Is prevention of vascular dementia possible? The Syst-Eur Vascular Dementia Project

Forette, Françoise; Améry, A; Staessen, Jan A; Strasser, T.; Thijs, Lutgarde; Beevers, D. G.; Bert, P; Clément, Denis; Jl, Cox; Leeuw, Peter W. de; Plaen, J. F. De; Donnarel, G.; Escande, Marie-Christine; Fagard, Robert; Girerd, Xavier; Hickey, Aodhán; Pandita-Gunawardena, N. D.; Perilliat, I.; Ruilope, M.; Slovick, D I; Terzoli, L.; Varis, R.; Webster, Ruth

doi:10.1007/bf03324039

Cited by 24 publications

(18 citation statements)

References 53 publications

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“…104,[116][117][118] A significant correlation with hypertension exists in all forms of vascular dementia. [118][119][120][121] Other risk factors include increasing age, 122 low education, 123 coronary heart disease, 122,124 atrial fibrillation, 125 diabetes, [126][127][128] transient ischaemic attacks and cerebrovascular accidents, 124 high hematocrit level 120 and smoking.…”

Section: Vascular Dementiamentioning

confidence: 99%

Cerebral complications of hypertension

Rigaud

Staessen

et al. 2000

J Hum Hypertens

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Ischaemic and degenerative brain diseases are a major health problem leading to a devastating loss of autonomy. Hypertension has been shown to carry an increased risk not only for cerebrovascular morbidity and mortality but also for cognitive impairment and dementia. Although diastolic blood pressure is considered an important risk factor, it is now clear that isolated systolic hypertension and elevated pulse pressure also play an important role in the development of brain complications. Therefore the treatment of these conditions must urgently become a widespread tool of prevention. All the randomised placebo-controlled trials completed for the last 30 years have shown a reduction in fatal and/or non-fatal strokes. In the most recent trials in isolated systolic hypertension in older patients, the benefit was even greater because of the higher risk in these populations. The new classes of drugs, in particular, calcium-channels blockers and angiotensin-

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Section: Vascular Dementiamentioning

confidence: 99%

Cerebral complications of hypertension

Rigaud

Staessen

et al. 2000

J Hum Hypertens

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“…Finally, the vascular dementia project, set up in the framework of the Syst-Eur trial, [30][31][32] investigated whether antihypertensive drug treatment could reduce the incidence of dementia. Compared with placebo (n = 1180), active treatment (n = 1238) reduced the rate of dementia by 50% from 7.7 to 3.7 cases per 1000 patient-years (21 vs 11 patients in the intention-to-treat analysis, P = 0.05).…”

Section: Discussionmentioning

confidence: 99%

Systolic Hypertension in Europe (Syst-Eur) Trial Phase 2: objectives, protocol, and initial progress

