Risk Assessment and Comparative Effectiveness of Left Ventricular Assist Device and Medical Management in

Ambulatory Heart Failure PatientsAssessment of Patient Characteristics and Impact on Patient Decision-Making

Joseph Rogers, MDProfessor of MedicineDuke University

Disclosures: None

Decision-Making Challenges:The ROADMAP for Medical Patients

INTERMACS 9th Annual MeetingMCSD: Evolution, Expansion, and Evaluation

May 15-16, 2015

ROADMAP Patient Populations

11 11 22 22 33 33 44 44 55 55 66 66 77 77INTERMACS

Profiles

CMS Coverage: Class IVCMS Coverage: Class IVCMS Coverage: Class IVCMS Coverage: Class IV

FDA Approval: Class IIIB/IVFDA Approval: Class IIIB/IVFDA Approval: Class IIIB/IVFDA Approval: Class IIIB/IV

Currently Not Approved Limited Adoption Acceptance

NYHA Class IIINYHA Class III Class Class IIIBIIIB

Class IV Class IV (Ambulatory(Ambulatory

))

Class IVClass IV(On Inotropes)(On Inotropes)

1.0% 1.4% 3.0% 14.6% 29.9% 36.4% 14.3%Percent of current implants in INTERMACS

Objectives and Study Design

• Primary Objectives

– Evaluate and compare the effectiveness of HM II LVAD support vs. optimal medical management (OMM) in

– ambulatory NYHA Class IIIB/IV patients

– not dependent on intravenous inotropic support (INTERMACS ≥ 4), and

– meet the FDA approved indications for HM II LVAD destination therapy

• Trial Design

– Prospective, multi-center, non-randomized, controlled, observational study

– Permits characterization of real-world advanced HF treatments strategies in varied health care delivery systems

– Includes collaborating cardiologists not directly involved in LVAD care

– Includes patients who do not desire LVAD treatment

– LVAD indication is already FDA approved – additional data needed to improve patient selection

3Rogers JG et al: ROADMAP Trial Design: Am Heart J 2015;169:205-10

Key Inclusion and Exclusion Criteria

Inclusion Criteria

•NYHA Class IIIB or IV ; Age 18 to 85

•Left ventricular ejection fraction (LVEF) ≤ 25%

•Not listed (or planned) for heart transplantation

•On optimal medical management (OMM)

•6MWT < 300 meters

•At least 1 hospitalization for HF in last 12 months, or 2 unscheduled ED or infusion clinic visits for HF in last 12 months

Exclusion Criteria

•Any inotrope use within 30 days

•Inability to perform 6MWT

•Any ongoing MCS (including IABP & temporary devices) at enrollment

•CRT or coronary revascularization within 3 months

4Rogers JG et al: ROADMAP Trial Design: Am Heart J 2015;169:205-10

Endpoints

• Primary Endpoint

– Composite of survival with improvement in 6-MWT distance from baseline of ≥75 meters at 12 months

• Secondary Endpoints– Actuarial survival

– Health-related Quality of Life (HRQoL) using the EQ-5D-5L Visual Analog Scale (VAS)

– Depression using Patient Health Questionnaire-9 (PHQ-9)

– Questionnaire on patient decisions related to LVAD therapy versus OMM

– Functional status using 6-MWT distance and NYHA Classification

– Adverse events, rehospitalizations

5

Baseline Data

* Median [range]6

Baseline Data

* Median [IQR]7

Reasons Provided for Choosing LVAD or OMM at Baseline

8

Physician Reason for selecting OMM N (%)

Physician believes patient isn’t good surgical candidate 14 (14%)

Physician believes patient isn’t sick enough 11 (11%)

Other (Drug and alcohol abuse, financial, compliance concerns, etc.) 9 (9%)

Patient Reason for Selecting OMM N (%)

Patient doesn’t like the idea of major device implantation surgery 40 (39%)

Patient doesn’t want to depend on a machine 26 (25%)

Patient doesn’t feel sick enough 25 (24%)

Patient is worried about too many complications with a LVAD 21 (20%)

Patient doesn’t think a LVAD will improve quality of life 13 (13%)

Patient Reason for selecting LVAD N (%)

Patient thinks it will improve chances to live longer 81 (84%)

Patient thinks it will improve QoL 79 (81%)

Patient thinks it will improve heart failure symptoms 72 (74%)

Patient thinks it will help them return to activities they enjoy 72 (74%)

Patient Questionnaire at Baseline

Impact of Baseline QoL Satisfaction

9

Not or slightly satisfied (n=123) Moderately to extremely satisfied (n=123)

Primary End-Point *Significantly more LVAD than OMM patients were alive

at 12 months on original therapy with increase in 6MWD by 75m

10

O.R. = 2.4 [1.2-4.8]P=0.017

O.R. = 3.7 [1.1-12.2]P=0.026

O.R. = 1.7 [0.6-4.6]P=0.423

N= 85 81 57 26 26 54

Stratified by INTERMACS Profile

***17% of OMM patients crossed over to LVAD

Secondary Endpoints

• VAD Treated Patients Experienced– Better improvements in NYHA Class– Better improvements in 6 MWD– Better improvement in health-related QoL– Better improvement in depression scores

Summary and Conclusions

• ROADMAP demonstrated that patients with advanced heart failure not treated with inotropes have a better improvement in survival associated with an increase in 6MWD > 75m treated with VAD vs. OMM

• Patients selecting VAD in ROADMAP:– Reported worse symptoms – Had lower submaximal exercise performance– Had lower heath-related QoL and were dissatisfied with QoL– Had more depression– Thought VAD would improve survival, QoL and functionality