Update on the Systolic Hypertension in Europe (Syst-Eur) Trial
1999; Lippincott Williams & Wilkins; Volume: 33; Issue: 6 Linguagem: Inglês
10.1161/01.hyp.33.6.1476
ISSN1524-4563
AutoresJan A. Staessen, Lutgarde Thijs, W. H. Birkenhäger, Christopher J. Bulpitt, Robert Fagard, on behalf of the Syst-Eur Investigators,
Tópico(s)Blood Pressure and Hypertension Studies
ResumoHomeHypertensionVol. 33, No. 6Update on the Systolic Hypertension in Europe (Syst-Eur) Trial Free AccessOtherPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessOtherPDF/EPUBUpdate on the Systolic Hypertension in Europe (Syst-Eur) Trial Jan A. Staessen, Lutgarde Thijs, Willem H. Birkenhäger, Christopher J. Bulpitt, Robert Fagard and on behalf of the Syst-Eur Investigators Jan A. StaessenJan A. Staessen From the Studiecoördinatiecentrum, Hypertensie en Cardiovasculaire Revalidatie Eenheid, Campus Gasthuisberg, Leuven, Belgium. , Lutgarde ThijsLutgarde Thijs From the Studiecoördinatiecentrum, Hypertensie en Cardiovasculaire Revalidatie Eenheid, Campus Gasthuisberg, Leuven, Belgium. , Willem H. BirkenhägerWillem H. Birkenhäger From the Studiecoördinatiecentrum, Hypertensie en Cardiovasculaire Revalidatie Eenheid, Campus Gasthuisberg, Leuven, Belgium. , Christopher J. BulpittChristopher J. Bulpitt From the Studiecoördinatiecentrum, Hypertensie en Cardiovasculaire Revalidatie Eenheid, Campus Gasthuisberg, Leuven, Belgium. , Robert FagardRobert Fagard From the Studiecoördinatiecentrum, Hypertensie en Cardiovasculaire Revalidatie Eenheid, Campus Gasthuisberg, Leuven, Belgium. and on behalf of the Syst-Eur Investigators on behalf of the Syst-Eur Investigators From the Studiecoördinatiecentrum, Hypertensie en Cardiovasculaire Revalidatie Eenheid, Campus Gasthuisberg, Leuven, Belgium. Originally published1 Jun 1999https://doi.org/10.1161/01.HYP.33.6.1476Hypertension. 1999;33:1476–1477The Syst-Eur trial was stopped after the second of 4 planned interim analyses, when predefined stopping rules1 revealed that active treatment diminished the incidence of stroke, the primary endpoint. The ethics committee unanimously resolved that all endpoints that had occurred before February 14, 1997, at 5 pm should be included in the final analysis. The long communication lines between the coordinating office and 198 centers in 23 countries made the practical implementation of this recommendation very difficult. The coordinating office had to strike a delicate balance between reporting long-awaited outcome results or postponing publication until a greater number of terminating report forms had been returned. In the initial Syst-Eur report,2 116 (5.1%) of 2297 placebo patients and 121 (5.0%) of 2398 patients randomized to active treatment were classified as lost to follow-up because in the preceding year no report had reached the coordinating office. However, after publication of the outcome results on September 13, 1997,2 efforts to locate all patients continued. This short letter provides an update based on the final Syst-Eur database.The number of patients lost to follow-up decreased to 61 (2.7%) in the placebo group and to 63 (2.6%) in the active-treatment group; 1559 and 1795 patients, respectively, were in double-blind follow-up, 147 and 135 had died, 283 and 150 were in supervised open follow-up, and 247 and 255 were in non-supervised follow-up. The number of patient-years accumulated in the placebo and active-treatment groups increased from 5709 to 5844 and from 5995 to 6140, respectively. The greater number of endpoints available for analysis did not affect the conclusions of the initial Syst-Eur report2 (Table). Fatal and non-fatal cancer (change with active treatment: −12%; 95% CI: −36% to 20%; P=0.42) and bleeding episodes not including cerebral and retinal hemorrhage (−9%; 95% CI: −50% to 65%; P=0.75) occurred with similar frequency in both treatment groups. Of the 4695 patients, 1994 (42.5%) had been recruited in eastern Europe. However, because of the longer follow-up of the western European patients (median: 3.4 versus 1.1 years), more deaths (230 versus 52) and non-fatal cardiovascular endpoints (176 versus 39) were noticed in western European patients.The number of Syst-Eur patients initially reported as lost to follow-up2 was substantially lower than, for instance, in the 176 general practices taking part in the Medical Research Council trial of mild hypertension (19%).3 In the final Syst-Eur