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Outcomes in Patients With Unprotected Left Main Coronary Disease: Comparison Between Drug-Eluting Stents and Coronary Artery By-Pass Grafting
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and persists for a few weeks, along with the inverted T waves, long after the myocardial stunning has completely resolved and left ventricular function has been restored to the baseline state.6,7 The ST-segment elevation in TTS is implicitly attributed to myocardial ischemia, along the current conceptualization of its mechanism in acute coronary syndromes. It is conceivable that ST-segment elevation in TTS is partially (or even totally) due to the dyskinesia displayed by the apical “ballooning,” along the pathophysiologic paradigm of VA. Not every patient with TTS presents with STsegment elevation on electrocardiography. As cases of TTS are reported, a possible association of ST-segment elevation with dyskinesia could be explored using the routinely performed initial transthoracic 2-dimensional echocardiography, by documenting apical and midventricular systolic stretching in combination with basal hyperkinesia. According to this reasoning, patients with apical and midventricular systolic hypokinesia or akinesia would be expected not to show contemporaneously STsegment elevation on electrocardiography. John E. Madias, MD New York, New York 12 October 2012
1. Ford RV, Levine HD. The electrocardiographic clue to ventricular aneurysm. Ann Intern Med 1951;34:998e1116. 2. Madias JE. Electrocardiography in myocardial infarction. J Electrocardiol 1979;12:411e423. 3. Arvan S, Varat MA. Persistent ST-segment elevation and left ventricular wall abnormalities: 2-dimensional echocardiographic study. Am J Cardiol 1984;53:1542e1546. 4. Hamani A, Khatouri A, Kendoussi M, Aouad A, Elyounassi B, Zbir E, Nazzi M. Correlation between the persistence of ST elevation and left ventricular aneurysm in the post-infarction period. Ann Cardiol Angeiol (Paris) 1995;44:361e364. 5. Galiuto L, Barchetta S, Paladini S, Lanza G, Rebuzzi AG, Marzilli M, Crea F. Functional and structural correlates of persistent ST elevation after acute myocardial infarction successfully treated by percutaneous coronary intervention. Heart 2007;93:1376e1380. 6. Migliore F, Zorzi A, Marra MP, Basso C, Corbetti F, De Lazzari M, Tarantini G, Buja P, Lacognata C, Thiene G, Corrado D, Iliceto S. Myocardial edema underlies dynamic T-wave inversion (Wellens’ ECG pattern) in patients with reversible left ventricular dysfunction. Heart Rhythm 2011;8:1629. 7. Tada H. Unraveling the riddle of transient T-wave inversion (Wellens’ ECG pattern): T2-weighted magnetic resonance imaging identifies myocardial edema. Heart Rhythm 2011;8:1635. http://dx.doi.org/10.1016/j.amjcard.2012.11.001
Outcomes in Patients With Unprotected Left Main Coronary Disease: Comparison Between Drug-Eluting Stents and Coronary Artery By-Pass Grafting In comparing outcomes between drug-eluting stents (DES) and coronary artery bypass grafting for unprotected left main coronary disease, the metaanalysis by Jiang et al1 included 16 studies in which major adverse cardiac and cerebrovascular events (MACCEs) were assessed with a follow-up period of 2 years. We reexamined the same 16 studies (and their results on the basis of this follow-up length) to determine whether any temporal trend could be detected in the risk ratio (RR) for 3 main outcome measures (MACCEs including target vessel revascularization [TVR], MACCEs excluding TVR, and TVR). Temporal trends were investigated using standard meta-regression methods2e5; as usual, RR values were log transformed. We reextracted the event frequencies from the primary studies because Jiang et al1 did not present crude event rates. Two of us (A.M. and D.M.) separately carried out this extraction; differences were resolved by consensus, but priority was assigned to outcomes determined after a follow-up period of about 2 years. In analyzing temporal trends, individual studies were represented by the midpoint of their enrollment interval. Figure 1 shows the results of our metaregression. The 2 end points of MACCEs including TVR and MACCEs excluding TVR showed substantial stability in their RRs over time (with a slight increase from 2002 to 2007, particularly for the second end point, but significance was absent in