Effects of immediate versus delayed antihypertensive therapy on outcome in the Systolic Hypertension in Europe Trial.
BACKGROUND
To assess the impact of immediate versus delayed antihypertensive treatment on the outcome of older patients with isolated systolic hypertension, we extended the double-blind placebo-controlled Systolic Hypertension in Europe (Syst-Eur) trial by an open-label follow-up study lasting 4 years.


METHODS
The Syst-Eur trial included 4695 randomized patients with minimum age of 60 years and an untreated blood pressure of 160-219 mmHg systolic and below 95 mmHg diastolic. The double-blind trial ended after a median follow-up of 2.0 years (range 1-97 months). Of 4409 patients still alive, 3517 received open-label treatment consisting of nitrendipine (10-40 mg daily) with the possible addition of enalapril (5-20 mg daily), hydrochlorothiazide (12.5-25 mg daily), or both add-on drugs. Non-participants (n = 892) were also followed up.


RESULTS
Median follow-up increased to 6.1 years. Systolic pressure decreased to below 150 mmHg (target level) in 2628 participants (75.0%). During the 4-year open-label follow-up, stroke and cardiovascular complications occurred at similar frequencies in patients formerly randomized to placebo and those continuing active treatment. These rates were similar to those previously observed in the active-treatment group during the double-blind trial. Considering the total follow-up of 4695 randomized patients, immediate compared with delayed antihypertensive treatment reduced the occurrence of stroke and cardiovascular complications by 28% (P = 0.01) and 15% (P = 0.03), respectively, with a similar tendency for total mortality (13%, P = 0.09). In 492 diabetic patients, the corresponding estimates of long-term benefit (P < 0.02) were 60, 51 and 38%, respectively.


CONCLUSIONS
Antihypertensive treatment can achieve blood pressure control in most older patients with isolated systolic hypertension. Immediate compared with delayed treatment prevented 17 strokes or 25 major cardiovascular events per 1000 patients followed up for 6 years. These findings underscore the necessity of early treatment of isolated systolic hypertension.
Staessen
Jan A
JA
Thijisq
Lutgarde
L
Fagard
Robert
R
Celis
Hilde
H
Birkenhäger
Willem H
WH
Bulpitt
Christopher J
CJ
de Leeuw
Peter W
PW
Fletcher
Astrid E
AE
Forette
François
F
Leonetti
Gastone
G
McCormack
Patricia
P
Nachev
Choudomir
C
O'Brien
Eoin
E
Rodicio
José L
JL
Rosenfeld
Joseph
J
Sarti
Cinzia
C
Tuomilehto
Jaakko
J
Webster
John
J
Yodfat
Yair
Y
Zanchetti
Alberto
A
D000368:Aged; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects*; D002121:Calcium Channel Blockers / Q000627:therapeutic use; D003920:Diabetes Mellitus / Q000188:drug therapy; D004095:Dihydropyridines / Q000627:therapeutic use; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004656:Enalapril / Q000008:administration & dosage; D005060:Europe / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000150:complications / Q000401:mortality; D006801:Humans; D006852:Hydrochlorothiazide / Q000008:administration & dosage; D006973:Hypertension / Q000188:drug therapy* / Q000401:mortality; D015994:Incidence; D016014:Linear Models; D008297:Male; D009203:Myocardial Infarction / Q000150:complications / Q000453:epidemiology; D009568:Nitrendipine / Q000008:administration & dosage; D020521:Stroke / Q000150:complications / Q000188:drug therapy; D015996:Survival Rate; D013997:Time Factors; D016896:Treatment Outcome
D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D006852:Hydrochlorothiazide; D004656:Enalapril; C038806:1,4-dihydropyridine; D009568:Nitrendipine