Meta-analysis and Evidence-based Medicine Training in Cardiology
December 2007 newsletter (posted on 8/12/2007)
Awaiting the end of the year and reflecting on advances in cardiology in the last 12 months, there is ample evidence that the potential risk of thrombosis associated with drug-eluting stents initially raised at Barcelona in 2006 had likely been overestimated (please see the pertinent newsletter). These conclusions largely depend on the several independent meta-analyses published on this topic in 2007, which are indeed recommended reading (eg Ellis et al, Kastrati et al, Mauri et al, Moreno et al, Spaulding et al, and Stone et al).
One of our major ambitions, here at METCARDIO, would be now to award the most influential and rigorous meta-analysis published during this year in the field of interventional cardiology (please refer to our Awards section for selection criteria and means to propose candidate studies and posting your vote).
Finally, for those of you avid of interventional cardiology meetings, we do recommend attending the upcoming 3rd International Interventional Forum, directed by Drs. Garcia, Lefevre and Sheiban, which will be held on 17th-18th January 2008 in Turin, Italy (advertisement and registration details can be find online).
November 2007 newsletter (posted on 7/11/2007)
The recent American Heart Association 2007 Scientific Sessions have brought intriguing data from late breaking clinical trials in the field of cardiovascular medicine. Specifically, the COURAGE imaging substudy has shown that percutaneous coronary revascularization reduces the amount of ischemic myocardium in comparison to optimal medical therapy. The MASS Stent Registry reported favorable results (including lower case fatality) for drug-eluting versus bare-metal stents in a state-wide cohort of patients, even if selection bias cannot be completely excluded. The OAT quality of life/cost-effectiveness substudy has confirmed the overall OAT results, ie that percutaneous coronary revascularization may not confer major benefits in low-risk subjects with an occluded infarct-related artery presenting late after the acute myocardial infarction. The TRITON-TIMI 38 Tiral has provided promising results supporting the superior efficacy of prasugrel in comparison to clopidogrel in patients with acute coronary syndromes, albeit at the price of increased bleedings. Finally, the CorE 64 Study has shown that multislice coronary angiography by means of computed tomography may offer good diagnostic performance in comparison to standard invasive coronary angiography, at least in carefully selected patients.
October 2007 newsletter (posted on 26/10/2007)
Time for major changes here as the former COMET website has become the website you are now watching: metcardio.org. We hope indeed that this development will translate into more user-friendly and comprehensive tools for clinicians and researchers with a specific interest in interventional cardiology, meta-analysis, and evidence-based cardiovascular medicine.
On top of this, important additions to the current evidence base in cardiovascular medicine have been provided at the recent Transcatheter Cardiovascular Therapeutics meeting. Among the many important studies we can quote the AMIHOT II, BBK, CHREDIT, ENDEAVOR IV, HORIZONS AMI, NOBORI I, NORDIC II, and SPIRIT III trials.
Another pivotal development has been the hot-new redefinition of myocardial infarction, likely to dominate clinical research and practice for many years.
September 2007 newsletter (posted on 13/9/2007)
After some exciting holidays, we are back with many novel data presented at the 2007 European Society of Cardiology Congress in Wien. To nominate just a few of the important studies presented, we can cite the CARESS in AMI, FINESSE, GRACE-DES, OASIS-5, PRAGUE-8, RIO-Trial, SCAAR, and STEEPLE trials.
Specifically, CARESS in AMI has reported on the comparison between facilitated percutaneous coronary intervention (PCI) after transfer versus on-site thrombolysis in patients with acute ST-elevation myocardial infarction (AMI), showing the superiority of the former strategy. FINESSE has conversely definitely demonstrated the inferiority of routine pharmacologic facilitation before PCI for AMI.
Whereas long-term results from SCAAR have not confirmed any major risk from drug-eluting stents (DES) in a nation-wide Swedish registry, GRACE investigators provokingly reported on the potential increased risk of late adverse events after DES implantation for acute coronary syndromes (ACS). The OASIS-5 WOMEN substudy also focused on ACS, but selectively enrolled females. Intriguingly, this randomized trial suggested an increased risk of death and bleeding when women with ACS are managed with a routinely invasive strategy, yet the small sample size limits internal and external validity.
