Preliminary data from the Sibutramine Cardiovascular Morbidity/Mortality Outcomes in Overweight or Obese Subjects at Risk of a Cardiovascular Event (SCOUT) study showed that cardiovascular events were reported in 11.4 percent of patients using Meridia compared to 10 percent of patients using a placebo. According to a US Food and Drug Administration’s (FDA) Early Communication issued in November, this difference was higher than expected, suggesting Meridia is associated with an increased cardiovascular risk in the study population. Also, based on the SCOUT findings, the European Medicines Agency found that “the risks of these medicines are greater than their benefits.” Meridia has since been banned in Europe.
Recently published final data indicate that Meridia increases heart attack and stroke risk in patients with cardiac disease, said Reuters noting that those patients on Meridia lost an average of 8.8 pounds from an average weight of 211 pounds. Patients taking Meridia experienced a 16 percent increased risk of heart problems versus those taking a placebo, the study showed, said Reuters. While an increased risk of death was not seen, there was an increased risk of blood pressure and heart rate, noted Reuters.
Meanwhile, an FDA hearing is scheduled in two weeks to determine what future action should be taken against the medication, said Reuters.
"When you put those ... things together, you have to wonder if the drug should be on the market any longer," said Dr. Gregory Curfman, executive director of the New England Journal of Medicine, which published the study, quoted Reuters. "That's what you're trying to prevent through weight loss. You're trying to prevent people from having heart attacks, and here this drug caused more," said Curfman, a cardiologist, wrote Reuters.
Preliminary study results were released to US and European health officials late last year, which led to the European ban and to strengthening of the FDA’s warning concerning risks to patients with preexisting heart disease, said Reuters. The agency asked for a public meeting with external advisors.
New England Journal of Medicine editors just wrote an editorial describing Meridia as "another flawed diet pill," asking if the drug should remain on the market, wrote Reuters.
SCOUT, which began in 2002, involved patients 55 years of age or older, who were overweight or obese, and with a history of heart disease or type 2 diabetes plus one additional cardiovascular risk factor. Patients who recently had a heart attack or stroke, or had poorly controlled congestive heart failure were not included. The trial looked at 10,744 patients and ran to March 2009, noted Reuters.
Abbott claims Meridia is safe, arguing that Abbott only studied the medication in riskier demographics due to regulatory approval mandates, said Reuters.
According to Public Citizen's Health Research Group Director Sidney Wolfe, the FDA took too long to act. "FDA has unconscionably allowed this drug, which should not have been approved in the first place, to stay on the market," said Wolfe, quoted Reuters previously. "The agency appears immobilized to act against drugs that have no unique benefits but unique, serious dangers." The FDA denied Wolfe’s request pending—in part—SCOUT trial results, said Reuters.
The call for a European ban came after a study of 10,000 patients suggested it put them at a higher risk for heart disease. The study, Sibutramine Cardiovascular Morbidity/Mortality Outcomes in Overweight or Obese Subjects at Risk of a Cardiovascular Event (SCOUT), was begun in 2002, and involved patients ho were 55 years of age or older, overweight or obese, and had a history of heart disease or type 2 diabetes plus one additional cardiovascular risk factor. Patients who recently had a heart attack or stroke, or had poorly controlled congestive heart failure were not included in the study.
Preliminary data from SCOUT showed that cardiovascular events were reported in 11.4% of patients using Meridia compared to 10% of patients using a placebo. According to the FDA Early Communication issued in November, this difference was higher than expected, suggesting that Meridia is associated with an increased cardiovascular risk in the study population.
Based on the SCOUT findings, the European Medicines Agency found that "the risks of these medicines are greater than their benefits." Its decision will now get passed to the European Commission for review.
Yesterday, the U.S. Food & Drug Administration (FDA) announced that because of the SCOUT findings, Abbott Laboratories had agreed to add a new contraindication to the Meridia label that it not be used in patients with a history of heart disease, including heart attacks, uncontrolled hypertension and heart-rhythm problems. Previously, the Meridia label only recommended against use of the drug by patients with a history of heart disease.
