In Reply: The meta-analysis by Drs Bavry and Kumbhani1 using selective inclusion of trials of invasive vs conservative therapy performed after 1999 is consistent with the overall results of our meta-analysis, which includes the totality of data from all of the randomized trials addressing this question. Figure 5 of our article reports a subgroup analysis of trials performed after 1999 and shows consistent benefit of the invasive strategy in these latter trials. However, the analysis by Bavry and Kumbhani did not show a mortality benefit at 12 months and included a trial that allocated patients to management strategy according to day of the week, potentially producing a biased result in favor of invasive therapy.2 Second, randomized trials evaluating the use of stents have not found stent use to reduce mortality or MI.3 Third, the overwhelming majority of patients in the recent trials did not actually use Gp IIb/IIIIa inhibitors: only 10% in FRISC II,4 less than 5.2% in RITA 3,5 and 0% in VINO.6
It is therefore not clear that the benefits of an invasive strategy were due to the use of these agents and stents. The only trial to use Gp IIb/IIIa antagonists in the majority of individuals was TACTICS-TIMI-18,7 in which there was no impact on mortality at follow-up. By contrast, the only trial to show a mortality benefit with invasive therapy was the FRISC II trial,3 in which Gp IIb/IIIa antagonists were not used routinely. In the most recent large-scale trial, ICTUS, nearly all patients undergoing percutaneous coronary intervention received a Gp IIb/IIIa antagonist and a stent, but there was no impact on mortality.8
With regard to the small early mortality hazard, in the TACTICS trial there was a 2-fold increase in the point estimate for mortality in the invasive group at hospital discharge, despite the use of intravenous Gp IIb/IIIa antagonists. Thus, the important issue should not be whether an early hazard exists but rather how to optimize the benefits of an invasive strategy and minimize its risks.
Regarding Dr Carbajal's concern about the lack of blinding in these trials, it would have been impossible to blind patients and physicians to an invasive or conservative management strategy. The key is to have unbiased assessment of outcomes, including a focus on objective end points (such as death or MI), and to have blinded assessment of outcome events by a central adjudication committee, which was performed in all of the trials included in our meta-analysis. Second, all the trials included in our meta-analysis had concealed randomization (a requirement for trial inclusion) as well as a properly performed intention-to-treat analysis, both of which were confirmed by the trial principal investigators in their reports and in personal communications.
Financial Disclosures: None reported.
Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature
Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal
Instructions
Comments are moderated and will appear on the site at the discretion of the Journal of American Medical Association editors. Comments should not exceed 500 words of text and 10 references.
Do not submit personal medical questions or information that could identify a specific patient, questions about a particular case, or general inquiries to an author. Only content that has not been published, posted, or submitted elsewhere should be submitted. By submitting this Comment, you and any coauthors transfer copyright to the journal if your Comment is posted.
* = Required Field
Disclosure of Any Conflicts of Interest* Indicate all relevant conflicts of interest of each author below, including all relevant financial interests, activities, and relationships within the past 3 years including, but not limited to, employment, affiliation, grants or funding, consultancies, honoraria or payment, speakers’ bureaus, stock ownership or options, expert testimony, royalties, donation of medical equipment, or patents planned, pending, or issued. If all authors have none, check "No potential conflicts or relevant financial interests" in the box below. Please also indicate any funding received in support of this work. The information will be posted with your response.
Register and get free email Table of Contents alerts, saved searches, PowerPoint downloads, CME quizzes, and more
Subscribe for full-text access to content from 1998 forward and a host of useful features
Activate your current subscription (AMA members and current subscribers)
Some tools below are only available to our subscribers or users with an online account.
Download citation file:
Customize your page view by dragging & repositioning the boxes below.
and access these and other features:
Register Now
Enter your username and email address. We'll send you a reminder to the email address on record.
Athens and Shibboleth are access management services that provide single sign-on to protected resources. They replace the multiple user names and passwords necessary to access subscription-based content with a single user name and password that can be entered once per session. It operates independently of a user's location or IP address. If your institution uses Athens or Shibboleth authentication, please contact your site administrator to receive your user name and password.