Kuantan, Malaysia - Use of the appetite suppressants phentermine and sibutramine (Merida, Abbott Laboratories) appear to have caused MI in two young women, say Malaysian doctors [1]. Dr Shah M Azarisman (International Islamic University, Kuantan, Malaysia) and colleagues report their findings in a letter in the November 1, 2007 issue of the New England Journal of Medicine.

Azarisman told heartwire that he believes these two cases are the tip of the iceberg. "Anecdotally, there has been quite an increase in the number of myocardial-associated adverse drug reactions associated with appetite suppressants; it has been small talk around the dinner table," he said. "There has also been some evidence from [adverse drug reaction reports] with these kind of drugs reported to our pharmacology colleagues," he added.

Azarisman said he would now like to see industry registries set up to monitor these kinds of reactions to appetite suppressants.

Although appetite suppressants have been around for a number of years in Malaysia, "they have only recently become more widely obtainable," Azarisman explained. In fact, while phentermine is available legally in Malaysia, sibutramine is not, because its introduction was withheld in 2002 due to concerns about poor tolerability. However, it is widely obtainable on the black market, he noted.

Five years ago, in the US, sibutramine was lambasted by Public Citizen, the Washington, DC-based consumer-advocacy group, which called for the FDA to withdraw the drug from the market. Public Citizen said sibutramine contributed to major cardiovascular problems and was not particularly effective in aiding weight loss. Of particular concern was the propensity for sibutramine to significantly increase blood pressure and heart rate. At that time, Abbott said the safety of sibutramine had been assessed in more than 12 000 patients in clinical trials. In placebo-controlled trials, there was no increase in MI, congestive heart failure, cardiac arrhythmias, or death in the sibutramine-treated patients as compared with controls, the company noted.

Azarisman says the problems with sibutramine with regard to hypertensive crises "are well-known and well-documented," but that it is the association with MI that seems to be new and is of most concern now.

The Malaysian doctors report on two otherwise-healthy young women who had MI with acute ST-segment elevation The first, aged 35, developed acute STEMI and hypotension following general anesthesia for liposuction. She was a nonsmoker but was overweight (body mass index 29), and she had undergone two previous liposuction procedures.

Cardiac biomarkers were elevated (creatine kinase 445 U/L; troponin T 1.86 µg/L), and echocardiography revealed septal hypokinesia. Results of coronary angiography were normal. The only medication she reported using recently was phentermine, which she had taken intermittently in the past and for three consecutive days before her admission for this procedure.

[We] conclude that the use of appetite suppressants was responsible for the MI in each of the two patients.

The second patient was 24 years old and presented to the emergency room with severe, recurrent retrosternal chest pains. The ECG showed acute inferior MI. Peak levels of serum creatine kinase and troponin T were 3450/L and 4.25 µg/L, respectively. Results of coronary angiography were normal. This patient was also a nonsmoker and had no other illnesses. The only medication she reported taking was sibutramine for the previous three months. In both patients, the ECG showed complete resolution within 24 hours.

The doctors investigated and ruled out all other possible causes of MI, including cocaine abuse, viral myocarditis, aortic dissection, hypercoagulable states, and autoimmune vasculitis.

"The absence of any attendant cardiovascular risk factors and the negative results of other studies led us to conclude that the use of appetite suppressants was responsible for the MI in each of the two patients," they conclude.

Azarisman told heartwire that although there hasn't been long-term follow-up on these two women, they have not come back complaining of any recurrent problems. They were advised to stop taking appetite suppressants.

He added that there has only been one prior report of MI associated with appetite suppressants, and this was with phenylpropanolamine (Dexatrim, Chattem). This was a case report plus a review of seven other cases of myocardial injury associated with the same drug [2]. "I suspect that is why the New England Journal of Medicine accepted our correspondence," he told heartwire.

He believes that this issue needs investigating and that perhaps a registry could be set up to monitor such events. "We really need to get down and work with industry on this," he noted.