Heart Failure

case studies / Sacubitril Valsartan switchover

Julia deCourcey,

HF Nurse Consultant

King’s College Hospital,

London UK

2019

Case study 1

Mr W-M age 75

ENT17-C221 | October 2017

History (at time of referral to HF team)

Ischaemic LV systolic dysfunction

(index EF 30- 35% June 2016, EF 22% Aug17)

Collapsed /VT whilst on list for ICD - runs of VT 24 tape

Angiogram 2016 showed unobstructed grafts

CRT-D (MRI conditional) in July 2016 (VT presentation)

Coronary artery bypass graft in 1997 at GSTT

Previous myocardial infarctions - 1992 and 1996

Type 2 diabetes Bisoprolol 1.25 mg od added when admitted for CRT ICD

Social: Caucasian male, lives with wife, retired architect, like long non smoker, < 7

units red wine per week. Independent with no mobility issues.

June 2016 – seen in a

Community clinic

Progressive dyspnoea

for 4/12 symptoms c/w

CCF supported by

cardiomegaly on chest

x-ray

Findings:

No significant peripheral

oedema

BP 148.

HR - not mentioned but

LBBB

PLAN: urgent 24-hr tape / advised might need CRT-D device, chase echo.

“ In parallel” advised GP “start Bisoprolol 1.25 mg and up-titrate to maximum tolerated dose as well as increase

Perindopril but will be considered for a newer heart failure drug. Furosemide should be continued for symptomatic relief”

Follow up in Pacing clinic 6th December 2016

3

Optimisation of conventional therapy 16th Dec 2016 to 21st Feb 2017

Mr M-W age 75

ENT17-C221 | October 2017

Note – Pacing improved with optimisation of drug therapy / reduction of ectopics

Combination of face to face and phone clinics for therapy titration/ICD/ Educ

Seen in HFN Clinic

for therapy

optimisation

Echo and HFC OPA

scheduled for April ‘17

Declined by local rehab

Referred to KCH HF

rehab/psychologist MLWHF 40 /105

low mood (as per discussion)

PHQ-9 GAD-7 none done

No referral to psychology

Drugs

Ramipril 5 mg bd (last increased on 29.12.16)

Bisoprolol 10 mg od (last increased to 10 mg dose on 21.02.17)

Eplerenone 25 mg od (commenced on 20.01.17 )

Frusemide 20 – 40 mg daily (alters dose according to fluid congestion)

Atorvastatin 20 mg od nocte (low dose - due to leg fatigue)

Metformin 500 mg bd

Aspirin 75 mg od

Allergies: None

Intolerances: high dose statins – leg ache

Medication management issues: none, self titrating own diuretics

Pacing check: CRT paced 95%. Rate response off .ICD shock Aug

2016 and using home monitor for downloads

April 2017 Does he fit criteria for sacubitril / valsartan

Mr M-W age 75 referral for Sac Val

ENT17-C221 | October 2017

Would you consider a functional exercise assessment?

Ensure that he has HF helpline contact

Patient seen in HFC

OPA April 2017

BP 110/62mmHg

HR 62

ECG Paced SR

April Rehab assessment:

MLWHF – none done

HAD:

• Anxiety 0

• Depression 1

Prognostic drugs - fully optimised

Diuretics: low dose and uses prn only

Echo: EF 22%

Blood pressure: 110/62

Bloods: Creatinine 92, EGFr 70. - good liver function.

NYHA: 1

Admissions: none

PLAN: See in 4- 6 months

August 2017 Does he fit criteria for sacubitril / valsartan

Mr M-W age 75 referral for Sac Val

ENT17-C221 | October 2017

Note – what about slightly high heart rate?

Would you consider Ivabradine?

Patient phoned not as

well despite higher

diuretic use

Seen in HFC OPA

August

BP 119/60mmHg

HR 79

ECG Paced SR with ectopi

Completed Rehab 11/07/17

Attended Ed sessions inc the

group psychology session.

