Recalls and Safety Alerts Involving Pacemakers and Implantable Cardioverter-Defibrillator Generators FREE

Permanent pacemakers and implantable cardioverter-defibrillators (ICDs) are 2 of the most remarkable medical and technological advances of the 20th century. While these devices are life-saving in many instances, they may occasionally malfunction.¹ The US Food and Drug Administration (FDA) is responsible for the safety and oversight of all medical devices in the United States. Weekly FDA Enforcement Reports are issued that include recalls and safety alerts (referred to collectively as advisories), a number of which have involved pacemakers and ICDs.

Safety issues involving pacemaker leads have received much attention and have been well studied.^2- 3 Recognition of lead abnormalities, such as a tendency to fracture,² have resulted in recalls, close follow-up, improved lead design, and the development of safer methods of lead extraction. In contrast to lead advisories, alerts and recalls involving pacemaker and ICD generators are poorly characterized.

With the aging of the US population, the number of pacemakers implanted will likely increase.⁴ In addition, novel indications for pacing, such as prevention of atrial fibrillation and biventricular pacing for congestive heart failure, are being developed.^5- 9 Likewise, the number of ICD generators implanted will likely continue to increase because of the results of several randomized clinical trials demonstrating a survival benefit of ICDs in specific high-risk patients.^10- 14 With the increasing number, variety, and complexity of implantable devices, recalls and safety alerts necessitated by unanticipated device malfunctions may become increasingly common.

This study was undertaken to determine pacemaker and ICD generator advisory rates, to identify trends in these rates, and to examine the clinical and financial implications of device advisories to the health care system.

Recalls and safety alerts (advisories) are classified by the FDA into 4 categories: class I, class II, class III, or safety alerts (Table 1). The number of pacemaker and ICD advisories was determined by reviewing all weekly FDA Enforcement Reports from January 1990 through December 2000 and verifying all recalls and safety alerts with the manufacturer, when possible.^15- 20 Only advisories affecting pacemaker or ICD pulse generators were included; advisories involving pacemaker or ICD leads were excluded. When the precise number of devices recalled in the United States was not reported by the FDA, the recalled number of US devices was calculated based on the number of affected devices worldwide and the estimated proportion of these devices implanted in the United States.²¹

To calculate the annual advisory rate (ie, the annual number of pacemakers and ICDs subject to recall or safety alert divided by the number of patients living with a device in a given year), the number of patients with pacemakers and ICDs in the United States was estimated.

For pacemakers, estimates were calculated by applying age- and sex-related prevalence rates for permanent pacemakers in the United States from the 1988 National Health Interview Survey Medical Device Implant Supplement⁴ to the annual US Bureau of Census age and sex population estimates.²² By using age and sex population estimates, annual pacemaker prevalence was adjusted for the aging of the population and accounted for the higher prevalence of pacemaker implantation in men.⁴ In addition, annual pacemaker implantation rates by age and sex were obtained from the National Center for Health Statistics' National Hospital Discharge Survey^23- 35 and were used to account for sex and age fluctuations in annual implantation rates.

The annual prevalence of patients who have ICDs in the United States was calculated using estimated ICD prevalence in 1990³⁶ and the number of new implants in the United States per year (based on the rate of new implants³⁶ and the US Bureau of Census annual population estimates²²). For the years 1998 to 2000, for which exact implant rates and implant numbers were unavailable, implant rates were estimated assuming continued increased ICD implantation rates similar to those observed throughout the 1990s (16%-33% increase per year).^36- 37 The mortality rates for patients with ICDs were assumed to be similar to those observed in the major ICD clinical trials.^10- 14

The recommendations issued by the manufacturer for the management of a specific recall or alert were used to determine the clinical impact of an advisory. If specific recommendations were unavailable, device replacement was assumed to occur only under the following 3 circumstances: (1) device malfunction that could not be corrected with reprogramming, (2) pacemaker dependency in a patient with a pacemaker that could fail without warning, or (3) presence of an ICD that could fail to deliver appropriate cardioversion/defibrillation therapy. Pacemaker dependency was estimated to be 18% based on the rate at which patients with pacemaker failure present emergently.³⁸