Gąsowski¹,

Staessen²,

Celis³

et al. 1999

J Hum Hypertens

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on behalf of the Systolic Hypertension in Europe InvestigatorsThe Systolic Hypertension in Europe (Syst-Eur) trial proved that blood pressure (BP) lowering therapy starting with nitrendipine reduces the risk of cardiovascular complications in older (у60 years) patients with isolated systolic hypertension (systolic BP у160 mm Hg and diastolic BP Ͻ95 mm Hg). After the completion of the Syst-Eur trial on 14 February 1997, 3506 consenting patients (93.0% of those eligible) were enrolled in phase 2 of the Syst-Eur trial. This open follow-up study aims to confirm the safety of long-term antihypertensive therapy based on a dihydropyridine. To lower the sitting systolic BP below 150 mm Hg (target BP), the first-line agent nitrendipine (10-40 mg/day) may be associated with enalapril (5-20 mg/day), hydrochlorothiazide (12.5-25 mg/day), both add-on study drugs, or if required any other antihypertensive agent. On 1 November 1998, 3248 patients were still being followed, 86 patients had proceeded to non-supervised follow-up, and 43 had died. The median follow-up in Syst-Eur 2 was 14.3 months. At Keywords: calcium-channel blockade; elderly; dihydropyridine; isolated systolic hypertension IntroductionIn 1989 the European Working Party on High Blood Pressure in the Elderly started the placebo-controlled double-blind Systolic Hypertension in Europe trial (Syst-Eur). 1 Active treatment was initiated with the dihydropyridine calcium-channel blocker nitrendipine 2 with the possible addition of enalapril, hydrochlorothiazide or both drugs. The Syst-Eur trial stopped on 14 February 1997 according to predefined rules, 3 because the second of four planned interim analyses had shown a significant benefit for stroke, the primary end-point. 1 At the Syst-Eur investigators meeting in March 1997, the decision was taken to keep the Syst-Eur patients in followup. This article summarizes the rationale and protocol of this study, named Systolic Hypertension in Correspondence: Dr Jan A Staessen, Klinisch Laboratorium Hypertensie, Inwendige Geneeskunde-Cardiologie, UZ Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium Received 14 October 1998; accepted 21 October 1998 the last available visit, systolic/diastolic BP in the patients formerly randomised to placebo (n = 1682) or active treatment (n = 1824), had decreased by 13.2/5.2 mm Hg and by 4.6/1.6 mm Hg, respectively, so that the between-group BP difference was 1.7 mm Hg systolic (95% Cl: 0.8 to 2.6 mm Hg; P Ͻ 0.001) and 0.9 mm Hg diastolic (95% Cl: 0.4 to 1.5 mm mm Hg; P Ͻ 0.001). At the beginning of Syst-Eur 2, the goal BP was reached by 25.4% and 50.6% of the former placebo and activetreatment groups; at the last visit these proportions were 55.9% and 63.1%, respectively. At that moment, 45.9% of the patients were on monotherapy with nitrendipine, 29.3% took nitrendipine in combination with other study drugs. Until the end of 2001, BP control of the Syst-Eur 2 patients will be further improved. Cardiovascular complications and adverse events, such as cancer or gastro-intestinal bleeding, wi...

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“…21 Another novel finding in Syst-Eur was that the calcium antagonist therapy reduced the onset of dementia, which presumably is caused by microvascular disease in the brain, rather than dementia of the Alzheimer type. [24][25][26] This finding has prompted many of the new clinical trials now underway to include dementia as a new endpoint, treated with various drugs, including the new angiotensin-receptor blockers.…”

Section: Recent Calcium-channel Blocker Trials and Analysesmentioning

confidence: 99%

Clinical trial experience around the globe: Focus on calcium-channel blockers

White

2003

Clin Cardiol

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Summary:Although certain classes of drugs appear to possess benefits apart from their blood-pressure lowering capability, reduction of blood pressure remains the single most important action of antihypertensive therapy. Calcium-channel blockers (CCBs) have long been recognized as potent agents for hypertension therapy. This is especially true for the prevention of stroke in hypertensive patients as evidenced from the Systolic Hypertension in Europe (Syst-Eur) and Systolic Hypertension in China (Syst-China) trials with a long acting dihydropyridine CCB. The same can be said for beta blockers in patients post myocardial infarction. However, most recent clinical trials have underscored the necessity of multiple drug therapy to achieve the goals of blood pressure reduction coupled with outcomes reduction. For example, the many recent large-scale clinical trials have required an average of three or more agents to achieve goal. Thus, the paradigm for hypertension management has been altered to determine the best treatment regimen rather than the best initial agent. While response rates to individual agents across a wide spectrum of patients vary little, not all drugs are equally suited as companion products. In this article, we discuss the most recent outcome trials with the long acting CCBs alone or in combination with other drugs. The evidence shows that calcium antagonists remain an important part of hypertension management, including in those individuals at risk of cardiac and cerebrovascular events.

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Is prevention of vascular dementia possible? The Syst-Eur Vascular Dementia Project

Cited by 24 publications

References 53 publications

Cerebral complications of hypertension

Cerebral complications of hypertension

Systolic Hypertension in Europe (Syst-Eur) Trial Phase 2: objectives, protocol, and initial progress

Clinical trial experience around the globe: Focus on calcium-channel blockers

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