February 28, 2012 (Abu Dhabi, United Arab Emirates) — A telemedicine program in Germany facilitates interaction between internists and ophthalmologists and helps to identify patients at increased risk for cardiovascular events using information from the retina, according to a study presented here at the World Ophthalmology Congress 2012.
"The eye mirrors vascular and neurodegenerative diseases," said study presenter Georg Michelson, MD, from the University of Erlangen in Germany. "In particular, retinal microangiopathy correlates with certain systemic diseases such as arterial hypertension, stroke, and diabetes." For instance, retinal vessel-wall thickness, which is increased in stroke, can be seen using a nonmydriatic fundus camera.
Dr. Michelson described previous research done by his team, which showed that stroke risk increased 6.35-fold when cotton-wool spots were observed, and increased 4.71-fold with microaneurysms; stroke risk was 4.25-fold higher with blot hemorrhages.
These proven associations led Dr. Michelson to develop his TalkingEyes program, consisting of a network of 31 internists in private practice. The physicians use a mobile nonmydriatic fundus camera to take digital photographs of the retina in the office. These retinal images are uploaded to a Web-based patient chart, where they are evaluated by an ophthalmologist, who then adds a report to the patient's e-chart.
"If we can connect ophthalmologists to internists with a telemedicine network, this could improve patient care," Dr. Michelson explained.
In this study, 6999 patients had retinal exams performed in the general practitioner's office. Median patient age was 54 years, median body mass index was 27.6 kg/m², 40% reported a history of arterial hypertension, and 11.1% had type 2 diabetes.
During the examination, physicians took 45° photographs of the retina, obtained blood samples, and measured blood pressure. They then calculated cardiovascular risk using the PROCAM index. An ophthalmologist analyzed the fundus images remotely.
Dr. Michelson reported that 9% of the cohort had relevant morphologic changes in retinal vessels, such as arteriovenous crossings, retinal bleeding, microaneurysms, and microinfarcts.
Using the PROCAM index, only 2% of patients were found to be at high risk for a cardiovascular event. However, in 55 patients (0.8%) where no risk was indicated, "we found relevant retinal microangiopathic changes," he reported.
"We have now performed this in about 60,000 patients, and we believe that identifying these unique risk factors is having an impact on therapy," said Dr. Michelson.
He believes changes are occurring in 2 ways. "First, individuals who were screened gained a greater awareness of their risk factors overall, so they are motivated to go to the doctor more often for observation." Second, physicians are responding to evidence of elevated risk.
"In about 20% of cases, we see that therapeutic decisions are being made based on these findings."
Dr. Michelson has disclosed no relevant financial relationships.
World Ophthalmology Congress (WOC) 2012: Abstract IS-TEL-FR 65. Presented February 17, 2012.
[CLOSE WINDOW]Authors and DisclosuresJournalistNeil CanavanNeil Canavan is a freelancer for Medscape.
Missing Data Lead FDA Panel to Vote Against Rivaroxaban for ACS May 23, 2012 (Updated May 24, 2012) (Silver Spring, Maryland) — The missing data issues plaguing the ATLAS ACS 2 TIMI 51 trial of the factor Xa inhibitor rivaroxaban (Xarelto, Bayer Healthcare/Janssen Pharmaceuticals) have prevented the drug from earning the endorsement of the FDA Cardiovascular and Renal Drugs Advisory Committee. At its May 23 meeting, the panel voted six to four (with one abstention) against recommending that the FDA approve rivaroxaban for reducing the risk of thrombotic cardiovascular events in patients with acute coronary syndrome or unstable angina in combination with aspirin, aspirin plus clopidogrel, or ticlopidine. Janssen's application is based on the results of the ATLAS ACS 2 phase 3 and the ATLAS ACS TIMI 46 phase 2 trial. The placebo-controlled ATLAS ACS 2 showed rivaroxaban reduced the risk of both all-cause and cardiovascular mortality while increasing the risk of bleeding and intracranial hemorrhage, but the studies were hindered by early patient withdrawals and missing data. We Don't Know What We're Missing Based on the ATLAS ACS 2 results, FDA reviewer Dr Karen Hicks recommended approval of rivaroxaban for the requested indications except all-cause mortality. However, another FDA reviewer, Dr Thomas Marciniak, was adamant that the trial results are not interpretable because about 12% of the patients had incomplete follow-up, far higher than the 1% to 1.5% differences in the end-point rates between rivaroxaban and placebo. A total of 1294 subjects discontinued the trial