Asymptomatic or mildly symptomatic cardiac patients randomised to an implanted cardiac resynchronisation device with defibrillator (CRT-D) have a 34% lower risk of heart failure or death than those receiving a standard implanted cardioverter defibrillator (ICD-only) (HR 0.66, p=0.001), according to results from the MADIT-CRT (Multicenter automatic defibrillator implantation trial with cardiac resynchronisation therapy) study.
The results were published by the New England Journal of Medicine and presented during a Hotline session at the annual European Society of Cardiology (ESC) Congress in Barcelona, Spain.
The MADIT-CRT study was a randomised trial designed to determine if CRT-D therapy would reduce the primary endpoint (all-cause mortality or heart failure events, whichever occurred first) when compared to patients receiving ICD-only therapy. The study population involved cardiac patients in New York Heart Functional Class I or II (no or mild symptoms) who had either ischaemic or non-ischaemic heart disease with left ventricular dysfunction (ejection fraction <30%) and QRS duration of >130ms on ECG.
Cardiac resynchronisation therapy (CRT) with or without a defibrillator is indicated for use in patients with severe heart failure (New York Heart Association Class III/IV), and CRT has been shown to reduce symptoms, mortality and hospitalisation in very sick cardiac patients. The question that remained was whether CRT would improve heart function and slow or prevent the development of heart failure in the less severe NYHA class I/II cardiac patients (moderately high risk, but with no or mild symptoms) by intervening early in the course of the disease before the development of advanced symptoms.
The MADIT-CRT trial enrolled and followed 1,820 patients from 110 centres in Europe, Canada, and the US during a 4.5-year period between December 2004 and 22 June 2009, when the trial was officially ended because of the superiority of the cardiac resynchronisation therapy (p=0.001). Patients were randomised in a 3:2 fashion to receive either CRT-D or ICD alone, and all patients received optimal medical therapy for heart failure during the trial.
The superiority of CRT-D therapy was found to be present in all patient sub-groups, including those with ischaemic and non-ischaemic types of heart disease, as well as in males and females, younger and older patients, and those with mild and more advanced heart dysfunction.
Commenting on the results, the study’s principal investigator, Arthur J Moss from the University of Rochester Medical Center, New York, US, said: “Cardiac resynchronisation therapy was dramatically effective in this large study population, with a 34% reduction in the risk of all-cause mortality or heart failure. The benefit is dominated by a 41% reduction in heart failure events. These results validate a new indication for cardiac resynchronisation therapy in the prevention of heart failure in at-risk asymptomatic or mildly symptomatic cardiac patients. It seems likely that this preventive CRT-D therapy will have widespread application and utilisation.”
“The MADIT-CRT Executive Committee anticipated that the benefit for the CRT-D therapy group would be dominated by a reduction in heart failure events and the data overwhelmingly confirm that,” said Moss. “Furthermore, CRT-D therapy showed an equal benefit in both ischaemic and non-ischaemic patients. The MADIT-CRT data are compelling and help bridge a clinical gap in our understanding of heart failure in Class I and II patients.”
The study was sponsored by Boston Scientific.