Fixed-dose combination medications for the treatment of hypertension: a critical review

Aside from the retrospective analysis of Clark and Troop (1), no large-scale controlled study has been designed specifically to assess the advantages and disadvantages of fixed-dose antihypertensive combinations. The use of fixed-dose antihypertensive combinations is no longer the anathema of the academician. The principal advantages of fixed-ratio combinations are simplicity of use, potentiation of blood-pressure-lowering efficacy, and potential counterbalancing of certain side effects. An additional advantage might be improvement in broad-based cost effectiveness, that is, a potential reduction in the need for frequent laboratory surveillance and in the frequency of office visits. The principal disadvantage is the relative inflexibility of dosage adjustment. Antihypertensive therapy should be initiated with a single drug preparation, with subsequent substitution of a combination product when appropriate. Tables 4 and 5 summarize, respectively, some of the important factors to consider and the theoretical requirements when contemplating the use of fixed-dose antihypertensive combinations. Diuretic/beta-blocker combinations are particularly attractive because of the enormous long-term experience with each component, their proven efficacy and additional salutary effects, their generally acceptable and sometimes offsetting side effects, and their potential for once-a-day dosing. It seems likely that CEI/diuretic and perhaps calcium-channel blocker/diuretic combinations also have great merit.