Systolic CHF Therapy
Rogers Kyle, MD
10/2/12
Learning Objectives
• Review the staging and evaluation of patients
with systolic heart failure
• Review the current guidelines for therapy of
systolic heart failure
• Identify the classes and dosing of medications
used in the therapy of systolic heart failure
• 5 million people in US
– 500,000 new cases annually
– 1 million hospitalizations/yr as primary dx
– 50,000+ CHF as primary dx deaths annually
– 10 yr mortality almost 90%
• Most frequent cause of hospitalization in the
elderly
• $38 billion, (over 5% of total healthcare cost)
Staging
• Stage A - high risk, no structural disease
– HTN, DM, CAD, Obesity, met syn, cardiotoxins
• Treat underlying med probs…ACE/ARB
• Stage B - structural disease but no s/s CHF
– LVH, ↓EF, MI, asymptomatic valvular disease
• ACE/ARB, β-blocker
• Stage C - structural disease with current or prior sx’s (NYHA
I-IV)
– Sx’c ↓EF or asymptomatic on Rx
• Diuretics, ACE, β-blocker, also aldo antag, ARB, dig, hydral/nitrates
• ICD, CRT
• Stage D – refractory HF
– Recurrent hosp despite Rx, need for transplant/VAD
Physical Examination
• Physical diagnostic accuracy (Escape Trial)
CHF - Staging
CHF - Staging
CHF - Staging
• Stage A – control risk
– HTN
– DM
– Met Syn
– Lifestyle mod (tob, etoh, drug abuse, etc.)
CHF - Staging
• Stage B
– All of A
– Recent MI – ACE, β-blocker
– Reduced EF (no CAD) – ACE, β-blocker. ARB if ACE
intol
– Valvular disease
– LVH – ACE/ARB
– ICM - > 40 days p-MI, EF ≤ 30% → ICD
– NO dig, CCB with (-) inotropy
CHF - Staging
• Stages C, D (refractory sx’s)
– A, B
– Diuretics, Na restrict if vol overloaded
– ACE/ARB if ACE intol. ACE+ARB with ↓EF if still with sx’s on max
rx (IIB)
– β – Blocker – bisoprolol, carvedilol, metoprolol sustained release
(succinate)
– Aldosterone antagonist – preserved Cr (< 2.5), nl K+
– Hydralazine/nitrate – AA with continued CHF sx’s on optimal
ACE, β-blocker, diuretics (level I) – all non-AA (level II)
– Digoxin – reduced EF
– ICD’s, CRT
– NO ACE/ARB/Aldo antag combo, CCB
CHF - Staging
• Stages C, D (refractory sx’s)
– A, B
– Diuretics, Na restrict if vol overloaded
– ACE/ARB if ACE intol. ACE+ARB with ↓EF if still with sx’s on max
rx (IIB)
– β – Blocker – bisoprolol, carvedilol, metoprolol sustained release
(succinate)
– Aldosterone antagonist – preserved Cr (< 2.5), nl K+…DM?
– Hydralazine/nitrate – AA with continued CHF sx’s on optimal
ACE, β-blocker, diuretics (level I) – all non-AA (level II)
– Digoxin – reduced EF
– ICD’s, CRT
– NO ACE/ARB/Aldo antag combo, CCB
‘Order of Drugs’
• Loop diuretic
• ACE/ARB
– ACE vs. ARB; ACE + ARB?
• β – Blocker
– CIBIS-III – bisoprolol vs. enalapril first ( no
difference)
• After that…
Diuretics
• Studies date back to the 60’s (!)
• Lasix most studied
– Bumetanide, torsemide both better absorbed,
torsemide lasts longer
• Torsemide may have less readmissions (vs. lasix) for
CHF (AJM 2001; 111(7):513) - ? Cost effective; now
generic. Also, one observational study suggesting lower
mortality (Eur J Heart Fail 2002; 4(4): 507)
Diuretics
• Dosing strategy (NEJM 2011; 364(9): 797)
– Comparison of dose and route of administration
of lasix in acute decompensated CHF
• Low dose (equivalent to outpatient dose) or high dose
(2.5 x outpatient dose)
• Given as bolus Q12 or continuous infusion
Diuretics
• Other options?
– Add thiazide
– ? Ultrafiltration
– Inotropes (milrinone - inc mortality)
– Other – nesiritide (no mort/morbid benefit), VR2A
(hypoNa+)
ACE/ARB
• Multiple trials have established benefit (sx’s
and mortality) of ACE in all stages of CHF.
