Guest Post by Dr. Eldad Einav, MD, FACC
Luckily, we are starting to have some quality data from the Qsymia trials showing cardiovascular safety of incremental doses of Phentermine (up to 15mg). It is pretty evident that there is significant improvement in cardiovascular risk factors and no excess of cardiovascular events in the patients receiving phentermine and topiramate (4). Heart rate was only mildly increased compared to placebo and mostly in the high dose of 15mg.
Exclusion criteria from the Qsymia phase-3 trials were
1. Stroke, myocardial infarction, life-threatening arrhythmia, or coronary revascularization within the past 6 months
2. Unstable angina, New York Heart Association Class II-IV congestive heart failure, or known or suspected clinically significant cardiac valvulopathy
On the official Qsymia prescribing information sheath – coronary disease is not listed as contraindication or as caution. It does however suggest that patients follow their heart rate.
1. Phentermine can be prescribed safety with Topirimate at similar doses as in Qysmia for patients who have stable cardiac condition if you go by the exclusions listed above.
2. Other cardiac patients can benefit and higher doses than 15mg can be used. However, it would be more off-label and you should discuss it with your patient and get an informed consent.
3. coronary events occurring while taking Qsymia do not imply causation and Qsymia effect could even be protective to some extent.
Not much data on cardiac arrhythmia like atrial fibrillation, but me as a cardiologist will not be too concerned if heart rate is controlled with AV nodal agents.
4. When in doubt, be cautious and get a cardiology consult who is aware of the pros and the cons of obesity meds.
1. Rothman, R. B., & Hendricks, E. J. (2009). Phentermine cardiovascular safety. The American Journal of Emergency Medicine,27(8), 1010-1013.
2. Makaryus, J. N., & Makaryus, A. N. (2008). Cardiac arrest in the setting of diet pill consumption. The American Journal of Emergency Medicine, 26(6), 732.e1-3.
3. Coleman, Eric MD. 15 July 2010, Advisory Committee meeting for phentermine/topiramate; FDA Memorandum
4. Davidson, M. H., Tonstad, S., Oparil, S., Schwiers, M., Day, W. W., & Bowden, C. H. (2013). Changes in cardiovascular risk associated with phentermine and topiramate . The American Journal of Cardiology, 111(8), 1131.”
“Great summary Eldad! I concur with your analysis and conclusions. In the absence of long term CV outcomes data for Phentermine at higher doses, we have to weigh the circumstantial evidence. Obesity and obesity related conditions are some of the strongest drivers of cardiovascular risk - Phentermine improves these conditions. There is a long history of use of Phentermine in non-cardiac patients as well as patients with CV risk factors such as hypertension with no credible reports of adverse outcomes. There are many drugs that are utilized for the treatment of non-cardiac conditions in patients with cardiovascular disease that have not been studied in regards to cardiovascular outcomes. In an ideal world, they would be, but, absent such data, we still use these medications to improve quality of life and relieve suffering. In my view, there is no reason that Phentermine should be held to a higher bar. That it often is held to this standard stems from past problems with other obesity drugs and likely from prejudice regarding people viewing obesity as a moral failing rather than a disease.
My practice is to use Qsymia preferentially for cardiovascular patients since it is better studied than Phentermine and works well. However, for patients who cannot afford or tolerate Qsymia, I have no reservations about using Phentermine as long as the CV disease is stable. I agree with the importance of informed consent and I follow these patients closely.”