heart failure therapy and the general internist: what’s new? · learning objectives. 1. to review...

Heart Failure Therapy and the General Internist:

What’s New?• Finlay A. McAlister

• Division of General Internal Medicine• University of Alberta and the Mazankowski Alberta Heart Institute

CSIM Annual Meeting 2017

Speaker: McAlister – November 3, 2017

The following presentation represents the views of the speakerat the time of the presentation. This information is meant foreducational purposes, and should not replace other sources

of information or your medical judgment

Conflict Disclosures

I have no conflicts to declare

Learning Objectives1. To review recent evidence on new therapies for heart

failure that are relevant for general internists

2. To compare the pros and cons of these new therapies.

3. To review the current Canadian Cardiovascular Society Heart Failure Guidelines from the perspective of a general

internist

Case- Mr. Willie Maykit

• 62 year old male• multiple CV risk factors (obese, HTN, dyslipid)• MI 6 years ago, cath’d, DES stent x 1 in LAD• Now referred with ankle swelling, SOBOE (NYHA III),

PND, but no angina, palps, or syncope

Question 1 and 1a

• How soon would you see him?

• Would you measure BNP?

When to see

CCS guidelines

for the diagnosis of

HFEzekowitz, Can J Cardiol 2017.

Canadian Journal of Cardiology DOI: (10.1016/j.cjca.2017.08.022) Copyright © 2017 Terms and Conditions

http://www.elsevier.com/termsandconditions

Now:

TroponinHemoglobinCreatininePotassium

SodiumBNP/NT-proBNP

Newer:

ST2MR-proANPProcalcitonin

Galectin-3N-GAL

MR-proADM

Not yet known:

WS4Apelin

Urinary cGMP?panels

Key blood biomarkers in HF

BNP Guided Therapy MA/SR: Mortality(12 RCTs, 2686 pts)

Savarese G, et al. PLoS ONE. 2013;8:e58287.Troughton RW, et al. Eur Heart J. 2013.

Meta analysis of published data Pooled patient data from all available trials

Objectives of the GUIDE-IT Trial

To compare the efficacy of a strategy of NT-proBNP-guided therapy vs. usual care on the composite endpoint of time to cardiovascular death or first heart failure (HF) hospitalization in high risk patients HF patients with left ventricular systolic dysfunction.

Screening

Randomization

Follow-up

Endpoints

High-Risk Heart Failure with Reduced EFLVEF ≤ 40 within 12 months

HF event (hospitalization, ED visit, outpatient IV diuretics) within prior 12 mosNT-proBNP > 2000 pg/mL within prior 30 days

Usual Care

N=550

Primary endpoint: Time to CV death or first HF hospitalizationSecondary endpoints: • All-cause mortality

• Total days alive and out of hospital during follow-up• CV mortality or CV hospitalization• Safety• Health-related quality of life• Resource utilization, costs, cost effectiveness

Biomarker-GuidedNT-proBNP < 1000 pg/mL

N=550

Follow up: 2 wks, 6 wks, 3 months, then Q3 month for 12–24 mos

Additional 2-week follow-up after changes in therapy

Baseline CharacteristicsNT-proBNP-Guided

N = 446Usual Care

N = 448

Age (median) 62 64Gender (female) 31% 33%Race (% AA) 39% 35%

Ethnicity (% Hisp) 7% 6%

EF (median) 24% 25%

Etiology (% IHD) 46% 55%

Diabetes (%) 44% 47%

Afib (at enrollment) 36% 44%

SBP (median) 114 mmHg 114 mmHg

Serum Cr (median) 1.3 mg/dL 1.3 mg/dL

NT-proBNP (median) 2632 pg/mL 2668 pg/mL

Primary Endpoint(HF hospor CV death)

