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To adjust, or not to adjust, that is the question
514
Letters to the Editor
To adjust, or not to adjust, that is the question Hisato Takagi ⁎, Takuya Umemoto and For the ALICE (All-Literature Investigation of Cardiovascular Evidence) Group Department of Cardiovascular Surgery, Shizuoka Medical Center, Shizuoka, Japan
a r t i c l e
i n f o
Article history: Received 18 May 2014 Accepted 5 July 2014 Available online 12 July 2014 Keywords: Drug-eluting stent Meta-analysis Mortality Observational study Off-pump coronary artery bypass grafting
We have read with great interest a meta-analysis by Lu et al. [1] that was recently online-published in the International Journal of Cardiology. The cumulative rate of all-cause death at 3 years from only 3 nonrandomized observational cohort studies [2–4] (enrolling a total of 2417 patients) was lower in the off-pump coronary artery bypass grafting (OPCAB) than drug-eluting stent (DES) group (risk ratio [RR], 0.56; 95% confidence interval [CI], 0.33 to 0.96; P = 0.03) [1]. The authors [1] abstracted the number of events/total from nonrandomized studies, generated “unadjusted” (but not “adjusted”) RR for death, and then combined them in their meta-analysis. In such unadjusted univariable analyses, however, it can be never determined whether DES is an “independent” protective predictor of death. To find independent predictors, multivariable logistic or Cox proportional hazards regression (MCPHR) are used, generating an adjusted odds ratio or hazard ratio (HR). Alternatively, pseudo-randomization by means of propensity-score matching may be performed. In our recent meta-analysis [5], where adjusted hazard ratios (HRs) were extracted from 6 nonrandomized observational studies [4,6–10] enrolling a total of 3874 patients and then combined, OPCAB was not associated with improved survival (=was not associated with reduced death) during ≥1-year (range, 1- to 5.5-year) follow-up over DES (HR, 0.72; 95% CI, 0.45 to 1.17; P = 0.19). Although the study design of randomized trials, which balance both known and unknown confounders across treatment groups, is least vulnerable to bias, patients enrolled in them may not be representative of patients typically seen in clinical practice. On the other hand, because potential biases must be greater for observational studies compared with randomized trials, results should be always interpreted with caution when they are included in meta-analyses [11]. Particular
⁎ Corresponding author at: Department of Cardiovascular Surgery, Shizuoka Medical Center, 762-1 Nagasawa, Shimizu-cho, Sunto-gun, Shizuoka 411-8611, Japan. Tel.: + 81 559752000. E-mail address: [email protected] (H. Takagi).
http://dx.doi.org/10.1016/j.ijcard.2014.07.048 0167-5273/© 2014 Elsevier Ireland Ltd. All rights reserved.
concerns arise in terms of differences between patients in different intervention groups (selection bias). Unlike for randomized trials, it would usually be appropriate to analyze adjusted (i.e. attempting to control for confounding), rather than unadjusted, risk estimates [11]. To reduce the effect of treatment-selection bias and potential confounding in observational studies, rigorous adjustment for significant differences in the baseline characteristics of patients should be conducted. Furthermore, adjusted (but not unadjusted) estimates ought to be pooled in a meta-analysis that includes observational studies. In our recent meta-analysis [5], we exclusively abstracted (then combined in a meta-analysis) adjusted (but not unadjusted) relative risk estimates from observational studies. To adjust, or not to adjust, that is the question. The authors report no relationships that could be construed as a conflict of interest. References [1] Lu D, Nie X, Wan J, et al. Is off-pump coronary artery bypass grafting superior to drug-eluting stents for the treatment of coronary artery disease? A meta-analysis of randomized and nonrandomized studies. Int J Cardiol 2014;174(3):640–53. [2] Yamagata K, Kataoka Y, Kokubu N, et al. A 3-year clinical outcome after percutaneous coronary intervention using sirolimus-eluting stent and off-pump coronary artery bypass grafting for the treatment of diabetic patients with multivessel disease. Circ J 2010;74(4):671–8. [3] Yi G, Youn YN, Yoo KJ, Hong YS. Comparison of off-pump coronary artery bypass grafting with percutaneous coronary intervention versus drug-eluting stents for three-vessel coronary artery disease. Ann Thorac Surg 2008;86:1438–43. [4] Yi G, Joo HC, Youn