Diastolic heart failure diuretics

Further support for using blood pressure as a surrogate endpoint is provided by the concordance of evidence from a number of clinical trials in which blood pressure lowering with low-dose diuretics and P-blockers was shown to reduce the incidence of stroke/ coronary artery disease/ and congestive heart failure in hypertensive patients (19). Of particular interest is a meta-analysis that was conducted to compare the extent of blood pressure reduction achieved in different clinical trials with the maximum benefit that was anticipated on epidemiolgic grounds (Table 17.3) (20). The decrease in stroke incidence anticipated for a 5- to 6-mm Hg average reduction in diastolic blood pressure was fully realized with only 2 to 3 years of antihypertensive therapy. 

Several mechanisms have been postulated to underlie the benefits of aldosterone receptor antagonists in heart failure (30). Aldosterone-induced cardiac fibrosis may reduce systolic function, impair diastolic function, and promote intracardiac conduction defects, with the potential for serious dysrhythmias. Aldosterone may also increase vulnerability to serious dysrhythmias by other mechanisms. The diuretic and hemodynamic effects of spironolactone in RALES and EPHESUS were subtle, and there were no significant changes in body weight, sodium retention, or systemic blood pressure. 

Thiazide diuretics or -blockers have been compared with either ACE inhibitors or CCBs in elderly patients with either systolic or diastolic hypertension or both. In a Swedish trial, no significant differences were seen between conventional drugs and either ACE inhibitors or CCBs. However, there were significantly fewer myocardial infarctions and cases of heart failure in the ACE inhibitor group compared with the CCB group. These data suggest that overall treatment may be more important than specific antihypertensive agents in this population. 

Diuretics and angiotensin-converting enzyme (ACE) inhibitors decrease cardiac output, dLYP/d, and end-diastolic pressure-volume relationships in normals but change these parameters, little, in heart failure patients. Studies in normals depend principally on decreasing preload, and effects on patients with diseases that increase preload would be/may be ntissed. 

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