Goal achieved : to have

confidence to go back to

local gym

ETT improved by 30 meters

Prognostic drugs - fully optimised

Diuretics: higher doses but uses prn

Echo: EF 22%

Blood pressure: 117/60

Bloods: Creatinine 92, EGFr 71. K+ 4.4 - good liver

function but Gamma GT and bilirubin up

NYHA: 2

Admissions: none

PLAN: Higher dose diuretics, referred for Sacubitril

Valsartan

Visit 1

F to F

Visit 2

TFC

Visit 3

TFC

Visit 4

F to F Pacing

clinic

Visit 5 TFC HFC

OPA

1st Sept 17 14th Sept 17 27th Sept 17 2 Nov 17 7th Dec 17 Aug 18

BP 108/68 102/70 92/55 105/60 110/60 119/60

HR 68 64 66 64 58 bpm 55 bpm

Symptoms NYHA 2 / 3 NYHA 1/2

Improved

NYHA 1 NYHA 1 NYHA 1 NYHA 1

Bloods EGFr 81

Creatinine 90

Potassium 4.4

NT Pro BNP 2121

Liver NAD

EGFr 79 EGFr 80 EGFr 77

Sample

haemolysed

EGFr 81

Creatinine 90

Potassium 4.4

NT Pro BNP 1347

Liver NAD

EGFr 81

Creatinine 90

Potassium 4.4

NT Pro-BNP 1150

Liver NAD

MLWHF 2/105

Weight 81 kg 80 kg 79 kg 80.4 kg 80.6 kg 83 kg

Comments no contraindication mild dizziness

Passing lots

more urine

Dizziness on

standing

Improved

Vague dizziness

low Blood sugar

Improved HBA1c low

improved

Plan Sac Val 49/51 mg

added on 4th

Sept

Sac Val 97/103

mg bd from 18th

Sept if BP < 100

mmhg

Reduce or stop

diuretic use

Increase fluid intake

Call if not better

and reduce Sac Val

if BP < 85- 90 mmhg

regularly

Nil new to add

as no problems

with pacing

Advised GP re

blood sugars

Transfer of care

Back to GP on

Sac Val 97/103 mg

bd

No echo

requested

Metformin

stopped by GP

Weight / urine output are very helpful in managing how to respond to lower BP

NT – pro BNP is not a requirement

Post Sac Val Echo is not a requirement unless you need cut off point for another intervention

We know from PARADIGM that

Switchover to Sacubitril Valsartan Sept 1st to Dec 7th 2017

Bloods

Patient reported QOL Case study 1

10

QOL / Readmissions since switchover to Sac Val

11

Call to HF helpline

Unable to get drug from GP / drug recalled !!

Issued a month supply from KCH and see

GP for next script within 2/52

Called Community Pharmacy - provided

pharmacy with Customer care helpline for

Sacubitril Valsartan supply ( 0845 741 9442)

Another call to HF helpline s still no drug

Called GP - transpired that it was Valsartan

that was under a recall

Use Sac Val card / advice sheet issued

Alerted the local community medicines

management team for Bexley

12

Case study 2

Case study 2 Mr B- F age 62

ENT17-C221 | October 2017

August 2018 –referred to CHFCNS for Sac

Val post HFC OPA

Ongoing dyspnoea and

reduced exercise

capacity

Findings:

No significant peripheral

oedema or congestion

BP: none mentioned.

HR: 90 – 120 on pacing

PLAN: Discussed referral with Hospital based CNS

Kings Community supported MDT

History:

1. Dilated cardiomyopathy, reduced Systolic function (Unknown aetiology )

READ code 585f (known hypertension)

2. CRT-Pacemaker 2014

3. Normal coronary angio 2012

4. Asthma as per patient history, Restrictive breathing pattern c/o HF.

5. COPD excluded by spirometry on 2 occasions (s/b Resp team)

6. Paroxysmal atrial fibrillation and TIA.

7. Dyslipidaemia and Hypertension

8. Depression and Anxiety.

9. Iron deficient - had IV iron 02/07/18

10.Migraine and Insomnia

11.Surgery on her right foot

Social History: Black lady of mixed ethnicity (Caribbean and Italian decent, lives

alone, transport for OPAs, Walks with a stick since surgery on foot ( ex wheelchair

use) Ex smoker of 8 yrs ( 3 to 4 menthol cigarettes a day for between 4 and 5 years)

No alcohol Has POC ? one provided by NHS and another by a private provider.

Referral to CHF CNS July 2018

I reviewed this lady in clinic today. She is very short of breath, has not really had any benefit from

inhalers. I note that respiratory do not think she has COPD but she might have a degree of

asthma. Her mobility remains very limited firstly because of problems with her foot but also

because of breathlessness on walking very short distances. She did not currently have any

PND or orthopnoea. I note that she has run into problems with her vision after starting

Ivabradine. I have asked her to stop taking this today and asked her to go with her dosette box to

the pharmacy who gives her the box and ask them to take it out.

