Despite the availability of many newer antihypertensive agents, hypertensive patients remain at higher risk of premature death than the general population. This persistence of morbidity and mortality may be accounted for by the frequent failure to achieve adequate blood pressure reduction despite an extensive array of available antihypertensive agents. Such considerations have led to reassessment of the potential role of fixed-dose combination agents in the antihypertensive armamentarium. The rationale for combination therapy relates to the concept that antihypertensive efficacy may be enhanced when 2 classes of agents are combined. In addition, combination therapy enhances tolerability—1 drug of a fixed combination can antagonize some of the adverse effects of the second drug. Fixed-dose combination therapy simplifies the treatment regimen, preventing treatment failures that might result from missed doses. An additional novel concept is the possibility of enhancing salutary effects on target organs, including regressing left ventricular hypertension and retarding progression of renal disease, by combination therapy over and above the effects expected from the fall in arterial pressure alone. The recent approval by the Food and Drug Administration of 2 fixed-dose angiotensin-converting enzyme inhibitor/calcium antagonist combinations has focused attention on and prompted reexamination of this issue.
Arch Intern Med. 1996;156:1969-1978