TCT 2010: SYNTAX Trial

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TCT 2010: SYNTAX Trial

  1. 1. Press Conference<br />Transcatheter Aortic Valve Implantation in Inoperable Patients with Severe Aortic Stenosis<br />Martin B. Leon, MD<br />on behalf of the<br />PARTNER Investigators<br />TCT 2010; Washington, DC; September 23, 2010<br />
  2. 2. PARTNER Study Design<br />Total = 1058 patients<br />n=358<br />n= 700<br />2 Parallel Trials: Individually Powered<br />High Risk<br />Inoperable<br />ASSESSMENT: Transfemoral Access<br />ASSESSMENT: Transfemoral Access<br />High Risk TA<br />High Risk TF<br />1:1 Randomization<br />1:1 Randomization<br />1:1 Randomization<br />Not In Study<br />TAVI<br />Trans<br />femoral<br />Surgical AVR<br />Standard Therapy<br />(usually BAV)<br />TAVI<br />Trans<br />femoral<br />Surgical AVR<br />TAVI<br />Trans<br />femoral<br />VS<br />VS<br />VS<br />Primary Endpoint: All Cause Mortality (1 yr)(Non-inferiority)<br />Primary Endpoint: All Cause Mortality over length of trial (Superiority)<br />Symptomatic Severe Aortic Stenosis<br />ASSESSMENT: High Risk AVR Candidate<br />3105 Total Patients Screened<br />
  3. 3. Primary and Co-Primary Endpoints<br />PRIMARY: All-cause mortality over the duration of the study<br />Superiority test (two-sided), 85% power to detect a difference, α = 0.05, sample size = 350 total patients<br />CO-PRIMARY: Hierarchical composite of all-cause mortality and repeat hospitalization<br />Non-parametric method described by Finkelstein and Schoenfeld (multiple pair-wise comparisons)<br />> 95% power to detect a difference, α = 0.05 <br />Positive study if both endpoints P < 0.05, or if either endpoint is < 0.025<br />
  4. 4. Study Devices<br />Retroflex 1<br />Edwards-SAPIEN THV<br />23mm and 26mm<br />valve sizes<br />22F and 24F<br />sheath sizes<br />
  5. 5. Inclusion Criteria<br />Severe calcific aortic stenosis defined as echo derived valve area of < 0.8 cm2(EOA index <0.5cm2), and mean gradient > 40 mmHg or jet velocity > 4.0 m/s<br />NYHA functional class II or greater<br />Risk of death or serious irreversible morbidity as assessed by cardiologist and two surgeons must exceed 50% <br />
  6. 6. All Cause Mortality<br />Standard Rx<br /> TAVI<br />HR [95% CI] =0.54 [0.38, 0.78]<br />P (log rank) < 0.0001<br />All-cause mortality (%)<br />Months<br />
  7. 7. All Cause Mortality<br />Standard Rx<br />∆ at 1 yr = 20.0%NNT = 5.0 pts<br /> TAVI<br />50.7%<br />All-cause mortality (%)<br />30.7%<br />Months<br />
  8. 8. Finklestein & Schoenfeld Analysis(hierarchical multiple pair-wise comparison)<br />Compare, at random, every TAVI patient with every Standard Rx patient; 179 x 179 (32,041) patient pairs, which did better?<br />#1, compare “time to death”<br />72% chance that we know who died first<br />If so, 63% chance that Standard Rx patient died first and 37% chance that TAVI patient died first<br />#2, if necessary, compare “time to repeat hospitalization” <br />17% chance that we know who had repeat hosp first<br />If so, 75% chance that Standard Rx patient had repeat hosp first and 25% chance that TAVI patient had repeat hosp first <br />FS Method<br />Produces a P-value<br />< 0.0001<br />
  9. 9. Clinical Outcomes at 30 Days & 1 Year<br />
  10. 10. Clinical Outcomes at 30 Days & 1 Year<br />
