International Nifedipine GITS study: Intervention as a Goal in Hypertension Treatment - INSIGHT
The INSIGHT trial compared the effects of the calcium-channel blocker nifedipine once daily with the diuretic combination co-amilozide on cardiovascular mortality and morbidity in highrisk patients with hypertension.
The primary hypothesis was there would be a 25% relative difference in the primary outcome between nifedipine and co-amilozide. The secondary hypothesis was that there would be non-inferiority in the primary outcome between nifedipine and co-amilozide, defined as a non-significant absolute difference.
Patients Enrolled: 6321
Mean Follow Up: 3 years
Mean Patient Age: 55-80 years
Systolic blood pressure >=150 mm Hg and diastolic blood pressure >=95 mm Hg, or systolic blood pressure >=160 mm Hg. One of the following cardiovascular risk factors: hypercholesterolemia; smoker; family history of myocardial infarction in parent or sibling before age 50 years; current left-ventricular hypertrophy, confirmed by echocardiography; coronary heart disease, defined as stable angina or symptomless coronary heart disease; left-ventricular strain; peripheral vascular disease, defined as intermittent claudication, resting pain, or gangrene; proteinuria. Age 55-80.
Documented secondary or malignant hypertension. History of sub-arachnoid hemorrhage. PTCA or CABG in the 6 months prior to entering the study. Myocardial infarction or stroke in the 12 months prior to entering the study, or patients whose ejection fraction post-MI is <40%. Congestive heart failure with a known ejection fraction <40%. Known hypersensitivity to dihydropyridines.
Composite of death from any cardiovascular or cerebrovascular cause, non-fatal stroke, myocardial infarction, and heart failure
Total mortality Death from a vascular cause Non-fatal vascular events including transient ischemic attacks, angina (new or worsening), and renal failure
Nifedipine, 30 mg daily; or co-amilozide (hydrochlorothiazide 25 mg, amiloride 2.5 mg daily). All patients received one active and one placebo tablet taken at the same time of day.
The primary outcome (Composite of death from any cardiovascular or cerebrovascular cause, non-fatal stroke, myocardial infarction, and heart failure) occurred in 6.3% of patients in the nifedipine group and in 5.8% in the co-amilozide group (RR 1.10, 95% CI 0.91-1.34, p=0.35). Mean blood pressure fell from 173/99 mm Hg to 138/82 mm Hg in both groups. There were fewer serious adverse events in the nifedipine group than in the co-amilozide group (25% vs 28%, p=0.02). Groups did not differ for all-cause mortality, non-fatal endpoints, or the combined secondary endpoints (p=NS for all).
Nifedipine once daily and co-amilozide had a similar efficacy in high risk patients with hypertension, suggesting the choice of drug can be determined by tolerability and blood-pressure response rather than long-term safety or efficacy.
Keywords: Intermittent Claudication, Myocardial Infarction, Stroke, Gangrene, Angina, Stable, Diuretics, Risk Factors, Proteinuria, Hypercholesterolemia, Nifedipine, Peripheral Vascular Diseases, Calcium Channel Blockers, Drug Combinations, Heart Failure, Hydrochlorothiazide, Hypertrophy, Hypertension, Echocardiography
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