From 1992 to 1997, the prescription medications fenfluramine and phentermine were used in combination for the long-term treatment of obesity. Fenfluramine and phentermine have been prescribed separately for the treatment of obesity since the 1970s. The combination of fenfluramine (or another form of fenfluramine called dexfenfluramine) and phentermine was sometimes called fen-phen.

Early studies showed that people who used a combination of fenfluramine and phentermine had a 20% to 30% risk of developing heart valve disease in the mitral, aortic, and tricuspid heart valves.¹ Following the publication of these findings, fenfluramine and dexfenfluramine were removed from the market in Canada, the United States, and Europe. The role of phentermine in heart valve disease remains unclear. However, it is still prescribed separately for the treatment of obesity.

Follow-up studies suggested the incidence of heart valve disease associated with the use of fenfluramine and phentermine in combination may be lower than earlier thought. These studies have shown a 1% to 26% risk of heart valve disease associated with the use of fenfluramine and phentermine in combination.¹

How long fenfluramine and phentermine were used is also an issue. The prevalence of aortic valve regurgitation for those who used fenfluramines for:²

• 3 months was 1.4%.
• More than 3 months was 13%.
• More than 18 months was 21.2%.

The prevalence of mitral regurgitation for the combined use of fenfluramine and phentermine was 5.1%, and there was no significant duration effect.²

The exact role of weight-loss medications in the development of heart valve disease is not known. However, recent research indicates that the progression of mitral or aortic regurgitation is unlikely to continue 13 to 26 months after discontinuing the use of fenfluramine and phentermine. In some cases, aortic regurgitation regressed.¹

The U.S. Department of Health and Human Services currently recommends that any person who has taken fenfluramine or dexfenfluramine (either alone or in combination with phentermine or other weight-loss medications) should undergo a medical examination for possible heart valve disease. If the person has symptoms of valve disease, or if the physical examination suggests valve disease, an echocardiogram is recommended.¹