Cardiac resynchronization therapy: a meta-analysis of randomized controlled trials

Abstract

Background: Studies of cardiac resynchronization therapy in addition to an implantable cardioverter defibrillator in patients with mild to moderate congestive heart failure had not been shown to reduce mortality until the recent RAFT trial (Resynchronization/Defibrillation for Ambulatory Heart Failure Trial). We performed a meta-analysis including the RAFT trial to determine the effect of cardiac resynchronization therapy with or without an implantable defibrillator on mortality.

Methods: We searched electronic databases and other sources for reports of randomized trials using a parallel or crossover design. We included studies involving patients with heart failure receiving optimal medical therapy that compared cardiac resynchronization therapy with optimal medical therapy alone, or cardiac resynchronization therapy plus an implantable defibrillator with a standard implantable defibrillator. The primary outcome was mortality. The optimum information size was considered to assess the minimum amount of information required in the literature to reach reliable conclusions about cardiac resynchronization therapy.

Results: Of 3071 reports identified, 12 studies (n = 7538) were included in our meta-analysis. Compared with optimal medical therapy alone, cardiac resynchronization therapy plus optimal medical therapy significantly reduced mortality (relative risk [RR] 0.73, 95% confidence interval [CI] 0.62-0.85). Compared with an implantable defibrillator alone, cardiac resynchronization therapy plus an implantable defibrillator significantly reduced mortality (RR 0.83, 95% CI 0.72-0.96). This last finding remained significant among patients with New York Heart Association (NYHA) class I or II disease (RR 0.80, 95% CI 0.67-0.96) but not among those with class III or IV disease (RR 0.84, 95% CI 0.69-1.07). Analysis of the optimum information size showed that the sequential monitoring boundary was crossed, which suggests no need for further clinical trials.

Interpretation: The cumulative evidence is now conclusive that the addition of cardiac resynchronization to optimal medical therapy or defibrillator therapy significantly reduces mortality among patients with heart failure.

Figure 1:

Flow diagram of selection of studies for the meta-analysis.

Figure 2:

Results of random-effects meta-analysis of overall mortality among patients with heart failure given cardiac resynchronization therapy (CRT) in addition to optimal medical therapy (OMT) or implantable cardioverter defibrillator (ICD). Values less than 1.0 indicate a decreased risk of death with cardiac resynchronization therapy. Note CI = confidence interval, RR = relative risk. For complete study names, see Box 1. *All patients received optimal medical therapy.

Figure 3:

Results of random-effects meta-analysis of overall mortality among patients with heart failure given cardiac resynchronization therapy plus an implantable cardioverter defibrillator (CRT-ICD) versus an implantable defibrillator (ICD), by New York Heart Association (NYHA) class. Values less than 1.0 indicate a decreased risk of death with cardiac resynchronization therapy. Note CI = confidence interval, RR = relative risk. For complete study names, see Box 1. *All patients received optimal medical therapy.

Figure 4:

Cumulative meta-analysis of the effect on overall mortality of cardiac resynchronization therapy in addition to optimal medical therapy or implantable defibrillator therapy among patients with mildly symptomatic or advanced heart failure. With the addition of the RAFT study, the cumulative Z score crosses the Lan–DeMets sequential monitoring boundary, which indicates that the cumulative evidence supporting cardiac resynchronization therapy in addition to optimal medical therapy or defibrillator therapy is now conclusive. For complete study names, see Box 1.