coap.pptx

5-Year Follow-Up After Transcatheter
Repair of Secondary Mitral Regurgitation
The COAPT™ Trial
Dr Victor Gimenez
See Important Safety Information referenced within. ©2023 Abbott. All rights reserved. MAT-2301485 v1.0 | Item approved for U.S. use only.

The COAPT™ Trial
Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy
for Heart Failure Patients with Functional Mitral Regurgitation
A parallel-controlled, open-label, multicenter trial in 614 patients with
heart failure and moderate-to-severe (3+) or severe (4+) secondary MR
who remained symptomatic despite maximally-tolerated GDMT
Randomize 1:1*
GDMT alone
N=312
MitraClip + GDMT
N=302
*Stratified by cardiomyopathy etiology (ischemic vs. non-ischemic) and site
Stone GW et al. N Engl J Med. 2018;379:2307-18

Background
• In the COAPT trial, treatment of symptomatic patients
with heart failure (HF) and severe secondary MR with
the MitraClip safely improved survival through 24 months,
reduced HF hospitalizations (HFH), and improved quality-
of-life compared with maximally-tolerated guideline-
directed medical therapy (GDMT) alone
• Per protocol, subjects randomized to GDMT were
not allowed to “crossover” to the MitraClip prior to
24 months, but were permitted to do so after 24 months

Objectives
The present study sought to:
1) Describe the final 5-year clinical outcomes
of patients enrolled in the COAPT trial
2) Analyze the impact of MitraClip treatment
in patients assigned to GDMT alone

Key Inclusion Criteria
1. Moderate-to-severe (3+) or severe (4+) secondary MR
confirmed by an echo core laboratory (US ASE criteria)
2. LVEF 20%-50% and LVESD ≤70 mm
3. NYHA class II-IVa despite a stable maximally-tolerated
GDMT regimen and CRT (if appropriate) per societal
guidelines
4. HFH within 12 months and/or weight-adjusted BNP ≥300
pg/ml* or NT-proBNP ≥1500 pg/ml*

Key Exclusion Criteria
1. ACC/AHA stage D HF, hemodynamic instability or shock
2. CAD requiring revascularization
3. COPD requiring continuous home O2 or chronic oral steroid use
4. Severe PHTN or mod/sev RV dysfunction
5. AV or TV disease requiring surgery or transcatheter intervention
6. MV orifice area <4.0 cm2 by site-assessedTTE

MitraClip + GDMT
N=302
GDMT alone
N=312
Initial treatment
MitraClip
GDMT alone
30-day follow-up
1-year follow-up
2-year follow-up
3-year follow-up
4-year follow-up
5-year follow-up
N=293
N=9
Withdrew 4 1 Lost to follow-up
N=297/302 (98.3%)
N=294/302 (97.4%)
N=286/302 (94.7%)
N=282/302 (93.4%)
N=275/302 (91.1%)
N=270/302 (89.4%)
N=1
N=311
N=307/312 (98.4%)
N=291/312 (93.3%)
N=277/312 (88.8%)
N=269/312 (86.2%)
N=265/312 (84.9%)
N=264/312 (84.6%)
N=614 at 78 sites
in the US and Canada
Randomized

Baseline Characteristics (i)
MitraClip +
GDMT (N=302)
GDMT alone
(N=312)
MitraClip +
GDMT (N=302)
GDMT alone
(N=312)
Age (years) 71.7 ± 11.8 72.8 ± 10.5 BMI (kg/m2) 27.0 ± 5.8 27.1 ± 5.9
Male 66.6% 61.5% CrCl (ml/min) 50.9 ± 28.5 47.8 ± 25.0
Diabetes 35.1% 39.4% - ≤60 ml/min 71.6% 75.2%
Hypertension 80.5% 80.4% Anemia (WHO) 59.8% 62.7%
Hyperchol. 55.0% 52.2% BNP (pg/mL) 1015 ± 1086 1017 ± 1219
Prior MI 51.7% 51.3% NT-proBNP (pg/mL) 5174 ± 6567 5944 ± 8438
Prior PCI 43.0% 49.0% STS replacement sc 7.8 ± 5.5 8.5 ± 6.2
Prior CABG 40.1% 40.4% - ≥8 41.7% 43.6%
Prior stroke or TIA 18.5% 15.7% Surgical risk (central eligibility committee)
PVD 17.2% 18.3% - High* 68.6% 69.9%
COPD 23.5% 23.1% - Not-high 31.4% 30.1%
H/o atrial fibr 57.3% 53.2% * STS repl score ≥8% or one or more fa ctors present predicting extrem ely high surgical risk