both cases). Likewise, the temporal analysis of RR for TVR found that although DES were clearly associated with increased risk for TVR, the RR for this end point showed only a modest decrease over time, which however remained far from statistical significance. More interestingly, despite the use of the same primary studies, our metaanalytic values of pooled RRs were not exactly the same as those calculated by Jiang et al.1 We found in fact the following results (all expressed for DES vs coronary artery bypass grafting): an RR of 1.37 (95% confidence interval [CI] 1.11 to 1.69, p <0.01) for MACCEs including TVR, an RR of 0.92 (95% CI 0.69 to 1.24, p ¼ 0.55) for MACCEs
779
excluding TVR, and an RR of 3.14 (95% CI 2.13 to 4.63, p <0.01) for TVR (see the Appendix for further details). The main difference is that the pooled RR for the end point of MACCEs including TVR reported by Jiang et al1 did not reach significance (RR 1.14, 95% CI 0.87 to 1.49), whereas our result was clearly significant. This difference depends on some differences in the RRs of individual studies, which in turn reflects extraction of different event frequencies. In the absence of more detailed information on the work of Jiang et al,1 several reasons could explain these differences in the study-specific event frequencies: (1) the choice of different time points during follow-up, (2) the availability of adjusted and unadjusted values, a condition that markedly increases the complexity of these analyses; or (3) misinterpretation of the results presented in clinical studies. In any case, this example indicates that, for the purposes of meta-analysis, complex composite end points such as MACCEs are susceptible to different interpretations by different researchers. In conclusion, in our analysis, the temporal trends of outcomes were estimated in patients with unprotected left main coronary disease treated from 2002 to 2007; this is novel information in this area, although the lack of statistical significance in these trends diminishes the scientific originality of our findings. In addition, another set of quite different meta-analytic results was obtained from the analysis of the same 16 studies examined by Jiang et al.1 Appendix This Appendix includes Table A1 (complete bibliographies for the 16 studies included in our analysis), Table A2 (details on the source of information from which our event frequencies were extracted), and Figure A1 (traditional meta-analysis comparing DES vs coronary artery bypass grafting on the basis of the end points of MACCEs including TVR, MACCE excluding TVR, and TVR). This material can be obtained from the authors on request or can be downloaded at http:// www.osservatorioinnovazione.net/papers/ messori-ajc-2012-supplement.pdf. Andrea Messori, MD Dario Maratea, PharmD
780
The American Journal of Cardiology (www.ajconline.org)
Figure 1. Comparison between DES implantation and coronary artery bypass grafting (CABG) in patients with unprotected left main coronary disease: temporal trends of RR for (1) MACCEs including TVR (A) (16 studies), (2) MACCEs excluding TVR (B) (14 studies), and (3) TVR (C) (14 studies). Because of the logarithmic transformation, the case of equal risk between the 2 treatment options corresponds to y ¼ 0 (not to y ¼ 1). The regression equations were as follows: (A) log(RR) ¼ 0.0379 YEAR 75.799 (p ¼ 0.41), (B) log(RR) ¼ 0.0769 YEAR 154.101 (p ¼ 0.17), and (C) log(RR) ¼ 0.038198 YEAR þ 77.003 (p ¼ 0.58). Each study is represented by a circle, the diameter of which is proportional to its statistical weight. YEAR ¼ midpoint of the enrollment interval.
Valeria Fadda, PharmD Sabrina Trippoli, PharmD Prato, Italy 2 November 2012
1. Jiang WB, Zhao W, Huang H, Li CL, Zhang JH, Wang Y, Fu GS. Meta-analysis of effectiveness of first-generation drug-eluting stents versus coronary artery bypass grafting for unprotected left main coronary disease. Am J Cardiol 2012;110: 1764e1772.
2. Biondi-Zoccai GG, Abbate A, Agostoni P, Testa L, Burzotta F, Lotrionte M, Trani C, Biasucci LM. Long-term benefits of an early invasive management in acute coronary syndromes depend on intracoronary stenting and aggressive antiplatelet treatment: a metaregression. Am Heart J 2005;149:504e511. 3. Messori A, Maratea D, Fadda V, Trippoli S. Antipsychotic drugs for relapse prevention in schizophrenia. Lancet 2012;380:1055e1056.
