SCOPE

SCOPE^? : Study on Congnition and Prognosis in the Elderly.

Lithell H, Hansson L, Skoog I, Elmfeldt D, Hofman A, Olofsson B, Trenkwalder P, Zanchetti A ; SCOPE Study Group. The Study on Cognition and Prognosis in the Elderly (SCOPE) : principal results of a randomized double-blind intervention trial. J Hypertens. 2003 ;21:875-86. 12714861

Cette étude a inclus 4 964 patients âgés de 70 à 89 ans qui recevaient soit un ARA2^? (candésartan) soit un placebo. Un autre traitement antihypertenseur pouvait être introduit et particulièrement le groupe placebo pouvait recevoir un diurétique thiazidique. Sur un critère principal d’évaluation reposant sur un événement cardiovasculaire majeur, un infarctus du myocarde ou un AVC^? non fatal, il n’a pas été observé de différence significative entre les deux stratégies. Cependant au regard des critères secondaires, l’incidence^? des AVC non fatals est moindre dans le groupe candésartan avec une RRR^? de - 27,8 %.

BACKGROUND :
The prognostic benefits of blood pressure lowering treatment in elderly hypertensive patients were established more than a decade ago, but are less clear in those with mildly to moderately elevated blood pressure.

OBJECTIVE :
To assess whether candesartan-based antihypertensive treatment in elderly patients with mildly to moderately elevated blood pressure confers a reduction in cardiovascular events, cognitive decline and dementia.

DESIGN :
Prospective, double-blind, randomized, parallel-group study conducted in 1997-2002.

SETTING AND PARTICIPANTS :
The study was of 4964 patients aged 70-89 years, with systolic blood pressure 160-179 mmHg, and/or diastolic blood pressure 90-99 mmHg, and a Mini Mental State Examination (MMSE) test score >or= 24. A total of 527 centres in 15 countries participated in the study.

INTERVENTION :
Patients were assigned randomly to receive the angiotensin receptor blocker candesartan or placebo, with open-label active antihypertensive therapy added as needed. As a consequence, active antihypertensive therapy was extensively used in the control group (84% of patients). Mean follow-up was 3.7 years.

MAIN OUTCOME MEASURES :
The primary outcome measure was major cardiovascular events, a composite of cardiovascular death, non-fatal stroke and non-fatal myocardial infarction. Secondary outcome measures included cardiovascular death, non-fatal and fatal stroke and myocardial infarction, cognitive function measured by the MMSE and dementia.

RESULTS :
Blood pressure fell by 21.7/10.8 mmHg in the candesartan group and by 18.5/9.2 mmHg in the control group. A first major cardiovascular event occurred in 242 candesartan patients and in 268 control patients ; risk reduction with candesartan was 10.9% [95% confidence interval (CI), -6.0 to 25.1, P = 0.19]. Candesartan-based treatment reduced non-fatal stroke by 27.8% (95% CI, 1.3 to 47.2, P = 0.04), and all stroke by 23.6% (95% CI, -0.7 to 42.1, P = 0.056). There were no significant differences in myocardial infarction and cardiovascular mortality. Mean MMSE score fell from 28.5 to 28.0 in the candesartan group and from 28.5 to 27.9 in the control group (P = 0.20). The proportions of patients who had a significant cognitive decline or developed dementia were not different in the two treatment groups.

CONCLUSIONS :
In elderly hypertensive patients, a slightly more effective blood pressure reduction during candesartan-based therapy, compared with control therapy, was associated with a modest, statistically non-significant, reduction in major cardiovascular events and with a marked reduction in non-fatal stroke. Cognitive function was well maintained in both treatment groups in the presence of substantial blood pressure reductions. Both treatment regimens were generally well tolerated.

Papademetriou V, Farsang C, Elmfeldt D, Hofman A, Lithell H, Olofsson B, Skoog I, Trenkwalder P, Zanchetti A ; Study on Cognition and Prognosis in the Elderly study group. Stroke prevention with the angiotensin II type 1-receptor blocker candesartan in elderly patients with isolated systolic hypertension : the Study on Cognition and Prognosis in the Elderly (SCOPE). J Am Coll Cardiol. 2004 Sep 15 ;44(6):1175-80. 15364316

OBJECTIVES :
The aim of this study was to test the hypothesis that the angiotensin II type 1 receptor blocker (ARB) candesartan can reduce the risk of stroke in elderly patients with isolated systolic hypertension (ISH^?).

BACKGROUND :
Isolated systolic hypertension is the predominant form of hypertension in the elderly, and stroke is the most common cardiovascular (CV) complication.

METHODS :
In the Study on Cognition and Prognosis in the Elderly (SCOPE), 4,964 patients age 70 to 89 years were randomly assigned to double-blind candesartan or placebo with open-label antihypertensive therapy (mostly thiazide diuretics) added as needed to control blood pressure. Of the 4,964 patients, 1,518 had ISH (systolic blood pressure >160 mm Hg and diastolic blood pressure <90 mm Hg). The present study is a predefined subgroup analysis of outcome results in the ISH patients.

RESULTS :
Of the ISH patients, 754 were randomized to the candesartan group and 764 to the control group. Over the study period, blood pressure was reduced by 22/6 mm Hg in the candesartan group and by 20/5 mm Hg in the control group (difference between treatments 2/1 mm Hg ; p = 0.101 and 0.064). A total of 20 fatal/non-fatal strokes occurred in the candesartan group (7.2/1,000 patient-years) and 35 in the control group (12.5/1,000 patient-years) ; relative risk (RR^?) was 0.58 (95% confidence interval 0.33 to 1.00), that is, a RR reduction of 42% (p = 0.050 unadjusted, p = 0.049 adjusted for baseline risk). There were no marked or statistically significant differences between the treatment groups in other CV end points or all-cause mortality.

CONCLUSIONS :
In elderly patients with ISH, antihypertensive treatment based on the ARB candesartan resulted in a significant 42% RR reduction in stroke in comparison with other antihypertensive treatment, despite little difference in blood pressure reduction.