Baseline Characteristics (ii)
HF parameters
MitraClip +
GDMT (N=302)
GDMT alone
(N=312)
Echo core lab
MitraClip +
GDMT (N=302)
GDMT alone
(N=312)
Etiology of HF MR severity
- Ischemic 60.9% 60.6% - Mod-to-sev (3+) 49.0% 55.3%
- Non-ischemic 39.1% 39.4% - Severe (4+) 51.0% 44.7%
NYHA class EROA, cm2 0.41 ± 0.15 0.40 ± 0.15
- I 0.3% 0% LVESD, cm 5.3 ± 0.9 5.3 ± 0.9
- II 42.7% 35.4% LVEDD, cm 6.2 ± 0.7 6.2 ± 0.8
- III 51.0% 54.0% LVESV, mL 135.5 ± 56.1 134.3 ± 60.3
- IV 6.0% 10.6% LVEDV, mL 194.4 ± 69.2 191.0 ± 72.9
HF hosp w/i 1 year 58.3% 56.1% LVEF, % 31.3 ± 9.1 31.3 ± 9.6
Prior CRT 38.1% 34.9% - 40% 82.2% 82.0%
Prior defibrillator 30.1% 32.4% RVSP, mmHg 44.0 ± 13.4 44.6 ± 14.0

Primary Effectiveness: All Heart Failure
Hospitalizations Through 5-Year Follow-up
0 6 48 60
MitraClip + GDMT
GDMT alone
Cumulative
HF
Hospitalizations
(n)
Time After Randomization (Months)
No. at Risk:
12 18 24 30 36 42 54
500
450
400
350
300
250
200
150
100
50
0
MitraClip 302 269 238 219 205 186 167 151 138 124 79
GDMT 312 272 224 188 156 133 120 106 94 84 59
HR [95% CI] =
0.51 [0.39, 0.66]
Analyzed using a joint frailty
model to account for
correlated events and the
competing risk of death

Primary Effectiveness: All Heart Failure
Hospitalizations Through 5-Year Follow-up
0 6
MitraClip + GDMT
GDMT alone
314
in 151 pts
447
in 208 pts
Cumulative
HF
Hospitalizations
(n)
No. at Risk:
33.1%/yr in the device group vs.
57.2%/yr in the control group
HR [95% CI] = 0.53 [0.41-0.68]
12 18 24 30 36 42 48 54 60
500
450
400
350
300
250
200
150
100
50
0
MitraClip 302 269 238 219 205 186 167 151 138 124 79
GDMT 312 272 224 188 156 133 120 106 94 84 59
Analyzed using a joint frailty
model to account for
correlated events and the
competing risk of death

Primary Safety: Outcomes Through 5 Years
MitraClip implant attempts (n=293)
30
Days
12
Months
24
Months
36
Months
48
Months
60
Months
All safety events 4 (1.4) 9 (3.3) Primarysafety en dpoint
Device-specific events 4 (1.4) 4 (1.4)
- SLDA 2 (0.7) 2 (0.7)
- Device embolization 1 (0.3) 1 (0.3)
- Endocarditis requiring surgery 0 (0.0) 0 (0.0)
- Mitral stenosis* requiring surgery 0 (0.0) 0 (0.0)
- Any device-related complication
requiring non-elective CV surgery
1 (0.3) 1 (0.3)
Progressive HF unrelated to device
complications
0 (0.0) 5 (2.0)
- LVAD 0 (0.0) 3 (1.2)
- Heart transplantation 0 (0.0) 2 (0.8)
SLDA = single leaflet device attachment. LVAD = left ventricular assist device. *Mitral valve area <1.5 cm2 by echo core laboratory measurement.

