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).
BACKGROUND
The efficacy of antihypertensive drugs newer than diuretics and beta-blockers has not been established. We compared the effects of the calcium-channel blocker nifedipine once daily with the diuretic combination co-amilozide on cardiovascular mortality and morbidity in high-risk patients with hypertension.


METHODS
We did a prospective, randomised, double-blind trial in Europe and Israel in 6321 patients aged 55-80 years with hypertension (blood pressure > or = 150/95 mm Hg, or > or = 160 mm Hg systolic). Patients had at least one additional cardiovascular risk factor. We randomly assigned patients nifedipine 30 mg in a long-acting gastrointestinal-transport-system (GITS) formulation (n=3157), or co-amilozide (hydrochlorothiazide 25 mg [corrected] plus amiloride 2.5 mg; n=3164). Dose titration was by dose doubling, and addition of atenolol 25-50 mg or enalapril 5-10 mg. The primary outcome was cardiovascular death, myocardial infarction, heart failure, or stroke. Analysis was done by intention to treat.


RESULTS
Primary outcomes occurred in 200 (6.3%) patients in the nifedipine group and in 182 (5.8%) in the co-amilozide group (18.2 vs 16.5 events per 1000 patient-years; relative risk 1.10 [95% CI 0.91-1.34], p=0.35). Overall mean blood pressure fell from 173/99 mm Hg (SD 14/8) to 138/82 mm Hg (12/7). There was an 8% excess of withdrawals from the nifedipine group because of peripheral oedema (725 vs 518, p<0.0001), but serious adverse events were more frequent in the co-amilozide group (880 vs 796, p=0.02). Deaths were mainly non-vascular (nifedipine 176 vs co-amilozide 172; p=0.81). 80% of the primary events occurred in patients receiving randomised treatment (157 nifedipine, 147 co-amilozide, difference 0.33% [-0.7 to 1.4]).


CONCLUSIONS
Nifedipine once daily and co-amilozide were equally effective in preventing overall cardiovascular or cerebrovascular complications. The choice of drug can be decided by tolerability and blood-pressure response rather than long-term safety or efficacy.
Brown
M J
MJ
Clinical Pharmacology Unit, University of Cambridge, UK. morris.brown@cai.cam.ac.uk
Palmer
C R
CR
Castaigne
A
A
de Leeuw
P W
PW
Mancia
G
G
Rosenthal
T
T
Ruilope
L M
LM
D000368:Aged; D000369:Aged, 80 and over; D000584:Amiloride / Q000008:administration & dosage*; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D002121:Calcium Channel Blockers / Q000008:administration & dosage*; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D004232:Diuretics / Q000627:therapeutic use*; D004311:Double-Blind Method; D004338:Drug Combinations; D006801:Humans; D006852:Hydrochlorothiazide / Q000008:administration & dosage*; D006973:Hypertension / Q000150:complications* / Q000188:drug therapy* / Q000401:mortality; D015993:Life Tables; D008875:Middle Aged; D009543:Nifedipine / Q000008:administration & dosage*; D011446:Prospective Studies; D012307:Risk Factors; D016896:Treatment Outcome
D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D003692:Delayed-Action Preparations; D004232:Diuretics; D004338:Drug Combinations; D006852:Hydrochlorothiazide; C010247:amiloride, hydrochlorothiazide drug combination; D000584:Amiloride; D009543:Nifedipine