In this ACCEL interview, David Dixon, PharmD, AACC, a pharmacist at Virginia Commonwealth University School of Pharmacy in Richmond, VA, shares perspectives on new anti-obesity drugs, including pharmacology, drug-drug interactions and efficacy, and deciding which drug is best for a patient. C. Noel Bairey-Merz, MD, FACC, led the conversation.
Dr. Bairey-Merz: Cardiologists in general are likely to shy away from prescribing anti-obesity drugs, because of the memory of the fen-phen situation. Why should they prescribe these drugs?
Dr. Dixon: The current anti-obesity agents might be a way to help patients lose enough weight that they can become more physically active. This increase in physical activity is good for heart health in any patient. In particular, these drugs may be beneficial for patients who have finished cardiac rehab and have not achieved their personal weight loss goal, despite making lifestyle modifications.
Would you use anti-obesity drugs for a patient who has incorporated some lifestyle changes?
Absolutely. If you look at the clinical trials, all the participants had fairly intensive lifestyle education and lifestyle modification. These drugs are simply an adjunct to this.
The anti-obesity drugs are indicated for a BMI of 40, 35, 30, 25? What is the cut-off for using these drugs?
The current recommendation says these drugs are worth considering for patients with a BMI of 30 or greater. This is especially true for patients with an elevated BMI and at least one additional risk factor, such as hypertension, diabetes or dyslipidemia.
Are there contraindications for cardiac patients for the anti-obesity drugs? Again, we cardiologists remember the previous formulations and are cautious.
That’s an interesting question. For the naltrexone and bupropion product, as well as the phentermine-topiramate combination, the blood pressure should be closely monitored. An increase in blood pressure, particularly with the phentermine and bupropion components, can be seen because these agents have a stimulatory effect. Clearly, monitoring blood pressure and heart rate would be critical.
Let’s talk about fen-phen, because that is what will be on the minds of most cardiologists. Why should we be thinking about using the new anti-obesity drugs?
The fen-phen product, which was removed from the market in 1997, caused valvulopathies. It was really the pulmonary hypertension that caused some deaths and was concerning. A key difference with the lorcaserin product is that it targets the serotonin 2B receptor, which is found only or mostly in the hypothalamus, whereas the fenfluramine product targeted 5-HT2C, which is in the valves.
"The current anti-obesity agents might be a way to help patients lose enough weight that they can become physically active." — David Dixon, PharmD, AACC
The lorcaserin product that is highly selective for the 2B receptor, appears, at least based on the data available, to be safe. Looking at the incidence of valvulopathies in the studies that have been completed, there has been no statistically significant difference between the placebo group and those patients receiving lorcaserin. There is a large cardiovascular trial under way with lorcaserin – CAMELLIA-TIMI – so in 2018 I would say we would feel much more comfortable prescribing that particular agent once we see the data.
Lorcaserin is available now and approved for weight loss. Presumably the big clinical trial will not only show safety but maybe efficacy for reducing cardiovascular disease?
That is the hope.
New products are available. They are approved by the Food and Drug Administration. They are found to be effective for weight loss. What could we expect to see? Five pounds, 10 pounds, 20 pounds?
The combination phentermine and topiramate product at the highest dose actually is considered to be the most efficacious. Over half of the patients who take that higher dose will achieve at least a five percent weight loss. The naltrexone and buproprion product would be considered the next best in terms of weight loss.
It’s really about setting the goal with the patient and understanding what they’re trying to do. If a patient comes into your office and says, “I would love to lose 100 pounds, and that’s my goal,” these drugs are not going to do that. They may be adjuncts to get patients started, but really, it’s going to be about them taking responsibility and making some permanent lifestyle changes to maintain weight loss and achieve such a high goal.
Let’s talk a bit more about side effects.
I would say lorcaserin is fairly well tolerated. There are more patients who discontinue the medicine due to adverse effects compared to placebo.
Around what percent?
Close to about 10 percent of patients. Not bad. However, for the naltrexone and buproprion product, you’re really looking at a discontinuation rate of almost one-quarter of patients, and that’s going to be due to side effects. So again, tolerability is key.
For liraglutide for weight loss, which has been reformulated at a higher dose compared to the liraglutide we use for diabetes, nausea is a huge side effect, and about 40 percent of patients will experience that. The nausea does improve within two to four weeks. So it’s about coaching patients through that, because the data do show that tolerability of that agent improves dramatically. There are definitely some issues in terms of gastrointestinal side effects with that product.
Another concern with liraglutide is the potential risk for acute pancreatitis, and there is the black-box warning for medullary thyroid cancers. Clearly, there are some big things that you want to look at, and make sure that the drugs are appropriate for these patients.
In cardiology, we are evaluating patients for chest pain, shortness of breath and hypertension. Many cardiac patients have hypertension. Would you rank-order these drugs in terms of which ones are going be a stimulant and which have less of that?
Phentermine is a sympathomimetic amine, and you’re definitely going get a stimulatory effect, with an increase in blood pressure and heart rate. That’s the product I would watch closely. In addition, the bupropion in the bupropion and naltrexone combination can increase blood pressure and is an antidepressant.
Like the other selective serotonin reuptake inhibitors can do sometimes.
Correct, and it [bupropion] has an effect on norepinephrine. It inhibits the reuptake of norepinephrine, you’ll get a little bit of increase in blood pressure and heart rate. So, with lorcaserin, not much of an effect on blood pressure. Maybe it will go down a few points, and same thing with liraglutide. I think, generally, from a blood-pressure perspective, those’d be the considerations. I wouldn’t start a patient on the buproprion or phentermine products who had highly uncontrolled blood pressure. Obviously, [we’d first be] getting the blood pressure controlled, and then consider the addition of those agents.
Clinical Topics: Cardiac Surgery, Diabetes and Cardiometabolic Disease, Dyslipidemia, Heart Failure and Cardiomyopathies, Prevention, Pulmonary Hypertension and Venous Thromboembolism, Vascular Medicine, Aortic Surgery, Cardiac Surgery and Heart Failure, Pulmonary Hypertension, Hypertension
Keywords: ACC Publications, Cardiology Magazine, Anti-Obesity Agents, Antidepressive Agents, Aorta, Aortic Rupture, Benzazepines, Blood Pressure, Body Mass Index, Bupropion, Diabetes Mellitus, Dyslipidemias, Drug Interactions, Dyspnea, Endovascular Procedures, Fructose, Hypertension, Hypertension, Pulmonary, Hypothalamus, Mentors, Naltrexone, Pancreatitis, Receptor, Serotonin, 5-HT2B, Risk Factors, Serotonin Uptake Inhibitors, Sympathomimetics, Thrombosis, United States Food and Drug Administration
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