Welcome to Assurance of Care. Please utilize our excellent database of medical-legal links. If you have a specific topic you would like for us to provide you with evidenced based practice information, please let us know.
Thanks,
Assurance of Care
AP
WASHINGTON (Feb. 21) - Drugs prescribed to treat attention deficit hyperactivity disorder will include guides to alert patients and parents of the risks of mental and heart problems, including sudden death
Karen Elshout, St. Louis Post-Dispatch / MCT
A patient takes part in a study on attention deficit hyperactivity disorder. The FDA ordered manufacturers to warn patients that ADHD drugs carry risks, including sudden death. Jump Below: Drug List | Talk About It: Post Thoughts
The Food and Drug Administration said Wednesday that it directed the manufacturers of Ritalin, Adderall, Strattera and all other ADHD drugs to develop the guides. In May 2006, the agency told manufacturers to revise the labels of the drugs to reflect concerns about the cardiovascular and psychiatric problems. Draft versions of the guides posted on the FDA Web site include discussion of reports of increased blood pressure and heart rate in ADHD patients, as well as cases of sudden death in some who have heart problems and heart defects. In adult patients, the reported problems also include stroke and heart attack. The alerts also cover psychiatric problems, such as hearing voices, unfounded suspicions and manic behavior, of which there is a slightly increased risk in patients who take the drugs, the FDA said. The guides also tell patients and their parents of precautions they can take to guard against the risks. Affected Drugs
The FDA announced its order applies to 15 drugs: Adderall Tablets
· Adderall XR Extended-Release Capsules
· Concerta Extended-Release Tablets
· Daytrana Transdermal System
· Desoxyn Tablets
· Dexedrine Spansule Capsules and Tablets
· Focalin Tablets
· Focalin XR Extended-Release Capsules
· Metadate CD Extended-Release Capsules
· Methylin Oral Solution
· Methylin Chewable Tablets
· Ritalin Tablets
· Ritalin SR Sustained-Release Tablets
· Ritalin LA Extended-Release Capsules
· Strattera Capsules
[March 2007 - Letter - Takeda Pharmaceuticals North America, Inc.] 
ROCKVILLE, MD — March 30, 2007 — FDA is issuing this public health advisory to inform patients and health care professionals that the sponsor of Zelnorm (tegaserod maleate), Novartis Pharmaceuticals Corporation, has agreed to stop selling Zelnorm. Zelnorm is being taken off the market because a new safety analysis has found a higher chance of heart attack, stroke, and worsening heart chest pain that can become a heart attack in patients treated with Zelnorm compared to those treated with a sugar pill they thought was Zelnorm.
FDA announces the following, effective immediately:
· At FDA’s request, Novartis Pharmaceuticals Corporation has agreed to stop selling Zelnorm.
· Patients being treated with Zelnorm should contact their physician to discuss alternative treatments for their condition.
· Patients who are taking Zelnorm should seek emergency medical care right away if they experience severe chest pain, shortness of breath, dizziness, sudden onset of weakness or difficulty walking or talking or other symptoms of a heart attack or stroke.
· Physicians who prescribe Zelnorm should work with their patients and transition them to other therapies as appropriate to their symptoms and need.
Zelnorm is a prescription medication approved for short term treatment of women with irritable bowel syndrome with constipation and for patients younger than 65 years with chronic constipation. In late February and early March 2007, Novartis Pharmaceuticals gave FDA the results of new analyses of 29 clinical studies of Zelnorm for treatment of a variety of gastrointestinal tract conditions; the data from all the studies were combined to assess the chance of side effects on the heart and blood vessels. In each study, patients were assigned at random to either Zelnorm or a sugar pill they thought was Zelnorm. These 29 studies included 11,614 patients treated with Zelnorm and 7,031 treated with a sugar pill. The average age of patients in these studies was 43 years and most patients — 88% — were women.
The number of patients who suffered a heart attack, stroke or severe heart chest pain that can turn into a heart attack was small. However, patients treated with Zelnorm had a higher chance of having any of these serious and life-threatening side effects than did those who were treated with a sugar pill. Thirteen patients treated with Zelnorm (0.1%) had serious and life-threatening cardiovascular side effects; among these, four patients had a heart attack (one died), six had a type of severe heart chest pain which can quickly turn into a heart attack, and three had a stroke. Among the patients taking the sugar pill, only one (or 0.01%) had symptoms suggesting the beginning of a stroke that went away without complication.