Secondary Endpoints

NT-proBNP-Guided

Usual Care

HR(95% CI) P value

Mortality, No (%) 66 (15) 77 (17) 0.86 (0.62-1.20) 0.37

CV mortality, No (%) 53 (12) 57 (13) 0.94 (0.65-1.37) 0.75

Non-CV mortality, No (%) 13 (3) 20 (5) 0.66 (0.33-1.32) 0.24

First HF hosp., No, (%) 147 (33) 141 (32) 1.04 (0.82-1.31) 0.08

Total HF hosps, No. 350 277 1.29 (0.97-1.72) 0.08

Days alive and not hosp. for CV reasons, Mean (SD) 581 (14) 562 (15) Mean difference

19 (-22 to 60) 0.36

Quality of Life: KCCQ Overall Summary Score

57.5

68.8 70.4 68.4 70.2

57.7

69.2 70.1 70.3 71.6

0

20

40

60

80

100

Baseline 3 month 6 month 12 month 24 month

KCCQ BG KCCQ UC

0 to 100 scale, with higher scores reflecting better quality of lifeDifference in KCCQ scores. Biomarker strategy minus usual care. 95% CI.

NT-proBNP Over Time

12

6

10

4

0

5

10

Clinic Visits (median) Adjustments to HFtherapy (median)

Process of CareP=0.002

P<0.001

NT-proBNP-GuidedUsual Care

Conclusions

in high-risk patients with HFrEF, a strategy of guiding therapy based on NT-proBNP levels was not more effective than a usual care strategy in reducing the composite endpoint of time-to-first HF hospitalization or cardiovascular death

Defining strategies to optimize evidence-based Rx in high risk heart failure patients remains a pressing medical need

“Optimal” GDMT: BB, RAAS, MRA at ≥ 50% Target Dose

0%

5%

10%

15%

20%

25%

Biomarker-Guided Usual Care

P<0.001 P<0.01 Baseline12 months

Case- Mr. Willie Maykit

• 62 year old male• multiple CV risk factors (obese, HTN, dyslipid)• MI 6 years ago, cath’d, DES stent x 1 in LAD• Now referred with ankle swelling, SOBOE (NYHA III),

PND, but no angina, palps, or syncope• HR 92, reg BP 120/70 RR 16• bibasilar creps, JVP 5 cm ASA (+HJR), bipedal edema,

S3, mitral regurg murmur

Question 2

• Would you send him for repeat cath?– Mark Hansen’s workshop Saturday November 4

• What would you send him for?

Case- Mr. Willie Maykit• 62 year old male• multiple CV risk factors• MI 6 years ago, cath’d, DES stent x 1 in LAD• Now referred with ankle swelling, SOBOE, PND, but no

angina, palps, or syncope• HR 92, reg BP 120/70 RR 16• bibasilar creps, JVP 5 cm ASA (+HJR), bipedal edema, S3,

mitral regurg• Echo: LVEF 25-30%, ECG: NSR, LBBB

Question 3

• What would you treat him with?

a) Daily hot bath and prn leeches b) Digoxin + loop diureticc) Double therapy (ACEi/ARB, BB, and MRA) +/- loop diureticd) Triple therapy (ACEi/ARB, BB, and MRA) +/- loop diuretic

Patients with HFrEF

Ezekowitz, Can J Cardiol 2017.

Treatment Strategies in HF

ACEi/(ARB)

Titrated use of BBs/(ARB)

Spironolactone

Digoxin/Nitrates

No addedsalt

2 gm NaHF clinicsfollow-up

Customizedlifestyle program

CRT (LBBB), CPAP

Asymptomatic Mild/Mod Severe Refractory

Risk of SD — AICD

ACE InhibitorsGarg R, et al. JAMA 1995;273:1450-6.Flather et al. Lancet 2000;355:1575-81.

• 32 RCTs in CHF, 7105 pts; 12 763 pts in 5 large RCTs• Clinical Outcomes:

– Total mortality: 0.77 (0.67-0.88) and 0.74 (0.66-0.83)– Mortality or hosp: 0.65 (0.57-0.74) and -------------------– HF hospitalizations: -------------------- and 0.67 (0.61-0.74)

• Which ACEI? – Likely class effect, but definite evidence for captopril, enalapril, ramipril,

lisinopril, trandolapril

ACE InhibitorsGarg R, et al. JAMA 1995;273:1450-6.

