FDA Advisory Committee Meeting

GAITHERSBURG, MD. – A Food and Drug Administration advisory panel narrowly voted to support expanding the approval of Medtronic’s Cardiac Resynchronization Therapy (CRT) devices to include patients with atrioventricular dysfunction and left ventricular systolic dysfunction.

At a meeting on Oct. 8, the Circulatory System Devices Panel voted 4-3, with one abstention, that the benefits of treatment with Medtronic’s CRT defibrillators and CRT pacemakers outweigh the risks for patients who meet the criteria in the company’s proposed indication for use – which the panel slightly modified before the vote.

Medtronic has proposed that approval of the company’s CRT-pacemaker (CRT-P) and CRT-defibrillator (CRT-D) devices be expanded to include treatment of patients who meet the following criteria: class I or class IIa indications for pacemaker implantation in accordance with American College of Cardiology/American Heart Association/Heart Rhythm Society guidelines, have New York Heart Association (NYHA) class I, II, or III heart failure, left ventricular ejection fraction (LVEF) less than or equal to 50%, with at least one of the following: third- or second-degree AV block; first-degree AV block with symptoms similar to pacemaker syndrome; or documented Wenckebach or PR interval greater than 300 ms when paced at 100 ppm. (Patients eligible for CRT-D also would need to be at risk of a life-threatening ventricular arrhythmia.)

The panel modified the proposed indication by dropping the segments on first-degree AV block and the documented Wenckebach or PR interval in response to issues that included uncertainty over whether this group of patients would benefit from treatment. This was changed to patients with first-degree AV block who are judged, with reliable confidence, to be in need of pacing most of the time.

The company’s proposed indication is based on the results of the BLOCK HF (Biventricular versus Right Ventricular Pacing in Heart Failure Patients with Atrioventricular Block) study, which randomized 691 patients with an indication for pacing with AV block; NYHA class I, II, or III heart failure; and a LVEF of 50% or less to right ventricular or biventricular pacing with a CRT-P or CRT-D.

The primary endpoint, a composite of death, an urgent care visit for HF that required intravenous therapy, or at least a 15% increase in the left ventricular end-systolic volume index (LVESVI), was met by 45.8% of those in the biventricular pacing arm vs. 55.8% of those in the right ventricular pacing arm, a statistically significant difference and a 27% reduction in risk of the primary outcome. The rate of left ventricular lead complications was 6.4% (N. Engl. J. Med. 2013;368:1585-93).

Currently, the CRT-P devices are approved for NYHA class III and IV patients who remain symptomatic despite stable, optimal medical therapy and have an LVEF of 35% or less and a prolonged QRS duration.

The CRT-D devices are approved for ventricular antitachycardia pacing and ventricular defibrillation for automated treatment of life-threatening ventricular arrhythmias, and for providing CRT in heart failure patients who remain symptomatic despite optimal medical therapy and meet any of the following classifications: NYHA class III or IV heart failure with an LVEF of 35% or less and a prolonged QRS duration; left bundle branch block with a QRS duration of 130 ms or more; an LVEF of 30% or less; and NYHA class II heart failure.

Panelists who said that the benefits did not outweigh the risks cited the potential long-term left ventricular lead complications as a concern. Those voting in favor also wrestled with this issue but agreed BLOCK HF was a well-conducted trial with results that some panelists found more compelling than others.

The FDA usually follows the recommendations of its advisory panels. Panelists have been cleared of potential conflicts of interest related to the topic of the meeting.

[email protected]

GAITHERSBURG, MD. – A Food and Drug Administration advisory panel narrowly voted to support expanding the approval of Medtronic’s Cardiac Resynchronization Therapy (CRT) devices to include patients with atrioventricular dysfunction and left ventricular systolic dysfunction.

At a meeting on Oct. 8, the Circulatory System Devices Panel voted 4-3, with one abstention, that the benefits of treatment with Medtronic’s CRT defibrillators and CRT pacemakers outweigh the risks for patients who meet the criteria in the company’s proposed indication for use – which the panel slightly modified before the vote.

Medtronic has proposed that approval of the company’s CRT-pacemaker (CRT-P) and CRT-defibrillator (CRT-D) devices be expanded to include treatment of patients who meet the following criteria: class I or class IIa indications for pacemaker implantation in accordance with American College of Cardiology/American Heart Association/Heart Rhythm Society guidelines, have New York Heart Association (NYHA) class I, II, or III heart failure, left ventricular ejection fraction (LVEF) less than or equal to 50%, with at least one of the following: third- or second-degree AV block; first-degree AV block with symptoms similar to pacemaker syndrome; or documented Wenckebach or PR interval greater than 300 ms when paced at 100 ppm. (Patients eligible for CRT-D also would need to be at risk of a life-threatening ventricular arrhythmia.)

The panel modified the proposed indication by dropping the segments on first-degree AV block and the documented Wenckebach or PR interval in response to issues that included uncertainty over whether this group of patients would benefit from treatment. This was changed to patients with first-degree AV block who are judged, with reliable confidence, to be in need of pacing most of the time.