There may be patients for whom no other treatment options are available and in whom the benefits of Zelnorm treatment outweigh the chance of serious side effects. FDA will work with Novartis to allow access to Zelnorm for those patients through a special program.
FDA has also indicated to Novartis a willingness to consider limited re-introduction of Zelnorm at a later date if a population of patients can be identified in whom the benefits of the drug outweigh the risks. However, before FDA makes a decision about limited re-introduction, any proposed plan would be discussed at a public advisory committee meeting.
SOURCE: FDA
A patient takes part in a study on attention deficit hyperactivity disorder. The FDA ordered manufacturers to warn patients that ADHD drugs carry risks, including sudden death.
KETEK ALERT
The Food and Drug Administration notified healthcare professionals and
patients that it completed its safety assessment of Ketek
(telithromycin), indicated for the treatment of acute exacerbation of
chronic bronchitis, acute bacterial sinusitis and community acquired
pneumonia of mild to moderate severity, including pneumonia caused by
resistant strep infections. The drug has been associated with rare cases
of serious liver injury and liver failure with four reported deaths and
one liver transplant after the administration of the drug. FDA
determined that additional warnings are required and the manufacturer is
revising the drug labeling to address this safety concern. FDA is
advising both patients taking Ketek and their doctors to be on the alert
for signs and symptoms of liver problems. Patients experiencing such
signs or symptoms should discontinue Ketek and seek medical evaluation,
which may include tests for liver function.
Read the complete MedWatch 2006 Safety summary, including links to the
FDA news release and previous alerts, at:
http://www.fda.gov/medwatch/safety/2006/safety06.htm#Ketek2
TEQUIN
BMS notified FDA and healthcare professionals about proposed changes to the
prescribing information for Tequin, including an updating of the existing
WARNING on hypoglycemia (low blood sugar) and hyperglycemia (high blood
sugar), and a CONTRAINDICATION for use in diabetic patients. The changes
also include information identifying other risk factors for developing low
blood sugar and high blood sugar, including advanced age, renal
insufficiency, and concomitant glucose-altering medications while taking
Tequin. The proposed changes are highlighted in the following “Dear
Healthcare Provider” letter issued by BMS. Specific wording of these
additions and revisions to the labeling is pending FDA review and approval.
Read the complete MedWatch 2006 Safety summary, including links to the Dear
Healthcare Professional letter and proposed revised label at:
http://www.fda.gov/medwatch/safety/2006/safety06.htm#Tequin
Epoetin alfa (marketed as Procrit, Epogen), Darbepoetin alfa (marketed as Aranesp)
Recent reports of studies with erythropoiesis-stimulating agents (ESAs) have shown a higher chance of serious and life-threatening side effects and greater number of deaths in patients treated with these agents. ESAs stimulate the bone marrow to make more red blood cells and are FDA approved for use in reducing the need for blood transfusions in patients with chronic kidney failure, patients with cancer on chemotherapy, patients scheduled for major surgery (except heart surgery) and patients with HIV that are using AZT. Because all ESAs work the same way, the findings from these studies apply to all ESAs; the FDA is re-evaluating the safe use of this drug class.
Patients currently using or considering the use of an ESA should know the following:
Important study results include the following:
Physicians who prescribe ESAs should consider the important study results above and:
FDA and Amgen, the manufacturer of these products, and Ortho Biotech Products, L.P, a Johnson & Johnson Pharmaceuticals Research and Development subsidiary, the distributor of Procrit, have agreed to change the labeling for Aranesp, Epogen, and Procrit to reflect the new safety information and to provide additional instructions for their use.
FDA-approved uses of ESAs are: for the treatment of anemia in chronic kidney failure patients, in patients with cancer whose anemia is caused by chemotherapy, in patients with HIV whose anemia is caused by AZT (zidovudine), and to reduce the number of transfusions in patients scheduled for major surgery (except heart surgery).
You can find more details about the use of ESAs in FDA’s Information for Healthcare Professional.
The FDA asks health care professionals and patients to report serious side effects after using ESAs to the FDA through the MedWatch program by phone (1-800-FDA-1088) or by the Internet at http://www.fda.gov/medwatch
is a bisphosphonate medication used for bone loss. Users of Fosamax have suffered , also known as Jaw Necrosis, ONJ, Bis-Phossy Jaw or Dead Jaw. This painful and disfiguring condition causes the jaw bone to decay and die. Symptoms of osteonecrosis may lead to infection of the jaw and exposed portions of bone inside the mouth. Merck, the manufacturer of Fosamax, failed to warn users of this side effect.