  11. 11. Six-Minute Walk Tests<br />Walking Distance<br />P = 0.002<br />P = 0.67<br />P = 0.004<br />P = 0.55<br />Walking distance (meters)<br />Baseline<br />1 Year<br />30 Days<br />
  12. 12. Percent<br />TAVI<br />Standard Rx<br />TAVI<br />Standard Rx<br />TAVI<br />Standard Rx<br />TAVI<br />Standard Rx<br />Treatment<br />Visit<br />Baseline<br />30 Day<br />6 Month<br />1 Year<br />NYHA Class Over TimeSurvivors<br />P = 0.68<br />P < 0.0001<br />P < 0.0001<br />P < 0.0001<br />I<br />II<br />III<br />IV<br />
  13. 13. Standard Rx<br />70<br /> TAVI<br />44.6<br />44.4<br />60<br />39.5<br />50<br />33.0<br />40<br />Mean Gradient (mm Hg)<br />30<br />43.2<br />12.1<br />11.3<br />10.8<br />20<br />10<br />0<br />Mean Gradients Over Time<br />P < 0.0001<br />6 Months<br />N=100<br />1 Year<br />N=89<br />Baseline<br />N=163<br />30 Day<br />N=143<br />Error bars = ± 1 Std Dev<br />
  14. 14. 30 Day<br />6 Month<br />1 Year<br />Paravalvular Regurgitation: TAVI<br />No changes over time<br />None/Trace<br />Moderate<br />Mild<br />Severe<br />
  15. 15. Conclusions - 1<br />In patients with severe AS and symptoms, who are not suitable candidates for surgery…<br /><ul><li>Standard therapy (including BAV in 83.8% of pts) did not alter the dismal natural history of AS; all-cause and cardiovascular mortality at 1 year was 50.7% and 44.6% respectively
  16. 16. Transfemoral balloon-expandable TAVI, despite limited operator experience and an early version of the system, was associated with acceptable 30-day survival (5% after randomization in the intention-to-treat population) </li></li></ul><li>Conclusions - 2<br /><ul><li>TAVI was superior to standard therapy, markedly reducing the rate of…
  17. 17. all-cause mortality by 46%, P < 0.0001, NNT = 5.0 pts
  18. 18. cardiovascular mortality by 61%, P < 0.0001, NNT = 4.1 pts
  19. 19. all-cause mortality and repeat hospitalization
  20. 20. hierarchical (FS method), P < 0.0001
  21. 21. non-hierarchical (KM analysis) by 54%, P < 0.0001, NNT = 3.4 pts </li></li></ul><li>Conclusions - 3<br /><ul><li>TAVI improved cardiac symptoms (NYHA class, P < 0.0001) and six minute walking distance (P = 0.002), after 1-year follow-up
  22. 22. TAVI resulted in more frequent complications at 30 days, including…
  23. 23. major vascular complications, 16.2% vs. 1.1%, P < 0.0001
  24. 24. major bleeding episodes, 16.8% vs. 3.9%, P < 0.0001
  25. 25. major strokes, 5.0% vs. 1.1%, P = 0.06 </li></li></ul><li>Conclusions - 4<br /><ul><li>Serial echocardiograms in TAVI patients indicated…
  26. 26. reduced mean gradients (P < 0.0001) which were unchanged during 1-year FU
  27. 27. frequent paravalvular AR, which was usually trace or mild (~90%), remained stable during 1-year FU, and rarely required further Rx. </li></li></ul><li>Clinical Implications <br /><ul><li>Balloon-expandable TAVI should be the new standard of care for patients with aortic stenosis who are not suitable candidates for surgery!
  28. 28. Next generation devices (e.g. SAPIEN XT) may help to reduce the frequency of procedure-related complications in the future.
  29. 29. The ultimate value of TAVI will depend on careful assessment of bioprosthetic valve durability, which will mandate obligatory long-term clinical and echocardiography FU of all TAVI patients.</li></li></ul><li>September 22, 2010 on NEJM.org<br />

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