Meeting NewsPerspective

In ICD, CRT-D trials, serious events declined over time

Valentina Kutyifa
Valentina Kutyifa

SAN FRANCISCO — In patients with HF enrolled in the MADIT studies of implantable cardioverter defibrillators and cardiac resynchronization therapy defibrillators, rates of ventricular arrhythmia events, sudden cardiac death and all-cause death declined over time, according to findings presented at the Heart Rhythm Society Annual Scientific Sessions.

“There are no comprehensive data available on the rate of ventricular arrhythmias or cause-specific death in clinical trials enrolling HF patients with ICD or CRT-D spanning almost 3 decades,” Valentina Kutyifa, MD, PhD, FESC, associate professor of medicine at the University of Rochester Medical Center School of Medicine and Dentistry, said during a press conference.

To obtain such data, Kutyifa and colleagues analyzed 4,066 patients from the MADIT-II (mean age, 64 years; 16% women), MADIT-CRT (mean age, 63 years; 25% women) and MADIT-RIT (mean age, 63 years; 29% women) trials. MADIT-II enrolled from 1997 to 2001, MADIT-CRT from 2004 to 2008 and MADIT-RIT from 2009 to 2011.

The outcomes of interest were life-threatening ventricular arrhythmias, defined as ventricular tachycardia (VT) of at least 200 beats per minute (bpm) or ventricular fibrillation (VF), all-cause mortality and specific causes of death. The researchers accounted for competing death risks.

According to the researchers, the MADIT-II cohort had higher rates of the following outcomes than the MADIT-CRT and MADIT-RIT cohorts: VT/VF (P < .001), VT/VF of at least 200 bpm (P = .004), death (P < .001), sudden cardiac death (P < .001) and death from causes other than sudden cardiac arrest (P < .001).

Compared with MADIT-II, the cumulative percent reduction in death was –62% for MADIT-CRT and –57% for MADIT-RIT, the cumulative percent reduction in VT/VF was –26% for MADIT-CRT and –35% for MADIT-RIT, suggesting a greater reduction in death compared with the reduction in ventricular arrhythmia events, likely due to improved medical management of these patients, Kutyifa said.

After multivariable adjustment, VT/VF of at least 200 bpm was significantly lower in MADIT-RIT compared with MADIT-II (HR = 0.69; 95% CI, 0.5-0.96), but that was not the case for MADIT-CRT compared with MADIT-II, she said.

A multivariable analysis of death favored the MADIT-CRT group (HR = 0.6; 95% CI, 0.43-0.84) and the MADIT-RIT group (HR = 0.5; 95% CI, 0.35-0.71) over the MADIT-II group, according to the researchers. Both groups also had lower risk for sudden cardiac death and the MADIT-RIT group also had lower risk for nonsudden cardiac death compared with the MADIT-II group.

“Interestingly, we also found that among patients with a wide QRS, CRT was linked with a significantly lower rate of life-threatening ventricular arrhythmia events across the MADIT trials, while among those with a narrow QRS and an implanted ICD, the rate of life-threatening ventricular arrhythmic events has not declined over the past 3 decades,” Kutyifa told Cardiology Today.

“We have shown a change over time in the risk of ventricular arrhythmia events, sudden cardiac death and nonsudden cardiac death in HF patients with an ICD or CRT-D enrolled in the MADIT studies during the past 3 decades,” Kutyifa said during the press conference. “The risk of mortality showed a proportionally greater decline compared to the reduction in VT/VF events, suggesting that ICD therapy is still warranted for primary prevention in low EF patients. At least part of the reduction observed in VT/VF appears to be explained by the beneficial effects of CRT-D in ischemic patients with a wide QRS. Accordingly, our findings suggest the need for further studies on contemporary risk stratification strategies in low EF patients that will account for the use of CRT and improved medical management.” – by Erik Swain

Reference:

Kutyifa V, et al. LBCT02-02. Presented at: Heart Rhythm Society Annual Scientific Sessions; May 8-11, 2019; San Francisco.

Disclosure: Kutyifa reports she has received research grants from Biotronik, Boston Scientific and Zoll and consultant fees from Biotronik and Zoll.

Valentina Kutyifa
Valentina Kutyifa

SAN FRANCISCO — In patients with HF enrolled in the MADIT studies of implantable cardioverter defibrillators and cardiac resynchronization therapy defibrillators, rates of ventricular arrhythmia events, sudden cardiac death and all-cause death declined over time, according to findings presented at the Heart Rhythm Society Annual Scientific Sessions.

“There are no comprehensive data available on the rate of ventricular arrhythmias or cause-specific death in clinical trials enrolling HF patients with ICD or CRT-D spanning almost 3 decades,” Valentina Kutyifa, MD, PhD, FESC, associate professor of medicine at the University of Rochester Medical Center School of Medicine and Dentistry, said during a press conference.