4. Messori A, Maratea D, Fadda V, Trippoli S. Temporal trend of overall survival in patients with advanced non-small cell lung cancer given first-line cytotoxic treatments. Lung Epub 2012 Oct 19. 5. Fadda V, Maratea D, Trippoli S, Messori A. Mechanical endovascular therapy in ischemic stroke: temporal trend of outcomes. Int J Stroke. In press. http://dx.doi.org/10.1016/j.amjcard.2012.11.007
and persists for a few weeks, along with the inverted T waves, long after the myocardial stunning has completely resolved and left ventricular function has been restored to the baseline state.6,7 The ST-segment elevation in TTS is implicitly attributed to myocardial ischemia, along the current conceptualization of its mechanism in acute coronary syndromes. It is conceivable that ST-segment elevation in TTS is partially (or even totally) due to the dyskinesia displayed by the apical “ballooning,” along the pathophysiologic paradigm of VA. Not every patient with TTS presents with STsegment elevation on electrocardiography. As cases of TTS are reported, a possible association of ST-segment elevation with dyskinesia could be explored using the routinely performed initial transthoracic 2-dimensional echocardiography, by documenting apical and midventricular systolic stretching in combination with basal hyperkinesia. According to this reasoning, patients with apical and midventricular systolic hypokinesia or akinesia would be expected not to show contemporaneously STsegment elevation on electrocardiography. John E. Madias, MD New York, New York 12 October 2012
1. Ford RV, Levine HD. The electrocardiographic clue to ventricular aneurysm. Ann Intern Med 1951;34:998e1116. 2. Madias JE. Electrocardiography in myocardial infarction. J Electrocardiol 1979;12:411e423. 3. Arvan S, Varat MA. Persistent ST-segment elevation and left ventricular wall abnormalities: 2-dimensional echocardiographic study. Am J Cardiol 1984;53:1542e1546. 4. Hamani A, Khatouri A, Kendoussi M, Aouad A, Elyounassi B, Zbir E, Nazzi M. Correlation between the persistence of ST elevation and left ventricular aneurysm in the post-infarction period. Ann Cardiol Angeiol (Paris) 1995;44:361e364. 5. Galiuto L, Barchetta S, Paladini S, Lanza G, Rebuzzi AG, Marzilli M, Crea F. Functional and structural correlates of persistent ST elevation after acute myocardial infarction successfully treated by percutaneous coronary intervention. Heart 2007;93:1376e1380. 6. Migliore F, Zorzi A, Marra MP, Basso C, Corbetti F, De Lazzari M, Tarantini G, Buja P, Lacognata C, Thiene G, Corrado D, Iliceto S. Myocardial edema underlies dynamic T-wave inversion (Wellens’ ECG pattern) in patients with reversible left ventricular dysfunction. Heart Rhythm 2011;8:1629. 7. Tada H. Unraveling the riddle of transient T-wave inversion (Wellens’ ECG pattern): T2-weighted magnetic resonance imaging identifies myocardial edema. Heart Rhythm 2011;8:1635. http://dx.doi.org/10.1016/j.amjcard.2012.11.001
Outcomes in Patients With Unprotected Left Main Coronary Disease: Comparison Between Drug-Eluting Stents and Coronary Artery By-Pass Grafting In comparing outcomes between drug-eluting stents (DES) and coronary artery bypass grafting for unprotected left main coronary disease, the metaanalysis by Jiang et al1 included 16 studies in which major adverse cardiac and cerebrovascular events (MACCEs) were assessed with a follow-up period of 2 years. We reexamined the same 16 studies (and their results on the basis of this follow-up length) to determine whether any temporal trend could be detected in the risk ratio (RR) for 3 main outcome measures (MACCEs including target vessel revascularization [TVR], MACCEs excluding TVR, and TVR). Temporal trends were investigated using standard meta-regression methods2e5; as usual, RR values were log transformed. We reextracted the event frequencies from the primary studies because Jiang et al1 did not present crude event rates. Two of us (A.M. and D.M.) separately carried out this extraction; differences were resolved by consensus, but priority was assigned to outcomes determined after a follow-up period of about 2 years. In analyzing temporal trends, individual studies were represented by the midpoint of their enrollment interval. Figure 1 shows the results of our metaregression. The 2 end points of MACCEs including TVR and MACCEs excluding TVR showed substantial stability in their RRs over time (with a slight increase from 2002 to 2007, particularly for the second end point, but significance was absent in both cases). Likewise, the temporal analysis of RR for TVR found that although DES were clearly associated with increased risk for TVR, the RR for this end point showed only a modest decrease over time, which however remained far from statistical significance. More interestingly, despite the use of the same primary studies, our metaanalytic values of pooled RRs were not exactly the same as those calculated by Jiang et al.1 We found in fact the following results (all expressed for DES vs coronary artery bypass grafting): an RR of 1.37 (95% confidence interval [CI] 1.11 to 1.69, p <0.01) for MACCEs including TVR, an RR of 0.92 (95% CI 0.69 to 1.24, p ¼ 0.55) for MACCEs
