Medical therapy for CTEPH: what is the standard of care in

An expert panel discussion recorded in July 2020

This educational activity is supported by an educational grant from Merck and Co

Medical therapy for CTEPH: what is the standard

of care in 2020?

touchPANEL DISCUSSION

CTEPH, chronic thromboembolic pulmonary hypertension.

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Agenda

Multidisciplinary assessment of CTEPH and treatment decisionsPresentation: Irene LangPanel discussion: Nick Kim and Hiromi Matsubara; moderated by Irene Lang

Targeted medical therapy in technically inoperable patientsPresentation: Irene LangPanel discussion: Nick Kim and Hiromi Matsubara; moderated by Irene Lang

CTEPH, chronic thromboembolic pulmonary hypertension; PEA, pulmonary endarterectomy.

Persistent/recurrent symptomatic disease following PEAPresentation: Irene LangPanel discussion: Nick Kim and Hiromi Matsubara; moderated by Irene Lang

Multidisciplinary assessment of CTEPH

CTEPH, chronic thromboembolic pulmonary hypertension.

Prof. Irene Lang (Chair)Professor of Vascular Biology,Medical University of Vienna,Austria

The role of the multidisciplinary team is critical in assessment of patients with CTEPH

A multidisciplinary CTEPH team ensures that procedures necessary for the diagnosis and choice of a suitable therapeutic strategy are performed

CTEPH, chronic thromboembolic pulmonary hypertension.Siennicka A, et al. Ther Adv Respir Dis. 2019;13:1753466619891529.

Assessment of operability is subjective and challenging

PEA, pulmonary endarterectomy; PVR, pulmonary vascular resistance; RV, right ventricle; WHO FC, World Health Organization functional class.Galiè N, et al. Eur Respir J. 2015;46:903–75.

Preoperative WHO FC II–IV

Surgical accessibility of thrombi in the main, lobar or segmental pulmonary arteries

Advanced age per se is not a contraindication for surgery

No PVR threshold or measure of RV dysfunction that can be considered to preclude PEA

Case 1: June 2015

6-MWD, six-minute walking distance; BP, blood pressure; CI, cardiac index; mPAP, mean pulmonary artery pressure; NT-proBNP, N-terminal pro B-type natriuretic peptide; NYHA FC, New York Heart Association functional classification; PAWP, pulmonary capillary wedge pressure; PVR, pulmonary vascular resistance; RAP, right atrial pressure; s/d/m, systolic/diastolic/median; SVI, stroke volume index; SvO2, mixed venous oxygen saturation; WU, Wood units.

• 60 years of age• Female• Pharmacist• Iron deficient• Dyspnea• Palpitations

NYHA FC III

6-MWD (m) 325

RAP (mmHg) 6

PAWP (mmHg) 8

mPAP (mmHg) 38

CI (L/min/m2) 2.50

PVR (WU) 6.90

SvO2 (%) 66.60

SVI (mL/m2) 28

BP (s/d/m; mmHg) 110/70/86

NTproBNP (pg/mL) 448

Case 1: June 2015 imaging

NYHA FC III

6-MWD (m) 325

RAP (mmHg) 6

PAWP (mmHg) 8

mPAP (mmHg) 38

CI (L/min/m2) 2.50

PVR (WU) 6.90

SvO2 (%) 66.60

SVI (mL/m2) 28

BP (s/d/m; mmHg) 110/70/86

NTproBNP (pg/mL) 448

Case 1: July 2016 following PEA

II

580

4

13

19

2.65

1.01

68.80

35.68

144/74/100

115


Targeted medical therapy in technically inoperable patients


Treatment options for patients with CTEPH: When to consider medical therapy?

a. Multidisciplinary: pulmonary endarterectomy surgeon, pulmonary hypertension expert, BPA interventionalist and radiologist.b. Treatment assessment may differ depending on the level of expertise. c. BPA without medical therapy can be considered in selected cases.

