Heart Failure Part 2 Flashcards
Neurohormonal Blockers
- RAS Inhibitors: Angiotensin Receptor Neprilysin Inhibitors (ARNI); Angiotensin Converting Enzyme Inhibitors (ACEI); Angiotensin Receptor Blockers (ARB)
- Beta-blockers (BB)
- SGLT2 Inhibitors
- Mineralocorticoid Receptor Antagonists (MRA)
- Hydralazine/ISDN
RAS inhibitors
decrease BP + perfusion; causes system to be activated; we want to block this system b/c it enhances hypertrophy of the cardiac cells, cell death, fibrosis, arrhythmias
ACE Inhibitors
- Cornerstone agent
- Numerous studies suggest that ACE Inhibitors: Reduce symptoms, improve NYHA, improve clinical status, decrease hospitalizations (~30% RRR), improve exercise tolerance and QOL; Reduce mortality (~25-50 % RRR) and slow progression of HF
- Benefit occurs regardless of etiology or severity of disease, must be used in all without contraindications
- Additional benefits in IHD, CKD, post-MI, DM
ACE Inhibitors: Rationale and Mechanism
inhibition of angiotensin II formation - block conversion of angiotensin 1 –> angiotensin II; enhancement of bradykinin
Mechanism of ACE Inhibitor Benefit in Heart Failure
improved endothelial function, decreased NE, inhibition of cardiac hypertrophy (reduction in remodeling in myocardium), improved cardiac hemodynamics, decreased endothelin-1, reduced vasoconstriction, reduced aldosterone, decreased arginine vasopressin, reduced Na and water retention
ACEi used in HF
enalapril, captopril, lisinopril, quinapril, ramipril, fosinopril, trandolapril, benazopril, moexipril, perindopril
Dosing of ACE Inhibitors
- What are the proper doses of ACE Inhibitors?: Clinical trial dosing vs. dosing to response; Why are these doses so important; Are lower doses as effective? Or do they maintain some efficacy? - ATLAS trial suggests higher doses may have greater benefit
- Why are ACE Inhibitors underdosed and underused?: CKD: Lower doses; Hypotension: Symptomatic vs Low blood pressure
Clinical Dosing of ACEi
- Dosages: titrate slowly to the target dose used in clinical trials: Start low and double dose every 1-4 weeks; Some improvement may be evident in several
weeks; Caution if: Volume depleted, SBP<80; K>5, SeCr >3 - Lower doses and more monitoring are required with serum creatinine > 3.0 and/or ClCr < 30 mL/min.
Absolute Contraindications of ACEi
- Pregnancy or intending to become pregnant
- History of angioedema (<1%) or hypersensitivity
- Bilateral renal artery stenosis
- History of WELL-DOCUMENTED intolerance due to symptomatic hypotension, decline in renal function, hyperkalemia or cough.
Monitoring of ACEi
- Volume status (normalize prior to initiation)
- Regular Mx of renal function and K, esp in high risk: Prior to therapy, 1-2 weeks after each increase in dose and at 3-6 months intervals; When other treatments are added that may decrease renal function; In patients with a history of renal dysfunction; SeCr may rise after initiation (<30 % acceptable)
- Blood pressure: Avoid symptomatic hypotension
- Other adverse effects
Adverse Effects ACEi
- Hypotension
- Functional renal insufficiency
- Hyperkalemia
- Skin rash and dysgeusia (captopril)
- Cough (~20%)
- Angioedema (~1%)
Angiotensin II Receptor Antagonists
more blockade of AT1 receptor: prevents an increase in myocardial fibrosis, NE, vasoconstriction, and PAI/endothelin
directly antagonize angiotensin II receptor
Angiotensin II Receptor Antagonists used in HF
losartan, valsartan, candesartan
never use with ACEi
ARBs vs. ACEIs
- Place in Therapy: Not superior to ACEi; Alternative if: ARB for another reason; Unable to take ACEi due to cough; ACEi-induced angioedema (with caution and close follow-up)
- Monitoring: See ACE inhibitor (except cough) discussion
Angiotensin Receptor Neprilysin Inhibitors
dual mechanism of action: NP system and RAAS
inhibits degradation of BNP to promote vasodilation and blocks AT1 receptor to inhibit vasoconstriction
ARNI
sacubitril/valsartan - inhibits degradation of BNP, blocks AT1-receptor
Sacubitril/Valsartan
- Sacubitril: Metabolite inhibits Neprilysin…increase natriuretic peptides
- Valsartan: ARB
- Indication: Reduce the risk of CV death/hospitalization
