Effect on Survival and Hospitalization of Initiating Treatment for Chronic Heart Failure With Bisoprolol Followed by Enalapril, as Compared With the Opposite Sequence

Abstract

on behalf of the CIBIS III InvestigatorsBackground-In patients with chronic heart failure (CHF), a ␤-blocker is generally added to a regimen containing an angiotensin-converting-enzyme (ACE) inhibitor. It is unknown whether ␤-blockade as initial therapy may be as useful. Methods and Results-We randomized 1010 patients with mild to moderate CHF and left ventricular ejection fraction Յ35%, who were not receiving ACE inhibitor, ␤-blocker, or angiotensin receptor blocker therapy, to open-label monotherapy with either bisoprolol (target dose 10 mg QD; nϭ505) or enalapril (target dose 10 mg BID; nϭ505) for 6 months, followed by their combination for 6 to 24 months. The 2 strategies were blindly compared with regard to the combined primary end point of all-cause mortality or hospitalization and with regard to each of these end point components individually. Bisoprolol-first treatment was noninferior to enalapril-first treatment if the upper limit of the 95% confidence interval (CI) for the absolute between-group difference was Ͻ5%, corresponding to a hazard ratio (HR) of 1.17. In the intention-to-treat sample, the primary end point occurred in 178 patients allocated to bisoprolol-first treatment versus 186 allocated to enalapril-first treatment (absolute difference Ϫ1.6%, 95% CI Ϫ7.6 to 4.4%, HR 0.94; 95% CI 0.77 to 1.16). In the per-protocol sample, 163 patients allocated to bisoprolol-first treatment had a primary end point, versus 165 allocated to enalapril-first treatment (absolute difference Ϫ0.7%, 95% CI Ϫ6.6 to 5.1%, HR 0.

Atualização da diretriz brasileira de insuficiência cardíaca crônica - 2012

“…O primeiro estudo com BB com maior número de pacientes foi o estudo MDC, que incluiu 383 pacientes com cardiomiopatia dilatada idiopática e utilizou tartarato de metoprolol na dose alvo de 100-150 mg 92 . Obteve-se tendência a menor número de desfechos primários (p = 0,058) e de redução de pressão de capilar pulmonar (p = 0,06), melhora da FEVE (p < 0,0001) e da capacidade de exercício (p = 0,046 97 . Recentemente, um estudo randomizado prospectivo com pequeno número de pacientes testou a manutenção de carvedilol versus substituição com propranolol (109 ± 43mg ao dia), mantendo o mesmo grau de betabloqueio avaliado através da frequência cardíaca semelhante em repouso e em exercício 98 .…”

“…Os BB são os fármacos de maior impacto na redução da morte súbita arrítmica em pacientes com IC, quer seja terapêutica combinada com IECA/BRA ou como monoterapia 89,90,97,115,116 . Também têm indicação na terapia adjuvante ao cardiodesfibrilador implantável (CDI), aumentando a sua eficácia na redução da morte súbita 117 .…”

Epidemiology and treatment of chronic heart failure; use of bisoprolol

“…A bisoprolollal szívelégtelenségben végzett, placebóval kontrollált mortalitástanulmányok főbb adatai [7][8][9] A CIBIS-II vizsgálatban már 2647 szívelégtelenség-ben szenvedő beteg vett részt (NYHA III-IV. stádium, ejekciós frakció ≤35%).…”

“…A három CIBIS tanulmány főbb adatait a 2. táblázat tartalmazza. A CIBIS-III tanulmány alapján szívelégtelenségben, amennyiben nincs jelentős mennyiségű folyadékreten-ció, akkor ACE-gátlóval vagy béta-receptor-blokkolóval egyaránt el lehet kezdeni a kezelést, a betegek ezt kö-vetően amúgy is gyógyszer-kombinációt kapnak majd, de a dózisok feltitrálása az individuális gyógyszerválasz-tás miatt egyszerűbbé válik [1,9].…”

Cardiovascular clinical trials in Japan and controversies regarding prospective randomized open-label blinded end-point design

“…These end points might be defined by objective criteria, but if the attending physician deems the patient requires hospitalization or can be medically controlled in an outpatient setting is, for example, at the discretion of the physician. As shown in Table 2, most cardiovascular clinical trials with PROBE designs conducted in the West 18,19,[21][22][23][24][25][26][27][28][29][30][31][32][33] use only hard end points. In contrast, four major Japanese PROBEdesigned trials with clinical outcomes specified as primary end points used soft end points such as unstable angina, exacerbation of heart failure or coronary revascularization procedures.…”