• Same OR: men/women; young/old; ischemic/non-ischemic• Other subgroups:

– NYHA I 0.69 (0.44-1.09)– NYHA II 0.68 (0.57-0.81)– NYHA III 0.58 (0.46-0.73)– NYHA IV 0.69 (0.43-1.10)– EF < 0.25 0.53 (0.43-0.65)– EF > 0.25 0.85 (0.69-1.04)

CHARM-Alternative: Primary outcome (CV death or CHF hospitalisation)

0 1 2 3 years0

10

20

30

40

50

Placebo

Candesartan

%

HR 0.77 (95% CI 0.67-0.89), p=0.0004Adjusted HR 0.70, p<0.0001

3.5

406 (40.0%)

334 (33.0%)

RRR=23%

Date of download: 10/24/2017

From: Meta-Analysis: Angiotensin-Receptor Blockers in Chronic Heart Failure and High-Risk Acute Myocardial Infarction Ann Intern Med. 2004;141(9):693-704. doi:10.7326/0003-4819-141-9-200411020-00011

Copyright © American College of Physicians. All rights reserved.

Versus Placebo:

Mortality: 0.83 (0.69-1.00)

HF hosp: 0.64 (0.53-0.78)

24 RCTs, 38 080 pts

http://www.acponline.org/


From: Meta-Analysis: Angiotensin-Receptor Blockers in Chronic Heart Failure and High-Risk Acute Myocardial Infarction Ann Intern Med. 2004;141(9):693-704. doi:10.7326/0003-4819-141-9-200411020-00011


Versus ACEi:

Mortality: 1.06 (0.90-1.26)

HF hosp: 0.95 (0.80-1.13)


Hydralazine and Nitrates (V-HeFT I&II)

RRR: 28.2%: ARR 5.4% vs. H/NRRR: 34%: ARR 8.7% vs. placebo

HR and Outcomes in HF


From: Meta-analysis: β-Blocker Dose, Heart Rate Reduction, and Death in Patients With Heart FailureAnn Intern Med. 2009;150(11):784-794. doi:10.7326/0003-4819-150-11-200906020-00006


Death RR: 0.76 (0.68-0.84)Hosp RR: 0.64 (0.57-0.71)

23 RCTs, 19 209 pts


From: Beta-blockers for heart failure with reduced, mid-range, and preserved ejection fraction: an individual patient-level analysis of double-blind randomized trialsEur Heart J. Published online October 10, 2017. doi:10.1093/eurheartj/ehx564Eur Heart J | Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions,please email: [email protected].

LVEF:

From: Beta-blockers for heart failure with reduced, mid-range, and preserved ejection fraction: an individual patient-level analysis of double-blind randomized trialsEur Heart J. Published online October 10, 2017. doi:10.1093/eurheartj/ehx564Eur Heart J | Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: [email protected].


From: Meta-analysis: β-Blocker Dose, Heart Rate Reduction, and Death in Patients With Heart Failure

Ann Intern Med. 2009;150(11):784-794. doi:10.7326/0003-4819-150-11-200906020-00006

Meta-regression line for magnitude of heart rate reduction and risk ratio of all-cause mortality.The mortality logarithm of relative risk is plotted against the reduction in heart rate. Circles are the observed estimates; size is based on the inverse of the SE of each trial. The 3 lines are the fitted and the upper and lower bounds of the 95% CIs.

