Heart Failure Drugs Flashcards
How can HF be classified?
HF Stages: Acute / Decompensated vs Chronic vs Advanced
Left Ventricular Ejection Fraction
NYHA Classification: severity of symptoms & functional status
Define chronic HF
persistent and progressive (CHF = chronic heart failure
Define acute/decompensated HF?
Acute/decompensated: gradual or rapid change in signs and symptoms, resulting in the need for urgent therapy
Define advanced HF
frequent decompensations, mechanical devices, transplantations, palliative
What is LVEF?
Left Ventricular Ejection Fraction (LVEF) – amount of blood that is in the heart that is being pumped out
Heart Failure definitions based on LVEF
o If LVEF ≥50% = HF-pEF
–> HF with preserved EF
–> Diastolic dysfunction where there are problems with heart stiffness and ventricular relaxation and filling.
–> More so in elderly, females, DM, AF, HTN
–> Slow onset
If LVEF 41-49% = HF-mEF
–> HF with mid-range or mildly reduced EF
LVEF ≤40% = HF-rEF
HF with reduced EF
Systolic dysfunction where there are problems with the heart pump/ventricular contractility
Usually after an acute CAD event
HF-impEF
baseline LVEF >40%, &
≥10% increase in EF, &
a second measurement of LVEF >40%
Once had HF-REF
New York Heart Association Classifications
Class I: no limitation of physical activity, ordinary physical activity does not cause symptoms
Class II: slight limitation, ordinary physical activity causes symptoms
Class III: marked limitation, less than ordinary activity causes symptoms
Class IV: severe limitation, symptoms present even at rest
Diagnosis of HF
Describe the pharmacotx for HF
HF-ref LVEF < or = to 40%
ARNi or ACEi /ARB than substitiute ARNI
Beta Blocker
MRA
SGLT-2 Inhibitor
Goal of pharmacotx
o Benefits: Decreased risk of mortality and hospitalizations
o Improve HF symptoms
o Strive to initiate the standard therapies within 3-6 months after diagnosis, and then titrate to target or max tolerated dose
Describe the RAAS systems
ACEi Heart Failure Types and Dose
Captopril 10mg BID,
enalapril 20-35mg OD
lisinopril 4-8 mg OD,
ramipril 5mg BID
trandolapril 4mg OD
Can everyone listen, rats talk
Titration Acei
double dose every 1-3 weeks
C.I. ACEi
- Bilateral renal artery stenosis or unilateral if only 1 kidney
- History of angioedema
- Pregnancy
Cautions of ACEi
- High potassium, SCr >220umol/L, or eGFR <30mL/min
- SBP less than 90mmHg or symptomatic hypotension
- Moderate to severe stenosis
Drug Interactions Acei
- increased risk of hyperkalemia with K+ supplements, K+ sparing diuretics, MRA (spironolactone), renin inhibitors, TMP, NSAIDs, low salt supplements high in K+
- Lithium
ADverse effects ACEi
- Hypotension
- Angioedema – facial, lip, tongue, and upper airway swelling, develops over hours. Symptoms resolve within 48-72 hours of stopping.
- Dry cough (dry and absent prior to initiation)
- Hyperkalemia ( range range 3.5 to 5mmol/L
mild hyperkalemia (i.e. K+ up to 5.5mmol/L) is often acceptable - Worsening of renal function (up to 30% decrease of eGFR is acceptable)
ARB’s used in HF and dose
Candesartan 32mg OD, valsartan 160mg BID
Indication for ARB in HF
ACEi intolerance (cough and angioedema) but no difference between the two, just more evidence with an ACEi.
Do NOT combine with ACE due to increased risk of hypotension, hyperkalemia, and renal dysfunction.
C.I., D.I., A.e, of ARB
Contraindications, cautions, drug interactions, adverse effects, monitoring, and titration are the same as ACEi
What is an ARNI
ARNI: sacubitril/valsartan (Entresto)
Angiotensin receptor neprilysin inhibitor
MOA of ARNI
Paradigm Trial Findings
Entresto vs enalapril
- Higher reduction in hospitalization and CV death compared to enalapril
- Adverse effects: Entresto had more symptomatic hypotension (and SBP <90mmHg), and angioedema (not stat signficant)
- But less SCr elevation, cough, and discontinuations
Indication of ARNI
Those who remain symptomatic despite treatment to decrease CV death, HF hospitalizations, and symptoms (strong recommendation).