prematurely, and the company was only able to contact 183, of which 177 were confirmed to be alive. Because of the patient dropouts, the company adopted a "modified intention-to-treat analysis," whereby patients were observed for 30 days after randomization or the global end date for the trial, instead of observing all the patients until the end of the trial as the FDA originally suggested. Marciniak criticized the sponsor's efforts to follow the patients and said that three patient deaths not counted in the modified intention-to-treat analysis may just be the "tip of the iceberg." Because the percentage of patients whose ultimate vital status remains unknown is much greater than the reported differences in mortality rates, the claimed mortality benefits are not reliable. The majority of the panel sided with Marciniak. For example, Dr Sanjay Kaul (University of California, Los Angeles) voted "no" because "there was enough uncertainty in the quality and robustness of the data that dissuaded me from voting yes. . . . The 'missingness' of the data doesn't invalidate it, but it certainly makes it hard to infer [the conclusion]." Dr Steven Nissen (Cleveland Clinic, OH) said that the decision to use the modified intention-to-treat analysis had a "profound impact" on the interpretability of the data. "It's saying we don't care what happens after 30 days, [and] that colored the trial in ways we couldn't recover from." Given the risk of major bleeding, "I want to see better evidence that this strategy of adding an Xa inhibitor or a direct thrombin inhibitor or something else to a good antiplatelet agent is robustly better for the patient," Nissen said. He recommends that the companies run a new trial of the 2.5 twice-daily dose of rivaroxaban using a strict intention-to-treat approach, but, he said, "I don't expect the death benefit to be too robust." Several panelists said they were concerned that the patients who dropped out of the trial were disproportionately likely to have a bleeding event, which led them to quit the trial, or a "protopathic" event, as statistician Dr Scott Emerson (University of Washington, Seattle) put it. "We're worried that an impending event is what is changing their behavior. We see that all the time in clinical trials--that regularly measured end points do not pick up [all of] the events," he said. He said that since the company was only able to contact 183 of the over 1200 patients who dropped out, it is possible that the dropouts skew the outcomes comparison of the trial. "Differential event rates after dropout are the number-one thing we're afraid of, so you have to explore it" in a statistical sensitivity analysis of the potential impact of these unknown outcomes. "It would not surprise me if, at the end of the day, these data did not hold up under a proper sensitivity analysis," he said. "What I want to know is, among the people who had events, how differential was the follow-up, but I can tell you by just looking at it, there was a very slightly different amount of follow-up of the people in the treatment arm. But I don't know whether everyone in the treatment arm was cured and they were trekking in the Himalayas and everyone in the placebo arm went home to die. I don't know that that's not the case." Dr Maury Krantz (University of Colorado, Denver) voted in favor of approval but said he does not know how rivaroxaban would perform in general clinical practice, especially when used with aspirin and clopidogrel. "I felt very much torn by this. This isn't a simple paradigm shift. It means going to triple therapy, which is really a three-headed monster in many ways. I think that what you're going to see in practice, if this is not done carefully with the proper labeling and secondary studies, is really dramatic magnification of bleeding and perhaps minimization of the efficacy benefit."
May 23, 2012 (Updated May 24, 2012) (Silver Spring, Maryland) — The missing data issues plaguing the ATLAS ACS 2 TIMI 51 trial of the factor Xa inhibitor rivaroxaban (Xarelto, Bayer Healthcare/Janssen Pharmaceuticals) have prevented the drug from earning the endorsement of the FDA Cardiovascular and Renal Drugs Advisory Committee. At its May 23 meeting , the panel voted six to four (with one abstention) against recommending that the FDA approve rivaroxaban for reducing the risk of thrombotic cardiovascular events in patients with acute coronary syndrome or unstable angina in combination with aspirin, aspirin plus clopidogrel , or ticlopidine . Janssen's application is based on the results of the ATLAS ACS 2 phase 3 and the ATLAS ACS TIMI 46 phase 2 trial. The placebo-controlled ATLAS ACS 2 showed rivaroxaban reduced the risk of both all-cause and cardiovascular mortality while increasing the ri...
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