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The Controversy over Guidant's Implantable Defibrillators
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     On October 4, 2001, Joshua Oukrop, a Minnesota teenager with hypertrophic cardiomyopathy and a high risk of sudden death from ventricular fibrillation, received an implantable cardioverter–defibrillator (ICD). The device was a Ventak Prizm 2 DR Model 1861 manufactured by Guidant (Indianapolis). After it was implanted, Oukrop's physicians at the Minneapolis Heart Institute Foundation checked it every three months (most recently on January 31, 2005) and found no problems.1

    On March 14, 2005, Oukrop, then a 21-year-old college student, collapsed and died in a remote area of southeastern Utah during a spring-break bicycling trip with his girlfriend.1,2 An autopsy revealed no clinically significant pathology beyond his massive left ventricular hypertrophy. His physicians were stunned by his death. ICDs have been shown to be almost invariably successful in preventing sudden death in young patients with hypertrophic cardiomyopathy, as long as they do not have end-stage heart failure — which Oukrop did not.3 When the manufacturer analyzed his ICD, it determined that the device had short-circuited internally while trying to deliver high-voltage therapy and had been permanently disabled (see diagram). Moreover, its memory had been destroyed, making the time of failure impossible to pinpoint.1,4

    Diagram Showing Components of the Ventak Prizm 2 Device before Modification in April 2002.

    A failure involving a deterioration in a wire insulator can result in an electrical short between the DFN wire and the backfill tube. Diagram courtesy of Guidant.

    Oukrop's physicians at the Minneapolis Heart Institute Foundation included Dr. Barry Maron, the director of the Hypertrophic Cardiomyopathy Center; Dr. Robert Hauser, a senior consulting cardiologist at the institute; and Dr. Charles Gornick, who had implanted the ICD. After a company official told Maron what had happened, Maron called Hauser. Hauser searched the Manufacturer and User Facility Device Experience (MAUDE) database maintained by the Food and Drug Administration (FDA), which contains reports of adverse events involving medical devices. There, he found other reports from Guidant of instances in which the Prizm 2 DR Model 1861 had short-circuited in exactly the same way as Oukrop's had done. Forty-seven other patients with this device are followed at the institute, including Oukrop's father and 10 others who have hypertrophic cardiomyopathy.

    In June, Maron recalled: "We became very concerned. We were keeping a secret not just from our patients and their physicians, but also from all the patients with the device and their physicians. On May 12, four Guidant officials came to my office and gave a very educational presentation. I asked, `What are we going to do about this? We are in an untenable situation ethically and morally with our patients. How are we going to get the word out?' They said, `Well, we are not. We don't think we need to. And we don't think it's advisable.' The officials expressed doubt that the patients would be able to understand the medical issues involved in determining whether or not to replace the devices. I said, `I think this is the biggest mistake you will ever make.' They said they didn't agree."

    It was subsequently disclosed that Guidant, the second-largest manufacturer of implantable defibrillators, had identified the electrical flaws in the Prizm 2 DR in February 2002 and had made manufacturing changes, on April 16 and November 13 of that year, in an effort to prevent this rare but unpredictable and catastrophic type of failure.4 To date, there have been no reports of failures of such devices built after the April 2002 change. Guidant, however, continued to sell devices that had been manufactured before that change was made and issued no public statements about the problem or the corrections. The company's first announcement came on May 23, 2005 — more than three years after Guidant had become aware of the problem and hours before the New York Times published an article about Oukrop's death.2 Between May 23 and June 24, Guidant informed physicians and patients about problems with many of its ICD devices and came under intense regulatory and public scrutiny. After the company provided physicians at the Minneapolis Heart Institute Foundation with a list of the 47 patients with the potentially defective ICDs, all were contacted. As of July 5, nine had had their devices replaced and four had replacements scheduled.

    Guidant is still working its way through the ICD issue. On June 17, 2005, the company noted in a statement that "after making the manufacturing changes, Guidant sold products manufactured before the April 2002 change. At that time data did not show an unusual failure rate and Guidant believed the device to be reliable."4 Since November 2003, Dr. Beverly Lorell, a professor of medicine at Harvard Medical School, has been vice president and chief medical and technology officer at Guidant. In a written statement, Lorell said that the company's "first priority is patient safety and this is the foundation of trust by physicians and patients. We also understand that physicians and individual patients may make different choices regarding treatment options even when the risks of an adverse clinical event related to a life-sustaining device . . . are very low in frequency. For this reason, Guidant's recent voluntary physician communications and recalls for separate and distinct device safety issues reflect a very stringent approach by the firm in the communication of potential safety issues related to marketed devices."

