Dihydropyridine calcium-channel blockers for antihypertensive treatment in older patients--evidence from the Systolic Hypertension in Europe Trial.
OBJECTIVE
The Syst-Eur study investigated whether active antihypertensive treatment could reduce cardiovascular complications in elderly patients with isolated systolic hypertension.


METHODS
Randomised, placebo-controlled, double-blind outcome trial.


METHODS
Hypertension clinics or general practitioners' surgeries in 198 centres in 23 Western and Eastern European countries.


METHODS
Patients aged > or = 60 years with sitting systolic blood pressure (BP) 160-219 mmHg and sitting diastolic BP < 95 mmHg during run-in phase.


RESULTS
Four thousand, six hundred and ninety-five patients were randomly assigned to active treatment (N = 2,398), i.e. nitrendipine, with the possible addition of enalapril and hydrochlorothiazide, or to matching placebos (N = 2,297). In the intention-to-treat analysis, the between-group difference in blood pressure (BP) amounted to 10.1/4.5 mmHg (P < 0.001). Active treatment reduced the incidence of fatal and non-fatal stroke (primary endpoint) by 42% (P = 0.003). On active treatment all cardiac endpoints decreased by 26% (P = 0.03) and all cardiovascular endpoints by 31% (P < 0.001). Cardiovascular mortality was slightly lower on active treatment (-27%, P = 0.07), but all-cause mortality was not influenced (-14%, P = 0.22). For total (P = 0.009) and cardiovascular mortality (P = 0.09), the benefit of antihypertensive treatment weakened with advancing age, and for total mortality it decreased with lower systolic BP at entry (P = 0.05). The benefits of active treatment were not independently related to sex or to the presence of cardiovascular complications at entry. The antihypertensive regimen was more effective in patients with diabetes than in those without diabetes at entry. Further analyses also suggested benefit in patients who were taking nitrendipine as the sole therapy. The per-protocol analysis largely confirmed the intention-to-treat results. Active treatment reduced all strokes by 44% (P = 0.004), all cardiac endpoints by 26% (P = 0.05) and all cardiovascular endpoints by 32% (P < 0.001). Total mortality was reduced by 26% (P = 0.05), but a similar reduction in cardiovascular mortality did not reach statistical significance in this analysis. Compared with placebo, active treatment also reduced the incidence of dementia by 50%.


CONCLUSIONS
Stepwise antihypertensive drug treatment, starting with the dihydropiridine calcium-channel blocker nitrendipine, improves prognosis in elderly patients with isolated systolic hypertension.
Staessen
J A
JA
Studiecoördinatiecentrum, Laboratorium Hypertensie, Campus Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium.
Thijs
L
L
Celis
H
H
Gasowski
J
J
Wang
J G
JG
Fagard
R H
RH
D000368:Aged; D000428:Alcohol Drinking; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000209:etiology / Q000517:prevention & control*; D004095:Dihydropyridines / Q000627:therapeutic use*; D004311:Double-Blind Method; D005060:Europe; D005260:Female; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009568:Nitrendipine / Q000627:therapeutic use*; D011379:Prognosis; D012907:Smoking / Q000009:adverse effects; D016896:Treatment Outcome
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; C038806:1,4-dihydropyridine; D009568:Nitrendipine