16. Effect of carvedilol on progression of congestive heart failure All randomized patients Endpoint Placebo Carvedilol (n=134) (n=232) Primary endpoint 28 (21%) 25 (11%)* Death due to CHF 4 (3%) 0 (0%) Hospitalization due to worsening CHF 8 (6%) 9 (4%) Increase in CHF medication 16 (12%) 16 (7%) * Placebo vs. carvedilol, p = 0.008 Drugs of Today 1998; 34 (Suppl B): 1-23.
17. COPERNICUS: Effect on Mortality 35% Mortality (%) 22nd Congress of European Society of Cardiology, August 2000
18. COPERNICUS: Mortality reduction in special patient groups with carvedilol Mortality reduction (%) 22nd Congress of European Society of Cardiology, August 2000 EF<20%, hospitalised for heart failure in year prior to study entry EF < 15%, hospitalised 3 or more times during prior year for worsening heart failure
23. The role of angiotensin II in the progression of heart failure Coronary artery disease Cardiac overload Cardiomyopathy Left ventricular dysfunction Arterial blood pressure Angiotensin II Peripheral organ blood flow Skeletal muscle blood flow Exercise intolerance Renal blood flow Oedema Cardiac remodelling Renin release Aldosterone release Vasoconstriction Na+ and water retention Inotropy and hypertrophy of vascular and cardiac cells Left ventricular dilation & hypertrophy Pump failure
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33. ACE Inhibitor Therapy in Heart Failure Patients (Ejection Fraction < 0.40) Systolic Blood Pressure <100 mmHg (or elevated creatinine) 100-139 mmHg (or recent intense diuresis) > 140 mmHg Lowest Dose, Short-Acting Usual Starting Dose, Long-or Short-Acting Intermediate Dose, Long- or Short-Acting Follow-Up Every 1-2 Weeks Stable BP and Creatinine Level Symptomatic Low BP or Rising Creatinine Level Residual Excess Fluid? Stop Diuretic and ACE Inhibitor Therapy Return to Baseline BP and Creatinine Level ? Increase ACE Inhibitor Dose; Follow-Up Every 1-2 Weeks Target Dose Resume ACE Inhibitor Titration Refer to specialist Stop ACE Inhibitor Therapy Y N Y N