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This article was originally published in The Gray Sheet

Executive Summary

CPI'S VENTAK PRx OVERALL ONE-YEAR SURVIVAL RATE IN CLINICALS IS 86.6%, slightly lower than the 89.4% one-year survival rate for the earlier-generation Ventak P, according to data provided in Cardiac Pacemaker Inc.'s premarket approval application for the new device. The comparative survival rates were discussed by FDA's circulatory system devices advisory panel at an Aug. 2 meeting in Bethesda, Maryland. The panel concluded that the Ventak PRx is approvable with certain modifications to labeling and software. CPI's submission to FDA included data on 372 patients, 86% of whom were male, with an average age of 63. Implants began after November 1990; the PMA included data up to March 1993. Of 14,614 spontaneous events occurring during clinicals, efficacy of initial therapy was 90% for anti-tachycardia pacing, 86% for low-energy shocks and 99.9% for high-energy shocks. The device's overall conversion rate was 99.9%. FDA asked the panel to comment on comparative overall survival rates for the Ventak PRx and Ventak P models, as well as operative mortality rates. According to the FDA reviewer for the device, the operative mortality rate for the PRx in clinical trials was 4.6%, compared with 2.7% for the Ventak P. Debra Echt, a panel member from Vanderbilt University, Nashville, Tennessee, called PRx mortality rates "comparable to other devices." According to CPI data, Echt said, the PRx's overall mortality is "in range" with the other third-generation implantable defibrillators, Ventritex' Cadence and Medtronic's PCD. Echt did, however, request that the firm include data on expected device longevity in PRx labeling. According to Wyatt Stahl, field clinical engineer for CPI, the device, which is designed to power 275 34-joule shocks, typically lasts two to three years in a patient. In a system set for 100% pacing at 5 volts output, 0.5 milliseconds and a 60 beat-per-minute heart rate, the current drain increases by about 30%, for a possible device longevity of under two years. "I think that is a substantially shorter life than...some other products," Echt said. "People should know about that." The panel also recommended that there be close postmarket surveillance for device failure because of the 5.5% rate of confirmed or alleged device failures during clinicals. CPI attributed the failure figure to the number of components in the device and the firm's conservative definition of failure. For example, CPI included in its tally of 19 returned devices a hex wrench that broke off during reoperation for lead evaluation. The firm also noted that device failure did not necessarily correspond with device inability to detect and treat arrhythmias. Although four devices were cited for seal plug damage, "if you actually pull a seal plug out of a device, it will still function normally," said Stahl. Other issues addressed by the panel included some of the device's programmable features. For example, the device allows the number of cycles between arrhythmia detection and shock therapy initiation to be programmed by the physician. Echt asked that the 20-100 cycle post-shock detection delay option be omitted from the device. After discussion with CPI, however, she withdrew that amendment. Acknowledging that the 100-beat allowance was a "little long," CPI investigator Richard Fogoros, MD, Allegheny General Hospital, Pittsburgh, maintained that "it may be reasonable to allow more than 20 post shocks." He said this "particularly becomes an issue if you have a patient who has relatively slow [ventricular tachycardia] that you may have your lowest rate zone fairly low and if you could avoid redetecting that for a period of time after the first treatment, you may have less treatments." The panel recommended that the PRx be approved for basically the same indications as the earlier device: sustained or induced tachyarrhythmia with symptoms consistent with ventricular tachycardia (VT), and use in survivors of cardiac arrest due to hemodynamically unstable ventricular tachycardia unassociated with acute myocardial infarction. CPI's proposed labeling originally stipulated that PRx patients be "inducable into sustained [VT] and or ventricular fibrillation [VF] despite conventional anti-arrhythmic drug therapy," according to FDA reviewer Carole Carey, division of cardiovascular, respiratory and neurological devices. FDA asked the panel to consider whether CPI's deletion of the drug therapy requirement was "appropriate." Patients who have "cardiomyopathy with poor ventricular function even if they're not inducable on a drug" have recurrent fibrillar mortality and sudden death rates that "are significantly higher than similar patients who get the defibrillators," according to CPI investigator Hugh Culkins, The Johns Hopkins Hospital, Baltimore, Maryland. Panel member Michael Domanski, MD, National Institutes of Health, agreed: "The efficacy of drug testing in that setting is...not demonstrated," he said. "To add that to the indication for a defibrillator would not be a good idea." Noting that VT or VF can be induced in patients for whom an implantable cardioverter-defibrillator (ICD) would not be appropriate, Domanski also recommended that the labeling be "focused much more carefully" to include only patients with additional appropriate symptoms. Without the limitation, Domanski said, "this indication would put the FDA on record as saying that the device is indicated for things for which there's simply no scientific basis." If approved by FDA, the PRx will become the third-generation pacer-cardioverter-defibrillator on the U.S. market, along with the PCD and the Cadence. The quest is now to be the first firm to market a transvenous lead in conjunction with a third-generation ICD. Although CPI has already received an approvable letter from FDA for its Endotak 60 transvenous lead system, it apparently is not yet in a position to capitalize on both technologies in the U.S. market. CPI representatives told the panel that the company has European data on 314 patients who have received the Ventak PRx with the Endotak 60; this data has not been submitted to FDA, so the firm will not be able to label the devices for use together. CPI has been marketing the Endotak 60 in Europe since December 1991; a newer version, the Endotak 70 was released there in May 1992. The firm received an investigational device exemption for and is now conducting U.S. trials on the PRx and the Endotak 70. Medtronic, whose Transvene lead system just passed panel muster, may be the first firm to market a transvenous lead system approved for use with its third-generation defibrillator.

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