Those who are admitted to hospital due to acute decompensated HF should be switched before discharge (strong recommendation).
Those who are admitted to the hospital with a new diagnosis should be treated with ARNI as first line therapy. (weak recommendation)
EDS Criteria ARNi
HF with NYHA class II or III with LEVH <40, symptoms despite more than four weeks of triple therapy, elevated BNP, under care of a HF specialist.
Unique of ARNI Initiation
Needs a 36 hour washout period if switching from an ACEi (not required for ACEi)
C.I. of ARNI
History of ACEi/ARB angioedema
Concurrent Acei
CAution of ARNi
recent symptomatic hypotension
Drug Interactions, A/e, and monitoring of ARNi
Drug interaction/adverse effects/monitoring – same as ACEi/ARB
Dosing of ARNi
Dosing: target = 200 mg BID
* >50% ACE/ARB target dose: start 100mg BID, then double in 3-6wks
* <50% ACE/ARB target dose, high risk of hypotension, or ARB naïve: start 50mg BID, then double in 6 weeks
Beta-blockers HF and Initiation
Bisoprolol 10mg OD, carvedilol 25mg/50mg (>85kg) BID, metoprolol XL 200mg OD
Double dose every 2-4wks when titrating
Avoidabrupt withdrawal. tape rover 1-2 weeks
MOA BB
Blocks norepinephrine at the beta-adrenergic receptors.
Improves myocardial function by prolonging ventricular filling time, resulting in a more productive heartbeat
C.I. BB
2/3rd degree AV block or HR <50bpm in the absence of a pacemaker
PR interval greater than 0.24seconds
Severe/uncontrolled asthma
Severe PAD
Caution BB
NYHA class IV or HF exacerbation within 4 weeks. SBP < 90 mmHg or HR <50bpm
A/e of BB
Hypotension: 90-100mmHg without symptoms is acceptable
Bradycardia: 50-60bpm without symptoms acceptable
Worsening HF symptoms/fatigue: may get worse before better
initial negative inotropic effect, may cause fluid retention.
Start low and titrate up slowly
Efficacy of BB
Metoprolol succinate (LX) showed benefit vs placebo. Not available in Canada though
Carvedilol was superior to metoprolol tartrate (SR)
Safety BB
Bisoprolol and metoprolol are cardio-selective.
Carvedilol is not cardio-selective and effects B1, B2, a1 receptors which lowers blood pressure more and effects the lungs
Drug Interactions BB
risk of bradycardia / AV block with verapamil, diltiazem, amiodarone, digoxin
risk of hypertensive crisis with clonidine
risk of reduced -blocker efficacy with phenobarbital
MRA HF
o Spironolactone 25-50mg OD, eplerenone 50 mg OD
Double dose ever 4-8 weeks when titrating. We are happy with lower dose spironolactone
MOA MRA
Inhibits aldosterone which prevents reabsorption of sodium and water.
Is a weak natriuretic agent and minimally impacts blood pressure unless it is elevated (pathway-2 trial for resistant hypertension)
Use of MRA in HF vs HTN
Used in HF for neurohormonal benefit whereas loop diuretics are used for congestion/fluid overload
Minimalimpact on blood pressure
C.I. of MRA
hyperkalemia (K+ greater than 6), severe hepatic impairment for eplerenone
Caution MRA
high potassium (>5+)
CrCl <30mL/min (spironolactone – beers list - hyperkalemia)
A/e of MRA
Hyperkalemia
Spironolactone: gynecomastia, erectile dysfunction, menstrual irregularities
D.I> of MRA
o Drug interactions: same as ACEi
Spironolactone: increases digoxin
Eplerenone: Caution with strong CYP 3A4 inhibitors and 25 mg daily with modertae
Monitoring of MRA
Potassium and Scr baseline and 1 wk after starting/titrating. Then every 3 months, then every 6 months
EDS MRA
Eplerenone is much way more expensive. EDS criteria if previously tried spironolactone
SGLT2I used in HF
Dapagliflozin (Forxgia)
Empagliflozin (Jardiance
MOA of SGLT-2i
Unknown
increases natriuresis and diuresis in the kidney, reduces preload and afterload, decreases hypertrophy, fibrosis, and O2 demand
Monitor A1C in HF
NO
A1C SGLT2-I
the A1c-lowering effect of SGLT2i is diminished in the presence of CKD:
minor at eGFR 30-45mL/min
absent at an eGFR <30mL/min
DAPA-HF trial
decreases CV death or worsening HF (hospitalization)
Emperoror-reduceed trial
decreases HF hospitalization, but CV death was non-statistically significant
See a renal decline in 15-20% Will see rebound and renal protection
SGLT-2i trials findings
o Trials showed volume depletion as an adverse effect, but this can be a good thing in HF patients and we can back off on the furosemide.