database, the proportion of patients lost to follow-up is similar to that in the Hypertension Optimal Treatment trial (2.6%), which stopped according to plan after 1100 events and after all patients had been followed for at least 3 years.4 In conclusion, the Syst-Eur experience confirms that in large multicenter trials terminating early not all endpoints will be available when the main outcome results are published. Trial researchers should be encouraged to continue searching for unreported endpoints and to publish a final complete analysis. However, the update will not lead to different conclusions unless there was selective under-reporting of events in one treatment group. Table 1. Updated Endpoints in the Systolic Hypertension in Europe TrialNature of EndpointRate per 1000 Patient-Years (number of endpoints)Relative Difference With Rate in Placebo GroupPlacebo (n=2297)Active (n=2398)% Rate (95% CI)PMortalityTotal25.2 (147)22.0 (135)−13 (−31 to 10)0.28Cardiovascular14.0 (82)10.4 (64)−26 (−46 to 3)0.08Non-cardiovascular11.0 (64)10.8 (66)−2 (−30 to 38)0.94Non-fatal endpointsStroke10.4 (60)5.7 (35)−45 (−64, −17)0.004Cardiac endpoints12.8 (73)8.8 (53)−32 (−52, −2)0.04Fatal and non-fatal endpoints combinedStroke13.9 (80)8.0 (49)−42 (−60 to −18)0.002Cardiac endpoints120.9 (119)15.6 (94)−25 (−43 to −2)0.03Heart failure8.9 (51)6.6 (40)−26 (−51 to 12)0.16Myocardial infarction8.1 (47)5.9 (36)−27 (−53 to 12)0.16All fatal and non-fatal cardiovascular endpoints34.6 (194)24.2 (145)−30 (−44 to −13)<0.0011Non-fatal and fatal cardiac endpoints included fatal and non-fatal heart failure, fatal and non-fatal myocardial infarction, and sudden death.FootnotesCorrespondence to Jan A. Staessen, MD, PhD, Studiecoördinatiecentrum, Hypertensie en Cardiovasculaire Revalidatie Eenheid, Campus Gasthuisberg, Herestraat 29, B-3000 Leuven, Belgium. References 1 Amery A, Birkenhäger W, Bulpitt CJ, Clement D, De Leeuw P, Dollery CT, Fagard R, Fletcher A, Forette F, Leonetti G, O'Brien ET, O'Malley K, Rodicio JL, Rosenfeld J, Staessen J, Strasser T, Terzoli L, Thijs L, Tuomilehto J, Webster J. Syst-Eur. A multicentre trial on the treatment of isolated systolic hypertension in the elderly: objectives, protocol, and organization. Aging (Milano).1991; 3:287–302.MedlineGoogle Scholar2 Staessen JA, Fagard R, Thijs L, Celis H, Arabidze GG, Birkenhager WH, Bulpitt CJ, de Leeuw PW, Dollery CT, Fletcher AE, Forette F, Leonetti G, Nachev C, O'Brien ET, Rosenfeld J, Rodicio JL, Tuomilehto J, Zanchetti A. Randomised double-blind comparison of placebo and active treatment for older patients with isolated systolic hypertension. The Systolic Hypertension in Europe (Syst-Eur) Trial Investigators. Lancet.1997; 350:757–764.CrossrefMedlineGoogle Scholar3 Medical Research Council Working Party. MRC trial of treatment of mild hypertension: principal results. Br Med J.1985; 291:97–104.CrossrefMedlineGoogle Scholar4 Hansson L, Zanchetti A, Carruthers SG, Dahlof B, Elmfeldt D, Julius S, Menard J, Rahn KH, Wedel H, Westerling S. Effects of intensive blood pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. The HOT Study Group. 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Krasińska B, Cofta S, Szczepaniak-Chicheł L, Rzymski P, Trafas T, Paluszkiewicz L, Tykarski A and Krasiński Z (2019) The Effects of Eplerenone on the Circadian Blood Pressure Pattern and Left Ventricular Hypertrophy in Patients with Obstructive Sleep Apnea and Resistant Hypertension—A Randomized, Controlled Trial, Journal of Clinical Medicine, 10.3390/jcm8101671, 8:10, (1671) Hara A, Thijs L, Asayama K, Jacobs L, Wang J, Staessen J and Fuchs F (2014) Randomised Double-Blind Comparison of Placebo and Active Drugs for Effects on Risks Associated with Blood Pressure Variability in the Systolic Hypertension in Europe Trial, PLoS ONE, 10.1371/journal.pone.0103169, 9:8, (e103169) Verdecchia P, Angeli F, Cavallini C, Gattobigio R, Gentile G, Staessen J and Reboldi G (2008) Blood pressure reduction and renin-angiotensin system inhibition for prevention of congestive heart failure: a meta-analysis, European Heart Journal, 10.1093/eurheartj/ehn575, 30:6, (679-688) June 1999Vol 33, Issue 6 Advertisement Article InformationMetrics https://doi.org/10.1161/01.HYP.33.6.1476 Manuscript receivedMarch 23, 1999Manuscript acceptedApril 2, 1999Originally publishedJune 1, 1999 PDF download Advertisement
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