YN, Hong S, Yoo KJ. Stent versus off-pump coronary bypass grafting in the second-generation drug-eluting stent era. Ann Thorac Surg 2013;96:535–41. [5] Takagi H, Watanabe T, Mizuno Y, Kawai N, Umemoto T, for the ALICE (All-Literature Investigation of Cardiovascular Evidence) Group. A review with meta-analysis of observational studies for survival following off-pump coronary artery bypass versus drug-eluting stent implantation. Interact Cardiovasc Thorac Surg 2014;18(6):807–13. [6] Dohi S, Kajimoto K, Miyauchi K, et al. Comparing outcomes after off-pump coronary artery bypass versus drug-eluting stent in diabetic patients. J Cardiol 2012;59:195–201. [7] Moshkovitz Y, Mohr R, Braunstein R, et al. Revascularization of left anterior descending coronary artery in patients with single and multivessel disease: comparison between off-pump internal thoracic artery and drug-eluting stent. Chest 2005;128:804–9. [8] Yan Q, Changsheng M, Shaoping N, et al. Percutaneous treatment with drugeluting stent vs bypass surgery in patients suffering from chronic stable angina with multivessel disease involving significant proximal stenosis in left anterior descending artery. Circ J 2009;73:1848–55. [9] Yi G, Youn YN, Hong S, Song SW, Yoo KJ. Midterm outcome of off-pump bypass procedures versus drug-eluting stent for unprotected left main coronary artery disease. Ann Thorac Surg 2012;94:15–22. [10] Yi G, Youn YN, Hong S, Song SW, Yoo KJ. Comparison of long-term outcome of off-pump coronary artery bypass grafting versus drug-eluting stents in triplevessel coronary artery disease. Am J Cardiol 2012;109:819–23. [11] Reeves BC, Deeks JJ, Higgins JP, Wells GA. Chapter 13: including non-randomized studies. In: Higgins JP, Green S, editors. Cochrane handbook for systematic reviews of interventions version 5.1.0 (updated March 2011). The Cochrane Collaboration; 2011. [www.cochrane-handbook.org (1 May 2014, date last accessed)].
Letters to the Editor
To adjust, or not to adjust, that is the question Hisato Takagi ⁎, Takuya Umemoto and For the ALICE (All-Literature Investigation of Cardiovascular Evidence) Group Department of Cardiovascular Surgery, Shizuoka Medical Center, Shizuoka, Japan
a r t i c l e
i n f o
Article history: Received 18 May 2014 Accepted 5 July 2014 Available online 12 July 2014 Keywords: Drug-eluting stent Meta-analysis Mortality Observational study Off-pump coronary artery bypass grafting
We have read with great interest a meta-analysis by Lu et al. [1] that was recently online-published in the International Journal of Cardiology. The cumulative rate of all-cause death at 3 years from only 3 nonrandomized observational cohort studies [2–4] (enrolling a total of 2417 patients) was lower in the off-pump coronary artery bypass grafting (OPCAB) than drug-eluting stent (DES) group (risk ratio [RR], 0.56; 95% confidence interval [CI], 0.33 to 0.96; P = 0.03) [1]. The authors [1] abstracted the number of events/total from nonrandomized studies, generated “unadjusted” (but not “adjusted”) RR for death, and then combined them in their meta-analysis. In such unadjusted univariable analyses, however, it can be never determined whether DES is an “independent” protective predictor of death. To find independent predictors, multivariable logistic or Cox proportional hazards regression (MCPHR) are used, generating an adjusted odds ratio or hazard ratio (HR). Alternatively, pseudo-randomization by means of propensity-score matching may be performed. In our recent meta-analysis [5], where adjusted hazard ratios (HRs) were extracted from 6 nonrandomized observational studies [4,6–10] enrolling a total of 3874 patients and then combined, OPCAB was not associated with improved survival (=was not associated with reduced death) during ≥1-year (range, 1- to 5.5-year) follow-up over DES (HR, 0.72; 95% CI, 0.45 to 1.17; P = 0.19). Although the study design of randomized trials, which balance both known and unknown confounders across treatment groups, is least vulnerable to bias, patients enrolled in them may not be representative of patients typically seen in clinical practice. On the other hand, because potential biases must be greater for observational studies compared with randomized trials, results should be always interpreted with caution when they are included in meta-analyses [11]. Particular
⁎ Corresponding author at: Department of Cardiovascular Surgery, Shizuoka Medical Center, 762-1 Nagasawa, Shimizu-cho, Sunto-gun, Shizuoka 411-8611, Japan. Tel.: + 81 559752000. E-mail address: [email protected] (H. Takagi).
