In con- trast, for secondary protection in individuals with underlying comorbid illnesses such as IHD, CKD, or recurrent stroke, not all drug classes have been proven to confer optimal or even the same level of benefit. Whether there are class effects for antihypertensive drugs and whether each drug should be considered individually on the basis of trial results are not clearly known. 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. 