Figure Legend:



From: Aldosterone blockade and left ventricular dysfunction: a systematic review of randomized clinical trialsEur Heart J. 2008;30(4):469-477. doi:10.1093/eurheartj/ehn543Eur Heart J | Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2008. For permissions please email: [email protected]

Aldosterone blockers (14 RCTs, 10 807 pts)

Death RR: 0.80 (0.74-0.87)

Hosp RR: 0.77 (0.68-0.87)

Case- Mr. Willie Maykit – 6 months later• 63 year old male• no reversible ischemia• Stable, euvolemic, NYHA Class II • HR 64, reg BP 116/70• Echo: LVEF 25-30% ECG: NSR, LBBB

• On ramipril 5 mg bid, bisoprolol 5 mg daily, spiro 25 mg daily, lasix 40 mg daily

Question 4

• What next?

a) Continue to follow – if so, how frequently?b) Return to GPc) Refer to EP cardiology

Canadian Journal of Cardiology DOI: (10.1016/j.cjca.2017.08.022) Copyright © 2017 Terms and Conditions

http://www.elsevier.com/termsandconditions

Device referral

Case- Mr. Willie Maykit – one year later• 64 year old male• multiple CV risk factors; CAD but no reversible ischemia• NYHA Class II• euvolemic HR 64, reg BP 126/70• Echo: LVEF 35% after CRT-ICD and one year of Rx

• On ramipril 5 mg bid, bisoprolol 5 mg daily, spiro 25 mg daily, lasix 40 mg daily, with CRT-ICD in situ

Question 5

• He’s stable, but what now?

a) Continue to followb) Return to GPc) Switch ramipril to ARNId) Ivabradine

A common perspective– My patient is “stable” on current therapy– Why should I change anything?

• McMurray et al. N Eng J Med 2014;371:993-1004; Desai As et al Eur Heart J. 2015;36:1990-7.

763 of 2309 of first primary endpoints (intensification of medical therapy, ED visit, HF hospitalization or CV deaths) were CV deaths

33%467 of these 763 deaths were sudden

61%

PARADIGM-HF: Eligibility criteriaInclusion: • NYHA II-IV HF• LVEF ≤40 % [≤35% amend]• Elevated NPs

– BNP ≥150 pg/mL– NT-proBNP ≥600 pg/mL

• Guideline-recommended use of beta-blockers and MRA

Inclusion (cont)• Any ACEi or ARB, but able to

tolerate stable dose equivalent to at least enalapril 10 mg daily for at least 4 weeks

• Major Exclusions: • SBP < 95 mmHg• eGFR <30 ml/min/1.73 m2• K > 5.4 mEq/L

McMurray NEJM 2014

0

16

32

40

24

8

Enalapril(n=4212)

360 720 10800 180 540 900 1260Days After Randomization

41874212

39223883

36633579

30182922

22572123

15441488

896853

249236

LCZ696Enalapril

Patients at Risk

1117

Kapl

an-M

eier

Est

imat

e of

Cum

ulat

ive

Rate

s (%

)

914

LCZ696(n=4187)

HR = 0.80 (0.73-0.87)P = 0.0000002

PARADIGM-HF: Primary endpoint

McMurray NEJM 2014

Primary = CV death or HF Hospitalization

ARR 4.7% NNT 21

Kaplan–Meier Curves for Key Study Outcomes, According to Study Group.

McMurray JJV et al. N Engl J Med 2014;371:993-1004

Prespecified Subgroup Analyses.


PARADIGM: Recurrent HF hospitalizations

Packer, Circulation 2014

ARR 2.8% per year NNT 36

Adverse Events during Randomized Treatment.


Health Canada and CCS 2017 guidelines

Sac/Val: “heart failure with reduced ejection fraction (HFrEF), NYHA class II‐III despite GDMT, in combination with other heart failure therapies in place of an ACEI or ARB”

Date of download: 10/31/2017 Copyright © 2016 American Medical Association. All rights reserved.

From: Potential Mortality Reduction With Optimal Implementation of Angiotensin Receptor Neprilysin Inhibitor Therapy in Heart Failure

JAMA Cardiol. 2016;1(6):714-717. doi:10.1001/jamacardio.2016.1724

Date of download: 10/31/2017 Copyright © 2016 American Medical Association. All rights reserved.