Costs were estimated using annual Medicare reimbursement rates for the recommended pacemaker or ICD follow-up and for the recommended pacemaker or ICD generator replacements.^39- 44 Physician fees were calculated using Current Procedural Terminology (CPT) codes (metropolitan Boston rates). The following codes were used: CPT 93732 for pacemaker check and analysis with reprogramming; CPT 93731 for pacemaker check and analysis without reprogramming; CPT 93744 for ICD check and analysis with reprogramming; CPT 93743 for ICD check and analysis without reprogramming; CPT 33213 and 33233 for pacemaker generator change; CPT 33240 and 33241 for ICD generator change; and CPT 93641 for ICD testing at implant. Hospital fees (including the cost of the replacement pacemaker or ICD generator) were calculated using mean national rates for the appropriate diagnosis related group (DRG) (DRG 118 for pacemaker replacement and DRG 116 for ICD replacement). Calculations used a 4% annual discount rate and results are reported in year 2000 dollars.

Statistical comparisons were performed using SAS statistical software (version 6.12, SAS Institute, Cary, NC). A 2-sided P value of .05 or less was interpreted as being statistically significant. Student t and χ² tests were used to compare continuous and discrete outcomes, respectively. Mantel-Haenszel χ² tests were used to assess for trends during 3 periods that were selected a priori: 1990-1995, 1995-2000, and 1990-2000. Several potential sources of uncertainty in our cost model were explored: (1) variation in the cost of device analysis or replacement, (2) variation in the number of device analyses or replacements, and (3) variation in the discount rate.

The estimated number of patients with devices is shown in Figure 1. Overall, the number of patients living with implanted devices (pacemaker or ICD generator) increased 49% from 1990 to 2000. The number of pacemakers increased 22% from 1990 to 2000, while the number of patients with ICDs increased almost 11-fold during the same period due to an 11-fold increase in annual ICD implants between 1990 and 2000.

There were 52 advisories (range, 0-9; median [25th and 75th percentiles], 4 [4 and 7] per year) between January 1990 and December 2000 (Figure 2). Pacemakers were recalled in 9 of the 11 years studied while ICDs were recalled in 8 of the 11 years studied. Only 1990 was advisory-free. While recalls and safety alerts more often involved pacemakers than ICDs (67% vs 35%; P = .002), the annual percentage of advisories involving ICDs increased between 1990 and 2000 (P for trend <.001).

Between January 1990 and December 2000, 408 500 pacemakers and 114 645 ICDs (523 145 total devices) were subject to recalls or safety alerts (Figure 2). The annual number of affected devices varied from a low of 0 in 1990 to a high of 182 647 in 1999. Of the devices recalled since 1990, 65% have been recalled since January 1999 including 71% of the recalled pacemakers and 42% of the recalled ICDs.

Table 2 shows the FDA classification of recall or safety alert and the type of malfunction. Three quarters of all advisories were class I or II recalls. Of the 52 advisories, 35 (67%) were issued because of hardware malfunctions (electrical/circuitry malfunction, battery/capacitor malfunction, inadequate hermetic seal, defective crystals, device header abnormalities). Firmware (integral device computer programming) errors accounted for an additional 10 (19%) advisories. Overall, hardware (54%) and firmware (41%) malfunctions accounted for 95% of all advisory devices. The remaining recalls and alerts were due to either environment-device interactions (for example, ICD interactions with magnetic fields) or to nondevice-related problems (mislabeling of product, inappropriate product distribution). Selected examples of pacemaker and ICD advisories are listed in Table 3.

The annual advisory rate for devices ranged from 0 to 27 per 100 person-years for pacemakers, 0 to 71 per 100 person-years for ICDs, and 0 to 25 per 100 person-years for total devices (Figure 3). The overall mean (SD) device rate for 1990-2000 was 7.7 (1.1) advisories per 100 person-years. The ICD advisory rate was significantly greater than the pacemaker advisory rate (mean [SD], 16.4 [1.6] vs 6.7 [0.8] advisories per 100 person-years; P<.001). The difference remained significant even if 1992 and 1993 (years with high ICD advisory rates) were excluded from the analysis. No trend in advisory rates was apparent for 1990-1995 or 1990-2000. However, between 1995 and 2000 the advisory rate increased for pacemakers (P for trend <.001), ICDs (P for trend = .02), and total devices (P for trend <.001).

Manufacturers recommended clinical intervention (device check and analysis or replacement) for 79% of the advisories. For the management of pacemaker advisories, manufacturers most often (57%) recommended pacemaker replacement for pacemaker-dependent patients and close follow-up for nonpacemaker-dependent patients. Less frequently, recommendations advised replacement of all advisory pacemakers (6%), close follow-up and/or replacement of actual pacemaker failures only (6%), reprogramming of the pacemaker (9%), or no physician action (23%). The ICD advisories were managed with device replacement (72%), close follow-up, device reprogramming and/or replacement of actual ICD failures only (11%), or no physician action (17%).