The OPTIMIST study has originally shown that PCI for stent thrombosis is not a rare type of emergency procedure and is associated with an ominous rate of adverse clinical outcomes. PRAGUE-8 investigators provided compelling evidence that a high (600 mg) clopidogrel loading dose should be only administered following coronary angiography in stable coronary patients. Finally, routine abciximab should be best avoided in uncomplicated cases of lower limb intervention, according to the RIO-Trial.
July-August 2007 newsletter (posted on 27/7/2007)
Despite the season fraught with holidays for many of us, several intriguing data have been recenly become available, including the publication of the provoking data of the DELAYED RRISC Trial. In this update from a 75-patient-large randomized study comparing sirolimus-eluting versus bare-metal stents in saphenous vein grafts, Vermeersch, Agostoni and colleagues provided compelling data on the potential long-term hazard of drug-eluting stents in this lesion subset. Whether these results will hold true in further and larger trials is unclear, but to date this is the only well designed and conducted trial on this important clinical issue.
Changing topic, a common question among perusers of our website, is how we define a systematic review. Here is the definition recommended by The Cochrane Collaboration: "a review of a clearly formulated question that uses systematic and explicit methods to identify, select, and critically appraise relevant research, and to collect and analyse data from the studies that are included in the review. Statistical methods (meta-analysis) may or may not be used to analyse and summarise the results of the included studies".
June 2007 newsletter (posted on 13/6/2007)
After the successful 2007 EuroPCR meeting, and preparing for the summer holidays, there is time to critically read two important works recently published, which we strongly recommend to our visitors: the meta-analysis on the hazards associated with rosiglitazone (Nissen et al, New Engl J Med 2007), and the PROGRESS-AMS Study, focusing on the novel bioabsorbable magnesium coronary stent (Erbel et al, Lancet 2007). The systematic review by Nissen et al, with its inherent limitations and yet major clinical implications, is indeed a powerful example of the potentials and pitfalls of meta-analytic methods applied in clinical medicine.
May 2007 newsletter (posted on 14/5/2007)
Awaiting the upcoming 2007 EuroPCR meeting, which for the first time will be held in Barcelona, Spain, it may be worthwhile to have a look at a few articles recently published on off-label use of drug-eluting stents (Behoar et al; Win et al), as well as to the SWISSI II study, an interesting randomized trial on percutaneous revascularization in patients with recent myocardial infarction and silent ischemia, which indirectly challenges the OAT and COURAGE trials. Specifically, SWISSI II investigators randomized 201 patients with recent infarction, silent myocardial ischemia verified by stress imaging, and 1- or 2-vessel coronary artery disease to percutaneous coronary intervention aimed at full revascularization or intensive anti-ischemic drug therapy, finding after 10+-3 years major benefits in terms of overall and event-free survival in favor of percutaneous coronary intervention.
April 2007 newsletter (posted on 1/4/2007)
The 2007 annual American College of Cardiology meeting has just offered new important data on interventional cardiology. The technology is rapidly progressing in the field of percutaneous coronary intervention (PCI) and a new drug-eluting stent, the Abbott Xience V everolimus-eluting stent, is entering the market with an absolutely respectful portfolio, as it was shown to be superior, in angiographic and clinical endpoints, to the well-established Boston Scientific Taxus paclitaxel-eluting stent in a randomized trial enrolling >1000 patients (Stone GW. SPIRIT III results). Of course long-term data also on this stent are eagerly awaited. Moreover, preliminary data on bio-absorbable everolimus-eluting stents appear very promising in a small cohort of 30 patients, leading the way to futuristic approaches in the treatment of coronary stenoses (Serruys PW. ABSORB results).
On the other hand, the real clinical value of PCI in patients with stable angina has been questioned by the landmark 2287-patent randomized Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial. The study failed to show an additional benefit of PCI over optimal medical therapy in terms of death and myocardial infarction. However it should be noted, and probably it was not enough emphasized in the manuscript, that anginal symptoms were significantly reduced in the PCI group. Indeed, these data comes as no surprise, as similar results were already reported in a 1904-patient meta-analysis published by Bucher et al in 2000, and by a comparable 2950-patient systematic review authored by Katritsis et al in 2005.
