Contribution of fixed low-dose combinations to initial therapy in hypertension

A. Zanchetti

Research output: Contribution to journalArticlepeer-review


Fixed low-dose combinations of antihypertensive agents have several potential advances that make them suitable for frequent use in therapeutic practice even as an initial approach. In the randomized trials of antihypertensive therapy conducted during the 1970s and 1980s, in which very large doses of diuretics were employed as initial therapy, more than 50% of patients required treatment with combination therapy in order to achieve the blood pressure goal indicated in the trial protocol. This implies that an increase in the dose of the initial antihypertensive agent does not usually significantly increase the effectiveness of monotherapy. It is well known that high doses of almost all antihypertensive agents increase the risk and the severity of adverse effects. Adverse effects of drugs are the main cause of the low compliance of patients with antihypertensive therapy in practice. Essential hypertension has multiple mechanisms, and rational combination therapy allows interference with more than one of these mechanisms. Rational combination therapy not only reduces adverse effects because of the use of low doses of each combined agent, but can also take advantage of counteractions that each of the combined agents can exert on the undesirable actions of the other agent. Organ damage associated with hypertension can be more effectively prevented or reversed by combination therapy, not only because the blood pressure load is reduced to a greater extent but also because of specific actions exerted by the various agents used in the combination. Fixed dose combinations are an aid to the doctor, as the doses of the two components have been chosen on the basis of careful experimentation of various possible doses in order to obtain the greatest blood pressure decrease with the lowest incidence of adverse effects in the largest proportion of patients.

Original languageEnglish
JournalEuropean Heart Journal, Supplement
Issue numberL
Publication statusPublished - 1999


  • ACE inhibitors
  • Antihypertensive therapy
  • Combination therapy
  • Diuretics
  • Monotherapy

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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