COMBINATION THERAPY IN ANTIHYPERTENSIVE TREATMENT STRATEGY

The standard treatment of mild-to-moderate hypertension is monotherapy chosen from one of the five main classes of antihypertensives following the World Health Organisation and Joint National Committee guidelines. If first-line monotherapy fails, the physician must decide whether to increase the dose, choose a drug from a different class or add a second antihypertensive. However, greater efficacy must not be obtained at the cost of an unacceptable increase in side-effects. Sequential monotherapy is partly based on the impossibility of predicting the blood pressure response to a given antihypertensive. The validity of this strategy is supported by the findings of the Materson study, which suggest combination therapy only after the failure of at least two monotherapies. The aim of combination therapy is to optimize treatment by using two different classes of antihypertensives with synergistic effects. The anticipated advantages are ease of use, the enhancement or addition of the antihypertensive effects, and the possibility of administration to a wide population. This has led to the development of fixed combinations which are low-dosed to reduce the incidence of side-effects. Validated combinations (dosed differently according to the medicinal product) include: beta-blocker + diuretic, betablocker + dihydropyridine (DHP) calcium antagonist, angiotensin converting enzyme (ACE)-inhibitor + diuretic and in the future, ACE-inhibitor + calcium antagonist. The pharmacokinetic interaction of beta-blocker + DHP at the hepatic level must be considered to assess the efficacy of this combination. Pharmacodynamic interactions between ACE-inhibitor-diuretic and betablocker-DHP are beneficial, as shown in controlled trials with a greater efficacy for the combination than for the two antihypertensives administered separately. Combination therapy must be shown to be devoid of adverse metabolic effect; whether it is more effective in inducing regression of left ventricular hypertrophy remains to be proven. In terms of cost and compliance, a less expensive, established fixed combination has obvious advantages compared to 'free' combinations between its components, but one must not renounce individualized treatment nor prescription flexibility. Opting for combination