The FDA also will hold an advisory committee meeting to further discuss the safety and risks with Meridia, after Abbott submits a report on SCOUT. It is expected that the report will be completed in March.
Meridia (sibutramine) was approved by the FDA in 1997 for the management of obesity, including weight loss and maintenance of weight loss, in conjunction with a reduced calorie diet. It is only recommended for obese patients with an initial body mass index (BMI) ≥ 30 kg/m2, or BMI ≥ 27 kg/m2 with other risk factors (e.g., diabetes, high cholesterol, controlled high blood pressure).
In November, the FDA said that preliminary data from a study called Sibutramine Cardiovascular Morbidity/Mortality Outcomes in Overweight or Obese Subjects at Risk of a Cardiovascular Event (SCOUT) suggested that patients using Meridia experienced a higher number of cardiovascular events compared to those using a placebo. The preliminary data showed that cardiovascular events were reported in 11.4% of patients using Meridia compared to 10% of patients using a placebo. According to the FDA Early Communication issued at the time, this difference was higher than expected, suggesting that Meridia is associated with an increased cardiovascular risk in the study population.
SCOUT, which began in 2002, involved approximately 10,000 patients who were 55 years of age or older, overweight or obese, and had a history of heart disease or type 2 diabetes plus one additional cardiovascular risk factor. Patients who recently had a heart attack or stroke, or had poorly controlled congestive heart failure were not included in the study.
Additional data from the SCOUT study reviewed by FDA indicate that the increased risk for cardiovascular events with Meridia occurred only in patients with a history of cardiovascular disease. As a result, the FDA today informed healthcare professionals that it had requested and Abbot Laboratories has agreed to add a new contraindication to the Meridia label. The contraindication will state that Meridia is not to be used in patients with a history of cardiovascular disease, including:
• History of coronary artery disease (e.g., heart attack, angina)
• History of stroke or transient ischemic attack (TIA)
• History of heart arrhythmias
• History of congestive heart failure
• History of peripheral arterial disease
• Uncontrolled hypertension (e.g., > 145/90 mmHg)
The FDA also advised that healthcare professionals regularly monitor the blood pressure and heart rate of patients using Meridia and if sustained increases in blood pressure and/or heart rate are observed, the drug should be discontinued. Additionally, the agency said Meridia should be discontinued in patients who do not lose at least 5% of their baseline body weight within the first three to six months of treatment, as continued treatment is unlikely to be effective and exposes the patient to unnecessary risk.
The FDA said patients currently using Meridia should talk with their healthcare professional to determine if continued use of the drug is appropriate and discuss any questions they may have about their treatment.
Meridia (sibutramine) was approved by the FDA in 1997 for the management of obesity, including weight loss and maintenance of weight loss, in conjunction with a reduced calorie diet. It is only recommended for obese patients with an initial body mass index (BMI) ≥ 30 kg/m2, or BMI ≥ 27 kg/m2 with other risk factors (e.g., diabetes, high cholesterol, controlled high blood pressure).
The recent action by both the FDA and EMEA was prompted by analysis of preliminary data from a study called Sibutramine Cardiovascular Morbidity/Mortality Outcomes in Overweight or Obese Subjects at Risk of a Cardiovascular Event (SCOUT). Part of a post-approval commitment between the EMEA and Abbott Labs, SCOUT was designed to show that weight loss with Meridia and standard care was more effective in reducing the number of cardiovascular events compared to weight loss from a placebo and standard care. According to an FDA Early Communication issued in November, that analysis indicated that patients using sibutramine experienced a higher number of cardiovascular events compared to those using a placebo
In a press release issued December 18, the EMEA said it is reviewing data from SCOUT that indicate an increased risk of serious cardiovascular events, such as stroke or heart attack, with medicines containing sibutramine. In Europe, such products are sold under the brand names Reductil, Reduxade and Zelium.
The EMEA reminded doctors and patients to use sibutramine-containing medicines with caution, and only in accordance with the currently approved product information. In particular, the agency said these medicines should not be used in patients with coronary artery disease, congestive heart failure, peripheral arterial occlusive disease, arrhythmia and cerebrovascular disease (stroke or transient ischemic attack). All patients should be regularly monitored for increases in blood pressure and heart rate. Patients who do not lose at least 5% of their body weight within 3 months should stop treatment. The maximum treatment duration should not exceed one year.