– LVEF < 40%
– Elderly, women, maybe less beneficial in AA but
recommended
• Less evidence for ARB’s but considered
interchangeable (Cochrane Rev 2012)
ACE/ARB
• Choice of agent
– Class effect
– Enalapril most studied
• Dosing
– Usually started first
– Less azotemia, hypotension if started at low doses
• Enalapril 2.5 BID; captopril 6.25 TID; lisinopril 5 QD
• BUT…doses were high in the trials
– Enalapril 10-20 BID; lisinopril 20-40 QD
– Up-titrate doses every 2 weeks
• ARB
– Recommended for same indications as ACE in pts
intolerant of ACE
• Intolerance does NOT include azotemia or
hyperkalemia
• BUT should be considered in angioedema in ACE
– Add to ARB?
• CHARM-Added (+) vs. Val-HeFT (-) vs. VALIANT (p-MI)
• 2009 Update
– Consider adding to ACE in persistently sx’c pts with EF
< 40% on conventional therapy
– However…
• EMPAHSIS – HF (eplerenone)
• Routine use of ACE + ARB + aldo inhib is not recommeded
• Dosing
– Candesartan (most studied) – start at 4-8 mg QD,
titrate to 32 mg QD
– Valsartan 20-40 mg BID titrate to 160 mg BID
– Losartan 25-50 mg QD titrate to 50-100 mg QD
Beta Blockers
• Demonstrated to reduce sx’s and
hospitalizations and improve survival
– Meta analysis 2001 AIM; > 20 trials, > 10,000 pts
– Carvedilol (COPERNICUS); metoprolol ex release
(MERIT-HF); bisoprolol (CIBIS)
• 2005/09
– Current or prior CHF sx’s with reduced EF
– ‘09 added – minimal or no evidence fluid
retention, already on ACE
Beta Blockers
• Relative contraindications
– HR < 60
– Hypotension
– More than minimal fluid retention
– Peripheral hypoperfusion
– PR > 0.24, 2nd/3rd degree HB
– Asthma
– Resting LE ischemia from PVD
Beta Blockers
• Metoprolol - primarily β-1, some β-2 at doses
> 100 mg
– Start 12.5-25 mg QD, titrate to 200 mg QD
• Carvedilol - non-selective β + alpha blockade
– Start 3.125 mg BID, titrate to 25-50 mg BID
• Bisoprolol - primarily β-1, some β-2 at doses >
20 mg
– Start 1.25 mg QD, titrate to 5-10 mg QD
Aldosterone Antagonists
• Aldosterone levels tend to rise over time in pts on
ACE/ARB
• ?independent effect on structure/function
• Emphasis- HF (RALES) (NEJM 2011; 364(1): 11)
– Eplerenone added to usual rx
– EF < 30-35%, NYHA II or more
– 20% mortality benefit
• Risk is K+
– Careful with NSAIDS, ACE/ARBS, DM, renal dys (Cr > 2.5),
volume depletion
– Do not use in combination with ACE + ARB
• Start at 12.5 mg spironolactone, measure K+
Hydralazine + Nitrates
• Pre and afterload reduction
• Early trials –
– V-HeFT (hydralazine + nitrates similar to enalapril)
– A-HeFT (+ enalapril beneficial in AA)
• NYHA III, IV; EF < 40%, AA
• 2005/09
– AA on diuretic/ACE/BB for NYHA II, III
– Pts with sx’s depsite diuretic/ACE/BB
– Intol of ACE/ARB
• Dosing
– Start 25/20 mg TID; target 75/40 TID
Digoxin
• DIG trial
– Reduced hospitalization, not mortality
• 2005/09
– HYHA II, III, IV
– EF < 40%
– Sx’s despite diuretic/ACE/BB/aldo antag
Summary
References
• Hunt SA et al. (2009) 2009 Focused Update Incorporated Into the
ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart
Failure in Adults. Circulation. 119: e391-e479.
• Heran BS, Musini VM, Bassett K, Taylor RS, Wright JM. Angiotensin
receptor blockers for heart failure. Cochrane Database of Systematic
Reviews (2012), Issue 4. Art. No.: CD003040. DOI:
10.1002/14651858.CD003040.pub2.
• McAlister, FA, et al. 2009. Meta-analysis: -Blocker Dose, Heart Rate
Reduction, and Death in Patients With Heart Failure. Ann Intern Med
150:784-794.
• Willenheimer, R. et al. (2005) Effect on Survival and Hospitalization of
Initiating Treatment for Chronic Heart Failure With Bisoprolol Followed by
Enalapril, as Compared With the Opposite Sequence :Results of the
Randomized Cardiac Insufficiency Bisoprolol Study (CIBIS) III. Circulation
112: 2426-2435.
• Zannad, F. et al. (2011) Eplerenone in Patients with Systolic Heart Failure
and Mild Symptoms N Engl J Med 364 (1): 11-21.