INSIGHT trial

This trial compared the effects of the calcium-channel blocker nifedipine once daily with diuretic combination co-amilozide on cardiovascular mortality and morbidity in high-risk patients with hypertension.

• method - a randomised, prospective, double-blind trial involving 6,321 patients with hypertension (blood pressure >= 150/95 mmHg, >= 160 mmHg systolic) aged 55-80 years. Each patient had at least one additional cardiovascular risk factor. Patients were randomly assigned to nifedipine 30mg in a long-acting gastrointestinal-transport system (GITS) formulation or co-amilozide (hydrochlorothiazide 25mg plus amiloride 25 mg). Dose titration was via dose doubling, and addition of atenolol 25-50mg (or enalapril 5-10mg if atenolol contraindicated). Primary outcomes used were heart failure, myocardial infarction, cardiovascular death or stroke. 3157 patients on nifedipine and 3164 patients on co-amilozide completed 10976 and 11015 patient-years of treatment, respectively
  
  
• results - primary outcomes occurred in 182 patients (5.8%) in the co-amilozide group and 200 (6.3%) of patients in the nifedipine group (16.5 vs 18.2 events per 1000 patient-years); relative risk nifedipine compared with co-amilozide 1.10 (95% CI 0.91-1.34), p = 0.35. Serious adverse effects were more common in the co-amilozide group (880 vs 796) but there was an 8% excess of withdrawals from the nifedipine group because of peripheral oedema (725 vs 518, p <0.0001)
  
  
• conclusion - co-amilozide and nifedipine once daily were equally effective in preventing overall cardiovascular or cerebrovascular complications. Fewer patients, however, tolerated nifedipine (2)

Reference:

• (1) Brown MJ et al (2000). Morbidity and mortality in patients randomised to double-blind treatment with a long-acting calcium channel blocker or diuretic in the International Nifedipine GITS study: Intervention as a Goal in Hypertension Treatment (INSIGHT). Lancet, 356 (9227), 366-372.
• (2) Evidence-based medicine (2001), 6 (1), 10.