Practical Tips inPractical Tips in

ββ-blocker Therapy in CHF-blocker Therapy in CHFCMCC 11CMCC 11thth 11 11thth September 2009 September 2009

Rungsrit Kanjanavanit MD. Rungsrit Kanjanavanit MD. Cardiovascular Div. Dept. of MedicineCardiovascular Div. Dept. of Medicine

Faculty of Medicine , Chiang Mai Univ. Faculty of Medicine , Chiang Mai Univ.

Circulation. 2009;119:1977-2016.

25512551

βB/ ARB

Utilization of HF medications in clinical practiceUtilization of HF medications in clinical practiceEuro Heart SurveyEuro Heart Survey

87

62

37 36 33

21 21 17

0102030405060708090

100

Komajda M et al. Eur Heart J 2003

%

Trials excluded patients with relative contraindications

Not very old , mainly white men, no complicated medical history

In real life , more than 75% have at least one relative contraindication

Clinical trials VS Real world populationClinical trials VS Real world population

Co-morbidities CMU HF clinicCo-morbidities CMU HF clinic

15.6

20

33.3

62.2 6051.1

11.10

10

20

30

40

50

60

70

CAD DM HT dyslipid CRF COPD

44.4 % had > 3 comorbidities

Not adhering to guidelinesNot adhering to guidelines

Can the difference between the real world patients and RCT’s solely explain these findings?

No

83% of SOLVD-eligible were on ACEI Almost half of these received the target dose as recom

mended in the guidelines

54% of MERIT-HF-eligible were on β-blockers 10% of these received the target dose.

43% of RALES-eligible patients were on

aldosterone antagonist

Euro Heart Survey on Heart FailureEuro Heart Survey on Heart Failure

Lenzen MJ et al. European Heart Journal (2005) 26, 2706–2713

‘adherence’ related solely to physicians following guidelines,

not to patient compliance or persistence.

Barrier to Barrier to ββ-blocker prescription-blocker prescription

Uninformed clinicians Perceived complexity in initiation and up-titration

Lack of time and expertise for “micromanagement” required with complex regimen

Risk of intolerance and worsening of HF symptoms with initiation

Perceived delay in beneficial effects on outcomes

Economic restraints – in some hospital ,UC may not cover evidenced-based β-blocker for HF

1. Enalapril (20) ½ tab bid pc.1. Enalapril (20) ½ tab bid pc.

2. Bisoprolol (5) 1 tab OD.2. Bisoprolol (5) 1 tab OD.

3. Spironolactone (25) 1 tab OD.3. Spironolactone (25) 1 tab OD.

4. Digoxin (0.25) ½ tab E.O.D.4. Digoxin (0.25) ½ tab E.O.D.

5. Furosemide (40) 1 tab prn for 5. Furosemide (40) 1 tab prn for dyspnea ,edema or weight gain dyspnea ,edema or weight gain > 1 kg in 2 days> 1 kg in 2 days

13. Warfarin (3) ½ tab o OD. 13. Warfarin (3) ½ tab o OD. Except Mon. and Wed.Except Mon. and Wed.

14.14. Warfarin (5) ½ tab o OD. Warfarin (5) ½ tab o OD. Only on Mon. and Wed.Only on Mon. and Wed.

6. Glibencarmide(5) 1½ tab bid ac6. Glibencarmide(5) 1½ tab bid ac

7. Metformin (500) 1 tab tid pc7. Metformin (500) 1 tab tid pc

8. Aspirin (300) 1 tab OD.8. Aspirin (300) 1 tab OD.

9. ISDN (10) 2 tab tid ac9. ISDN (10) 2 tab tid ac

10. Isordil (5) 1 tab SL prn10. Isordil (5) 1 tab SL prn

11. Amlodipine (10) 1 tab OD.11. Amlodipine (10) 1 tab OD.

15.15. Lorazepam 1 tab prn hs.Lorazepam 1 tab prn hs.

16.16. Senekot 2 tab o hs Senekot 2 tab o hs

12. Atrovastatin (20) 1 tab pc evening12. Atrovastatin (20) 1 tab pc evening

Drugs Prescriptions of Mr. Had-enoughDrugs Prescriptions of Mr. Had-enough

POLYPHARMACYPOLYPHARMACY

17. Omeprazole (20) 1 tab o OD17. Omeprazole (20) 1 tab o OD

Patients with Sys HF

Patients with Sys HF without contraindication to β-blocker

Patients with Sys HF who are

given β-blocker( Doctor adherence to guideline)

Patients with Sys HF who are

actually taking β-blocker( Patients’ medical adherence )

Patients with Sys HF who are taking β-blocker at the target dose

We can do We can do better ! better !