From: Potential Mortality Reduction With Optimal Implementation of Angiotensin Receptor Neprilysin Inhibitor Therapy in Heart Failure

JAMA Cardiol. 2016;1(6):714-717. doi:10.1001/jamacardio.2016.1724

Angiotensin Receptor Neprilysin Inhibition (ARNI) Eligibility Flow DiagramDerivation of the population of patients with heart failure and reduced ejection fraction eligible for ARNI. ACEI indicates angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; HFpEF, heart failure with preserved ejection fraction; and SBP, systolic blood pressure.

Figure Legend:

That would be 84% of HF-rEF pts

and 40% of all HF pts

Health Canada and CCS 2017 guidelinesSac/Val: “heart failure with reduced ejection fraction (HFrEF), NYHA class II‐III despite GDMT, in combination with other heart failure therapies in place of an ACEI or ARB”

FM opinion: PLUS deterioration (LVEF, BNP, hospitalizations/ED visits)

Edmonton HFC approach

Edmonton HFC approach

• ACEi washout (at least 36 hours):– Last dose of ACEi Friday– Write STOP ACE on Rx– 1st dose of Sacubitril/Valsartan Monday

• Same f/u labs/phone as ACE/ARB• Consider reducing furosemide dose

Patients who shouldn’t be switched

• Low risk: NYHA 1, stable without exacerbations, low BNP • De novo HF• Acute instability (in hospital)• EF recovered >40% • HF-PEF• Patients who have s/e on every medication• Patients who are difficult to contact/risky

Question 5

• He’s stable, but what now?

a) Continue to followb) Return to GPc) Switch ramipril to ARNId) Ivabradine

Health Canada

Ivabradine: “heart failure with reduced left ventricular ejection fraction (≤ 35%) in …NYHA Class II or III who are in sinus rhythm with a resting heart rate ≥ 77 bpm, to reduce the incidence of cardiovascular mortality and hospitalizations for worsening heart failure.“

CCS Recommendation We recommend that ivabradine be considered in patients with HFrEF, who remain symptomatic despite treatment with appropriate doses of GDMT, with a resting heart rate > 70 beats per minute (bpm), in sinus rhythm, and a previous HF hospitalization within 12 months, for the prevention of cardiovascular death and HF hospitalization(Strong Recommendation; Moderate-Quality Evidence).

• =about 10% of pts in the UAH HFC

IvabradineActivation of three major neurohormonal systems

Decline in systolicfunction

↓ HR

Improves cardiacfunction

Ivabradine acts directly on cardiac function via lowering HR

Natriuretic peptide system

Renin angiotensin aldosterone system

Sympathetic nervous system

Ivabradine: pure heart rate reduction

If inhibition reduces the diastolic depolarization slope, thereby lowering heart rate

RR

Pureheart ratereduction

0 mV

-40 mV

-70 mV

closedopen

closed

Ivabradine

Thollon C, et al. Brit J Pharmacol. 1994;112:37‐42.

Swedberg K, et al. Eur J Heart Fail. 2010;12:75-81.

SHIFT: inclusion• Class II to IV NYHA heart failure• Ischemic/non-ischemic etiology• LV systolic dysfunction (EF <35%)• Heart rate >70 bpm• Sinus rhythm• Documented hospital admission for worsening

heart failure <12 months

0

10

20

30

40

50

60

70

80

90

100

BB at randomization

At least 50% target daily dose

Target daily dose

89

56

26

Ivabradine

Placebo89

56

26

Patients (%)

SHIFT-HF: Background Beta-blocker Rx

Swedberg K, et al. Lancet. 2010.

SHIFT: Primary endpoint

Swedberg, Lancet 2010

Primary endpoint: CVD/HFHHR 0.82 (0.75‐0.90)NNT 26

EF<35%HR>70 bpmSinus

89% on BB56% on >50% BB target dose

>77 bpm: CVD reduction

Standard Rx

Standard Rx + Ivabradine

Absolute effect (NNT) for prevention of recurrent hospitalizations in HF patients

Rogers et al. Curr Med Res Opin 2015; 31 (10): 1903–9.