Primary Safety: Outcomes Through 5 Years
MitraClip implant attempts (n=293)
30
Days
12
Months
24
Months
36
Months
48
Months
60
Months
All safety events 4 (1.4) 9 (3.3) 13 (5.2) 20 (8.8) 22 (10.1) 23 (10.8)
Device-specific events 4 (1.4) 4 (1.4) 4 (1.4) 4 (1.4) 4 (1.4) 4 (1.4)
- SLDA 2 (0.7) 2 (0.7) 2 (0.7) 2 (0.7) 2 (0.7) 2 (0.7)
- Device embolization 1 (0.3) 1 (0.3) 1 (0.3) 1 (0.3) 1 (0.3) 1 (0.3)
- Endocarditis requiring surgery 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0)
- Mitral stenosis* requiring surgery 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0)
- Any device-related complication
requiring non-elective CV surgery
1 (0.3) 1 (0.3) 1 (0.3) 1 (0.3) 1 (0.3) 1 (0.3)
Progressive HF unrelated to device
complications
0 (0.0) 5 (2.0) 9 (3.8) 16 (7.5) 18 (8.8) 19 (9.5)
- LVAD 0 (0.0) 3 (1.2) 6 (2.6) 11 (5.1) 12 (5.8) 13 (6.5)
- Heart transplantation 0 (0.0) 2 (0.8) 3 (1.3) 7 (3.4) 9 (4.7) 9 (4.7)
SLDA = single leaflet device attachment. LVAD = left ventricular assist device. *Mitral valve area <1.5 cm2 by echo core laboratory measurement.

Death or HF Hospitalization
Death
or
HFH
(%)
0%
20%
60%
40%
80%
100%
91.5%
73.6%
HR [95% CI] =
0.53 [0.44-0.64]
MitraClip + GDMT
GDMT alone
0 6 48 60
12 18 24 30 36 42 54
No. at Risk:
MitraClip 302 236 194 174 158 141 118 105 93 81 52
GDMT 312 206 157 122 95 58 43 37 33 26 17

5-Year
Death
or HFH
Subgroup
analysis

0%
20%
40%
60%
80%
83.0%
61.0%
HR [95% CI] =
0.49 [0.40-0.61]
100%
MitraClip + GDMT
GDMT alone
0 6 48 60
12 18 24 30 36 42 54
No. at Risk:
MitraClip 302 236 194 174 158 141 118 105 93 81 52
GDMT 312 206 157 122 95 58 43 37 33 26 17
First
Heart
Failure
Hospitalization
(%)
First Heart Failure Hospitalization

0%
20%
40%
60%
80%
100%
MitraClip + GDMT
GDMT alone
0 6 48 60
12 18 24 30 36 42 54
No. at Risk:
MitraClip 302 194 158 167 119 63
GDMT 312 157 95 119 82 43
34.3%
30.7%
HR [95% CI] =
0.46 [0.36–0.57]
HR [95% CI] =
0.85 [0.55–1.33]
46.8%
76.4%
First
Heart
Failure
Hospitalization
(%)
First Heart Failure Hospitalization

All-cause
Mortality
(%)
0%
20%
40%
60%
80%
100%
67.2%
57.3%
HR [95% CI] =
0.72 [0.58-0.89]
MitraClip + GDMT
GDMT alone
0 6 48 60
12 18 24 30 36 42 54
No. at Risk:
MitraClip 302 269 238 219 205 186 167 151 138 124 79
GDMT 312 272 224 189 157 135 122 107 94 84 59
All-cause Mortality

All-cause
Mortality
(%)
20%
0%
40%
60%
80%
100%
MitraClip + GDMT
GDMT alone
0 6 48 60
12 18 24 30 36 42 54
No. at Risk:
MitraClip 302 238 205 167 138 79
GDMT 312 224 157 122 94 59
42.8%
40.6%
HR [95% CI] =
0.62 [0.47–0.82]
28.1%
42.7%
HR [95% CI] =
0.88 [0.64–1.23]
All-cause Mortality

Randomized to GDMT alone
(N = 312)
No MitraClip treatment
before 2 years
(N = 138)
MitraClip treatment
before 2 years
(N = 5)
MitraClip treatment
after 2 years*
(N = 62 of 138; 44.9%)
Total crossovers
(N = 67 of 312; 21.5%)
No MitraClip
treatment
(N = 76)
Not eligible for
crossover at
2 years (N = 169)
Death: 124
LVAD: 16
Transplant: 9
Withdrawals: 26
Lost to follow-up: 3
Other: 2
Crossover Treatment in the Control Arm

Death or HFH After Crossovers
Death
or
HFH
(%)
0%
20%
60%
40%
80%
0 6 48 60
12 18 24 30 36 42 54
100%
MitraClip + GDMT
GDMT alone without MitraClip
GDMT alone after MitraClip
No. at Risk:
MitraClip 302 236 194 158 118 93 52
GDMT without MitraClip 312 205 156 93 40 32 16
GDMT after MitraClip 67 56 42 30 9 - -
For crossover patients,
follow-up duration is from the
crossover procedure date
Multivariable analysis in GDMT alone group
Adjusted HR [95% CI] after MitraClip
= 0.53 [0.36, 0.78]

