The Multicenter Automatic Defibrillator Implantation Trial – Cardiac Resynchronization Therapy (MADIT-CRT)
Status: Study met its primary endpoint June 2009.
MADIT-CRT is an important continuation of Boston Scientific’s sponsorship of landmark clinical trials such as MADIT, MADIT II, and COMPANION. MADIT-CRT is the world’s largest randomized NYHA Class I/II CRT-D trial and provides clinical evidence that early intervention with CRT can reduce death and heart failure events.
MADIT-CRT provides clinical evidence that in high-risk* NYHA Class I and II patients with LBBB, early CRT intervention reduces the relative risk of all-cause mortality or first heart failure event by 57% when compared to ICD therapy (p < 0.001).2
Further analysis shows:
- These impressive results were driven by a 35% relative reduction in the risk of all-cause mortality (p = 0.048) and a 63% relative reduction in the risk of first heart failure events (p < 0.001).1
- Notably, in the MADIT-CRT LBBB subgroup, 82% of the first heart failure events involved hospitalization.
- The Kaplan-Meier analysis reveals that improvement in the CRT-D arm is seen remarkably early — within a few months after implant — and continues for the duration of the trial.
- Delaying that first heart failure event in Class I and II patients is critical — in the MADIT-CRT trial, patients were 8 times more likely to have a recurring HF event after the initial event.
- Early CRT intervention reduces the relative risk of recurrent heart failure events by 43% in high-risk,3 NYHA Class I and II patients with LBBB.
In an exploratory analysis that is hypothesis-generating only, the MADIT-CRT LBBB subgroup experienced a 12% increase in LVEF with a CRT-D, as compared to a 3% increase with an ICD. Also, patients with a CRT-D experienced a greater reduction in left ventricular volumes.
* CRT therapy was ON during echographic measurements and may have influenced the results.
MADIT-CRT is the largest randomized NYHA Class I / II CRT-D trial to date
• Full Trial Population: 1820 patients
• LBBB Population: 1281 patients
- Male and female
- Over 21 years of age
- NYHA functional Class II, non-ischemic or ischemic cardiomyopathy or
- NYHA functional Class I, ischemic cardiomyopathy and
- Left ventricular dysfunction (LVEF ≤ 0.30) and
- Prolonged intraventricular conduction (QRS duration ≥ 130 ms) and
- Optimal HF pharmacologic therapy (OPT)
110 centers in 14 countries
- To determine whether CRT-D in high-risk* heart failure patients will reduce the combined endpoint of all cause mortality or HF intervention when compared to ICD therapy.
- Primary Endpoint: all-cause mortality or heart failure intervention, whichever occurs first.
- MADIT-CRT is an important continuation of Boston Scientific’s sponsorship of landmark clinical trials such as MADIT, MADIT II, and COMPANION. MADIT-CRT may prove that early intervention with CRT can slow the progression of heart failure.
- MADIT-CRT Study Design
Moss AJ, Brown MW, Cannom DS, et al. Multicenter Automatic Defibrillator Implantation Trial–Cardiac Resynchronization Therapy (MADIT-CRT): Design and clinical protocol. Ann Noninvasive Electrocardiol. 2005;10(4)(Suppl):34-43.
- MADIT-CRT Study Results
Moss AJ, Cannom DS, Brown MW, et al. Reduction in the Risk of Heart Failure Events with Preventive CRT (serial online). NEJM. Sept 2009 ePublication.
1. Left bundle branch block (LBBB) was not an inclusion parameter for the MADIT-CRT trial. However, a significant interaction between treatment and bundle branch block morphology was detected. Further analyses revealed that LBBB is an objective discriminator of patient benefit from CRT-D regardless of other baseline characteristics.
2. High-risk is defined as QRS width ≥ 130 ms, LVEF ≤ 30%, and LBBB
3. “Most likely” across the examined subgroups, including gender, NYHA Class, QRS width and bundle branch block morphology.