Skip to main content

Comorbidities Influence Three-Year Survival With Sapien TAVI: PARTNER B


MIAMI — New results from the PARTNER B trial of the Edwards Lifesciences Sapien transcatheter aortic valve in inoperable patients shows that the mortality benefit of the device persists at least three years and that the survival prognosis in patients undergoing transcatheter aortic-valve implantation (TAVI) correlates to the severity of their comorbidities at the time of implant [1,2].
Here at TCT 2012, Dr E Murat Tuzcu (Cleveland Clinic, OH) presented the three-year follow-up data from PARTNER B showing that all of the major benefits of TAVI vs standard therapy shown at a previous time point--measured by all-cause mortality, cardiovascular mortality, repeat hospitalization, and functional status--are sustained out to three years.
As reported by heartwire , PARTNER B compared Sapien with standard care in patients who were too ill to withstand surgery. PARTNER B initially randomized 179 patients to TAVI with Sapien and 179 to standard therapy. By the three-year follow-up, all but 19 of the control patients had either died or been "censored" because they received a Sapien valve, while there were 80 patients left in the TAVI group.
The Kaplan Meier estimated rates of death at three years were 54.1% in the TAVI patients and 81% percent in the standard-therapy group (p<0.0001), and the rates of cardiovascular death were 41.4 % and 74.5%, respectively (p<0.0001). By comparison, at two years, 68% of patients in the standard-therapy control group had died, compared with 43.3% in the TAVI group (p<0.001), and cardiovascular death was 62.4% in the standard-care group vs 31% in the TAVI group (p<0.001).
The rates of mortality plus stroke at three years were 80.9% in the control group and 57.5% in the TAVI group, a 23.4% difference. The additional risk of stroke with TAVI vs standard therapy grew slightly between the two- and three-year follow up, as the stroke rate in the TAVI group grew from 13.7% to 15.7% while it stayed flat at 5.5% in the standard-therapy group, but neither of the two strokes during year three in the TAVI group were device-related, Tuzcu said. Also, rehospitalization rates at three years were 75.7% in the control group and 43.3% in the TAVI group, a difference of 33.4% (p<0.0001).
Echocardiography studies by the PARTNER core lab showed no increase in the average transvalvular gradient or any decrease in the average effective orifice area of the valves.
Risk Score Predicts Survival With TAVI But Not Standard Therapy
The three-year PARTNER B data show that TAVI makes the biggest difference in patients with fewer or less severe comorbidities, as measured by baseline Society of Thoracic Surgeons (STS) score. In patients with an initial STS score from 0 to 4.9, mortality at three years was 100% in the control group and 33.2% in the TAVI group. For scores from 5 to 14.9, mortality was 77.5% and 55.2% for the control and TAVI groups, respectively, and for STS scores over 15, the three-year mortality rates were 86.6% and 65.8%.
"These data underscore the importance of patient selection before TAVI and the need for aggressive management of illnesses after TAVI, because when we stratified mortality according to STS score, we were quite surprised that the higher STS scores in the standard treatment groups were somewhat irrelevant," he said. "It doesn't matter what your STS score is if you are not treated by TAVI, but if you are treated with TAVI, it makes an impact."
Because patient selection is critical to success, Tuzcu emphasized the importance of the oft-promoted "heart-team" approach to aortic-valve repair. "We should not promote one procedure, we should promote a program of taking care of high-risk valvular heart disease patients--this may be surgical treatment, percutaneous treatment, or optimization of the patient's clinical status in the critical care unit, balloon valvuloplasty, or a wise solution to the patient's concomitant problems," he said. "We should not perceive what is accomplished with the PARTNER program only as a success with the procedure, but rather how the program can be established with multiple disciplines."
Tuzcu has no financial disclosures; he is a member of PARTNER Trial executive committee.

Comments

Post a Comment

Popular posts from this blog

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...
Post a Comment
Read more

Antidepressants Linked to Higher Diabetes Risk in Kids

Pediatric patients who use antidepressants may have an elevated risk for type 2 diabetes, the authors of a new study report. In a retrospective cohort study of more than 119,000 youths 5 to 20 years of age, the risk for incident type 2 diabetes was nearly twice as high among current users of certain types of antidepressants as among former users, Mehmet Burcu, PhD, and colleagues report in an article  published online October 16 in  JAMA Pediatrics . The risk intensified with increasing duration of use, greater cumulative doses, and higher daily doses of these antidepressants. The findings point to a growing need for closer monitoring of these products, including greater balancing of risks and benefits, in the pediatric population, the authors caution. They undertook the study because, despite growing evidence of an association between antidepressant use and an increased risk for type 2 diabetes in adults, similar research in pediatric patients was scarce. "To our know...
Post a Comment
Read more

Contact Precautions May Have Unintended Consequences

Contact precautions, including gloves, gowns, and isolated rooms, have helped stem the transmission of hospital pathogens but have also had some negative consequences, according to findings from a new study. Healthcare worker (HCWs) visited patients on contact precautions less frequently than other patients and spent less time with those patients when they did visit, report Daniel J. Morgan, MD, from the University of Maryland School of Medicine and the Veterans Affairs (VA) Maryland Health Care System, Baltimore, and colleagues. Moreover, patients on contact precautions also received fewer outside visitors. "Less contact with HCWs suggests that other unintended consequences of contact precautions still exist," Dr. Morgan and coauthors write. "The resulting decrease in HCW contact may lead to increased adverse events and a lower quality of patient care due to less consistent patient monitoring and poorer adherence to standard adverse event prevention methods (such...
Post a Comment
Read more