ββ blocker in heart failure blocker in heart failure

Contra-indication Strong indication

Tip # 1Tip # 1Implementation of Implementation of β blocker β blocker therapy -When?therapy -When?

A simplified criteria

1. Edema free

2. Not requiring intravenous

medication for HF

Which and what doseWhich and what dose

Starting dose(mg) Target dose(mg)

Bisoprolol 1.25 od 10 od

Metroprolol CR/XL 12.5-25 od 200 od

Carvedilol 3.125 bid 25-50 bid

Nebivolol 1.25 od 10 od

Titration period – weeks to monthsTitration period – weeks to months

Tip # 2 How to use Tip # 2 How to use ββ blocker blocker

Start early but with low dose

Double dose at not less than 2 weekly interval

Aim for target dose or highest tolerated dose

Some β blocker is better than no β blocker

Monitor HR,BP,BW and signs of congestion

Check blood chemistry 1-2 week after inhibition

and 1-2 week after final dose titration

Dry and Dry and WarmWarm

Wet and Wet and WarmWarm

Dry and Dry and ColdCold

Wet and Wet and ColdCold

Fluid statusFluid statusP

erfu

sion

Per

fusi

on

Dry Wet

Warm

Cold

Tip # 3Tip # 3Patient came in with decompensated HF Patient came in with decompensated HF

What to doWhat to do

Wet and warm IV diuretics No need to decrease dose of β-blocker Up-titrate dose of ACEi and β-blocker when stabilized

Wet and cold Positive inotropic support (PDE inhibitors) Decrease the dose of β-blocker by 50% Reintroduction or up-titrate β-blocker when stabilized

B-CONVINCEDB-CONVINCEDBeta-blocker CONtinuation Vs. INterrupion in Beta-blocker CONtinuation Vs. INterrupion in

patients with Congestive heart failure hospitalizED patients with Congestive heart failure hospitalizED for a decompensation episodefor a decompensation episode EHJ (2009) 30,1-7EHJ (2009) 30,1-7

During ADHF, continuation of β-blocker is not associated with delayed or lesser improvement, but with higher rate of chronic prescription of β-blocker therapy after 3 months

Keepβ-blocker

Stopβ-blockerADHF

69

78

HF improves at Day 3

92.8 %

92.3 %

β-blocker at 3 months

90 %

76 %

Plasma BNP, LOS, rehospitalization rate, death rate also similar

Tip # 4 How to use DiureticsTip # 4 How to use Diuretics

Lower the dose or stop before initiation of

ACEi and spironolactone

(avoid hypovolemia )

Increase the dose before initiation of

β- blocker

( make sure there is no fluid retention )

The most important tool in HF managementThe most important tool in HF management

Self daily weight monitoring :Self daily weight monitoring :

If weight increases > 1 kg within 1 or 2 days If weight increases > 1 kg within 1 or 2 days

double the dose of diuretics , until returns to ideal BWdouble the dose of diuretics , until returns to ideal BW

• Weigh every morningWeigh every morning

• After going to toiletAfter going to toilet

• Before getting dressedBefore getting dressed

• Before breakfastBefore breakfast

Tip # 5 Dealing with Tip # 5 Dealing with low heart ratelow heart rate

If < 50 bpm, halve dose of β-blockerReview other medications

Drug interaction to look for : DigitalisVerapamil / diltiazem - should be discontinueAmiodarone

Tips # 6Tips # 6

Be persistant ! Minor setback can be overcome

Any general sense of un-wellness will generally resolve in a few week

More than 85% will tolerate β blocker

Tip # Tip # 77Problem solving : HypotensionProblem solving : Hypotension

Asymptomatic low BP does not require any

change in therapy.

HypoPERFUSION not hypoTENSION is the

concern.

Dizziness,light-headedness and confusion D/C nitrates, CCB , other vasodilators

reducing dose of the diuretics if no signs/symptoms of

congestion

Tip # 8Tip # 8

Always measure supine and upright BP in every HF patients at every visit

CaseCase ผู้��ป่�วยชาย อาย� 21 ป่

ได้�รั�บการัว�นิ�จฉั�ยเป่�นิ DCM มาติ�ด้ติามการัรั�กษาหลั�งออกจากโรังพยาบาลั อาการัด้"ขึ้$%นิ จาก NYHA III เป่�นิ II ติรัวจรั&างกาย : HR 100 bpm

BP 100/60 mmHg No lung crepitation No edemaผู้ลัการัติรัวจห�องป่ฏิ�บ�ติ�การั serum Cr 1.3 mg/dl, K 4.0 mg/dlการัรั�กษาที่")ได้�รั�บ Ramipril 2.5mg/d Furosemide 40mg/d Digoxin 0.125mg/d

LV & RV Non-compaction

What would you do?What would you do?