    The fallout from the potentially preventable death of Joshua Oukrop has triggered a broad discussion about the propriety of Guidant's actions and the safety of ICDs and medical devices in general. It has also led to debate about the appropriate standards for informing physicians and patients about safety issues and the responsibilities of industry, the FDA, and the medical community. The matter is particularly urgent because the number of people with ICDs is increasing rapidly. In 2003, the Center for Medicare and Medicaid Services paid for 52,500 ICD implantations; in 2004, it paid for 65,000. With expanded coverage, more than 500,000 Medicare beneficiaries may become eligible for an ICD. Hauser has estimated that worldwide more than 200,000 ICDs will be implanted or replaced this year.

    On July 1, the FDA classified as class I recalls Guidant's recent notifications with regard to Prizm 2 DRs that were manufactured on or before April 16, 2002, and two other models of implantable defibrillators, the Contak Renewal Model H135 and the Contak Renewal 2 Model H155, that were manufactured on or before August 26, 2004. A class I recall indicates the highest level of risk, because "there is a reasonable probability that if a particular device is malfunctioning, the malfunctioning device will cause serious adverse health consequences or death."5 Of 42,000 affected devices of the three recalled types worldwide, 20,600 (including about 13,900 Prizm 2 DRs) are still implanted in patients.4,5 The devices are subject to the development of an internal short circuit when they are attempting to deliver an electrical shock to the heart — thereby preventing the treatment of arrhythmias. According to the FDA, "the problem is caused by deterioration of electrical insulation in the device and can only be detected after the device has already malfunctioned. The device does not give any sign of impending failure and there is no test that predicts whether the device will fail."5

    As of June 17, 2005, Guidant and the FDA were aware of 43 reports of device failures, including 28 involving Prizm 2 DR devices.4 They include in this count the death of Oukrop and the death on May 30, 2005, of a patient with a Contak Renewal Model H135 device that was manufactured in December 1999. Some failures of Prizm 2 DRs have been recognized while the device was being implanted or after a spontaneous defibrillator shock while the patient was still in the hospital.1

    In the 15 Contak Renewal failures, the short circuit diverted energy away from the heart, so that only about 20 percent of the intended shock energy was delivered. According to the report of the patient death that Guidant filed with the FDA, the device delivered multiple shorted shocks, but they did not convert the patient's ventricular tachycardia. In all cases, the device must be replaced if this short circuit occurs. The death remains under investigation.

    Guidant has acknowledged that the actual rate of failure may be higher than the reported rate and that the number of associated deaths may be underreported, since ICDs are not routinely evaluated after death.4 The FDA and Guidant have advised physicians and patients to make individual decisions about whether to remove and replace the affected defibrillators on the basis of the specific medical situation of the patient; Guidant will provide replacement devices at no charge.4

    The FDA classified Guidant's notifications about other ICDs as class II recalls, because "the malfunctioning product may cause temporary or medically reversible adverse health consequences, however the probability of serious adverse health consequences is remote."5 Three types of devices — the Ventak Prizm AVT, Vitality AVT, and Renewal AVT — are subject to a memory error that may limit their ability to provide therapy but that can be corrected with reprogramming. Among the 21,000 such devices that have been implanted worldwide, two incidents have been confirmed. Neither resulted in death or injury.

    Five devices — the Contak Renewal 3 and 4, Renewal 3 and 4 AVT, and Renewal RF — are subject to a rare type of component failure; four such failures have been confirmed among the approximately 46,000 devices implanted, and a fifth occurrence is suspected but has not been confirmed. This failure occurs when a magnetic switch sticks in the closed position. This malfunction may inhibit the device's ability to treat ventricular and atrial tachyarrhythmias and may accelerate the depletion of the battery. If this problem develops, the device emits an audible tone. As of June, there had been no injuries to patients beyond the need to replace the device in four instances; the other instance occurred before implantation. Guidant has recommended that physicians stop implanting these devices until further notice. In the case of devices that have already been implanted, it is recommended that physicians make a programming change to ensure that appropriate therapy can be delivered.

    Since February 2005, there have been "an above-average number" of notifications to physicians about problems with ICDs, according to Dr. William H. Maisel, a cardiologist at Beth Israel Deaconess Medical Center in Boston and the chair of the FDA's Circulatory System Devices Panel. The notifications involve all the leading manufacturers. In February, Medtronic (Minneapolis), the largest of these manufacturers, advised physicians about the potential for premature battery failure in some of its implantable defibrillators that could worsen over time and eventually affect 0.2 to 1.5 percent of the devices. Of 87,000 potentially affected units, about 13,000 had been replaced as of the end of May. No injuries or deaths have been reported. In June 2005, St. Jude Medical (St. Paul, Minnesota), the third-largest manufacturer, advised physicians about two anomalies that could affect 30,000 implanted ICDs in the United States and that can be corrected with a software download. No clinical complications have been reported.