http://dx.doi.org/10.1016/j.ijcard.2014.07.048 0167-5273/© 2014 Elsevier Ireland Ltd. All rights reserved.
concerns arise in terms of differences between patients in different intervention groups (selection bias). Unlike for randomized trials, it would usually be appropriate to analyze adjusted (i.e. attempting to control for confounding), rather than unadjusted, risk estimates [11]. To reduce the effect of treatment-selection bias and potential confounding in observational studies, rigorous adjustment for significant differences in the baseline characteristics of patients should be conducted. Furthermore, adjusted (but not unadjusted) estimates ought to be pooled in a meta-analysis that includes observational studies. In our recent meta-analysis [5], we exclusively abstracted (then combined in a meta-analysis) adjusted (but not unadjusted) relative risk estimates from observational studies. To adjust, or not to adjust, that is the question. The authors report no relationships that could be construed as a conflict of interest. References [1] Lu D, Nie X, Wan J, et al. Is off-pump coronary artery bypass grafting superior to drug-eluting stents for the treatment of coronary artery disease? A meta-analysis of randomized and nonrandomized studies. Int J Cardiol 2014;174(3):640–53. [2] Yamagata K, Kataoka Y, Kokubu N, et al. A 3-year clinical outcome after percutaneous coronary intervention using sirolimus-eluting stent and off-pump coronary artery bypass grafting for the treatment of diabetic patients with multivessel disease. Circ J 2010;74(4):671–8. [3] Yi G, Youn YN, Yoo KJ, Hong YS. Comparison of off-pump coronary artery bypass grafting with percutaneous coronary intervention versus drug-eluting stents for three-vessel coronary artery disease. Ann Thorac Surg 2008;86:1438–43. [4] Yi G, Joo HC, Youn YN, Hong S, Yoo KJ. Stent versus off-pump coronary bypass grafting in the second-generation drug-eluting stent era. Ann Thorac Surg 2013;96:535–41. [5] Takagi H, Watanabe T, Mizuno Y, Kawai N, Umemoto T, for the ALICE (All-Literature Investigation of Cardiovascular Evidence) Group. A review with meta-analysis of observational studies for survival following off-pump coronary artery bypass versus drug-eluting stent implantation. Interact Cardiovasc Thorac Surg 2014;18(6):807–13. [6] Dohi S, Kajimoto K, Miyauchi K, et al. Comparing outcomes after off-pump coronary artery bypass versus drug-eluting stent in diabetic patients. J Cardiol 2012;59:195–201. [7] Moshkovitz Y, Mohr R, Braunstein R, et al. Revascularization of left anterior descending coronary artery in patients with single and multivessel disease: comparison between off-pump internal thoracic artery and drug-eluting stent. Chest 2005;128:804–9. [8] Yan Q, Changsheng M, Shaoping N, et al. Percutaneous treatment with drugeluting stent vs bypass surgery in patients suffering from chronic stable angina with multivessel disease involving significant proximal stenosis in left anterior descending artery. Circ J 2009;73:1848–55. [9] Yi G, Youn YN, Hong S, Song SW, Yoo KJ. Midterm outcome of off-pump bypass procedures versus drug-eluting stent for unprotected left main coronary artery disease. Ann Thorac Surg 2012;94:15–22. [10] Yi G, Youn YN, Hong S, Song SW, Yoo KJ. Comparison of long-term outcome of off-pump coronary artery bypass grafting versus drug-eluting stents in triplevessel coronary artery disease. Am J Cardiol 2012;109:819–23. [11] Reeves BC, Deeks JJ, Higgins JP, Wells GA. Chapter 13: including non-randomized studies. In: Higgins JP, Green S, editors. Cochrane handbook for systematic reviews of interventions version 5.1.0 (updated March 2011). The Cochrane Collaboration; 2011. [www.cochrane-handbook.org (1 May 2014, date last accessed)].