for HFrEF patients with NYHA Class II-IV - Sacubitril (24, 49, 97 mg): Valsartan (26, 51, 103 mg) ; Valsartan equivalents: 26=40; 51=80; 103=160 mg
Enalapril 20/day =
captopril 150/day = lisinopril 20-40/day
Sacubitril/Valsartan AEs
- A/E’s (remember ARBs and ACEIs): Hypotension (> enalapril); Elevations in SeCr, SeK (< enalapril); Angioedema rare; Pregnancy: Same contraindication
very expensive
Must stop an ACEi within ____ hours of starting an ARNI
36
Recommendations for ARNi/ACEi/ARB
- Stage B: ACEi’s: Class I OR ARBs: If intolerant to ACEIs (Class I)
- Stage C: ARNi: Patients with current or previous Sxs; ACEi’s: Patients with current or previous Sxs (Class I) when use of ARNi not feasible; ARBs: If intolerant to ACEIs when ARNi not feasible (Class I) * ARBs are reasonable alternatives as first line agents
especially if taking an ARB for another indication (Class IIa); ARNi: Patients with current or previous Sxs who tolerate an ACEi or ARB, replacement with ARNi further reduces mortality
ARNI should not be administered to patients with a history of
angioedema
Summary: ACC/AHA Guidelines
- …inhibition of the RAS with ARNI, ACEI OR ARBs is recommended to reduce M/M.
- ARNIs are preferred and can be used rather than with pre-treatment with ACE/ARBs
- ACEIs/ARBs to reduce M/M is recommended in patients with cannot take ARNIs: ARBs to reduce M/M is recommended in patients with prior or current Sxs who are intolerant to ACE inhibitors because of cough or angioedema
Beta-Blockers
- Traditionally contraindicated in the management of HF
- Recent studies (in >20,000 patients, since mid 90s) suggest that some β-blockers provide symptomatic relief, QOL, and reduce hosp (~25%) and mortality (~35%)
- “Reverse remodeling” is proposed as one mechanism of benefit
- Carvedilol (Coreg, Coreg CR), Metoprolol succinate XL (Toprol XL) are approved by the FDA; Bisoprolol (EMEA) for the treatment of heart failure
Rationale beta-AR Pathway in Heart Failure
increased cardiac NE –> beta-AR pathway desensitization –> impaired exercise intolerance –> HF
increased cardiac NE –> myocyte toxicity –> myocardial dysfunction –> HF
want to block this
Rationale Beta-blockers in Heart Failure
Decrease: ventricular arrythmias, cardiac hypertrophy and cardiac cell death, VC and HR, cardiac remodeling
Patient Selection for Beta-Blockers
- STABLE and euvolemic (no marked signs of fluid retention) patients
- Symptomatic patients should receive diuretics also, esp with current or recent history of fluid retention
- Should be considered in patients with bronchospastic disease and asymptomatic bradycardia, but cautiously
- Initiation in hospitalized patients ?
- Do not abruptly discontinue - rebound HTN
b-blocker withdrawal syndrome: upregulation in # + function of beta-receptors, when you withdraw it, receptors are able to be activated
Beta blockers used in HF
bisoprolol, carvedilol, metoprolol XL
Carvedilol dose conversion
carvedilol 3.125 mg = coreg CR 10 mg QD
carvedilol 6.25 mg = coreg CR 20 mg QD
carvedilol 12.5 mg = coreg CR 40 mg QD
carvedilol 25 mg = coreg CR 80 mg QD
Beta-blockers Monitoring
- BP (and symptomatic hypotension), HR (1-2 weeks): Patients can also diary these numbers daily; symptomatic hypotension, bradycardia and dizziness are uncommon if slow titration (reduce dose ~50% if necessary); If hypotension only…reduce other drugs first
- Goal HR is not defined as in CAD
- Edema and fluid retention (1-2 weeks): Patients can also diary weight daily; Risk is 1-2 % (more than placebo) if stable, euvolemic patients are chosen; Intensify diuretic therapy
- Fatigue or weakness: Risk is 1-2 % (more than placebo); More difficult to address, may resolve on own or may require decrease or D/C
Consensus Panel Recommendations for Beta-blockers
- Stage B: In all patients with a recent or remote history of ACS and reduced EF, should
receive one of the agents shown to reduce mortality (Class I); All other patients should receive one of the agents shown to reduce mortality (Class I) - Stage C: Use one of agents shown to reduce mortality in all patients, with current or
previous symptoms unless contraindicated (Class I)
