Obesity and Antiplatelets-Does One Size Fit All?

Antiplatelet therapy has become a cornerstone in the management of many vascular diseases. With growing antiplatelet options, attention has focused on their comparative effectiveness in specific patient populations. Perhaps one of the least defined factors influencing efficacy of these agents is body mass and obesity. Evidence from preclinical models established that obesity promotes inflammation that in turn enhances platelet reactivity. Thus, adiposity has the potential to diminish or alter the therapeutic effect of antiplatelet therapy. Pharmacodynamic analyses suggest a potential need for dose adjustments of antiplatelet therapy in obese patients. Yet, obese patients paradoxically have better outcomes after acute coronary syndromes. In this review, we identify a critical need for clinical studies with outcome data to enable the development of recommendations for optimal antiplatelet regimens in obese individuals. Until such data exists, healthcare providers should be aware of the potential impact of obesity on the efficacy of anti-platelet therapy.

Rhabdomyolysis precipitated by possible interaction of ticagrelor with high-dose atorvastatin.

OBJECTIVE: To report a case of rhabdomyolysis possibly caused by interaction of ticagrelor with high-dose atorvastatin. SUMMARY: A 62-year-old woman originally from India underwent uncomplicated percutaneous coronary intervention following ST-elevation myocardial infarction. The patient was discharged on a secondary prevention drug regimen that included ticagrelor 90 mg twice daily, atorvastatin 80 mg once daily, metoprolol 25 mg twice daily, and aspirin 81 mg daily. Two months later, the patient was readmitted with complaints of muscle pain, nausea, vomiting, and poor oral intake. The patient was diagnosed with rhabdomyolysis based on her symptoms combined with elevated creatine kinase, urine myoglobin, and serum creatinine. Intravenous fluids were initiated and atorvastatin held. Throughout the second hospital stay, serial laboratory values revealed a decrease in creatine kinase and resolution of acute kidney injury and muscle pain. The patient was discharged on aspirin and clopidogrel. Low-dose statin therapy was started at a follow-up appointment with close monitoring without recurrence of rhabdomyolysis. RESULTS: A drug interaction between the cytochrome P450 3A4 inhibitor ticagrelor and substrate atorvastatin 80 mg may have precipitated development of rhabdomyolysis in this patient. The probability of this drug interaction is rated as "possible" on both the Naranjo Adverse Drug Reaction Probability Scale and the Drug Interaction Probability Scale. CONCLUSION: Rhabdomyolysis was observed possibly because of a drug interaction between once-daily ticagrelor and atorvastatin 80 mg. Clinicians need to be aware of this possible drug interaction via CYP3A4 and potential complications.

Subarachnoid hemorrhage in a patient taking phentermine for weight loss.

OBJECTIVE: To report the case of an angiography-negative subarachnoid hemorrhage (SAH) in association with increased use of the sympathomimetic phentermine. SUMMARY: A 45-year-old woman taking phentermine for weight loss presented with the "worst headache of her life," as well as nausea and some confusion. Her prior medical history was largely negative for pathology except for a 20-pack-year history of smoking. RESULTS: Upon admission to an inpatient facility, the patient was normotensive with a Glasgow Coma Score of 15. She was found on computed tomography to have a diffuse SAH (Hunt and Hess grade 2, Fisher grade 3). Digital subtraction angiography, performed on hospital day 2, was negative for aneurysm. The patient convalesced in the intensive care unit for 8 days and was treated as a typical patient with SAH (i.e., vasospasm prophylaxis with nimodipine and atorvastatin, ad lib diet with strict attention to fluid balance to maintain euvolemia). A repeat angiographic study on hospital day 8 also did not reveal an aneurysm or other cause for her SAH. She was discharged thereafter with intensive smoking cessation education and counseled to discontinue phentermine. Upon follow-up 6 weeks later, the patient was without complaints or neurologic deficits and had resumed her previous activities and work. CONCLUSION: Phentermine is a sympathomimetic agent found commonly in weight-loss products. Sympathomimetics have been linked to the development of hypertension, which can lead to cardiovascular and neurologic hemorrhages. We believe that the SAH in this patient was likely secondary to drug-induced hypertension or vasculopathy from the phentermine.