It is reasonable to assume that there are class effects for thiazide and thiazide- type diuretics, ACE inhibitors, and ARBs, which have a high degree of homogeneity in both their mechanisms of action and side effects.13,86,87 There are major pharmacological dif- ferences between drugs within more heterogeneous classes of agents such as the -blockers and CCBs.88,89 Finally, the most recent trials suggest that combining ACE inhibitors and ARBs is not beneficial for the secondary prevention of cardiovas- whereas combinations of renin-angiotensin blocking agents with thiazide diuretics or with CCBs show important clinical benefits.92 2.1.1. Thiazide and Thiazide-Type Diuretics Thiazide diuretics and the thiazide-type diuretics chlorthali- done and indapamide are highly effective in reducing BP and preventing cerebrovascular events, as demonstrated most con- vincingly in early studies such as the Veterans Administration the Medical Research Council (MRC) Trial,94 the Systolic Hypertension in the Elderly Program (SHEP),95 and the Hypertension in the Very Elderly Trial (HYVET).15 The benefit of chlorthalidone-based therapy in hypertension treatment is evident from the Antihypertensive and Lipid- Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) Since the publication of the results of ALLHAT, there have been concerns about whether thiazide-induced hyper- glycemia and diabetes mellitus contribute to long-term IHD risk not measured during the study interval,97 but this does not seem to be the case.98-100 -Blockers make up a heterogeneous class of antihyperten- sive drugs with differing effects on resistance vessels and on cardiac conduction and contractility. -Blocker administration remains the standard of care in patients with angina pectoris, those who have had an MI, and those who have LV dysfunc- tion with or without symptoms of HF unless contraindicated. The -blockers carvedilol, metoprolol, and bisoprolol have been shown to improve outcomes in patients with HF.1 2.1.3. 