Other similar bisphosphonates have also been implicated in the serious necrosis of the jaw. In the U.S. Package Insert for both Aredia and Zometa, the following information on osteonecrosis had previously been added to the Adverse Reactions section under Post-Marketing Experience:
“Cases of osteonecrosis (primarily involving the jaws) have been reported in patients treated with bisphosphonates. The majority of the reported cases are in cancer patients attendant to a dental procedure. Osteonecrosis of the jaw has multiple well documented risk factors including a diagnosis of cancer, concomitant therapies (e.g., chemotherapy, radiotherapy, corticosteroids) and co-morbid conditions (e.g., anemia, coagulopathies, infection, pre-existing oral disease). Although causality cannot be determined, it is prudent to avoid dental surgery as recovery may be prolonged.”
Levin Papantonio is investigating claims and Fosamax lawsuits nationwide for Fosamax users who have suffered damage to their jaw bone as a result of the popular medication. If you have been injured by Fosamax, Actonel , Aredia, or Zometa, contact our Fosamax Attorneys for a free legal consultation. You may be entitled to compensation for a jaw bone injury which could have been prevented.
| FOSAMAX | ON THE AIR: |
| Mike Papantonio, co-host of Air America Radio’s Ring of Fire, interviews Levin Papantonio partner Tim O’Brien about the drug Fosamax and how it can cause the jawbone to rot and die.
Fosamax is taken by millions of Americans to strengthen bones. Listen to their Fosamax Interview |
Fosamax® Links about Osteonecrosis from bisphosphonate medications for bone loss:
In the News: Fosamax & Jaw Decay
Fosamax® additional links of interest:
 |
 |
 |
|
 |
FDA Home Page | Search FDA Site | FDA A-Z Index | Contact FDA
| FOR IMMEDIATE RELEASE P07-69 April 17, 2007 |
Media Inquiries: |
U.S. Food and Drug Administration (FDA) investigators and U.S. Marshals today seized all implantable medical devices from Shelhigh, Inc., Union, N.J., after finding significant deficiencies in the company’s manufacturing processes. The deficiencies may compromise the safety and effectiveness of the products, particularly their sterility.
The products include pediatric heart valves and conduits (tube-like devices for blood flow), surgical patches, dural patches (to aid in tissue recovery after neurosurgery), annuloplasty rings (to help repair heart valves) and arterial grafts. The tissue-based devices are used in many surgical settings, including open heart surgery in adults, children and infants, and to repair soft tissue during neurosurgery and abdominal, pelvic and thoracic surgery. Critically ill patients, pediatric patients and immuno-compromised patients may be at greatest risk from the use of these devices.
All medical device companies must follow current good manufacturing practice, a set of requirements that help to ensure the safety and effectiveness of all medical products. Shelhigh’s violations include: manufacturing products in a facility with a poorly constructed and poorly maintained clean room where sterilized devices are further processed; failing to adequately monitor critical manufacturing environments for possible microbial contamination; failing to properly test products for sterility and fever-causing contaminants; and failing to scientifically support product expiration dates.
Physicians should consider using alternative devices. Physicians should also monitor patients with a Shelhigh implant for infections and proper device functioning over the expected lifetime of the device. Patients who think they may have received a Shelhigh device during surgery should contact their physician for more information. FDA will issue a Preliminary Public Health Notification to physicians and other health care professionals and a Preliminary Advice for Patients shortly with more information; those documents will be posted to FDA’s Web site.
The seizure follows an FDA inspection of the Shelhigh manufacturing facility last fall, as well as meetings with the company at which FDA warned Shelhigh that failure to correct its violations could result in an enforcement action. FDA also alerted the company to its manufacturing deficiencies and other violations in two warning letters.
Medical devices manufactured by Shelhigh include:
####
Additional Information
FDA Preliminary Public Health Notification
Preliminary Advice for Patients
|
|||||||||||||
[ClinicalTrials.gov] ).21 In the DREAM study, 2635 patients were randomly assigned to receive rosiglitazone and 2634 patients were assigned to receive placebo. The DREAM study was designed to determine whether rosiglitazone could prevent the development of type 2 diabetes in patients at high risk for this disorder. In the ADOPT trial, 1456 patients were randomly assigned to receive rosiglitazone and 2895 patients were assigned to receive either metformin or glyburide. The ADOPT study was designed to assess the durability of glycemic control with rosiglitazone therapy, as compared with therapy with metformin or glyburide.