In terms of taking things forward, she continues to run with sinus tachycardia and this is

clearly not helping matters. I note her heart rate histogram from the CRT download

sinus tachycardia generally around 90-110 beats per minute. She is on 10 mg of

Bisoprolol in that regard and clearly cannot tolerate Ivabradine and Digoxin is

unlikely to impact much on this either. Therefore I am going to refer her on to EP Dr

Francis Murgatroyd for an opinion whether there is anything else he thinks we can

actually do in that regard. I have also asked for some blood tests today to include a

BNP with a view to whether we can consider changing the patient on to Sacubitril

Valsartan to see whether she might benefit from this. I have also done her iron

studies today to make sure that we are not missing anything in that regard too. Lastly

I have referred the patient on to Ophthalmology from a visual perspective.

July 2018 Does she fit criteria for sacubitril / valsartan?

MS B- W age 75

ENT17-C221 | October 2017

Virtual review post

MDT

BP 135/92 mmHg

HR 100

ECG Paced SR

Pacing: no ICD

therapy and poor

HR control

Prognostic drugs - fully optimised but !!!

Diuretics: moderate dose, flexible use

Echo: EF 23% in Jan 2016

Blood pressure: 135/92

Bloods: Creatinine 100,EGFr 49/ K+ 4.2 mmol

good liver function

NYHA: 3

Admissions: 3 + in one year

Plan ECHO and see together at KCH on 03/08/19

Normal LV size with mild LVH & severe systolic function - 3D EF = 30%

Well known to Community HFCNS - sees her at home

Issues with

• Adherence

• Depression

• non conventional expectations from care providers

• Previously seen HF Pharmacist in home joint review

• Declined referral to Psychologist / 3DLC team in past

HF MDT :

Shared care to lessen burden and shared learning opportunity

Aim to give patient a sense of control

Invite a relative / friend and try engage into social activities

Aim to get her exercising and then possibly weight loss

Liaise with Community pharmacist weekly to check drugs / remove Ramipril from

dosette

Case d/w at the Kings supported Community HF MTD

Effect of co morbidity on HF admissions / mortality

Heart failure is rarely a stand alone problem

It is often accompanied by one or multiple cardiac and or non cardiac

comorbidities which impacts on making diagnosis and in the

management of HF more complicated.

These comorbidities are known to cause poorer outcomes and higher

hospitalisation rates 1, 2, 3

1 van Deursen et al Co-morbidities in heart failure. Heart Fail. Rev. 2014; 19: 163–172 2

2 Braunstein et al. Noncardiac comorbidity increases preventable hospitalizations and mortality among medicare beneficiaries with chronic

heart failure. J. Am. Coll. Cardiol. 2003; 42:

3 Baldi, I et al, Comorbidity-adjusted relative survival in newly hospitalized heart failure patients: a population-based study. Int. J.Cardiol. 2017

The Biggest Problem

Conrad N et al Lancet 2018;391;572

UK 2002-14

Prevalent HF ⬆⬆ 23%

To 920 616 (1.4%)

Mean age at 1st

presentation=77 from

76.5

Mean number of

comorbidities now 5.4

from 3.4

Non-cardiac comorbidities in HF with reduced (HFrEF) mid-range (HFmrEF )and

preserved ejection fraction (HFpEF)

International Journal of Cardiology Koen at al 2018 271, 132-139DOI: (10.1016/j.ijcard.2018.04.001)

Co Morbidity Burden / issues for Sac Val use

BIOSTAT CHF Esc May 2018 Netherlands Cardiovascular Research Initiative: an initiative with support of the Dutch Heart Foundation [

CVON2014-11 RECONNECT ] and a grant from the European Commission [ FP7-242209-BIOSTAT-CHF ; EudraCT 2010–020808–29 ].

Cancer - an important comorbidity – sacubitril valsartan now used to improve EF

Additionally a recognition of advanced heart failure, frailty, dementia, cognition is required - we

need to work with carers / address social support issues

HF NICE 2018 recognizes importance of Comorbidities!