Pacemaker advisories required electronic device check and analysis more often than ICD advisories (3.1 vs 0.4 analyses per advisory device; P<.001; Table 4). Over 1.2 million pacemaker checks and analyses were recommended, predominantly because many pacemaker recalls advised monthly follow-up for nonreplaced devices. Conversely, device replacement was recommended 10 times more frequently for ICD advisories than for pacemaker advisories (23 vs 2.3 replacements per 100 advisory devices; P<.001). Overall, replacement of 36 187 devices (74% were ICDs) was advised.

The total estimated cost of the device advisories was $870.2 million (Table 4). Although fewer devices were affected by ICD advisories than pacemaker advisories, ICD advisories were more costly because of the greater rate and cost of device replacement. The ICD advisories accounted for 22% of advisory devices but 76% of total advisory costs.

Sensitivity analysis was performed to assess the impact of changes in the cost model parameters on total device advisory costs. Total advisory costs were sensitive to changes in either the number or the unit cost of ICD replacements; although even with a 50% reduction in these parameters, total advisory costs for the 1990-2000 period exceeded $500 million. Total costs were relatively insensitive to significant changes in other model parameters, including the number and unit cost of pacemaker replacements, the number and unit cost of pacemaker and ICD analyses, and the discount rate.

Despite more than 25 years of medical device monitoring and recalls by the FDA,^45- 46 relatively little is known about the rates and trends of recalls and safety alerts in the United States. This study demonstrates that more than 500 000 permanent pacemaker and ICD generators were subject to recalls or alerts in the United States between 1990 and 2000 and that the annual rate of pacemaker and ICD generator advisories has been increasing since 1995. To the best of our knowledge, this is the first study to categorize causes of device advisories. While more than three quarters of advisory devices are pacemakers, the rate of recall or alert is higher for ICDs than for pacemakers. Advisories for ICDs accounted for three quarters of the $870 million spent on managing these recalls.

Several database registries have monitored the performance of pacemakers and ICDs, but have been limited by their relatively small size or voluntary nature. The Bilitch Registry evaluated 22 786 pacemakers from 6 sites over a 19.5-year period and 3520 ICDs from 13 sites over almost 12 years ending in December 1993.⁴⁷ Failures involving 50 different generator models were reported⁴⁸ and ultimately led to a recommendation for a North American Device/Lead Database that was not accepted by the FDA or manufacturers.⁴⁹

STIMAREC is an ongoing long-term device failure registry that publishes reports submitted by participating centers.⁴⁸ Between 1988 and 1996, 700 cases of pacemaker or ICD generator malfunction were reported to STIMAREC, including 370 dangerous cases involving loss of output or decrease in pulse amplitude.⁵⁰ Because malfunction reporting for this registry is voluntary and the number of at-risk patients for the registry is unknown, failure rates cannot be calculated.

The FDA Enforcement Reports present device failures that manufacturers discover during their own individual monitoring programs.⁴⁸ More than 250 000 pulse generators, leads, and pacemaker/ICD programmers were subject to FDA recalls and safety alerts between 1974 and 1987,⁴⁵ substantially less than the 523 145 pacemaker and ICD generators recalled during the 11-year period of this study. All 5 major manufacturers had an increase in the number of models of pulse generators, leads, and pacemaker/ICD programmers subject to FDA recalls and safety alerts between 1976 and 1995.⁴⁸ Our study demonstrates that the annual rate of pacemaker and ICD generator recall and safety alert has been increasing since 1995.

While this increase in generator advisory rate could be due to increased vigilance on the part of the FDA and manufacturers, it may also reflect other factors. Pacemakers have become increasingly complex—incorporating features to preserve battery life, promote intrinsic conduction, provide physiologic pacing, and increase diagnostic capabilities. These features include automatic threshold determination, automatic atrioventricular interval adjustment, dual chamber electrogram storage capabilities, and rate-responsive pacing using integrated sensors.

ICDs now incorporate single or dual-chamber pacing capabilities as well as increasingly sophisticated algorithms for recognition and treatment of tachyarrhythmias. Despite increasing complexity, ICDs continue to shrink in size while maintaining their battery life and high-energy capabilities. The observed ICD recall rate may be higher than the pacemaker recall rate because ICDs are technically more complicated than pacemakers. In addition, because ICD malfunctions are more likely to be perceived as life-threatening, manufacturers and the FDA may have a lower threshold for issuing an advisory.