o Trials showed that there is no effect on A1C in those without diabetes
SGLT-2i CI
severe renal or hepatic dysfunction
dapagliflozin CrCl <25mL/min
empagliflozin CrCl <20mL/min
Caution SGLT-2i
hypovolemia, acute illness (hold if dehydrated, i.e. SADMANS)
What is SADMANS
sulfonylurea, ACE-inhibitor, diuretic, metformin, angiotensin receptor blocker, and non-steroidal anti-inflammatory,SGLT-2
D.I. SGLT-2i
diuretics (monitor for hypovolemia)
A/E SGLT-2i
genital mycotic infections, euglycemic diabetic ketoacidosis in T2DM
Monitoring SGLT-2i
volume status
if euvolemic, consider reducing loop diuretic by 30-50% (40%)
SCr at 14 - 30 days, 60 days, the q4 months
early 15-20% reduction in eGFR is acceptable
A1c in T2DM
Secondary Meds
SHIFT TRIAL
IVAbradine
sinus rhythm with a resting HR ≥70bpm
No mortality benefit, just hospitilization reduction
Only benenfit if baseline hr of 77 bpm
Dose Ivabradine
start with 2.5mg BID in the elderly
only available in 5mg and 7.5mg tablet strengths, but the 5mg tablets are scored
double dose every 2-4 weeks if HR >60bpm
Target dos eof 7.5 mg BID
C.I. Ivabradine
3rd degree AV block, sick sinus syndrome, pacemaker dependence, prolonged QT interval, unstable CV conditions, severe renal or hepatic dysfunction
strong CYP 3A4 inhibitors
moderate CYP 3A4 inhibitors that reduce HR (e.g. verapamil, diltiazem)
D.I. Ivabradine
amiodarone (risk of QT prolongation, atrial fibrillation, excessive bradycardia)
digoxin (excessive bradycardia)
Verapamil, Diltazem –> Bradycardia
simvastatin (reduces simvastatin by 50%)
A/e Ivabradine
atrial fibrillation
transient flashes of light (phosphenes)
Monitoring Iva
HEART RATE
increase dose (up to 7.5mg BID) if HR > 60bpm
reduce dose if HR <50bpm or symptomatic bradycardia
Digoxin benefit
reduces the risk of HF hospitalizations, but not mortality
MOA digoxin
positive inotropic effect (i.e. strengthens myocardial contractions – improves CO)
offsets sympathetic nervous system activation
increases parasympathetic activity (“rest & digest”) and reduces HR (negative chronotropic effect), and therefore enhances diastolic filling
Digoxin C.I.
ventricular fibrillation
Caution Digoxin
acute MI, AV block, bradycardia, renal or thyroid dysfunction, hypokalemia
D.I. Digoxin
amiodarone (reduce digoxin by 50%), dronedarone, b-blockers, calcium channel blockers, flecainide, propafenone
clarithromycin, erythromycin
A/e Digoxin
toxicity (anorexia, nausea, vomiting, dizziness, visual changes)
Digoxin monitoring.What should be monitored?
