RATIONALE FOR DRUG COMBINATIONS: Essential hypertension is a heterogeneous disease. Different factors might interact, in an individual patient, to increase blood pressure. This explains why a drug that lowers blood pressure by a given mechanism may normalize blood pressure in some patients but not in others. combining two drugs with complementary mechanisms of action can increase the antihypertensive efficacy. DOSAGES USED IN DRUG COMBINATIONS: When administered in combination, lower doses of the separate components are generally necessary than when the drugs are prescribed as monotherapies, which may improve tolerability. Fixed-dose combination therapy is therefore an attractive approach to the treatment of hypertensive patients. It may be an appropriate choice, not only for second-line, but also for first-line therapy.