9/14/2019 Disclosures • This is a debate and meant to be fun, not personal • Polarizing views are artificial and no issue is A WCD Should be black and white Placed in Post-MI • Actual position is more nuanced than presented Patients with EF≤35% • I’ll be presenting data funded by: ? – NIH/NHLBI (U01HL089458 & U01HL089145) – ZOLL Jeffrey Olgin, MD Division of Cardiology, UCSF Background • SCD high early post MI in patients with low EF • Guidelines suggest waiting 90 days post MI before assessing for ICD implantation – IRIS and DINAMIT showed early implant of ICD does not decrease long-term mortality – EF will improve to >35% in over half of the patients – Competing risks of death • A wearable cardioverter defibrillator (WCD) can serve as a bridge to evaluation for ICD 1
9/14/2019 Guideline recommendations VEST Study design • Multi-center, randomized, open-label trial • Participants within 7 days of hospital d/c for acute MI & EF≤35% • Randomized 2:1 to receive: – Wearable cardioverter defibrillator (WCD) + GDMT or – Guideline-directed medical therapy alone • Primary Outcome: 90 day arrhythmic death (changed from total mortality) • Secondary Outcomes : Total Mortality, Non-SD, others • Analyses: Intention-to-treat & as-treated 2017 ACC/AHA/HRS Guideline for Management of Patients With Ventricular Arrhythmias. JACC 2017 Olgin, et al . NEJM 2018 Results: Outcomes, proportions analysis Results: Outcomes, proportions analysis 90-day Event Rates 90-day Event Rates WCD WCD 6% 6% Control Control Better Worse Better Worse P=0.04 P=0.04 5% 5% WCD WCD 4% 4% 0.67 0.67 Sudden Sudden 3% 3% Uncorrected P=0.18 Uncorrected P=0.18 P=0.18 P=0.18 Death (1°) Death (1°) P=0.15 P=0.15 2% 2% 0.64 0.64 Total Total 1% 1% Uncorrected P=0.04 Uncorrected P=0.04 mortality mortality 0% 0% Death, Non- Death, Non- Sudden Sudden Non-sudden 0.63 Non-sudden 0.63 any sudden any sudden (1°) (1°) Uncorrected P=0.15 Uncorrected P=0.15 Death Death death death cause death cause death Control 2.4% 4.9% 2.2% Control 2.4% 4.9% 2.2% 0 0.2 0.4 0.6 0.8 1 1.2 1.4 1.6 1.8 2 0 0.2 0.4 0.6 0.8 1 1.2 1.4 1.6 1.8 2 WCD 1.6% 3.1% 1.4% WCD 1.6% 3.1% 1.4% Relative Risk Relative Risk ARR 0.8% 1.8% 0.8% ARR 0.8% 1.8% 0.8% NNT 125 56 125 NNT 125 56 125 Of the 48 deaths in the WCD arm, only 12 were wearing the WCD at the time of death. 2
9/14/2019 Results: On treatment analysis Results: WCD wear-time WCD Control Total Mortality Sudden Death Non-Sudden Death Characteristic (N=1524) (N=778) Event Rate Rate Ratio Event Rate Rate Ratio 2.5 Event Rate 2.5 2.5 Rate Ratio WCD received, n (%) 1481 (97.2%) 20 (2.6%) * … Death Rate per 100 Person-Months Non-Sudden Death Rate per 100 SD Rate per 100 person-Months Median hours/day WCD worn [IQR] 18 [3.8-22.7] 0 [0-0]* P=0.02 1.4 P<0.001 P<0.001 1.4 1.4 2 2 2 Worse Worse Worse Average hours/day WCD worn ± SD 14.0 ± 9.3 0.4 ± 2.7 * 1.2 1.2 1.2 1.5 1 1 1.5 *P <0.001 1.5 1 Hours worn (incl non-users) Rate Ratio Rate Ratio Better 40 Better Better 0.8 0.8 0.8 Patient-Days (%) 1 1 1 0.6 30 0.6 0.6 0.4 0.4 0.4 0.5 20 0.5 0.5 0.2 0.2 0.2 10 0 0 0 0 0 0 0 0 6 12 18 24 Not wearing WCD Wearing WCD Rate Ratio Hours worn per day Olgin, et al . NEJM 2018 What do you call someone who posts a lot What do you call someone who posts a lot on Twitter? on Twitter? A. A Donald 3
9/14/2019 What do you call someone who posts a lot What do you call someone who posts a lot on Twitter? on Twitter? A. A Donald A. A Donald B. Someone with too much free time B. Someone with too much free time C. A Twit Science is like an onion. Discussion : How to interpret VEST It has layers, Jackass. • The WCD did not significantly reduce sudden death and thus did not meet 1 ° outcome Jackasses Ogres with PhDs Dumb Jackasses Ogres with MAs Trump Jackasses Ogres with BAs EP Jackasses 4