HR
SCr (caution if CrCl <30mL/min)
K+ (risk of arrhythmia with hypokalemia)
Digoxin dose
0.0625mg to 0.25mg po once daily
no HF target dose & no loading dose required for HF
consider lower doses
(0.0625mg or 0.125mg daily) in the elderly, females or those with renal impairment
Iva and DIgoxin both
lower raised resting heart rates in HF patients
reduce the risk of HF hospitalizations, but not mortality
Iva compared to digoxin
has less real-world experience, cannot be used in AF patients, is more expensive
has less drug interactions, does not require dose adjustments in renal impairment or therapeutic drug monitoring
Vericguat Benefit
reduces the risk of HF hospitalizations, but not mortality
MOA of Vericguat
NO reduced in HF –> NO sCG formation –> CGMP
Increases sCG increasing cGMP
Benefits of verigcout
Decreased mycocardial thickening and stifeening
Decreased ventricular remodelling
Decreased fibrosis
Decreased vasoconstriction
Dcereased vascular stiffness
C.I. Vericguat
concomitant use of other sGC stimulators, pregnancy
Vericguat D.I.
PDE5 inhibitors (e.g. sildenafil), long-acting nitrates
contraindicated with other sGC stimulators (i.e. riociguat)
Can use nitro spray
Vericguat A/e
anemia, symptomatic hypotension, syncope
Vericguat dose and titration
initial: 2.5mg po daily x 2 weeks
titration: increase to 5mg po daily x 2 weeks, then to 10mg po daily based on BP & clinical HF symptoms:
SBP ≥100mmHg: increase dose or maintain if on 10mg po daily
SBP 90-99mmHg: maintain dose
SBP <90mmHg & asymptomatic: reduce dose
SBP <90mmHg & symptomatic: hold dose
Monitoring vericguat
Hgb, BP
Hydralazine NItrate MOA
Hydralazine is a direct acting arterial vasodilator, which reduces afterload on the left ventricle and enhances the hearts ability to pump (i.e. enhances stroke volume & cardiac output)
Nitrates are venous dilators which reduce preload (SV and CO) and pulmonary / systemic edema formation
Hydralazine Benefit
Decreased all caus emortality and HF hospitilizations
C.I. Hydralqazine
acute dissecting aortic aneurysm, mitral valve rheumatic heart disease
D.I. Hydralazine
can reduce digoxin levels, & increase metoprolol levels
A/e Hydralazine
Hypotension, edema, tachycardia
Monitoring hydralazine
BP and HR
D.I. Isorbide dinitrate
Contraindicated within 24 to 48 hours of PDE5 inhibitors (increase hypotensive effect & HR)
avoid within 24hours of sildenafil and vardenafil, & 48 hours of tadalafil
sGC stimulators
A/e Isorbide dinitrate
hypotension, headache, lightheaded
Monitoring Isorbide dinitrate
BP and HR
Hydralazine/Isorbide dinitrate Target Dose
75-100 mg TID or QID/ 40 mg TID
Important counselling HYdralazine/Isorbide Dinitrate
Ensure 12-hour nitrate free interval to prevent tolerance, regardless of formulation
HfPef Meds
o Identify and treat underlying causes
o Identify and treat comorbid conditions that might exacerbate HF (HTN, DM, AF)
o Control symptoms – loop diuretics to control congestion and peripheral edema
o Consider spironolactone to reduce HF hospitalizations
o Candesartan may reduce HF hospitalizations
o Entresto did not reduce CV deaths or HF hospitalizations in HFpEF group
o Recommend empagliflozin to reduce hospitalizations for HF, however not clinically significant for CV death/renal outcome
o No treatment available to reduce mortality
Hf-mef TX
o Diuretics as needed
o SGLT2i
o Particularly for those with LVEF on the lower end of the spectrum:
ACEi/ARB/ARNI - particularly for those with LVEF on the lower end of the spectrum
MRA
Beta-blockers for HFrEF
Diuretics Use
o Used to reduce pulmonary and peripheral edema by decreasing preload and decreasing Na and water retention
Diuretics Benefit/ Drawback
o Benefit: most rapid symptomatic relief, improves exercise tolerance and QOL, reduce HF hospitalizations
o Does not alter survival or alter disease progression, irks delaying initiation/titration of medications that do
Goal of Diuretics
o Goal – Euvolemia
Dry weight (no extra fluid accumulation) with no or mild HF symptoms
o Volume deplete - Hypovolemia
Weight is below dry weight. Risk of worsening renal function and decreasing cardiac output. Identify and address causes, reduce diuretics
o Volume overload – Hypervolemia
Increase in weight and new or worsening HF symptoms. Identify and address causes, increase diuretics.
