anderson However, borderline P-values cannot be considered as a strong argument ei- The Heart Institute, Cincinnati Children’s Hospital Medical Center, ther for or against an intervention, and the risk–benefit ratio of thrombotic Cincinnati, OH, USA risk versus bleeding risk should be considered in treatment decision-making. Institute of Genetic Medicine, Newcastle University, Newcastle-upon-Tyne, The recently published EACTS Guidelines on perioperative medication in UK adult cardiac surgery recommends that ‘in patients on ASA who need to Received 14 November 2017; accepted 6 December 2017 undergo CABG surgery, continuing ASA throughout the preoperative period should be considered (Class IIa, Level of Evidence C)’ [6]. This is mainly based Keywords: Ventricular septal defect � Doubly committed ventricular septal on the meta-analysis by Hasting et al. [2], where the use of ASA resulted in a defect � Perventricular device closure � Device closure of ventricular septal 44% reduction in perioperative MI with an acceptable increase in the total chest blood drainage (mean + 168 ml). defect The Author(s) 2017/2018. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved. Downloaded from https://academic.oup.com/ejcts/article-abstract/53/6/1294/4775058 by Ed 'DeepDyve' Gillespie user on 20 June 2018

Journal

European Journal of Cardio-Thoracic SurgeryOxford University Press

Published: Dec 26, 2017

There are no references for this article.

You’re reading a free preview. Subscribe to read the entire article.


DeepDyve is your
personal research library

It’s your single place to instantly
discover and read the research
that matters to you.

Enjoy affordable access to
over 18 million articles from more than
15,000 peer-reviewed journals.

All for just $49/month

Explore the DeepDyve Library

Search

Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly

Organize

Save any article or search result from DeepDyve, PubMed, and Google Scholar... all in one place.

Access

Get unlimited, online access to over 18 million full-text articles from more than 15,000 scientific journals.

Your journals are on DeepDyve

Read from thousands of the leading scholarly journals from SpringerNature, Elsevier, Wiley-Blackwell, Oxford University Press and more.

All the latest content is available, no embargo periods.

See the journals in your area

DeepDyve

Freelancer

DeepDyve

Pro

Price

FREE

$49/month
$360/year

Save searches from
Google Scholar,
PubMed

Create lists to
organize your research

Export lists, citations

Read DeepDyve articles

Abstract access only

Unlimited access to over
18 million full-text articles

Print

20 pages / month

PDF Discount

20% off