Outcome Measures
We reviewed data summaries provided in the FDA review documents, the GlaxoSmithKline clinical-trial registry Web site, and published trial results and then abstracted from the adverse-event tabulations information on myocardial infarction and death from cardiovascular causes. With the exception of the DREAM study, the included trials did not describe adjudication of myocardial infarction or death from cardiovascular causes. Time-to-event data for cardiovascular events were not available in any of these trials, which precluded the calculation of hazard ratios. Because only summary data were available, it was not possible to discern whether the same patient had both events. Therefore, an outcome measure based on the composite of death or myocardial infarction could not be constructed. Accordingly, these two outcomes are reported separately.
Statistical Analysis
Many trials had few cardiovascular events, so the odds ratios and 95% confidence intervals were calculated with the use of the Peto method.22,23,24 Because all trials had similar durations of follow-up for all treatment groups, the use of odds ratios represents a valid approach to assessing the risk associated with the use of rosiglitazone. Trials in which patients had no adverse cardiovascular events in either group were excluded from analyses. All reported P values are two-sided. Statistical heterogeneity across the various trials was tested with the use of Cochran’s Q statistic. A P value of more than the nominal level of 0.10 for the Q statistic indicated a lack of heterogeneity across trials, allowing for the use of a fixed-effects model. For additional analyses, the active comparator control groups were subgrouped into the following four classes for comparison with rosiglitazone: metformin, sulfonylurea, insulin, and placebo. Odds ratios and 95% confidence intervals were calculated for each subgroup with the use of methods similar to those used in the pooled analyses. Data were analyzed with the use of Comprehensive Meta-Analysis software, version 2.2 (Biostat).
Results
Baseline Characteristics
Table 2 reports the doses of rosiglitazone and comparator drugs, baseline demographic characteristics, study periods, and glycated hemoglobin levels or fasting blood glucose levels for patients enrolled in the trials. The patients were relatively young, averaging less than 57 years of age for both the rosiglitazone group and the control group. Overall, there was a moderate predominance of men. Diabetes control was relatively poor, with a mean baseline glycated hemoglobin level of approximately 8.2% for both study groups.
|
Myocardial Infarction and DeathTable 3 reports the myocardial infarction events and deaths from cardiovascular causes that were reported in the 42 clinical trials we reviewed. There were 86 myocardial infarctions in the rosiglitazone group and 72 in the control group. There were 39 deaths from cardiovascular causes in the rosiglitazone group and 22 in the control group. Table 4 lists the odds ratios, 95% confidence intervals, and P values for myocardial infarction and death from cardiovascular causes for the rosiglitazone group and the control group. The summary odds ratio for myocardial infarction was 1.43 in the rosiglitazone group (95% confidence interval [CI], 1.03 to 1.98; P=0.03). The odds ratio for death from cardiovascular causes in the rosiglitazone group, as compared with the control group, was 1.64 (95% CI, 0.98 to 2.74; P=0.06). Table 4 also lists odds ratios and 95% confidence intervals for the pooled group of trials that were smaller and of shorter duration; results for the DREAM and ADOPT studies are shown separately.
|
|
Table 5 lists odds ratios for myocardial infarction and death from cardiovascular causes associated with rosiglitazone for subgroups defined according to the comparator drug. Similar results were obtained when the analysis excluded trials with an active comparator group. The heterogeneity P values were 0.53 for myocardial infarction and 0.68 for death from cardiovascular causes across subgroups. As compared with placebo or other antidiabetic regimens, the estimated odds ratios in all cases were greater than 1.0, suggesting that observed adverse effects during rosiglitazone treatment were not unique to any specific comparator regimen.
|
In an analysis that was not prespecified, we also studied the effects of rosiglitazone on death from any cause. The odds ratio for death from any cause was 1.18 (95% CI, 0.89 to 1.55; P=0.24). Discussion
Our data show that, as compared with placebo or with other antidiabetic regimens, treatment with rosiglitazone was associated with a significant increase in the risk of myocardial infarction and with an increase in the risk of death from cardiovascular causes that was of borderline significance. The similar odds ratio for comparison with placebo suggests that the increased risk associated with rosiglitazone was not a function of the protective effects of active comparator drugs. However, these findings are based on limited access to trial results from publicly available sources, not on patient-level source data. Furthermore, results are based on a relatively small number of events, resulting in odds ratios that could be affected by small changes in the classification of events. Nonetheless, our findings are worrisome because of the high incidence of cardiovascular events in patients with diabetes.4 Because exposure of such patients to rosiglitazone is widespread, the public health impact of an increase in cardiovascular risk could be substantial if our data are borne out by further analysis and the results of larger controlled trials.
