Interventional Cardiology Unit
S. Raffaele Hospital
"Vita e Salute" University
University of Milan
Via Olgettina
60 20132 Milan, Italy
Tel.: +39-349-4303888
Fax: +39-(0)45-914727
E-mail address: agostonipf{at}genie.it
Interventional Cardiology Unit
S. Raffaele Hospital
"Vita e Salute" University
University of Milan
Department of Biomedical and Surgical
Sciences
Section of Cardiology
University of Verona
Verona, Italy
Department of Biomedical and Surgical
Sciences
Section of Cardiology
University of Verona
Verona, Italy
Department of Biomedical and Surgical
Sciences
Section of Cardiology
University of Verona
Verona, Italy
Department of Biomedical and Surgical
Sciences
Section of Cardiology
University of Verona
Verona, Italy
Department of Medicine
Virginia Commonwealth University
Medical College of Virginia Campus
Richmond
VA, USA
Thoraxcenter
Erasmus MC
Rotterdam,
The Netherlands
Department of Biomedical and Surgical
Sciences
Section of Cardiology
University of Verona
Verona, Italy
Department of Biomedical and Surgical
Sciences
Section of Cardiology
University of Verona
Verona
Italy
Interventional Cardiology Unit
S. Raffaele Hospital
"Vita e Salute" University
University of Milan
Thoraxcenter
Erasmus MC
Rotterdam,
The Netherlands
We deeply appreciate the interest of Moreno et al. on our meta-analysis and we welcome the continuous debate regarding this issue. Unfortunately, we partially disagree with Moreno et al. on their response1 to our previous letter2 to the editor published in the Journal of the American College of Cardiology, and on their present criticisms.
In particular, concerning their previous reply letter in the Journal of the American College of Cardiology,1 we believe that they did not sufficiently evaluate the importance of statistical heterogeneity among trials, present both in our and their meta-analyses. Although a quantitative estimate may be obtained also in the case of statistical heterogeneity, using the random effect model, further analyses should be utilized to better investigate this heterogeneity and its possible value. Indeed, in all the meta-analyses we published, we always performed prehoc or posthoc subgroup analyses in order to confirm whether the main result was sufficiently robust to be maintained in the subgroups or if there were different trends, related to some other variables, that could explain the presence of heterogeneity. In addition, meta-regression, attempted by Moreno et al.1 should be performed based on standard methods, as clearly explained in Biondi-Zoccai et al.3 Next, the trial by Kinsara et al.,4 included in our meta-analysis, should have also been included in their meta-analysis, as long as it was published as an abstract in 1999.5
Regarding their present criticisms, first, we believe that, as a meta-analysis may be considered an original investigation, it should have its own primary endpoint which need not necessarily be the same as the one present in the trials included in the systematic review. Indeed, the major strength of a meta-analysis comes from the higher power (because of the larger sample size) to detect differences in outcomes that could not be adequately investigated by single trials.5,6 In addition, our predefined criterion for optimal balloon angioplasty (diameter stenosis <20%), although arbitrary as correctly stated by Moreno et al., in their current letter, came from previous suggestions and analyses done by experts (as we stated in our methods section) and it was a predefined form of subgroup analysis to assess whether the main result was also maintained in the subgroups, or there were different trends, as previously explained. Indeed, we also performed other subgroup analyses, but they were all burdened by significant heterogeneity. Moreover, the references 4 and 5 used by Moreno et al. in their current letter refer to two studies performed in coronary vessels with a large range of vessel size and not only small ones, thus the cut-off of 35% after angioplasty as residual stenosis indicating suboptimal result may not correctly apply to small vessels. Finally, in our opinion, the intention-to-treat analysis (including cross-over from balloon angioplasty to stent, considered in each trial as bail-out and not provisional) was the best approach as we did not want to simply compare stenting with balloon, but we would like to understand why there were different results in trials with similar design and whether the possible benefit of routine stenting was real or could be balanced by a strategy of provisional stenting.
The real value of a meta-analysis relies on the correct selection of data and also on the right statistical methods used.6,7 The best approach to reconcile Moreno's and our work would be an individual patient data meta-analysis, scientifically intriguing, but logistically and economically demanding.7
References
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