Estimated treatment effect* 95% CI P value NNT

Primary endpoint 0.82 0.75-0.90 < 0.0001 26

Heart failure hospitalizations

First hospitalizationRecurrent

hospitalizations

0.750.71

0.66-0.840.62-0.82

< 0.0001< 0.0001

2714

All-cause hospitalizations

First hospitalizationRecurrent

hospitalizations

0.890.83

0.83-0.960.72-0.95

0.0036< 0.0001

3710

Table 2. Estimated treatment effects and associated numbers to treat for SHIFT outcomes

CV death or hospitalization for HF Age Test for interaction

< 65 years≥ 65 years

SexMaleFemale

Beta-blockersNoYes

Etiology of heart failureNon-ischemic Ischemic

NYHA classNYHA class II NYHA class III or IV

DiabetesNoYes

HypertensionNoYes

Baseline heart rate< 77 bpm≥ 77 bpm

1.51.00.5Hazard ratio

p=0.029

Reduction of the primary endpoints with ivabradine was consistent in all prespecified subgroups except for HR

Favours ivabradine Favours placeboSwedberg et al. Lancet 2010; 376: 875-85.

Significant reduction

≥ 70 bpm ≥ 77 bpm

Primary endpoints

CV death or hospital admission for worsening HF 18% (p<0.0001) 25% (p<0.0001)

Mortality endpoints

All-cause mortality - 19% (p=0.0074)

Cardiovascular mortality - 19% (p=0.0137)

Death from HF 26% (p=0.014) 39% (p=0.0017)

Other endpoints

All-cause hospital admission 11% (p=0.003) 18% (p=0.0002)

The higher the HR at baseline, the greater the benefits

Ivabradine significantly reduced mortality

Swedberg et al. Lancet 2010; 376: 875-85;Krum & Sindone. Heart Lung Circ 2013; 22: s87-8.

Patients with baseline HR ≥ 70 and ≥ 77 bpm

p=< 0.001

Standard therapy & ivabradine

Standard therapyB

ette

rQoL

Ivabradine in addition to recommended therapy led to clinical benefits while preserving QoL

• Improvement was associated with the magnitude of HR reduction

0

11

10

7

4

2

9

8

6

3

1

5

-35 -30 5 10-25 -20 -15 -10 -5 0 15

Ekman et al. Eur Heart J 2011; 32(19): 2395-404.

9.6

8.6

6.4 6.2

5.15.6

5.0

4.13.7

2.1

Chan

ge in

KCC

Q O

SS a

t 12

mon

ths

Change in heart rate at 12 months(bpm)

-18%

-16%

-18%-…

-14%-13%

-15%

-17%-16% -16%

-20%

-15%

-10%

-5%

0%

Renaldysfunction

(eGFR < 60mL/

min/1.73m2)Overall

populationLow BP

(< 115 mmHg) Diabetes COPDIschemicetiology Angina NYHA III/IV

Severe HF (LVEF

< 20% and NYHA IV)

Elderly(≥ 75 years

old)

Ivabradine reduces CV death and HF hospitalizations regardless of the associated conditions

Borer et al. Cardiology 2017; 136: 138-44; Voors et al. Eur J Heart Fail 2014;16:426-34; Borer et al. Am J Cardiol 2014;113(3):497-503;Komajda et al. Eur J Heart Fail 2014;16(7):810-6’; Tavazzi et al. Int J Cardiol 2013;170(2):182-8; Tavazzi et al. Eur J Heart Fail 2013;15(11):1296-1303; Reil et al. Eur J Heart Fail 2013;15(9):1044-52.

Ivabradine is safe to use and well tolerated by HF patients

Safety• Less serious adverse events in the ivabradine group vs. the placebo group

– Explained by fewer cardiac events

• 1% of the patients withdrew from the trial because of bradycardia

• 3% of the patients had transient phosphenes, but this did not lead to more withdrawal

Tolerability• Ivabradine dosage: 7.5 mg twice daily

• Mean dosage: – 6.4 mg twice daily (28 days)– 6.5 mg twice daily (1 year)

• 70% of patients are taking the 7.5 mg twice daily dosage after 1 year

Phosphenes: experience of seeing light without light.Swedberg et al. Lancet 2010; 376: 875-85.