1. Increase dose of ramipril (target dose 10mg/d)

2. Add very low dose β-blocker

3. Increase dose of digoxin (to control HR)

4. Leave him with this regimen

(now asymptomatic)

ATLAS (Assessment of Treatment with ATLAS (Assessment of Treatment with Lisinopril and Survival)Lisinopril and Survival)

3164pt. NYHA II-IV, LV EF <30% F/U 45.7mo

Low (2.5-5.0mg) High (32.5-35mg)

Mortality (%) 44.9 42.5CV mortality (%) 40.2 37.2Hospitalization (no.)* 4327 3819HF hospitalization(no)* 1576 1999

Circ.1999;100:2312-2318

ATLAS : low dose VS high dose NNT to avoid rehospitalization = 4

LVESVI: Change From BaselineLVESVI: Change From Baseline

* P < 0.05, ** P < 0.001* P < 0.05, ** P < 0.001

EnalaprilEnalaprilCarvedilolCarvedilol

-10-10

-8-8

-6-6

-4-4

-2-2

00

22

44

**** **** ****

** ** **

L

VE

SV

I (m

l/m

LV

ES

VI

(ml/

m22 ))

M6M6 M12M12 M18M18 M6M6 M18M18M12M12 M6M6 M12M12 M18M18

Carvedilol &Carvedilol &EnalaprilEnalapril

CARMEN StudyCARMEN Study

LVEF: Change From BaselineLVEF: Change From Baseline

* P < 0.05; ** P < 0.01; *** P < 0.001* P < 0.05; ** P < 0.01; *** P < 0.001

EnalaprilEnalaprilCarvedilol &Carvedilol &EnalaprilEnalapril

CarvedilolCarvedilol

-1-1

00

11

22

33

44

55

L

VE

F (

%)

LV

EF

(%

)

****** ****** ******

****** ****** ****

**

M6M6 M12M12 M18M18 M6M6 M18M18M12M12 M6M6 M12M12 M18M18

CARMEN StudyCARMEN Study

Comparing two different strategies Comparing two different strategies in patients receiving low dose ACEi in patients receiving low dose ACEi

Increasing ACEi to Increasing ACEi to maximal dosesmaximal doses

Adding Adding ββ-blocker-blocker

Effect on symptomsEffect on symptoms No changeNo change Improved Improved

Effect on risk of Effect on risk of deathdeath

8% reduction8% reduction 30-40% reduction30-40% reduction

Effect on risk of Effect on risk of death and death and

hospitalizationhospitalization

12% reduction12% reduction 20-40% reduction20-40% reduction

ATLASATLAS MERIT HFMERIT HF

Combined use of low doses of several drugs is preferred to a large dose of a single agent.

Tip # 9 Tip # 9

Six patterns of taking medication among patients treatedSix patterns of taking medication among patients treatedfor chronic illnesses for chronic illnesses who continue to take their medicationswho continue to take their medications

perfect adherence

some timing irregularity

miss an occasional single day’s dose

drug holidays three to four times a year

drug holiday monthly or more

take few or no doses

1/6

1/6

1/6

1/6

1/6

1/6

N Engl J Med 2005;353:487-97

“ Good drugs do not work on patients who do not take them ”

C. Everett Koop, M.D.

Tip # 10Tip # 10FactFact

Inadequate education

poor self-motivation

poor compliance

forgetfulnesspoor family

supportdrugs side effectdrugs side effect

Complexity of the medication regimen

Excessive costDepression

Patient educationPatient education

Self managementSelf management

Heart transplantHeart transplant

RevascularizationRevascularization

Resynchronization TherapyResynchronization Therapy

Pharmacologic TherapyPharmacologic Therapy

“ “ filling the in the care of chronic filling the in the care of chronic diseases ”diseases ”

Disease management programDisease management program

Low tech – high touch therapy

G A PG A P

Pyramid of HF care

10 Practical Tips - Summary10 Practical Tips - Summary

1. A simplified criteria when to start

2. How to titrate and what to monitor

3. Do not stop blocker when patients come in with ADHF unless inotropes is needed (low output syndrome)

4. Know how to use diuretics effectively 1. Flexible regimen

2. Dealing with diuretic resistance

10 Practical Tips - Summary10 Practical Tips - Summary

5. Dealing with low heart rate

6. Be persistent

7. Hypotension VS hypoperfusion

8. Measure both supine and upright BP in every

HF patients at every visit

9. Combined use of low to moderate doses of

several drugs is preferred to a large dose of a

single agent

10. Nurses are doctor’s best friend

Thank youThank you