100%
90%
80%
70%
60%
50%
40%
30%
20%
10%
0% Device Control Device Control Device Control Device
(n=302) (n=311) (n=291) (n=288) (n=286) (n=278) (n=278)
Control Device
(n=266) (n=270)
Control
(n=258)
Device Control
(n=260) (n=263)
Device Control Device Control Device Control
(n=263) (n=255) (n=266) (n=247) (n=257) (n=249)
NYHA Class Throughout Follow-up
I II III IV Died
Class I or II 43.0% 35.4% 74.2% 46.5% 66.4% 47.1% 61.5% 43.2% 56.7% 39.5% 47.3% 37.8% 42.2% 25.1% 34.2% 18.6% 24.1% 15.7%
Diff (95% CI) 7.7% [-0.1, 15.3] 27.7% [19.9, 35.1] 19.3% [11.2, 27.1] 18.3% [9.9, 26.3] 17.1% [8.6, 25.3] 16.5% [8.2, 24.5] 17.1% [9.0, 24.9] 15.6% [8.0, 22.9] 8.5% [1.5, 15.3]
NYHA
class
(%)
Baseline 30 days 6 months 1 year 18 months 2 years 3 years 4 years 5 years

100%
90%
80%
70%
60%
50%
40%
30%
20%
10%
0%
Device Control Device Control Device Control Device
(n=302) (n=311) (n=273) (n=257) (n=240) (n=218) (n=210)
Control Device Control
(n=175) (n=177) (n=141)
Device
(n=167)
Control Device
(n=126) (n=120)
Control Device Control Device Control
(n=74) (n=80) (n=49) (n=57) (n=46)
MR Severity (Core Lab)
None 1+ 2+ 3+ 4+
MR ≤2+ 0% 0% 92.7% 34.2% 93.8% 38.1% 94.8% 46.9% 94.9% 45.4% 99.4% 46.8% 98.3% 85.1% 97.5% 79.6% 94.7% 91.3%
Diff (95% CI) - 58.4% [51.4, 64.5] 55.7% [48.1, 62.3] 47.9% [39.6, 55.5] 49.5% [40.2, 57.9] 52.6% [43.5, 61.1] 13.2% [5.9, 23.1] 17.9% [7.1, 31.3] 3.4% [-7.1, 15.6]
MR
grade
(%)
Baseline 30 days 6 months 1 year 18 months 2 years 3 years 4 years 5 years

Limitations
• Device treatment was unblinded, and withdrawals during follow-up were more
frequent in the control group.
All-cause death, the endpoint least prone to bias, was reduced, and the results
were consistent after multiple imputation to account for missing data.
• The present results reflect treatment with the first generation MitraClip.
MitraClip NTR/XTR and G4 may be more effective at reducing MR to ≤1+,
and outcomes with other mitral TEER and non-TEER systems are unknown.
• Angiotensin receptor-neprilysin inhibitors were used in < one-third of pts, and only
3 pts were treated with SGLT2 inhibitors (all during the last year of FU).
More frequent use of these agents may have decreased the pool of pts eligible
for enrollment but would likely not have decreased the effects of TEER.
• Whether correction of MR would safely improve outcomes in more or less critically
ill pts or in those with moderate MR is unknown.

Conclusions and Implications (1)
• In pts with heart failure and severe secondary MR who
remained symptomatic despite optimal medical therapy,
TEER with the MitraClip was safe, reduced the rate of
HFHs and improved survival during 5-year follow-up.
• These outcomes were consistent across all pre-specified
subgroups, regardless of patient age, sex, MR severity, left
ventricular function and volume, cardiomyopathy etiology,
and surgical risk.
• Symptomatic status (NYHA class) was also improved
throughout 5-year follow-up, and MitraClip treatment
provided durable repair of mitral regurgitation.

• Treatment effects were reduced after 2-3 years, in large part
due to MitraClip treatment in 44.9% of control group pts
surviving to 2 years.
• The prognosis of control group pts so treated was substantially
improved, similar to that of pts originally assigned to MitraClip
treatment.
• However, nearly half of control group pts had died before
becoming eligible for crossover at 2 years.
• Heart failure patients appropriate for TEER with the MitraClip
should therefore be identified and considered for treatment
as early as possible.

