RAAS blocker + B Blocker Troubleshooting Heart Failure ECHO Clinic Virtual Heart Failure Consultation and Education Prof Ken McDonald & Dr. Patricia Campbell 13 th March 2017
HF activates 3 neurohormonal systems Sympathetic nervous system Natriuretic peptide system NPRs NPs Vasodilation Blood pressure Sympathetic tone Natriuresis/diuresis Vasopressin Aldosterone Fibrosis Hypertrophy HF SYMPTOMS & PROGRESSION Epinephrine Norepinephrine Renin-angiotensinaldosterone system Ang II α 1, β 1, β 2 receptors Vasoconstriction RAAS activity Vasopressin Heart rate Contractility AT 1 R Vasoconstriction Blood pressure Sympathetic tone Aldosterone Hypertrophy Fibrosis Levin et al. N Engl J Med 1998;339:321 8 Nathisuwan & Talbert. Pharmacotherapy 2002;22:27 42 Kemp & Conte. Cardiovascular Pathology 2012;365 71 Schrier & Abraham. N Engl J Med 2009;341:577 85
HFrEF Triple Therapy Standard ESC HF Guidelines 2016. Eur J Heart Fail. 2016 Aug;18(8):891-975
Evolution of therapy in HF: Sacubitril/Valsartan as a new alternative to an ACEI or ARBs in patients with HFrEF 1 SNS β-blockers NP system Neprilysin inhibitors HF SYMPTOMS & PROGRESSION Epinephrine Norepinephrine α 1, β 1, β 2 receptors Vasoconstriction RAAS activity Vasopressin Heart rate Contractility NPRs NPs Vasodilation Blood pressure Sympathetic tone Natriuresis/diuresis Vasopressin Aldosterone Fibrosis Hypertrophy INACTIVE FRAGMENTS LCZ696 RAAS Ang II AT 1 R Vasoconstriction Blood pressure Sympathetic tone Aldosterone Hypertrophy Fibrosis RAAS inhibitors (ACEI, ARB, MRA) LCZ696: enhancement of natriuretic and other vasoactive peptides, with simultaneous RAAS suppression 1. McMurray et al. Eur J Heart Fail 2013;15:1062 73 Figure references: Levin et al. N Engl J Med 1998;339:321 8 Nathisuwan & Talbert. Pharmacotherapy 2002;22:27 42 Kemp & Conte. Cardiovascular Pathology 2012;365 71 Schrier & Abraham. N Engl J Med 2009;341:577 85
Further RAAS adjustments if ongoing issues ESC HF Guidelines 2016. Eur J Heart Fail. 2016 Aug;18(8):891-975
Dose matters Kidney + Heart Rate + BP also matter Ensure ACEi/ARB (ARNI) and B-blocker maximally uptitrated max dose max tolerated ACEi by BP/renal function B-blocker by BP/HR K+ level and creatinine Initiation and 2/52 after ACEi/ARB (ARNI) dose
Issues with ACEi + B-blocker ACEI Cough ARB Angioedema cross effect on ARB, alternative hydralazine/nitrate combination Renal dysfunction anticipate rise in creatinine (<20%), reflects beneficial effect on renal hemodynamics B-blocker Mild symptom exacerbation can happen (uncommon, not cause for alarm) Only exacerbates most brittle asthma or COPD Fatigue typically short lived, tolerable Symptomatic bradycardia
How to start MRA Start low and go slow! 12.5mg to start Up-titration after 4 weeks Check K+ at 1-2 weeks after starting/dose change Once stable rechecking U+E recommended 3 month intervals for a year Then 6 monthly If K+ >5.5mmol/l or creatinine >200umol/l = half dose If K+ >6mmol/l or creatinine>250umol/l = stop
Medications to watch out for Advice to patient K+ sparing diuretics e.g. Frumil NSAIDs Trimethoprim prophylaxis for UTI Low salt substitutes with high K+ content Months to notice change in symptoms (if any) Avoid OTC NSAIDS If diarrhoea and vomiting stop MRA If gynaecomastia on spironolactone switch to eplerenone
Add on medications B-blocker max tolerated, HR still >70 Ivabradine B-blocker max tolerated, AF rates poorly controlled Digoxin HTN, requiring high dose diuretics Nitrates
Thank you for your participation To apply for the CME Certification: Return signed CME form to: Ms Lisa McCudden E-mail: lisa@heartbeat-trust.org