Although we did not have access to the source data to construct a composite outcome that included myocardial infarction or death from cardiovascular causes, the increase in the odds ratios for both of these end points suggests that observed adverse effects associated with rosiglitazone were probably not due to chance alone. This meta-analysis included a group of trials that were of relatively short duration (24 to 52 weeks). The odds ratio for these shorter-term trials was similar to the overall results of the meta-analysis. Thus, in susceptible patients, rosiglitazone therapy may be capable of provoking myocardial infarction or death from cardiovascular causes after relatively short-term exposure. In contrast, long-term therapies that improve cardiovascular outcomes, such as statins and antihypertensive drugs, often take several years to provide benefits. Notably, the estimates for the odds ratios for myocardial infarction and death from cardiovascular causes appear elevated for rosiglitazone in comparison with placebo or other commonly prescribed antidiabetic therapies (Table 5).
The mechanism for the apparent increase in myocardial infarction and death from cardiovascular causes associated with rosiglitazone remains uncertain. One potential contributing factor may be the adverse effect of the drug on serum lipids. The FDA-approved rosiglitazone product label reports a mean increase in low-density lipoprotein (LDL) cholesterol of 18.6% among patients treated for 26 weeks with an 8-mg daily dose, as compared with placebo.25 In observational studies and lipid-lowering trials, elevated levels of LDL cholesterol were associated with an increase in adverse cardiovascular outcomes. Thus, an increase in LDL cholesterol of the magnitude observed in the rosiglitazone group may have contributed to adverse cardiovascular outcomes, although the rapidity and magnitude of the apparent hazard was not consistent with an effect produced by lipid changes alone.
Several other properties of rosiglitazone may contribute to adverse cardiovascular outcomes. Rosiglitazone and other thiazolidinediones are known to precipitate congestive heart failure in susceptible patients.26 Congestive heart failure is a physiological state that is associated with an increased intravascular volume. Volume overload increases stress on the left ventricular wall, a factor that determines myocardial oxygen demand. In susceptible patients, an increase in myocardial oxygen demand could theoretically provoke ischemic events. The administration of thiazolidinediones, including rosiglitazone, also produces a modest reduction in the hemoglobin level.25 In susceptible patients, a reduced hemoglobin level may result in increased physiological stress, thereby provoking myocardial ischemia. A study of rosiglitazone that was conducted in rats reported an increase in the rate of death after experimentally induced myocardial infarction.27
Rosiglitazone is not the first PPAR agonist that has been reported to increase adverse cardiovascular events. Muraglitazar, an investigational dual PPAR-
and PPAR-
agonist, increased adverse cardiovascular events, including myocardial infarction, during phase 2 and 3 testing.28 After publication of an analysis of cardiovascular outcomes, muraglitazar was not approved by the FDA, and further development was subsequently halted by the manufacturer. Development programs for many other PPAR agonists have been terminated after evidence of toxicity emerged during preclinical studies or initial trials in humans. According to a former FDA official, more than 50 Investigational New Drug applications for novel PPARs have been filed, but no additional drugs have successfully reached the market in more than 6 years.29 In some cases, these drugs have failed because of evidence of direct myocardial toxicity in studies in animals,29 but few data on toxicity are available in the public domain because of the common industry practice of not publishing safety findings for failed products.
PPAR agonists such as rosiglitazone have very complex biologic effects, resulting from the activation or suppression of dozens of genes.30 The patterns of gene activation or suppression differ substantially among various PPAR agonists, even within closely related compounds. The biologic effects of the protein targets for most of the genes influenced by PPAR agonists remain largely unknown. Accordingly, many different and seemingly unrelated toxic effects have emerged during development of other PPAR agents.29 Some drugs have provoked multispecies, multi–organ system cancers; others have resulted in rhabdomyolysis or nephrotoxicity.29 Troglitazone was withdrawn from the market for rare, but sometimes fatal, liver toxicity. Accordingly, it must be assumed that a variety of unexpected toxic effects are possible when PPAR agonists are administered to patients.