Meridia (sibutramine) was approved by the FDA in 1997 for the management of obesity, including weight loss and maintenance of weight loss, in conjunction with a reduced calorie diet. It is only recommended for obese patients with an initial body mass index (BMI) ≥ 30 kg/m2, or BMI ≥ 27 kg/m2 with other risk factors (e.g., diabetes, high cholesterol, controlled high blood pressure). About 294,000 prescriptions for Meridia were filled in the past 12 months, according to Public Citizen.
As we've reported previously, Meridia is already the subject of an FDA safety review. The review was announced after preliminary analysis of a study known as SCOUT (Sibutramine Cardiovascular Morbidity/Mortality Outcomes in Overweight or Obese Subjects at Risk of a Cardiovascular Event) suggested that patients using Meridia experienced a higher number of cardiovascular events compared to those using a placebo.
Public Citizen first sought to ban sibutramine, the active ingredient in Meridia, in 2002, stating that results of pre-approval clinical trials had demonstrated increases in blood pressure, pulse rate and palpitations in obese patients taking the drug. But the FDA rejected the petition four years ago because it was awaiting results of a large, randomized study that could provide more conclusive results. According to Public Citizen, the SCOUT trial has provided the data the FDA was waiting for.
Based on the new findings from the SCOUT study and Public Citizen’s updated figures based on an analysis of FDA data, the group calculates that there have been 84 post-approval cardiovascular deaths of patients taking Meridia. This includes 32 patients who were 50 or younger and 11 patients 30 or younger.
“If the FDA truly intends to operate as a public health agency, then it should acknowledge that the continued approval of this drug cannot be justified based on science,” Dr. Sidney Wolfe, director of Public Citizen’s Health Research Group, said in the press release. “The FDA should therefore tell Abbott to pull Meridia from the market immediately.”
Meridia (sibutramine) was approved by the FDA in 1997 for the management of obesity, including weight loss and maintenance of weight loss, in conjunction with a reduced calorie diet. It is only recommended for obese patients with an initial body mass index (BMI) ≥ 30 kg/m2, or BMI ≥ 27 kg/m2 with other risk factors (e.g., diabetes, high cholesterol, controlled high blood pressure).
The FDA Early Communication was prompted by analysis of preliminary data from a study called Sibutramine Cardiovascular Morbidity/Mortality Outcomes in Overweight or Obese Subjects at Risk of a Cardiovascular Event (SCOUT). Part of a post-approval commitment between the European Medicines Agency (EMEA) and Abbott Labs, SCOUT was designed to show that weight loss with Meridia and standard care was more effective in reducing the number of cardiovascular events compared to weight loss from a placebo and standard care.
SCOUT, which began in 2002, involved approximately 10,000 patients who were 55 years of age or older, overweight or obese, and had a history of heart disease or type 2 diabetes plus one additional cardiovascular risk factor. Patients who recently had a heart attack or stroke, or had poorly controlled congestive heart failure were not included in the study.
In the Early Communication, the FDA said it was recently made aware that the preliminary analysis of SCOUT's primary endpoint suggests that patients using Meridia experienced a higher number of cardiovascular events compared to those using a placebo. The preliminary data shows that cardiovascular events were reported in 11.4% of patients using Meridia compared to 10% of patients using a placebo. According to the FDA Early Communication, this difference is higher than expected, suggesting that Meridia is associated with an increased cardiovascular risk in the study population.
The preliminary study findings highlight the importance of avoiding the use of Meridia in patients with a history of heart disease, congestive heart failure, arrhythmias, or stroke, as recommended in the drug's current labeling, the FDA said. The agency also advised that healthcare professionals should continue to evaluate the benefits and risks of Meridia, taking into account individual patient medical histories. Patients should talk to their healthcare professional about whether Meridia is right for them, the FDA said.
Because of the serious nature of the SCOUT preliminary data, the FDA said it
is conducting an expedited safety review of Meridia. The agency will communicate its findings to the public as soon as this review is complete.