Randomised double-blind comparison of placebo and active treatment for older patients with isolated systolic hypertension

Staessen, Jan A.; Fagard, Robert; Thijs, Lutgarde; Celis, Hilde; Арабидзе, Г Г; Birkenhäger, W. H.; Bulpitt, C J; Leeuw, Peter W. de; Dollery, C. T.; Fletcher, Astrid; Forette, Françoise; Leonetti, Gastone; Nachev, C; O’Brien, Eoin; Rosenfeld, J; Rodicio, José L.; Tuomilehto, Jaakko; Zanchetti, Alberto

doi:10.1016/s0140-6736(97)05381-6

Cited by 2,693 publications

(1,625 citation statements)

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“…9 At the risk observed in the placebo group (intentionto-treat analysis), treating 1000 patients for 5 years could prevent 29 strokes or 53 major cardiovascular events. 3 Similar findings were obtained in two placebo-controlled trials in China, in which antihypertensive treatment was also started with a dihydropyridine. 10,11 In spite of the positive results in placebo-controlled outcome trials, 3,10,11 the controversy on the use of calcium-channel blockers as first-line antihypertensive agents continues.…”

Section: Rationale and Objective Of Syst-eursupporting

confidence: 67%

“…[5][6][7][8] The Syst-Eur trial proved that antihypertensive treatment starting with the dihydropyridine nitrendipine 2 reduced the risk of fatal and non-fatal stroke and cardiovascular complications in older (у60 years) patients with isolated systolic hypertension (systolic blood pressure у160 mm Hg and diastolic blood pressure Ͻ95 mm Hg). 3 Cardiovascular benefit was equally observed in the patients remaining on monotherapy with nitrendipine as in those pro-gressing to combined treatment with nitrendipine plus enalapril, hydrochlorothiazide, or both drugs. 9 At the risk observed in the placebo group (intentionto-treat analysis), treating 1000 patients for 5 years could prevent 29 strokes or 53 major cardiovascular events.…”

Section: Rationale and Objective Of Syst-eurmentioning

confidence: 98%

“…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.…”

Section: Introductionmentioning

confidence: 99%

“…Indeed, in the intention-to-treat analysis, 3 active treatment decreased the overall stroke rate from 13.7 to 7.9 end-points per 1000 patient-years (−42%; P = 0.003) and the incidence of all cardiovascular complications from 33.9 to 23.3 end-points per 1000 patient-years (−31%; P Ͻ 0.001). 3 At the rates observed in the placebo group, treating 1000 patients for 5 years could prevent 29 strokes or 53 major cardiovascular endpoints. 3 Whereas analysis by intention-to-treat reduces bias due to selective withdrawals, it may underestimate the true effects of treatment by including all end-points in the calculations, regardless of whether they occurred on randomised therapy or on open-label medication.…”

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confidence: 99%

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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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Section: Rationale and Objective Of Syst-eursupporting

confidence: 67%

Section: Rationale and Objective Of Syst-eurmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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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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“…Medications used as monotherapies in the CCB and the RAS blocker classes provide effective BP lowering together with specific benefits of reductions in stroke and all‐cause death (with CCBs) and heart failure (RAS blockers) 11, 12. A CCB and RAS blocker in combination has been shown to offer benefit in terms of CV event reduction relative to placebo and other medication classes investigated in patients with isolated systolic hypertension13 and in those with multiple CV risk factors, including previous CV events, diabetes, and left ventricular hypertrophy 14, 15…”

mentioning

confidence: 99%

Nifedipine GITS/Candesartan Combination Therapy Lowers Blood Pressure Across Different Baseline Systolic and Diastolic Blood Pressure Categories: DISTINCT Study Subanalyses

Kjeldsen

Cha

Villa

et al. 2016

The Journal of Clinical Pharma

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DISTINCT was an 8‐week, double‐blind, randomized study to investigate the antihypertensive efficacy and safety of various nifedipine gastrointestinal treatment system (GITS)/candesartan cilexetil (N/C) dose combinations, vs respective monotherapies or placebo, in patients with diastolic blood pressure (DBP) ≥95 to <110 mm Hg. The current prespecified analysis compared BP reduction in participants with mild vs moderate baseline hypertension (ie, systolic [S]BP <160 mm Hg vs ≥160 mm Hg and DBP <100 mm Hg vs ≥100 mm Hg). A total of 1362 patients were analyzed by descriptive statistics. In all patient subgroups investigated, the NC combinations (ie, N: 20, 30, or 60 mg; C: 4, 8, 16, or 32 mg daily) provided greater SBP and DBP lowering and higher rates of BP control (defined as BP <140/90 mm Hg) than respective monotherapies or placebo, with greatest absolute BP reductions observed in the moderately elevated SBP or DBP subgroups. A trend to dose‐response relationship was observed in each subgroup. In each SBP and DBP subgroup, treatment‐related vasodilatory events (flushing, headache, or edema) were less frequent for patients receiving NC combination therapy than N monotherapy. These analyses support the use of calcium antagonist and angiotensin receptor blocker combination therapy in patients with both mild and moderate hypertension, for whom effective BP normalization and good drug tolerance would greatly reduce the risk of cardiovascular events.

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Perspectives on Isolated Systolic Hypertension in Elderly Patients

Vardan

Mookherjee²

2000

Archives of Family Medicine

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Until the mid-20th century, clinicians' concern was directed mainly to the systolic component of blood pressure. Later, however, when systolic blood pressure was found to be elevated with advancing age and decreased compliance of the arterial wall, it began to be considered an inevitable consequence of aging. Based on this belief, physicians often concluded that only the diastolic blood pressure elevation, which reflected peripheral vascular resistance, was harmful, while systolic hypertension was innocuous. Therapeutic intervention was practiced mainly for diastolic hypertension, and research protocols were based on the levels of diastolic blood pressure alone. In the 1950s, even when life insurance companies' actuarial data revealed that systolic and diastolic blood pressure elevations were hazardous to health, few clinicians took heed. In 1962, the World Health Organization also defined hypertension as a blood pressure level of 165/95 mm Hg or higher for intervention purposes. However, until the 1991 Systolic Hypertension in the Elderly Program (SHEP) trial, many physicians were reluctant to pay credence to the need for therapy of elevated systolic blood pressure (vide infra).

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Randomised double-blind comparison of placebo and active treatment for older patients with isolated systolic hypertension

Cited by 2,693 publications

References 30 publications

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

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

Nifedipine GITS/Candesartan Combination Therapy Lowers Blood Pressure Across Different Baseline Systolic and Diastolic Blood Pressure Categories: DISTINCT Study Subanalyses

Perspectives on Isolated Systolic Hypertension in Elderly Patients

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