Medical Therapies for Heart Failure

Question 1

What is the first line treatment for heart failure?

Answer 1

ACEi, Beta blocker, and if congested, Diuretic-all Class 1 evidence

Question 2

What is the evidence for ACE Inhibitor use?

Answer 2

SOLVD-Treatment Trial 1991

• RCT of ACEi versus placebo
• 1300 in each arm
• Showed all-cause mortality reduced by 16%

Question 3

What is the evidence for Beta Blocker use?

Answer 3

COPERNICUS Trial, 2002

• RCT of Carvedilol versus placebo
• 1000 in each arm
• Reduced all-cause mortality by 35%
• Seemed to have a greater effect than ACE inhibitors but is likely that many patients took both so is a combined effect

Question 4

What if patients are still symptomatic despite ACEi and Beta blocker use?

Answer 4

Can add an MR Antagonist

Question 5

What is the evidence for MR Anatagonists?

Answer 5

EMPHASIS-HF 2011

• RCT placebo controlled
• eplerenone versus placebo
• 1300 patients in each arm

Reduced CV mortality and hospitalisation by 37%
*likely a result of combined medical therapy

Question 6

What if patients are still symptomatic despite ACEi, Beta blockers, MR antagonists?

Answer 6

Can add an ARNI

Question 7

What is the evidence for ARNI?

Answer 7

PARADIGM-HF Trial, 2014:

• RCT of Enalapril versus Entresto
• 4000 in each arm
• reduced death by CV causes by 20%

Question 8

What should be used for symptom control?

Answer 8

ESC guidelines suggest that diuretics can be used through heart failure to control the symptoms of congestion-class 1 evidence level B or C

Question 9

What is the evidence for Diuretic Use?

Answer 9

Ahmed et al, 2006

• A retrospective trial investigating long term diuretic use and mortality
• Found that chronic diuretic use is associated with mortality
• However this is limited evidence as the study wasn’t designed to show this (took data from the digoxin trial)

Question 10

What are the pitfalls of this drug evidence?

Answer 10

All of the drug trials had inclusion criteria of LVEF <40%, so there is no evidence for >40% or preserved EF (diastolic heart failure

Question 11

Guidelines suggest that in resistant congestion, oral diuretics be switched to I.V. What is the evidence for this?

Answer 11

• I.V furosemide has 100% bioavailability
• Oral = 10-90% depending on HF severity because of gut oedema that inhibits absorption
• Diuretic effect using I.V is apparent in 30 mins
• No formal trials to show this but is accepted clinical practice in acute settings

Question 12

What is the evidence for bolus versus continuous infusion of diuretic?

Answer 12

DOSE Trial, 2011

• Double blinded RCT
• Inclusion = patients with acute decompensated HF
• Patients assigned to bolus or infusion, and within that high dose or low dose
• Showed that bolus patients were more likely to require a dose increase than infusion patients
• Apart from requiring a dose increase there was NO DIFFERENCE between bolus and infusion
• Showed that patients on high doses were more likely to be switched to oral and had fewer symptoms
• But the high dose had a non-significant trend towards worsening renal function
• So high doses should not be used in patients with renal dysfunction