Effects of isradipine or enalapril on blood pressure in salt-sensitive hypertensives during low and high dietary salt intake. MIST II Trial Investigators.
This large multicenter study, tested the antihypertensive effects of isradipine, a dihydropyridine calcium channel blocker and enalapril, an angiotensin-converting enzyme inhibitor, in salt-sensitive hypertensive patients under low and high salt intake diets. After a 3-week (weeks -9 to -6) of ad lib salt diet, those patients who had a sitting diastolic blood pressure (SDBP) of > or =95 but < or =115 mm Hg qualified to enter a 3-week (weeks -6 to -3) placebo run-in low salt diet (50 to 80 mmol Na+/day). Then high salt (200 to 250 mmol Na+/day) was added to the placebo treatment for 3 weeks (weeks -3 to 0). Those patients who demonstrated an increase in SDBP > or =5 mm Hg from the low to high salt diet were considered salt sensitive and were randomized into a 4-week (weeks 0 to 4) double-blind treatment period of either isradipine 2.5 to 10 mg twice a day, enalapril 2.5 to 20 mg twice a day, or placebo. Then they entered a 3-week (weeks 4 to 7) placebo washout phase of low salt diet (50 to 80 mmol Na+/day). After week 7 and while the low salt diet was continued the patients were restarted on their double-blind treatment for 4 more weeks (weeks 7 to 11) and the study was completed. Of 1,916 patients screened, 464 were randomized into the double-blind treatment phase and 397 completed the study. Both isradipine and enalapril decreased the sitting systolic blood pressure (SSBP) and SDBP during the high salt diet, to a similar degree, whereas enalapril caused a greater reduction in SSBP and SDBP than isradipine during the low salt diet (11.3 +/- 1.2/7.7 +/- 0.7 mm Hg v 7.7 +/- 0.9/4.8 +/- 0.6 mm Hg, mean +/- SEM, respectively, P < .02). Within drugs, the effect of isradipine on blood pressure (BP) was higher during the high than the low salt diet (14.9 +/- 1.5 v 7.6 +/- 1.3 mm Hg for SSBP and 10.1 +/- 0.6 v 4.8 +/- 0.9 mm Hg for SDBP, P < .001), but enalapril exerted a similar effect during both diets. Because salt restriction lowered both SSBP and SDBP, the lowest BP achieved with both drugs were during the salt restriction phase.
Chrysant
S G
SG
Oklahoma Cardiovascular and Hypertension Center and the University of Oklahoma, Oklahoma City, USA. chrysantsg@pol.net
Weder
A B
AB
McCarron
D A
DA
Canossa-Terris
M
M
Cohen
J D
JD
Gunter
P A
PA
Hamilton
B P
BP
Lewin
A J
AJ
Mennella
R F
RF
Kirkegaard
L W
LW
Weir
M R
MR
Weinberger
M H
MH
D000367:Age Factors; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004311:Double-Blind Method; D004656:Enalapril / Q000494:pharmacology*; D005260:Female; D018565:Food-Drug Interactions / Q000502:physiology; D006801:Humans; D006973:Hypertension / Q000503:physiopathology*; D017275:Isradipine / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D010349:Patient Compliance; D012737:Sex Factors; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage* / Q000009:adverse effects*; D013997:Time Factors
D000806:Angiotensin-Converting Enzyme Inhibitors; D002121:Calcium Channel Blockers; D017673:Sodium Chloride, Dietary; D004656:Enalapril; D017275:Isradipine