Most advisories during this period can be classified as either hardware or firmware advisories. Hardware recalls and alerts, accounting for more than half the device advisories, usually occur due to manufacturing defects, unanticipated component failure, or poor design. More than two thirds of these advisories can be further classified as electrical and/or circuitry problems, battery and/or capacitor failure, or hermetic seal abnormalities. Firmware advisories, on the other hand, occur less frequently but tend to be larger. They account for more than 40% of the recalled devices. They are more enigmatic, occurring due to programming glitches that may be difficult to anticipate. Some who have studied incidents in other complex systems, such as the airline industry, nuclear weapons, or space flight, consider engineered (hardware) incidents predictable and therefore preventable, while system (firmware) incidents are inevitable due to complex processes combining in unforeseeable ways.⁵¹

Clinical management of patients with an advisory pacemaker or an advisory ICD generator is often challenging.^3,49 Manufacturers generally advise replacement of devices that may fail to deliver life-sustaining therapy (ie, patients who are dependent on pacemakers or who have an ICD). However, there are often little data to aid the clinician's decision whether to actually replace the recalled device and physicians must incorporate the manufacturer's recommendations into their assessment of the individual patient's risk. Factors affecting the decision to replace a device include the reason for the advisory, the type of device (ICD vs pacemaker), the degree of pacemaker dependency, the general medical condition of the patient, and the patient's wishes. Complicating the decision is the fact that not every recalled device is defective. For some advisories, manufacturers estimate fewer than 1% of recalled devices are affected.^52- 54 Another complicating factor is that initial estimates of failure rates are sometimes inaccurate.³ For some patients though, especially those who are dependent on pacemakers or who have an ICD, even a risk less than 1% may be deemed unacceptable.

Few deaths have been confirmed to be due to device malfunction^1,52 and our study does not directly challenge this claim. Patients with implanted devices, however, have coexisting cardiac disease and deaths may be attributed to a primary cardiac abnormality rather than device malfunction.³⁸ A prospective device database would be the most accurate way to determine if patients with advisory devices have increased mortality.

The psychological impact of recalls to patients with implanted devices should not be underestimated. Patients with ICDs or pacemakers often develop a psychological dependence on their device that can include anxiety related to a fear of device malfunction.^55- 56 Patients and their family members affected by actual ICD advisories demonstrate a marked decrease in confidence in their device.⁵⁷ Device advisories and the possibility of device failure may have considerable impact on the psychological well-being of affected patients.

The financial implications of pacemaker and ICD recalls and safety alerts are substantial. Recalls increase outpatient appointments, in-hospital patient days, and use of hospital resources.⁵⁸ We estimate these costs to total $870 million for the decade 1990-2000. Manufacturers may provide replacement devices at discounted prices and a nominal hospital and/or physician fee for replacement, but these costs are ultimately passed on to the health care system and are reflected in the cost of new devices. The issue of who actually pays for these recall costs has not been well studied and likely includes manufacturers, the federal government, hospitals, private insurers, physicians, and patients.⁵⁸ A decrease in the number or cost of ICD replacements due to advisory would have the largest impact in reducing the total advisory cost burden.

Because some manufacturers are no longer in business, the precise number of replaced devices could not be calculated. Similarly, the number of extra pacemaker and ICD checks and analyses is an estimate based on manufacturer recommendations. The actual number may vary if clinicians were more or less cautious in their follow-up of patients with devices that had received an advisory. Pacemaker and ICD lead advisories were not included in this study because lead malfunctions have already received much attention and occur for different reasons than generator failures. The purpose of this study was to focus attention on the previously underrecognized problem of pacemaker and ICD generator malfunctions.

We have demonstrated that (1) many patients are affected by pacemaker and ICD generator advisories, (2) ICDs are recalled at a greater rate than pacemakers, and (3) the annual advisory rate for pacemaker and ICD generators has increased since 1995. With the growing number of device implants and expanding indications for device therapy, the number of patients affected by device advisories can be expected to increase. Hopefully, the intense efforts, which have resulted in remarkable technological advances in pacemaker and ICD therapy, will be accompanied by an equally intense effort from manufacturers and the FDA to improve the overall safety of these devices and reduce the number and rate of recall.