• Finally, despite the favorable risk:benefit profile of the
MitraClip in this setting, adverse outcomes continued to
accrue in both groups such that 91.5% of control group pts
and 73.6% of device group pts had either died or been
hospitalized for heart failure within 5 years.
• These findings emphasize the need for further therapies to
address the underlying left ventricular dysfunction in this
high-risk population.

Rx Only
Important Safety Information
MITRACLIP™ CLIP DELIVERY SYSTEM
Indications forUse
 The MitraClipTM G4Systemisindicated for the percutaneous reduction of significant symptomatic mitral regurgitation (MR≥ 3+)due to primary abnormality of the mitral apparatus
[degenerative MR] in patients who have been determined to be at prohibitive risk for mitral valve surgery by a heart team, which includes a cardiac surgeon experienced
in mitral valve surgery and a cardiologist experienced in mitral valve disease, and in whom existing comorbidities would not preclude the expected benefit from reduction
of the mitral regurgitation.
 The MitraClipTM G4 System, when used with maximally tolerated guideline-directed medical therapy (GDMT), isindicated for the treatment of symptomatic, moderate-to-
severe or severesecondary(or functional) mitral regurgitation (MR;MR≥ GradeIII per AmericanSocietyof Echocardiographycriteria) in patients with aleft ventricularejection
fraction (LVEF)≥ 20%and ≤ 50%,and aleft ventricularend systolic dimension(LVESD)≤ 70 mm whose symptoms and MRseverity persistdespitemaximally tolerated GDMT as
determined by a multidisciplinary heart team experienced in the evaluation and treatment of heart failure and mitral valve disease.
Contraindications
The MitraClip G4 System is contraindicated in patients with the following conditions: Patients who cannot tolerate, including allergy or hypersensitivity to, procedural
anticoagulation or post procedural anti-platelet regime;Patients with known hypersensitivity to clip components (nickel/ titanium, cobalt, chromium, polyester), or with contrast
sensitivity; Active endocarditis of the mitral valve; Rheumaticmitral valve disease;Evidenceof intracardiac,inferior venacava(IVC)or femoralvenousthrombus
Potential Complications and Adverse Events
Thefollowing ANTICIPATEDEVENTShavebeenidentified aspossiblecomplicationsof the MitraClip G4 procedure: Allergic reactions or hypersensitivity to latex, contrast agent,
anaesthesia, devicematerials(nickel/ titanium, cobalt, chromium, polyester), and drug reactionsto anticoagulation, or antiplatelet drugs, Vascular access complications which may
require transfusion or vessel repair including: wound dehiscence, catheter site reactions, Bleeding (including ecchymosis, oozing, hematoma, hemorrhage, retroperitoneal
hemorrhage),Arteriovenous fistula, pseudoaneurysm,aneurysm,dissection, perforation / rupture, vascularocclusion,Emboli (air thrombotic material,implant, device component);
Peripheral Nerve Injury; Lymphatic complications; Pericardial complicationswhich mayrequire additional intervention, including: Pericardial effuseon, Cardiactamponade,Pericarditis;Cardiac
complicationswhich mayrequire additionalinterventions or emergencycardiacsurgery, including: Cardiacperforation, Atrial septaldefect;Mitral valve complications, which may
complicate or prevent later surgical repair, including: Chordalentanglement / rupture, SingleLeafletDeviceAttachment(SLDA),Thrombosis,Dislodgement of previously implanted
devices, Tissue damage, Mitral valve stenosis, Persistent or residualmitral regurgitation, Endocarditis; Cardiacarrhythmias (including conduction disorders,atrial arrhythmias,ventricular
arrhythmias); Cardiacischemicconditions (including myocardialinfarction, myocardialischemia,and unstable/ stableangina);Venousthromboembolism (including deepvein thrombosis,
pulmonary embolism, post procedure pulmonary embolism); Stroke/ Cerebrovascularaccident (CVA)andTransient IschemicAttack (TIA);Systemorgan failure: Cardio-respiratory arrest,
Worsening heart failure, Pulmonary congestion, Respiratory dysfunction / failure / atelectasis, Renalinsufficiency or failure, Shock(including cardiogenic and anaphylactic); Blood cell
disorders(including coagulopathy, hemolysis, and Heparin Induced Thrombocytopenia(HIT));Hypotension/ hypertension; Infection including: Urinary Tract Infection (UTI),Pneumonia,
Septicemia;Nausea/ vomiting; Chest pain; Dyspnea;Edema;Feveror hyperthermia;Pain;Death; Fluoroscopy,Transesophagealechocardiogram(TEE)and Transthoracicechocardiogram(TTE)

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