Combination therapy in angina: a review of combined haemodynamic treatment and the role for combined haemodynamic and cardiac metabolic agents.

The 1997 European Society of Cardiology guidelines emphasised medical therapy as the mainstay of treatment of stable angina. Until recently, the antianginal drugs available to control symptoms (nitrates, beta-blockers and calcium antagonists) have all been haemodynamic agents that eliminate or reduce angina attacks principally by decreasing myocardial oxygen demand. They may also improve myocardial perfusion. The haemodynamic agents are often used in combination. However, there is conflicting evidence for the efficacy of combination treatment. Two recently published large clinical studies, the Total Ischaemic Burden European Trial (TIBET) study and the International Multicenter Angina Exercise (IMAGE) study, suggest that combined haemodynamic treatment is no more effective than optimal monotherapy. The results from IMAGE suggest that most of the additional effect observed with combined therapy was attributable to recruitment by the second drug of patients who had not responded to monotherapy, and that most patients continued to have a disturbing frequency of anginal attacks after receiving combined therapy. Metabolic agents are a new class of drugs that directly modify the use of energy substrates in the heart, lessening ischaemic injury and improving cardiac performance during ischaemia. Due to their non-haemodynamic mode of action, metabolic agents such as trimetazidine or L-carnitine may provide independent benefit in ischaemia when used as monotherapy or additional benefit when used in combination with a conventional agent. Clinical trials have shown that combined haemodynamic and metabolic treatment is more effective than combined haemodynamic therapy and is well tolerated. It is suggested that combination haemodynamic and metabolic therapy is a logical new approach to patients whose angina is inadequately controlled despite optimal haemodynamic therapy.