Benefits of nifedipine GITS in stable coronary artery disease: Further analysis of the "ACTION" database.

INTRODUCTION

Retrospective analyses of specific subgroups of patients from the database of the ACTION study have evaluated the effectiveness of a nifedipine gastrointestinal therapeutic system (GITS) on clinical outcomes. These subgroups included those patients receiving: 1) full "optimal" therapy at baseline; 2) full "optimal" therapy at baseline but excluding renin angiotensin system (RAS)-blocking drugs; 3) treatment with nifedipine GITS who were not treated with RAS blockers versus those treated with RAS blockers but not nifedipine GITS.

METHODS

Analyses were performed on an intention-to-treat basis. Treatment groups were compared by log-rank test without adjustment for covariates. Hazard ratios with 95% confidence intervals were obtained using Cox proportional hazards models with treatment allocation as the only covariate.

RESULTS

2461 patients randomized in ACTION were receiving optimal therapy (beta blockers, nitrates, aspirin, statins) excluding RAS blockers at baseline. There were reductions associated with nifedipine GITS compared with placebo in all prespecified endpoints but statistical significance was only achieved for debilitating stroke (48%; P<0.02) and coronary angiography (14%; P<0.05). These benefits were paralleled by a -4.1 and -2.8 mmHg difference between the groups for systolic and diastolic blood pressure, respectively. Patients randomized to nifedipine GITS but no RAS blockers (n=2966) when compared to those receiving RAS blockers but no nifedipine GITS (n=880) had highly statistically significant reductions in cardiovascular events (22%), new-onset heart failure (53%), and debilitating stroke (45%). However, the groups differed in their baseline characteristics.

CONCLUSION

Addition of nifedipine GITS to the treatment regimen of selected patient groups with symptomatic coronary artery disease results in a significant reduction of cardiovascular morbidity. While the interpretation of these subgroup analyses must obviously be cautious, there is a clear message relating to "best practice" treatment of angina, which suggests that "reliance" on RAS blockade may be misplaced and greater attention should be directed towards control of blood pressure.