Ultimately, an appropriate antihypertensive regimen frequently consists of several drugs used in combination. Diuretic-based antihypertensive therapy has repeatedly been shown to prevent HF in a wide range of target populations.244 Thiazide or thiazide-type diuretics are effective in prevent- ing HF in hypertensive patients.222 Thiazide or thiazide-type diuretics are the drugs of choice in patients with mild HF because of a more sustained natriuretic and diuretic action than loop diuretics, particularly in those individuals in whom BP control may be more important than correction of volume overload. In more severe HF, diuretics are used to reverse vol- ume overload and associated symptoms. Loop diuretics such as furosemide and torsemide usually are used because they produce a greater diuresis for the same degree of natriuresis; they work even in the presence of renal impairment, a fre- quent accompaniment of severe HF; and their dose-response characteristics are linear and steep, which allows escalation to high doses. By inducing sodium and water loss, diuretics also activate several adverse mechanisms. There may be a decrease in right ventricular filling pressure, with a decrease in stroke volume and activation of the RAAS and the sympa- thetic nervous system,245 effects that would be expected to be This problem is avoided by combining diuretic therapy with an ACE inhibitor or ARB, a -blocker, and/or an aldosterone antagonist, all of which have been shown to provide effective therapy in HF. The Diuretic Optimization Strategies Evaluation (DOSE) trial in patients with acute HF demonstrated that a high-dose furosemide strategy was asso- ciated with a nonstatistically significant trend toward greater improvement in patients global assessment of symptoms but no significant difference in creatinine levels. Although there were greater diuresis with the high-dose strategy and more favorable outcomes in a few secondary measures, there was also transient worsening of renal function.248 6.7.2. 