Chronic cardiac failure
A scheme for the stepwise drug management of chronic cardiac failure is shown in Fig. 24.5. Points to emphasise in this scheme are that all patients, even those with mild failure, should receive an ACE inhibitor as first-line therapy. Several long-term studies have demonstrated improved survival even in mild cardiac failure. In the SOLVD studies, enalapril was compared with placebo in patients with either clinical features of heart failure, or reduced left ventricular function in the absence of symptoms; treatment reduced serious events (myocardial infarction and unstable angina) by approximately 20% and hospital admissions with progressive heart failure by up to 40%.16 Diuretics are very useful for symptom management but have no impact on survival. For
15 The Digitalis Investigation Group 1997 The effect of digoxin on mortality and morbidity in patients with heart failure. New England Journal of Medicine 336: 525-532.
16 SOLVD = Studies of Left Ventricular Dysfunction. The SOLVD Investigators 1991 Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. New England Journal of Medicine 325: 293-302.
most patients the choice will be a loop diuretic, e.g. frusemide (furosemide) starting at 20-40 mg/d. Because of the potassium-sparing effect of ACE inhibition amiloride is often not required, at least with low doses of a loop diuretic.
There is now overwhelming evidence that fi-blockade is beneficial in chronic heart failure despite the long-held belief that their negative inotropic effect was a contraindication. Early trials were underpowered but a meta-analysis did suggest a 31% reduction in mortality. Subsequently, the CIBIS-2 and MERIT-HF trials, have independently confirmed that chronic (3-blockade has a survival effect of this size in moderate to severe (NHYA III/TV) heart failure.17 The reduction is additive to ACE inhibition and the survival benefit is largely through a reduction in sudden deaths as opposed to the progressive pump failure benefit seen with ACE inihibitors. The only cautionary note is that patients must be ^-blocked very gradually with low starting doses (e.g. bisoprolol 1.25 mg/d or carvedilol 3.125 mg bd) and regular optimisation of other drugs, especially the dose of loop diuretic, to prevent decompensation of their heart failure control.
The use of spironolactone has received considerable support from the RALES trial,18 which implies that ACE inhibition even at high dose does not effectively suppress hyperaldosteronism in
17 Up until 1997,24 trials of P-blockade in heart failure provided just 3141 patients. MERIT-HF (Lancet 1999 353: 2001) alone contained 3991 patients and CIBIS-2 provided a further 2467 (Lancet 1999 353: 9). Both studies confirmed the one-third reduction in mortality. In MERIT-HF a life was saved for just 27 patient-years of treatment i.e. it was unsually cost effective — more so than ACE inhibitor therapy. The action is probably a class effect of p-blockade given the divergent pharmacology of the drugs used to date.
18 The RALES trial randomised 1663 patients with stable heart failure to either placebo or spironolactone (New England Journal of Medicine 1999 341: 709). All patients were maintained on their 'optimised' therapy that included ACE inhibitors. After 2 years of follow-up the trial was terminated prematurely due to a 30% reduction of mortality in the spironolactone treated patients; both progressive pump failure and sudden death were significanly reduced. Gynaecomastia or breast discomfort occurred in 10% of treated patients (1% in controls), but significant hyperkalemia occurred in surprisingly few patients. RALES was not adequately powered to decide whether the action of spironolactone is additive to that of a p-blocker.
Control of signs & symptoms
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