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US Carvedilol HF NEJM 1996; 334: 1349-55 Carvedilol (n=696) Placebo (n=398) Risk reduction = 65% p0.001 0 50 100 150 200 250 300 350 400 1.0 0.9 0.8 0.7 0.6 ?-Adrenergic Blockers 0.7 0.8 0.9 1.0 Survival % Days I-II HF Symptomatic heart failure Asymptomatic ventricular dysfunction - LVEF 35 - 40 % After AMI AHA / ACC HF guidelines 2001 ESC HF guidelines 2001 ?-Adrenergic Blockers: Indications Patient stable No physical evidence of fluid retention No need for i.v. inotropic drugs Start ACE-I / diuretic first No contraindications In hospital or not ?-Adrenergic Blockers When to start Initial Target Bisoprolol 1.25 / 24h 10 / 24h Carvedilol 3.125 / 12h 25 / 12h Metoprolol tartrate 6.25 / 12h 75 / 12h Metoprolol succinnate 12,5-25 / 24h 200 / 24h Start Low, Increase Slowly Increase the dose every 2 - 4 weeks ?-Adrenergic Blockers Dose (mg) Hypotension Fluid retention / worsening heart failure Fatigue Bradycardia / heart block ?-Adrenergic Blockers Adverse Effects Review treatment (+/-diuretics, other drugs) Reduce dose Consider cardiac pacing Discontinue beta blocker only in severe cases Digitalis: Mechanism of Action Blocks Na+ / K+ ATPase = Ca+ + ? Inotropic effect ? Natriuresis ? Neurohormonal control - Plasma Noradrenaline - Peripheral nervous system activity - RAAS activity - Vagal tone - Normalizes arterial baroreceptors NEJM 1988;318:358 Digitalis. Clinical Effects Improve symptoms Modest reduction in hospitalization Does not improve survival Digoxin toxicity Advanced A-V block without pacemaker Bradycardia or sick sinus without PM PVC’s and VT Marked hypokalemia W-P-W with atrial fibrillation Digoxin. Contraindications RENIN Angiotensinogen Angiotensin IANGIOTENSIN II ACE Other pathways Vasoconstriction Proliferative Action Vasodilatation Antiproliferative Action AT1 AT2 AT1 Receptor Blockers RECEPTORS Angiotensin II Receptor Blockers (ARB) Candesartan, Eprosartan, Irbesa
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