The question as to whether the observed risks of rosiglitazone represent a “class effect” of thiazolidinediones must also be considered. Pioglitazone is a related agent also widely used to treat type 2 diabetes mellitus. However, unlike rosiglitazone, pioglitazone has been studied in a prospective, randomized trial of cardiovascular outcomes, called Prospective Pioglitazone Clinical Trial in Macrovascular Events (PROACTIVE).31 The primary end point, a broad composite that included coronary and peripheral vascular events, showed a trend toward benefit from pioglitazone (hazard ratio, 0.90; P=0.095). A secondary end point consisting of myocardial infarction, stroke, and death from any cause showed a significant effect favoring pioglitazone (hazard ratio, 0.84; P=0.027). Notably, pioglitazone appears to have more favorable effects on lipids, particularly triglycerides, than does rosiglitazone.32
These emerging findings raise an important question about the appropriateness of the current regulatory pathways for the development of drugs to treat diabetes. The FDA considers demonstration of a sustained reduction in blood glucose levels with an acceptable safety profile adequate for approval of antidiabetic agents. However, the ultimate value of antidiabetic therapy is the reduction of the complications of diabetes, not improvement in a laboratory measure of glycemic control. Although reductions in blood glucose levels have been shown to reliably reduce microvascular complications of diabetes, the effect on macrovascular complications has proved to be unpredictable.33 After the failure of muraglitazar and the apparent increase in adverse cardiovascular outcomes with rosiglitazone, the use of blood glucose measurements as a surrogate end point in regulatory approval must be carefully reexamined.
Our study has important limitations. We pooled the results of a group of trials that were not originally intended to explore cardiovascular outcomes. Most trials did not centrally adjudicate cardiovascular outcomes, and the definitions of myocardial infarction were not available. Many of these trials were small and short-term, resulting in few adverse cardiovascular events or deaths. Accordingly, the confidence intervals for the odds ratios for myocardial infarction and death from cardiovascular causes are wide, resulting in considerable uncertainty about the magnitude of the observed hazard. Furthermore, we did not have access to original source data for any of these trials. Thus, we based the analysis on available data from publicly disclosed summaries of events. The lack of availability of source data did not allow the use of more statistically powerful time-to-event analysis. A meta-analysis is always considered less convincing than a large prospective trial designed to assess the outcome of interest. Although such a dedicated trial has not been completed for rosiglitazone, the ongoing Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycaemia in Diabetes (RECORD) trial may provide useful insights.34
Despite these limitations, our data point to the urgent need for comprehensive evaluations to clarify the cardiovascular risks of rosiglitazone. The manufacturer’s public disclosure of summary results for rosiglitazone clinical trials is not sufficient to enable a robust assessment of cardiovascular risks. The manufacturer has all the source data for completed clinical trials and should make these data available to an external academic coordinating center for systematic analysis. The FDA also has access to study reports and other clinical-trial data not within the public domain. Further analyses of data available to the FDA and the manufacturer would enable a more robust assessment of the risks of this drug. Our data suggest a cardiovascular risk associated with the use of rosiglitazone. Until better precision of the estimates of the risks of this treatment on cardiovascular events can be delineated in patients with diabetes, patients and providers should give careful consideration to the risks and benefits of their overall treatment plans.
Dr. Nissen reports receiving research support to perform clinical trials through the Cleveland Clinic Cardiovascular Coordinating Center from Pfizer, AstraZeneca, Daiichi Sankyo, Roche, Takeda, Sanofi-Aventis, and Eli Lilly. Dr. Nissen consults for many pharmaceutical companies but requires them to donate all honoraria or consulting fees directly to charity so that he receives neither income nor a tax deduction. No other potential conflict of interest relevant to this article was reported. We thank Craig Balog for statistical programming support.
Source Information From the Cleveland Clinic, Cleveland.
This article (10.1056/NEJMoa072761) was published at www.nejm.org on May 21, 2007. It will appear in the June 14 issue of the Journal. Address reprint requests to Dr. Nissen at the Department of Cardiovascular Medicine, Cleveland Clinic, 9500 Euclid Ave., Cleveland, OH 44195, or at nissens@ccf.org .
References
