Calcium antagonists such as nifedipine are used to relieve the symptoms of angina, but there have been doubts about their long-term safety. However, ACTION--A Coronary disease Trial Investigating Outcome with Nifedipine GITS--provides new information on the drug's long-term use. GITS (gastrointestinal therapeutic system) modifies the release of the drug to provide stable long-term concentrations of nifedipine in blood.
ACTION was designed to investigate the effects of long-acting nifedipine GITS on the clinical outcomes in patients with stable symptomatic coronary disease, half of whom had had a previous heart attack. Primary clinical outcomes included death from any cause, acute heart attack, and debilitating stroke. The occurrence of secondary outcomes - such as any cardiovascular event, any death and any vascular event or procedure - were also assessed.
Angina patients from 19 countries were randomly assigned to the nifedipine GITS group (3825 patients) or to the placebo group (3840 patients). After around 5 years follow-up there were similar mortality rates among both groups; however, the incidence of heart failure and of coronary interventions were lower in the group receiving nifedipine. About a third of patients in each group withdrew from the study.
Lead investigator Philip Pool-Wilson (Imperial College London, UK) concludes: "Nifedipine GITS can be used safely for the long-term treatment of patients with coronary disease and angina pectoris because, in addition to relieving symptoms of angina, it prolongs cardiovascular event and procedure free survival."
Bruce M Psaty (University of Washington, Seattle, USA) concludes in an accompanying commentary: "ACTION provides support for the long-term treatment of the symptoms of angina in patients already on b blockers and nitrates. However, long-acting nifedipine did not significantly reduce their risk of major cardiovascular events compared with placebo. In the past decade, many high-quality clinical trials have defined the proper role of various cardiovascular agents. Long-acting calcium-channel blockers are appropriate as: second-line or third-line treatment of symptomatic angina not responsive to b blockers or nitrates; and third-line or fourth-line treatment of high blood pressure not responsive to diuretics, b blockers, ACE inhibitors, or angiotensin-receptor blockers."
Contact: Professor Philip A Poole-Wilson, Department of Cardiac Medicine, National Heart & Lung Institute, Dovehouse Street, London, SW3 6LY, UK; T) +44 (0)20 7351 8179; p.poole-wilson@ic.ac.uk
Dr Bruce M Psaty, Cardiovascular Health Research Unit, Departments of Medicine, Epidemiology and Health Services, University of Washington, Seattle, WA 98101, USA; psaty@u.washington.edu
The Lancet