To obtain such data, Kutyifa and colleagues analyzed 4,066 patients from the MADIT-II (mean age, 64 years; 16% women), MADIT-CRT (mean age, 63 years; 25% women) and MADIT-RIT (mean age, 63 years; 29% women) trials. MADIT-II enrolled from 1997 to 2001, MADIT-CRT from 2004 to 2008 and MADIT-RIT from 2009 to 2011.

The outcomes of interest were life-threatening ventricular arrhythmias, defined as ventricular tachycardia (VT) of at least 200 beats per minute (bpm) or ventricular fibrillation (VF), all-cause mortality and specific causes of death. The researchers accounted for competing death risks.

According to the researchers, the MADIT-II cohort had higher rates of the following outcomes than the MADIT-CRT and MADIT-RIT cohorts: VT/VF (P < .001), VT/VF of at least 200 bpm (P = .004), death (P < .001), sudden cardiac death (P < .001) and death from causes other than sudden cardiac arrest (P < .001).

Compared with MADIT-II, the cumulative percent reduction in death was –62% for MADIT-CRT and –57% for MADIT-RIT, the cumulative percent reduction in VT/VF was –26% for MADIT-CRT and –35% for MADIT-RIT, suggesting a greater reduction in death compared with the reduction in ventricular arrhythmia events, likely due to improved medical management of these patients, Kutyifa said.

After multivariable adjustment, VT/VF of at least 200 bpm was significantly lower in MADIT-RIT compared with MADIT-II (HR = 0.69; 95% CI, 0.5-0.96), but that was not the case for MADIT-CRT compared with MADIT-II, she said.

A multivariable analysis of death favored the MADIT-CRT group (HR = 0.6; 95% CI, 0.43-0.84) and the MADIT-RIT group (HR = 0.5; 95% CI, 0.35-0.71) over the MADIT-II group, according to the researchers. Both groups also had lower risk for sudden cardiac death and the MADIT-RIT group also had lower risk for nonsudden cardiac death compared with the MADIT-II group.

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“Interestingly, we also found that among patients with a wide QRS, CRT was linked with a significantly lower rate of life-threatening ventricular arrhythmia events across the MADIT trials, while among those with a narrow QRS and an implanted ICD, the rate of life-threatening ventricular arrhythmic events has not declined over the past 3 decades,” Kutyifa told Cardiology Today.

“We have shown a change over time in the risk of ventricular arrhythmia events, sudden cardiac death and nonsudden cardiac death in HF patients with an ICD or CRT-D enrolled in the MADIT studies during the past 3 decades,” Kutyifa said during the press conference. “The risk of mortality showed a proportionally greater decline compared to the reduction in VT/VF events, suggesting that ICD therapy is still warranted for primary prevention in low EF patients. At least part of the reduction observed in VT/VF appears to be explained by the beneficial effects of CRT-D in ischemic patients with a wide QRS. Accordingly, our findings suggest the need for further studies on contemporary risk stratification strategies in low EF patients that will account for the use of CRT and improved medical management.” – by Erik Swain

Reference:

Kutyifa V, et al. LBCT02-02. Presented at: Heart Rhythm Society Annual Scientific Sessions; May 8-11, 2019; San Francisco.

Disclosure: Kutyifa reports she has received research grants from Biotronik, Boston Scientific and Zoll and consultant fees from Biotronik and Zoll.

    Perspective
    Daniel J. Cantillon

    Daniel J. Cantillon

    The MADIT analysis was very interesting to me. The main take-home message is that we are missing the mark of whom we are implanting defibrillators in with the current guidelines. In the 3-year reports from all the MADIT trials included in this analysis, the majority of patients who have defibrillators don’t need them by the 3-year mark, but at the same time, a very large number of sudden cardiac arrests happen worldwide in patients who don’t have defibrillators. This calls for us as a community to work to refine our ICD indications so we are better at getting these devices into the patients likely to need them. There has been decades of work in this space, going back to things like T-wave alternans and other novel modalities for predicting sudden cardiac arrest risk. It is very complicated. But these data make us realize we have to roll up our sleeves and try to understand sudden cardiac arrest better at a mechanistic level so we can translate that into better practice guidelines for utilization of these resources.

    A limitation of reporting that event rates went down over time is that these were three different trials with three different kinds of patients in different eras with different programming strategies. It’s important to look at these differences in event rates with that in mind.

    • Daniel J. Cantillon, MD, FACC, FHRS
    • Cardiology Today Next Gen Innovator
      Staff Physician, Section of Electrophysiology and Pacing
      Robert and Suzanne Tomsich Department of Cardiovascular Medicine
      Sydell and Arnold Miller Family Heart & Vascular Institute
      Medical Director, Central Monitoring Unit
      Cleveland Clinic

    Disclosures: Cantillon reports he consults for or serves on scientific advisory boards and steering committees for Abbott, Boston Scientific and Stryker Sustainability.

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