One of the primary goals of PCI, when introduced by Andreas Gruentzig in the late '70s, was symptomatic relief of ischemic chest pain. Thus, from the interventionist's point of view, the COURAGE trial can be also read differently: COURAGE tells us that we can achieve the goal of reducing or eliminating anginal symptoms safely and quickly, without an increase in "hard" events. Of interest, also in the Occluded Artery Trial, the same result (anginal symptoms reduction) was obtained in the PCI arm and it was "obscured" in a table presented only as an online supplement of the major publication. In addition, COURAGE suggests us that patients treated with PCI can take less medications. Specifically, patients randomized to the medical therapy were assuming significantly more nitrates than those in the PCI group. In this context, a recent report suggests a deleterious effect of nitrates on endothelial function in healthy individuals. Eventually, upcoming data form the cost-effectiveness and quality-of-life analyses of the COURAGE trial will offer additional information to this important debate.
In conclusion, this impact of PCI on patients' symptoms should be kept in mind as we should probably focus also and more on the quality of life of the people we treat and not only on the "amount". Trials direct specifically on this topic in our opinion are largely welcome and should constitute the basis also for the development of future devices. Unfortunately, most trials on drug-eluting stents did not report anginal symptoms and this should be seen as a major limitation.
March 2007 newsletter (posted on 1/3/2007)
Further fuel to the hot debate on drug-eluting stent safety has been provided by the recent publication of several meta-analyses in the New England Journal of Medicine as well as in other journals, with works by Ellis et al, Kastrati et al, Mauri et al, Moreno et al, Spaulding et al, and Stone et al. While a certain degree of duplication is evident in these papers (as well as with Holmes et al), we believe that novel data on potentials and drawbacks of these devices have been provided. Conversely, these papers also amount to a missed opportunity, as a single collaborative individual patient data systematic review and meta-analysis would have probably better served clinicians and researchers.
Changing topic, a number of visitors of this website have asked us for beginner's guidelines to interpret or conduct a systematic review and meta-analysis. While several pertinent sources are available, we recommend as starting points the handbook of The Cochrane Collaboration (Cochrane Handbook for Systematic Reviews of Interventions), and the report from the University of York Centre for Reviews and Dissemination (Undertaking systematic reviews of research on effectiveness: CRD's guidance for those carrying out or commissioning reviews).
February 2007 newsletter (posted on 10/2/2007)
While many of us are still recovering or involved in the winter holidays, the drug-eluting stent safety debate has promoted further recommendations from major organizations. Indeed, Hodgson et al have reported explicit advice from Society for Cardiovascular Angiography and Interventions, American College of Cardiology, and American Heart Association on indications and most appropriate use of drug-eluting stents, as well as appropriate adjunctive therapies.
In the meanwhile, we are all preparing for the results of the upcoming COURAGE clinical trial, comparing percutaneous coronary intervention versus best medical therapy among 2287 patients with symptomatic and documented stable angina. Preliminary results are expected to be presented at the 2007 American College of Cardiology Scientific Sessions.
January 2007 newsletter (posted on 16/1/2007)
A new exciting year is beginning and yet our mind goes to the momentous changes that have occurred in the field of interventional cardiology. Indeed, from the febrile enthusiasm on drug-eluting stents (DES) and other novel technologies of early 2006, we have reached the cautious realism of late 2006, with the somewhat disappointing recommendations of the FDA panel called to judge on the safety of DES. We urge you to read this important paper as well as the recent AHA/ACC/SCAI guidelines on clopidogrel maintainance. However, it seems odd that FDA panelists recognized the increased risk of stent thrombosis with DES, but yet dismissed claims of an excess in death or myocardial infarction. In our opinion this should be best seen as an issue of low statistical power.
Among novel features of this website, we have almost finished preparing an interesting section featuring exclusive interviews with international leaders in cardiovascular research. Finally, for those of you avid of reading novel and interesting works, we would like to recommend a recent appraisal of cost-effectiveness analyses focusing on DES, showing the potential detrimental impact of conflicts of interest on study findings (Ligthart et al, CMAJ 2007), and a pivotal book disclosing the debatable marketing strategies of medical drug and device companies (Moynihan and Cassels, Selling sickness).
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