The Effect of Nisoldipine as Compared with Enalapril on Cardiovascular Outcomes in Patients with Non-Insulin-Dependent Diabetes and Hypertension

Estacio, Raymond O.; Jeffers, Barrett W.; Hiatt, William R.; Biggerstaff, Stacy L.; Gifford, Nancy; Schrier, Robert W.

doi:10.1056/nejm199803053381003

Cited by 1,051 publications

(535 citation statements)

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“…However, the FACET trial had an open design and events were monitored by 'asking' the patients if they had been hospitalized or had experienced any other event. In contrast to the ABCD trial, 18 the worse outcome on amlodipine compared with the converting-enzyme inhibitor was not due to myocardial infarction (13 vs 10), but was driven by hospitalized angina (4 vs 0) and stroke (10 vs 4). The interpretation of the FACET results 17 is also rendered difficult, because 58 patients randomised to fosinopril (30.7%) and 50 of the amlodipine group (26.2%) crossed over and received the combination of both drugs.…”

Section: Discussionmentioning

confidence: 61%

“…For this reason, a first-ever-event analysis could have been helpful to correctly interpret the ABCD results, but was not presented. 18 In the Fosinopril versus Amlodipine Cardiovascular Events Randomized Trial (FACET), 17 the patients receiving fosinopril had a significantly lower risk of the combined outcome of acute myocardial infarction, stroke, or hospitalized angina pectoris than those receiving amlodipine (14/189 vs 27/191 events). However, the FACET trial had an open design and events were monitored by 'asking' the patients if they had been hospitalized or had experienced any other event.…”

Section: Discussionmentioning

confidence: 99%

“…The median follow-up of 2 years in the Syst-Eur trial 3 may have been too short to reveal the suspected adverse effects of dihydropyridines, such as cancer, 12,13 gastrointestinal bleeding, 14 or coronary complications in patients with pre-existing coronary heart disease 4,15,16 or diabetes mellitus. [17][18][19][20][21][22] Syst-Eur 2 will answer these reservations. Of the patients enrolled, 2.3% already experienced a major cardiovascular complication prior to the end of the Syst-Eur trial proper, and 12.2% have diabetes mellitus.…”

Section: Discussionmentioning

confidence: 99%

“…One of the arguments used is that the median follow-up of the Syst-Eur patients was only 2 years and that therefore they may not have been exposed to nitrendipine 2 for a period sufficiently long to elicit adverse effects, such as cancer, 12,13 gastro-intestinal bleeding, 14 or coronary complications in patients with pre-existing coronary heart disease 4,15,16 or diabetes mellitus. [17][18][19][20][21][22] In keeping with the expert recommendation 8 that wellconducted observational studies may answer issues of drug safety, the Syst-Eur patients will remain in open follow-up to confirm the safety and, ultimately the cost-effectiveness, of antihypertensive therapy based on a dihydropyridine calcium-channel blocker.…”

Section: Rationale and Objective Of Syst-eurmentioning

confidence: 91%

“…Myocardial infarction was only one of the secondary endpoints. 18 Treatment status and the doses of the double-blind study medications at the time of the infarcts were not reported. Because more diuretics (119 vs 93; P = 0.02) and beta-blockers (95 vs 89; P = 0.04) were prescribed in the enalapril group, and because the study medication was stopped slightly more frequently in the nisoldipine group (142 vs 129; P = 0.22), overall, medical cardiovascular protection could have been unbalanced in favour of the enalapril group.…”

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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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: Discussionmentioning

confidence: 61%

Section: Discussionmentioning

confidence: 99%