The company’s proposed indication is based on the results of the BLOCK HF (Biventricular versus Right Ventricular Pacing in Heart Failure Patients with Atrioventricular Block) study, which randomized 691 patients with an indication for pacing with AV block; NYHA class I, II, or III heart failure; and a LVEF of 50% or less to right ventricular or biventricular pacing with a CRT-P or CRT-D.

The primary endpoint, a composite of death, an urgent care visit for HF that required intravenous therapy, or at least a 15% increase in the left ventricular end-systolic volume index (LVESVI), was met by 45.8% of those in the biventricular pacing arm vs. 55.8% of those in the right ventricular pacing arm, a statistically significant difference and a 27% reduction in risk of the primary outcome. The rate of left ventricular lead complications was 6.4% (N. Engl. J. Med. 2013;368:1585-93).

Currently, the CRT-P devices are approved for NYHA class III and IV patients who remain symptomatic despite stable, optimal medical therapy and have an LVEF of 35% or less and a prolonged QRS duration.

The CRT-D devices are approved for ventricular antitachycardia pacing and ventricular defibrillation for automated treatment of life-threatening ventricular arrhythmias, and for providing CRT in heart failure patients who remain symptomatic despite optimal medical therapy and meet any of the following classifications: NYHA class III or IV heart failure with an LVEF of 35% or less and a prolonged QRS duration; left bundle branch block with a QRS duration of 130 ms or more; an LVEF of 30% or less; and NYHA class II heart failure.

Panelists who said that the benefits did not outweigh the risks cited the potential long-term left ventricular lead complications as a concern. Those voting in favor also wrestled with this issue but agreed BLOCK HF was a well-conducted trial with results that some panelists found more compelling than others.

The FDA usually follows the recommendations of its advisory panels. Panelists have been cleared of potential conflicts of interest related to the topic of the meeting.

[email protected]

GAITHERSBURG, MD. – A Food and Drug Administration advisory panel narrowly voted to support expanding the approval of Medtronic’s Cardiac Resynchronization Therapy (CRT) devices to include patients with atrioventricular dysfunction and left ventricular systolic dysfunction.

At a meeting on Oct. 8, the Circulatory System Devices Panel voted 4-3, with one abstention, that the benefits of treatment with Medtronic’s CRT defibrillators and CRT pacemakers outweigh the risks for patients who meet the criteria in the company’s proposed indication for use – which the panel slightly modified before the vote.

Medtronic has proposed that approval of the company’s CRT-pacemaker (CRT-P) and CRT-defibrillator (CRT-D) devices be expanded to include treatment of patients who meet the following criteria: class I or class IIa indications for pacemaker implantation in accordance with American College of Cardiology/American Heart Association/Heart Rhythm Society guidelines, have New York Heart Association (NYHA) class I, II, or III heart failure, left ventricular ejection fraction (LVEF) less than or equal to 50%, with at least one of the following: third- or second-degree AV block; first-degree AV block with symptoms similar to pacemaker syndrome; or documented Wenckebach or PR interval greater than 300 ms when paced at 100 ppm. (Patients eligible for CRT-D also would need to be at risk of a life-threatening ventricular arrhythmia.)

The panel modified the proposed indication by dropping the segments on first-degree AV block and the documented Wenckebach or PR interval in response to issues that included uncertainty over whether this group of patients would benefit from treatment. This was changed to patients with first-degree AV block who are judged, with reliable confidence, to be in need of pacing most of the time.

The company’s proposed indication is based on the results of the BLOCK HF (Biventricular versus Right Ventricular Pacing in Heart Failure Patients with Atrioventricular Block) study, which randomized 691 patients with an indication for pacing with AV block; NYHA class I, II, or III heart failure; and a LVEF of 50% or less to right ventricular or biventricular pacing with a CRT-P or CRT-D.

The primary endpoint, a composite of death, an urgent care visit for HF that required intravenous therapy, or at least a 15% increase in the left ventricular end-systolic volume index (LVESVI), was met by 45.8% of those in the biventricular pacing arm vs. 55.8% of those in the right ventricular pacing arm, a statistically significant difference and a 27% reduction in risk of the primary outcome. The rate of left ventricular lead complications was 6.4% (N. Engl. J. Med. 2013;368:1585-93).

Currently, the CRT-P devices are approved for NYHA class III and IV patients who remain symptomatic despite stable, optimal medical therapy and have an LVEF of 35% or less and a prolonged QRS duration.

The CRT-D devices are approved for ventricular antitachycardia pacing and ventricular defibrillation for automated treatment of life-threatening ventricular arrhythmias, and for providing CRT in heart failure patients who remain symptomatic despite optimal medical therapy and meet any of the following classifications: NYHA class III or IV heart failure with an LVEF of 35% or less and a prolonged QRS duration; left bundle branch block with a QRS duration of 130 ms or more; an LVEF of 30% or less; and NYHA class II heart failure.

Panelists who said that the benefits did not outweigh the risks cited the potential long-term left ventricular lead complications as a concern. Those voting in favor also wrestled with this issue but agreed BLOCK HF was a well-conducted trial with results that some panelists found more compelling than others.

The FDA usually follows the recommendations of its advisory panels. Panelists have been cleared of potential conflicts of interest related to the topic of the meeting.

[email protected]