Mortality in HFrEF and improvements in CHF REF Trials

Medication: All seen. Some in blister pack. Pharmacist Mahesh.vaghela@nhs.net

Sacubitril Valsartan 49 /51 mg until 19/08/18 and then 97mg/103 mg twice daily from

20/08/18 – patient has prescription until mid September)

Bisoprolol 10mg once daily

Eplerenone 25 mg once daily (switched from Spiro on 10/09/18 in dosette)

Furosemide 40 mg once daily (in dosette )

Rescue pack of Furosemide 40 mg for PRN outside of dosette box

Rivaroxaban 20 mg once daily (GP - please add to dosette box)

Atorvastatin 40 mg once daily

Omeprazole 40 mg once daily

Gaviscon

Topiramate 25mg once a day

Duloxetine 30mg once a day

Citalopram 20mg once a day

Diazepam ? dose prn but no more than 2 per day (outside blister pack)

Salbutamol inhaler

Zopiclone 7.5mg at night (outside blister pack)

Paracetmaol 500mg- (outside blister pack)

Doxycycline 100 mg issued 11/08/18 in ED

Lactulose 10 mg twice per day

Allergies: none known other than

seasonal allergic rhinitis

Drug cautions: Avoid NSAIDS

Do not give ACEI or Sartan if on

sacubitril -valsartan

Medication management issues:

dosette box via Pearl pharmacy

0207 622 3147, admits to

occasionally forgetting drugs but

overall adherence is thought to have

improved with dosette use

Drug cessation /Intolerances: Ivabradine stopped due to blurred

vision

Digoxin stopped ? rationale

Ramipril 5 mg bd stopped 03/08/18

with a 48 hr wash out period pre

sacubitril -valsartan (ARNI)

Spironolactone switched to Eplerenone

MHRA Yellow Card / PSI No

Case 2 1st Visit in clinic

Visit 1

F to F with echo

Visit to King’s

ED + HF CNS

call

Visit 2

TFC post DN

bloods / BP check

Visit 3

Home Visit

Visit 4

Community Clinic

HFC OPA

HF CNS OPA

3rd August 18 11th August 18 20th August 18 31st August 18 29th Nov 18 20/ 12/18 / Feb 19

BP 125/90 140/103 100/72 128/80 138/98 121/85 / 132/ 88

HR 106 92 82 84 bpm 80 bpm / 76

Symptoms NYHA 3 NYHA Improved NYHA ??? NYHA ?? NYHA NYHA II / III

Bloods EGFr 49

Creatinine 100

Potassium

4.2

NT Pro BNP 473

Liver NAD

EGFr 49

CRP 43

EGFr 39 EGFr 46 EGFr 53

Creatinine 93

Potassium 4.4

NT Pro-BNP 342

Liver NAD

MLWHF

PHQ-9

Gad- 7

91/105

None

None

completed

Weight 86 kg 85 kg 85 kg 83 kg 83 kg - 82.8 kg

Comments no ontraindication

Attended with

friend

Called at home

by HF CNS -

improved

Dizziness on

standing

Admits to feeling

better

Improved d/w by HFC re

transplantation

Referred to CPET

Plan Sac Val 49/51

mg added on

6th August

Called on 6th

August

Doing ok

Encouraged to

carry on with

exercise - now

outdoor walks for

20 mins

Sac Val 97/103 mg

20th August 19

Had self reduced

diuretic use

Seen by SAIL

Watching diet

Advised and

accepted

referral to

Rehab -

Transfer of care

Back to GP

Echo requested

EF - DNA ECHO

and CPET and

Rehab to date

Infection – be cautious and f/u more closely

Issued with Sacubitril and Valsartan Tablet 24/26mg, 2 Tablet(s), Oral, TWICE a day (0800 & 2000

Urine output was a very important measure and help guided her diuretic use

Post Sac Val Echo is not always required

Switchover to Sacubitril Valsartan August 3rd – Nov 29th 2018

+

25

Assess your patient - How are they coping with HF etc

Understand and manage patient’s expectations

Review co morbidities

Plan f/u to suit patient need

Adding Sac Val after previous use of ACEI /ARB is generally straight forward

but less so when patient is ACEI /ARB naive

Newer studies in the IP population

PIONEER HF - Drug added during IP stay

TRANSITION - Drug added during IP stay

HFpEF study: PARAGON and results expected in at ESC Aug 2019

Take home points

PIONEER HF and TRANSITION