    In the most serious situations, physicians are having difficult conversations with patients about device replacement. All ICDs must be replaced when their batteries wear out — after an average of five years. The surgical procedure, however, carries risks — principally, the risk of infection. Even if the statistical risk that a patient's implanted device will not save his or her life may be lower than the risks associated with replacing it, the uncertainty can weigh heavily. As Maisel said in a recent interview, "Evidence-based decision making cannot factor in the emotional consequences to patients of living every day knowing that their ICD might not work if it is needed. For some patients, this is a very valid reason to replace a device."

    The recalls have also focused attention on Guidant. In June 2003, Endovascular Technologies, a subsidiary of Guidant, pleaded guilty to 10 felony counts and agreed to pay $92.4 million in civil and criminal penalties related to its Ancure Endograft system, a stent–graft device inserted by means of a catheter for the treatment of abdominal aortic aneurysms. The company admitted that it had lied to the government and hidden thousands of serious health problems, including 12 deaths. The company stopped selling the system in March 2001, made changes, and reintroduced it to the market in August 2001.

    In 2004, Guidant sold $1.8 billion of implantable defibrillators, nearly half of its $3.8 billion in total sales. On December 15, 2004, it was announced that Johnson and Johnson would acquire Guidant for $25.4 billion. According to securities-fraud lawsuits that have been filed beginning in June 2005, Guidant and its executives have allegedly covered up the problems with the ICDs.

    Since the merger agreement was announced, Guidant executives have sold millions of dollars of company stock, according to filings with the Securities and Exchange Commission. For example, on May 17, 2005, Lorell, the chief medical and technology officer, sold 23,300 shares for $1.71 million. On May 23, 2005, the day before the problems with the Prizm 2 DR were the subject of a front-page article in the New York Times, she sold 22,667 more shares for $1.68 million. When asked to explain the transactions, Lorell did not respond.

    The FDA's investigation of Guidant's actions is continuing, and further information from both the company and the government is likely to be available soon. Later this year, the Heart Rhythm Society, a professional association of arrhythmia specialists, plans to develop guidelines regarding ICD recalls, manufacturer-notification standards, and when to replace devices. The society, however, receives 25 percent of its $8.5 -million annual budget from corporate support — including funds from Guidant, Medtronic, and St. Jude Medical — arousing concern about potential conflicts of interest. Many of its members also have consulting and other financial ties to device manufacturers. In addition, Guidant is establishing its own panel of experts to recommend guidelines for disseminating information.

    In the weeks ahead, the FDA will need to reexamine its regulations and procedures for device surveillance. It should consider making changes to better inform physicians and patients and to more thoroughly ensure the quality of medical devices. According to Hauser of the Minneapolis Heart Institute Foundation, "it is very important that the FDA get this done. It is long overdue. It is not just this one incident. It is broader than that." In addition, the entire industry will have to enhance the safety and reliability of these lifesaving devices. For more than three years, Guidant kept quiet about the serious malfunctions of some of its ICDs and continued to sell defective devices after it made manufacturing changes to fix the defects. The company will have to regain the trust of physicians and patients.

    Source Information

    Dr. Steinbrook is a national correspondent for the Journal.

    References

    Gornick CC, Hauser RG, Almquist AK, Maron BJ. Unpredictable implantable cardioverter-defibrillator pulse generator failure due to electrical overstress causing sudden death in a young high-risk patient with hypertrophic cardiomyopathy. Heart Rhythm 2005;2:681-683.

    Meier B. Maker of heart device kept flaw from doctors. New York Times. May 24,2005:A1.

    Maron BJ, Shen W-K, Link MS, et al. Efficacy of implantable cardioverter-defibrillators for the prevention of sudden death in patients with hypertrophic cardiomyopathy. N Engl J Med 2000;342:365-373.

    Gorsett A. Urgent medical device safety information & corrective action: VENTAK PRIZM 2 DR, model 1861. Indianapolis: Guidant Cardiac Rhythm Management, June 17, 2005. (Accessed July 6, 2005, at http://guidant.vanosteen.com/news/prizm2_dr.pdf.)

    FDA updates consumers on Guidant Corporation's implantable defibrillators. News release of the Food and Drug Administraton, Rockville, Md., July 1, 2005. (Accessed July 6, 2005, at http://www.fda.gov/bbs/topics/news/2005/new01198.html.)(Robert Steinbrook, M.D.)