≈ 60-65 bpm

80-86 bpm*75-79 bpm*

72-74 bpm*70-71 bpm*

-16 bpm -14 bpm -13 bpm

* Baseline HR at rest

-11 bpm

> 87 bpm*

-23 bpm

No excessive bradycardia: the higher the HR at baseline, the greater the reduction

• On top of guidelines-recommended therapy, including BB

Böhm et al. Lancet 2010; 376: 886-94.

Disease Study Treatment Conclusion

HF with LVSD SHIFT vs. placebo on top

of standard therapy

In HF patients with HR ≥ 70 bpm, ivabradine reduces the composite of CV death andHF hospitalizations

Stable CAD and angina

Initiative vs. atenolol(non-inferiority trial)

Ivabradine is at least as effective and safe asatenolol in reducing symptoms of patients with stable CAD and angina

Ruzyllo vs. amlodipine(non-inferiority trial)

Ivabradine is at least as effective and safe asamlodipine in reducing symptoms of patients with stable CAD and angina

Associate vs. placebo, on top of BB

Ivabradine further decreases symptoms inpatients with stable CAD and angina, on top of BB treatment

Stable CAD with LVSD BEAUTIFUL vs.placebo, on top

of standard treatment

Lowering heart rate with ivabradine in CAD patients with HR ≥ 60 bpm does not reduce the risk of CV death or nonfatal MI but, in patients with HR ≥ 70 bpm, ivabradine reduces the composite of fatal and non-fatal MI and the need for revascularization

Stable CAD without LVSD SIGNIFY vs. placebo, on top

of standard treatment

Lowering heart rate with ivabradine in CAD patients without clinical HF does not reduce the risk of CV death or nonfatal MI

Main trials in the clinical development of ivabradine

• In Canada, ivabradine isonly indicatedfor HF patients

Tools for practice

MED-HF• Free Medical app for the iphone / android

– Helps walk through the big 4 medications initiation, titration and problem management

– https://itunes.apple.com/ca/app/med-hf

**Ezekowitz/Koshman co-own copyright and patent

https://itunes.apple.com/ca/app/med-hf

Advanced HF: Management Despite optimal treatment, NYHA III or IV HF symptoms AND accompanied by >1 of:• LVEF < 25% • peak exercise oxygen consumption < 14 mL/kg/min (or less than 50% predicted).• Evidence of progressive end organ dysfunction• Recurrent HF hospitalizations (≥ 2 in 12 months) not due to a clearly reversible cause.• Need to progressively reduce or eliminate evidence-based HF therapies • Diuretic refractoriness associated with worsening renal function.• Requirement for inotropic support for symptomatic relief or to maintain end-organ function.• Worsening right heart failure and secondary pulmonary hypertension.• 6 minute walk distance less than 300 m.• Increased 1-year mortality (e.g., > 20%–25%) predicted by heart failure risk scores• Persistent hyponatremia (serum sodium < 134 mEq/L).• Cardiac cachexia.• Inability to perform activities of daily living.

What’s coming next: Ongoing studies• VICTORIA (vericiguat)• HEART‐FID (IV iron)• SODIUM (dietary Na+)• EMPA-Ref (e’gliflozin)• DAPA-Ref (d’gliflozin)• COMMANDER (rivaroxaban)• GALACTIC (omecamtiv)

• EMPA-Pef (e’gliflozin)• SPIRRIT (spiro)• PARAGON (sac/val)• SODIUM (dietary Na+)

Apelin analogues, finerenone, resveratrol, chymase inh, gut microbiome, etc etc

Summary• Diagnosis important: get it right• Work-up the etiology• Initiate and titrate therapies as needed• Stop drugs with limited or no benefit • Monitor appropriate labs and symptoms• Refer onwards when help is needed

heart failure therapy and the general internist: what’s new? · learning objectives. 1. to review...

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