9/14/2019 Discussion: Why primary outcome wasn’t met Spectrum of negative trials • Power insufficient to conclude WCD was not Treatment <-- Better — Worse --> effective MADIT – Broad confidence intervals VEST Inconclusive with suggestion of benefit • Rate of sudden death lower than expected CABANA • Possible misclassification of sudden deaths COURAGE – 5% of death adjudicated as indeterminate WHI Inconclusive with suggestion of harm – 4 of 9 SD’s wearing WCD had no VT/VF & confirmatory study HERS – Reducing power for SD outcome but not total mortality Clear harm CAST • Lower WCD wear time further reduced power 0 0.2 0.4 0.6 0.8 1 1.2 1.4 1.6 1.8 2 2.2 2.4 2.6 2.8 3 Relative Risk Discussion : How to interpret VEST Discussion: Correction for multiplicity • The WCD did not significantly reduce sudden • Bonferroni correction assumes complete death and thus did not meet 1 ° outcome independence of hypotheses testing – Inconclusive result due to insufficient power – Mortality outcomes are NOT independent but rather – Low WCD wear-time subsets of total mortality • The WCD was associated with a 36% reduction – Remains significant with less conservative corrections, of total mortality (nominal p=0.04) taking into account outcome correlations and importance of total mortality • Not all secondary outcomes are created equally – Total mortality is a different outcome than a combined outcome of mortality + hospitalizations + status decline 5
9/14/2019 Discussion: Sudden death etiology Discussion : How to interpret VEST • The WCD did not significantly reduce sudden Unwitnessed Witnessed death and thus did not meet 1 ° outcome N = 405 N = 120 • Autopsy-proven cause of – Inconclusive result due to insufficient power death – Low WCD wear-time •525 consecutive ”sudden Non-Cardiac • The WCD was associated with a 36% reduction N = 32 (27%) deaths” in SF County Non-Cardiac Cardiac, Arrhythmic of total mortality (nominal p=0.04) N = 178 (44%) (SAD) Cardiac, Arrhythmic • 98% autopsy rate. N = 215 (53%) Cardiac, Non (SAD) • As-treated analysis showed a significant Arrhythmic N = 78 (65%) N = 10 (8%) reduction in sudden death and total mortality Cardiac, Non Arrhythmic N = 12 (3%) Tseng, Z. et al Circulation , 2018 Discussion : How to interpret VEST Concluding Remarks • The WCD did not significantly reduce sudden death and thus did not meet 1 ° outcome – Inconclusive result due to insufficient power – Low WCD wear-time • The WCD was associated with a 36% reduction of total mortality (nominal p=0.04) • As-treated analysis showed a significant reduction in sudden death and total mortality • Very few serious adverse events • High WCD shock success rate, consistent with other studies 6
9/14/2019 Concluding Remarks How many electrophysiologists have stopped doing AF ablations as a result of CABANA? TWITTER 1min ago Concluding Remarks Concluding Remarks New message in feed • Mortality remains high immediately post-MI in • Mortality remains high immediately post-MI in patients with EF≤35%, despite PCI, optimal patients with EF≤35%, despite PCI, optimal medical therapy and EF recovery at 3 months in medical therapy and EF recovery at 3 months in ~60% of patients ~60% of patients • Given the totality of the results of VEST and • Given the totality of the results of VEST and prior series, it may be reasonable to prescribe prior series, it may be reasonable to prescribe the WCD post-MI in patients at highest risk for the WCD post-MI in patients at highest risk for sudden death and in whom a high compliance is sudden death and in whom a high compliance is expected expected – Shared decision making seems reasonable – Shared decision making seems reasonable 7
9/14/2019 And now, the counter argument… Concluding Remarks • Mortality remains high immediately post-MI in patients with EF≤35%, despite PCI, optimal medical therapy and EF recovery at 3 months in ~60% of patients 12:15 PM – 14 Sep 2019 • Given the totality of the results of VEST and prior series, it may be reasonable to prescribe the WCD post-MI in patients at highest risk for sudden death and in whom a high compliance is expected – Shared decision making seems reasonable 8
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