779
excluding TVR, and an RR of 3.14 (95% CI 2.13 to 4.63, p <0.01) for TVR (see the Appendix for further details). The main difference is that the pooled RR for the end point of MACCEs including TVR reported by Jiang et al1 did not reach significance (RR 1.14, 95% CI 0.87 to 1.49), whereas our result was clearly significant. This difference depends on some differences in the RRs of individual studies, which in turn reflects extraction of different event frequencies. In the absence of more detailed information on the work of Jiang et al,1 several reasons could explain these differences in the study-specific event frequencies: (1) the choice of different time points during follow-up, (2) the availability of adjusted and unadjusted values, a condition that markedly increases the complexity of these analyses; or (3) misinterpretation of the results presented in clinical studies. In any case, this example indicates that, for the purposes of meta-analysis, complex composite end points such as MACCEs are susceptible to different interpretations by different researchers. In conclusion, in our analysis, the temporal trends of outcomes were estimated in patients with unprotected left main coronary disease treated from 2002 to 2007; this is novel information in this area, although the lack of statistical significance in these trends diminishes the scientific originality of our findings. In addition, another set of quite different meta-analytic results was obtained from the analysis of the same 16 studies examined by Jiang et al.1 Appendix This Appendix includes Table A1 (complete bibliographies for the 16 studies included in our analysis), Table A2 (details on the source of information from which our event frequencies were extracted), and Figure A1 (traditional meta-analysis comparing DES vs coronary artery bypass grafting on the basis of the end points of MACCEs including TVR, MACCE excluding TVR, and TVR). This material can be obtained from the authors on request or can be downloaded at http:// www.osservatorioinnovazione.net/papers/ messori-ajc-2012-supplement.pdf. Andrea Messori, MD Dario Maratea, PharmD
780
The American Journal of Cardiology (www.ajconline.org)
Figure 1. Comparison between DES implantation and coronary artery bypass grafting (CABG) in patients with unprotected left main coronary disease: temporal trends of RR for (1) MACCEs including TVR (A) (16 studies), (2) MACCEs excluding TVR (B) (14 studies), and (3) TVR (C) (14 studies). Because of the logarithmic transformation, the case of equal risk between the 2 treatment options corresponds to y ¼ 0 (not to y ¼ 1). The regression equations were as follows: (A) log(RR) ¼ 0.0379 YEAR 75.799 (p ¼ 0.41), (B) log(RR) ¼ 0.0769 YEAR 154.101 (p ¼ 0.17), and (C) log(RR) ¼ 0.038198 YEAR þ 77.003 (p ¼ 0.58). Each study is represented by a circle, the diameter of which is proportional to its statistical weight. YEAR ¼ midpoint of the enrollment interval.
Valeria Fadda, PharmD Sabrina Trippoli, PharmD Prato, Italy 2 November 2012
1. Jiang WB, Zhao W, Huang H, Li CL, Zhang JH, Wang Y, Fu GS. Meta-analysis of effectiveness of first-generation drug-eluting stents versus coronary artery bypass grafting for unprotected left main coronary disease. Am J Cardiol 2012;110: 1764e1772.
2. Biondi-Zoccai GG, Abbate A, Agostoni P, Testa L, Burzotta F, Lotrionte M, Trani C, Biasucci LM. Long-term benefits of an early invasive management in acute coronary syndromes depend on intracoronary stenting and aggressive antiplatelet treatment: a metaregression. Am Heart J 2005;149:504e511. 3. Messori A, Maratea D, Fadda V, Trippoli S. Antipsychotic drugs for relapse prevention in schizophrenia. Lancet 2012;380:1055e1056.
4. Messori A, Maratea D, Fadda V, Trippoli S. Temporal trend of overall survival in patients with advanced non-small cell lung cancer given first-line cytotoxic treatments. Lung Epub 2012 Oct 19. 5. Fadda V, Maratea D, Trippoli S, Messori A. Mechanical endovascular therapy in ischemic stroke: temporal trend of outcomes. Int J Stroke. In press. http://dx.doi.org/10.1016/j.amjcard.2012.11.007