BPA, balloon pulmonary angioplasty; CTEPH, chronic thromboembolic pulmonary hypertension.

Kim NH, et al. Eur Respir J. 2019;53:1801915.

CTEPH diagnosis –continue lifelong anticoagulation

Treatment assessment byexpert CTEPH

teama,b

Persistent/recurrent symptomaticpulmonary

hypertension

Operable

Non-operable

Pulmonary endarterectomy

(treatment of choice)

Targeted medical therapy with or without BPAb,c

The evidence base for BPA in CTEPH

6MWD, six-minute walking distance; BPA, balloon pulmonary angioplasty; CI, cardiac index; mPAP, mean pulmonary arterial pressure; NR, not recorded; PVR, pulmonary vascular resistance; WU, Wood units.

Study Number of

patients

Mean number of

catheterization

procedures

Number on

vasodilator

therapy

Mean baseline

6MWD (m)

Mean baseline

mPAP (mmHg)

Mean baseline

CI (L/min/m2)

Mean baseline

PVR (WU)

Feinstein et al., 2001 18 2.7 NR 191.1 42.0 2.0 22.0

Roik et al., 2016 10 3.9 6 210.0 41.5 2.3 8.9

Moriyama et al., 2017 53 6.0 NR 351.4 37.2 2.2 8.4

Ogawa et al., 2017 308 8.3 222 318.1 43.2 2.6 10.7

Yamasaki et al., 2017 20 2.7 20 391.0 42.6 3.1 8.0

Kriechbaum et al., 2018 51 5.2 29 367.2 39.5 NR 6.5

Kurzyna et al., 2018 31 NR NR 306.0 50.7 2.3 10.3

Kwon et al., 2018 15 3.5 9 387.0 NR 2.9 7.6

Velazquez et al., 2018 46 NR 46 394.5 49.5 2.3 10.1

Yamagata et al., 2018 19 3.2 NR 308.1 40.1 NR 7.5

Brenot et al., 2019 184 5.4 105 396 44.1 2.7 7.6

Case 2: November 2015

• 49 years of age• Female

NYHA FC IV

6-MWD (m) 230

RAP (mmHg) 14

PAWP (mmHg) 12

mPAP (mmHg) 64

CI (L/min/m2) 2.10

PVR (WU) 13.70

SvO2 (%) 45.50

SVI (mL/m2) 19.15

BP (s/d/m; mmHg) 103/64/75

NTproBNP (pg/mL) 7,252


Case 2: November 2015 imaging

Persistent/recurrent symptomatic disease following PEA

PEA, pulmonary endarterectomy.


Persistent or recurrent CTEPH after PEA

CTEPH, chronic thromboembolic pulmonary hypertension; mPAP, mean pulmonary arterial pressure; PEA, pulmonary endarterectomy; PH, pulmonary hypertension; WHO FC, World Health Organization functional class.1. Jenkins D, et al. Eur Respir Rev. 2017;26:160111; 2. Freed DH, et al. J Thorac Cardiovasc Surg. 2011;141:383–7.

• Approximately one third of patients may have persistent PH despite apparently successful PEA surgery

• Persistent PH may be caused by concomitant small-vessel arteriopathy in patients with operable proximal disease, which is challenging to determine prior to surgery. It can also result from failure to surgically remove more distal chronic thromboembolic disease

• Recurrent PH is less common, of different aetiology, and is caused by a further thromboembolic episode after a successful PEA clearance (often associated with poor anticoagulation) and a confirmed reduction in PH post-PEA

• Data collected prospectively on 314 patients who underwent PEA in a continuous national series (between 1997 and Dec 2007). Residual PH was observed in 31% of patients

• Conditional survival after discharge from the hospital for the whole cohort was 90.0% at 5 years

