Implantation of a CRT-Pacemaker Rather than CRT-Defibrillator is Usually Preferred

Transcription

1 Implantation of a CRT-Pacemaker Rather than CRT-Defibrillator is Usually Preferred Professor John GF Cleland University of Hull Kingston-upon-Hull United Kingdom Conflict of Interest: Funding or Speakers Honoraria from Medtronic and Biotronik

2 J Chan

3 CRT-P v CRT-D CRT-D More expensive More technical problems Larger generator More generator problems RV Lead Shocks Therefore, only implant CRT-D if & when there is convincing evidence that it offers an outcome advantage compared to CRT-P.

4 Outcome in Patients Assigned to ICD in MADIT-II & SCD-HeFT % of Patients Benefit Lack of Benefit or Harm Shocks Lives Saved by ICD Deaths Despite ICD Survival not attributed to ICD MADIT-II SCD-HeFT Follow-up: MADIT-II (3 years); SCD-HeFT (5 years)

5 Arguments for CRT-P CRT-P is highly effective in improving cardiac function and symptoms and reducing SCD and WHF. CRT-D has never beaten CRT-P on a head-to-head comparison Incremental cost-effectiveness of CRT-D v. CRT-P is unfavourable (assuming CRT-D is superior) Lack of evidence of benefit from ICD in patients aged >75 years Lack of evidence that ICDs are effective in the presence of recent advances in treatment (CRT and MRA) Shocks are not benign Perverse Incentives

6 End-Systolic Volume Effect of CRT on End-Systolic Volume at 6 Months (LVESV not LVESVI) MIRACLE CRT -ICD -ICD-II CARE-HF REVERSE Control CRT Difference MADIT- CRT ESV: 228 ~ ESVI: IVMD:

7 Effect of CRT on Symptoms Outcome Medical Therapy Mean (SD) CRT Group Mean (SD) Difference in means (95% CI; P value) At 90 days NYHA class 2.65 (0.9) 2.08 (1.0) MLWHF score 40.0 (21.7) 31.1 (21.6) Euroqol EQ5D (0.289) (0.284) 0.56 (0.42 to 0.69; P < ) (-7.8 to -12.4; P < ) (0.037 to 0.115; P = )

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9 Survival CARE-HF Extension Study Effect of CRT on All-Cause Mortality 1.00 HR 0.60 (95% CI 0.47 to 0.77) Number at risk CRT Medical therapy Medical = 154 (38.1%) CRT Deaths = 101 (24.7%) Absolute difference = 53 (13.4%) Mean Follow-up 36.4 months (range 26.1 to 52.6) CRT Time (days) P< Medical Therapy

10 % Mortality at End of Study According to Adequacy of CRT at 3 Months 35 CRT + 30 CRT?. Control CRT + = known adequate CRT in CRT group. CRT? = no CRT or CRT unknown

11 Cardiac Resynchronization Therapy. A Meta-analysis of RCTs Wells G et al. Canadian Medical Journal 2011 N = 7,538

12 Trials of CRT v CRT-D: COMPANION Use CRT Use CRT Use CRT Use CRT

13 Survival Probability CARE-HF Lifetime Survival Base Case Analysis on 65 Year Old Cohort CRT-D effect calculated from SCD rate in CARE-HF and reduction in SCD in COMPANION With CRT-D v CRT Time To Death COMPANION Projected 7 year Survival CRT-ICD CRT-P MT

14 Cost per QALY $ Effect of Starting Age on Cost per QALY CRT-P vs. MT CRT-ICD vs. CRT-P CRT-ICD vs. MT COMPANION Incremental cost of CRT Starting Age $ 19,600 / QALY Incremental cost of CRT-D v CRT $ 172,000 / QALY Borderline Cost-Effective Cost-Effective Highly Cost-Effective

15 Patient Characteristics in Landmark Trials and ESC Survey MADIT- II SCD- HeFT COMPAN- ION CARE- HF ESC-CRT* Age (62-76) Women IHD NYHA III/IV I-III II-III 100 # 100 # 78 HR NA /-15 (IQR) (65-84) (60-78) LVEF # QRS >120ms (62% >150) ACEi /ARB BB MRA NA * Dickstein and Bogale Eur Heart J 2009.

16 Meta-analysis of RCTs in Younger v Older Patients Santangeli et al Ann Intern Med 2010 (with corrections 2011) Patients Aged <60/65 years Patients Aged >60/65 years (corrected Patients Aged >75 years

17 N = 252 AVID, CASH & CIDS Individual patients Metanalysis Eur Heart J 2007

18 Survival CARE-HF Extension Study Time to Sudden Cardiac Death HR 0.54 (95% CI 0.35 to 0.84) CRT P=0.006 Medical Therapy Medical = 54 sudden deaths (13.4%) CRT = 32 sudden deaths (7.8%) Absolute difference = 22 (5.6%) Mean Follow-up 36.4 months (range 26.1 to 52.6) Time (days)

19 We have lots of treatment for reducing SCD But do we use them? Reduction in SCD Relative Absolute Follow-up ACE inhibitors SOLVD 17% yrs TRACE 21% yrs Aldosterone antagonists RALES 25% yrs EPHESUS 17% yrs EMPHASIS 26% yrs Beta-Blockers CIBIS-II 40% yrs COPERNICUS 40% 4 1 yr CRT only CARE-HF 46% yrs ICD SCD-HeFT 23% 0, st yr, 5 yrs MADIT-II 67% yrs

20 SCD-HeFT No CRT in SCD-HeFT Placebo (N=847) ICD (N=829) ACE / ARB at enrollment 827 (98) 783 (94) at last follow-up 740 (88) 706 (86) Beta-Blocker at enrollment 581 (69) 576 (69) Heart Rate 73 (64-84) 74 (65-84) at last follow-up 662 (79) 672 (82) Loop Diuretic at enrollment 692 (82) 676 (82) at last follow-up 674 (80) 649 (79) Potassium-Sparing at enrollment 165 (19) 168 (20) at last follow-up 278 (33) 261 (32)

21 COMPANION Mode of Death. Circulation 2006 CONCLUSIONS: In CRT candidates, sudden cardiac death risk is associated with higher New York Heart Association class and renal dysfunction. In CRT-defibrillator recipients, reduction in the risk of an appropriate shock is associated with medical therapy with neurohormonal antagonists, female gender, and New York Heart Association functional class III versus IV clinical status. Shock therapy was associated with worse outcome Saxon, Bristow and Boehmer

22 Arguments for CRT-P CRT-P is highly effective in improving cardiac function and symptoms and reducing SCD and WHF (unrelated). CRT-D has never beaten CRT-P on a head-to-head comparison ICER unfavourable even if point estimates are true Lack of evidence of benefit from ICD in patients aged >75 years Lack of evidence that ICDs are effective in the presence of recent advances in treatment (CRT and MRA) Shocks are not benign Perverse Incentives

23 Conclusion Powerful evidence that adding CRT to an ICD improves outcome if LBBB or QRS >150ms But no robust evidence that adding an ICD to CRT improves outcome CRT-D might be considered in patients without substantial co-morbidity and with with mild heart failure most of these patients will be aged <69 yrs. CRT-P is preferred for other patients

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