Loop Diuretics MOA
inhibit Na-K-Cl2 transporter in the thick ascending limb of the loop of Henle
20-25% of filtered Na+ is reabsorbed here
increase renal blood flow contributes to natriuresis
via prostaglandins (blocked by NSAIDS, which ↓ diuretic efficacy)
Reduced Efficacy of Loop Diuretics
excessive dietary Na+ intake can also reduce efficacy
Thiazide vs Loop
Unlike thiazides, loop diuretics maintain efficacy in impaired renal function
Loop Diuretics and Dose
Furosemide (Lasix):
Initial dose: 20mg to 40mg po once daily to BID
Maximum dose: 200mg / day
Bumetanide (Bumex):
Initial dose: 0.5mg to 1mg po once daily
Maximum dose: 10mg daily
Ethacrynic acid (Edecrin):
Initial dose: 25mg to 50mg po once daily
Maximum dose: 200mg BID
No sulfa group (alternative for patients allergic to furosemide)
Loop Diuretics Dosing
Start with low doses (e.g. furosemide 20mg to 40mg po daily), & adjust based on symptom assessment and daily body weights
Change in body weight is a sensitive marker of fluid retention or loss
Wake void bladder weigh daily while nude or same amount of clothes on
When to call HCP
If weight ↑ 2lbs in one-two days or 5lbs over a week call healthcare provider for assessment
assess fluid intake, salt intake, inter-current illness, new medications, medication adherence
temporary ↑ in diuretic therapy
can prevent HF decompensation leading to hospital admission
Combining Diuretics. Benefits/Risk
Oral loop diuretics may not be adequately absorbed severe edema
Loop diuretics + thiazide or thiazide-like diuretic
less side effects than higher dose loop diuretics
Diuretic resistance
rebound Na+ retention: chronic loop diuretic use can lead to ↑ distal nephron Na+ reabsorption
Metolazone MOA, Dose, Onset and Duration
Thiazide-like diuretic
Dose: start with 2.5mg 2 to 3 times/week (outpatient), 5-10mg (inpatient)
Onset of action: 60 minutes
Duration of action: 12-24hr
Up to 48hrs in renal impairment or chronic dosing
Metolazone Admin with Furosemide
Onset of action: 60 minutes
Onset of action for oral furosemide: 30-60 minutes
Take 30 min sbefore Furosemide
Caution of Diuretics
Caution with over-diuresis
↓ cardiac output, renal perfusion, and symptoms of volume depletion
when initiating or titrating other HF medications can lead to hypotension and other adverse effects
Reduce Dose of Diuretic When:
weight loss beyond dry weight
volume depletion: hypotension or worsening renal function (e.g. ↑ in serum creatinine)
Decrease in 20 mg increments
Diuretic C.I.
anuria, hepatic coma or pre-coma
Cautoion Diuretics
hypokalemia, hyponatremia, eGFR <30mL/min (risk of worsening renal function if becomes hypovolemic), SBP <90mmHg
Diuretic D.I.
risk of digoxin toxicity if diuretic leads to hypokalemia
risk of lithium toxicity due to reduced lithium clearance
Diuretic A/e
hypotension, volume depletion, hyperuricemia, electrolyte disturbances (hyponatremia, hypokalemia, hypomagnesemia), ototoxicity with high doses (more so IV) (e.g. greater than 240mg furosemide / day)
Monitoring Diuretics
HF symptoms / daily morning weight
K+, Na+, SCr and urea at baseline & 5-7 days after diuretic adjustment
–> hold or reduce diuretic if SCr increase more than 30% from baseline
NTproBNP or BNP
BP Make sure were not too aggressive
Dietary Guides HF
We suggest that patients with heart failure should restrict their dietary salt intake to between 2 g/day and 3 g/day (Weak Recommendation, Low Quality Evidence).
We suggest that restriction of daily fluid intake to approximately 2 L/day should be considered for patients with fluid retention or congestion that is not easily controlled with diuretics