Incidence and definitions1Postoperative clinical status

and survival2

94% WHO FC I/II 74% WHO FC I/II

mPAP<30 mmHg

mPAP≥30 mmHg

Medical therapy for persistent or recurrent CTEPH

• Phase III CHEST-1 trial of patients with inoperable CTEPH or persistent/recurrent PH after PEA treated with placebo vs riociguat1

• Increase in 6MWD in patients with persistent/recurrent PH after PEA in the riociguat group of 26 m1

Current ESC/ERS guidelines recommend medical therapy in patients with persistent or recurrent CTEPH after PEA surgery4

6MWD, six-minute walking distance; CI, confidence interval; CTEPH, chronic thromboembolic pulmonary hypertension; ERS, European Respiratory Society; ESC, European Society of Cardiology; PEA, pulmonary endarterectomy.1. Ghofrani HG, et al. N Engl J Med. 2013;369:319–29; 2. Simonneau G, et al. Lancet Respir Med. 2016;4:372–80; 3. Klose H, et al. Am J Respir Crit Care Med. 2018;197:A5682; 4. Galiè N, et al. Eur Respir J. 2015;46:903–75.

• Prospective EXPERT registry study to assess the safety of riociguat in clinical practice3

• No new safety signals were identified, events of special interest remained infrequent and reported adverse events were consistent with the known safety profile of riociguat3

• CHEST-2 open-label, randomized, long-term extension trial of patients from CHEST-1 trial2

• Overall survival was 97% (95% CI 93–98) at 1 year and 93% (95% CI 89–96) at 2 years2


• 55 years of age• Male

NYHA FC IV

6-MWD (m) 230

RAP (mmHg) 13

PAWP (mmHg) 10

mPAP (mmHg) 50

CI (L/min/m2) 1.80

PVR (WU) 8.90

SvO2 (%) 51

SVI (mL/m2) 28

BP (s/d/m; mmHg) 130/78/97



NYHA FC IV

6-MWD (m) 230

RAP (mmHg) 13

PAWP (mmHg) 10

mPAP (mmHg) 50

CI (L/min/m2) 1.80

PVR (WU) 8.90

SvO2 (%) 51

SVI (mL/m2) 28

BP (s/d/m; mmHg) 130/78/97


Case 3: October 2005

III

460

5

14

46

2.30

5.90

59

36

130/80/99

1,220



NYHA FC IV

6-MWD (m) 230

RAP (mmHg) 13

PAWP (mmHg) 10

mPAP (mmHg) 50

CI (L/min/m2) 1.80

PVR (WU) 8.90

SvO2 (%) 51

SVI (mL/m2) 28

BP (s/d/m; mmHg) 130/78/97


Case 3: January 2007

III

460

5

14

46

2.30

5.90

59

36

130/80/99

1,220

II/III

510

4

10

40

2.70

4.70

64

45

145/80/103

550


NYHA FC IV

6-MWD (m) 230

RAP (mmHg) 13

PAWP (mmHg) 10

mPAP (mmHg) 50

CI (L/min/m2) 1.8

PVR (WU) 8.9

SvO2 (%) 51

SVI (mL/m2) 28

BP (s/d/m; mmHg) 130/78/97


Case 3: June 2019

III

460

5

14

46

2.3

5.9

59

36

130/80/99

1,220

II/III

510

4

10

40

2.7

4.7

64

45

145/80/103

550

II

750

3

5

24

2.6

3.0

65

44

131/71/ 92

156 6-MWD, six-minute walking distance; BP, blood pressure; CI, cardiac index; mPAP, mean pulmonary artery pressure; NT-proBNP, N-terminal pro B-type natriuretic peptide; NYHA FC, New York Heart Association functional classification; PAWP, pulmonary capillary wedge pressure; PVR, pulmonary vascular resistance; RAP, right atrial pressure; s/d/m, systolic/diastolic/median; SVI, stroke volume index; SvO2, mixed venous oxygen saturation; WU, Wood units.

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Medical therapy for CTEPH: what is the standard of care in