Chiefs’ Inquiry Corner- 9/20/2021

September 21, 2021

Chief residents of the NYU Langone Internal Medicine Residency give quick-and-easy, evidence-based answers to interesting questions posed by house staff, both in their clinics and on the wards.

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 Administration of antiplatelet therapy with a P2Y12 inhibitor is standard of care following PCI performed in the setting of ACS (Class I recommendation as per the American College of Cardiology/American Heart Association guidelines). Additional data has suggested that ticagrelor and prasugrel are more potent than clopidogrel, such that it is a Class IIa recommendation to choose either of those agents in preference to clopidogrel for maintenance P2Y12 inhibitor therapy, if available, (with the caveat that prasugrel can only be used in people who are not at high risk for bleeding complications and do not have a history of stroke or TIA). However, there is limited data when comparing efficacy of prasugrel to ticagrelor. In a recent prespecified analysis of a postrandomization subgroup of 3377 patients part of a larger multicenter, randomized clinical trial who presented with ACS and were treated with PCI, researchers investigated whether there was a difference in using prasugrel or ticagrelor following PCI. Primary endpoint was a composite comprised of all-cause death, myocardial infarction, or stroke at 12 months. Safety end point was significant bleeding (Bleeding Academic Research Consortium type 3-5). Results revealed that the incidence of the primary endpoint occurred more frequently in the group treated with ticagrelor than prasugrel (HR 1.41; 95% CI 1.11-1.78) and that the incidence of bleeding events between the two groups was not statistically significant. While this data is based on a postrandomization subgroup, it does suggest that prasugrel therapy is superior to ticagrelor therapy in patients with ACS who undergo PCI, and invites dedicated randomized clinical trials to confirm these findings.

References: Ticagrelor or Prasugrel for Patients With Acute Coronary Syndrome Treated With Percutaneous Coronary Intervention: A Prespecified Subgroup Analysis of a Randomized Clinical Trial
  The celiac plexus is a bundle of nerves that resides along the anterolateral wall of the aorta in the retroperitoneum and transmits nociceptive impulses from the upper abdominal viscera (stomach to the proximal transverse colon). Initially introduced in the 1910s, celiac plexus block or neurolysis can be used to treat intractable pain arising from abdominal malignancies, and occasionally from chronic pancreatitis. Celiac plexus block allows for temporary pain management with the injection of corticosteroids or long-acting local anesthetics while celiac plexus neurolysis leads to permanent celiac plexus destruction, usually with ethanol. The procedure is performed under CT-guidance and can utilize either an anterior or posterior approach, the latter of which can be transaortic, paravertebral, or transintervertebral. Contraindications to this procedure include presence of coagulopathy, abdominal aortic aneurysm, aortic mural thrombosis, atypical anatomy, intrabdominal infection, and bowel obstruction. The most common complication is back pain. Severe complications are rare but can include neurologic symptoms (e.g. monoplegia, bladder or bowel dysfunction), vascular injury (e.g. dissection, retroperitoneal bleed), infection, and damage to surrounding structures. Percutaneous celiac plexus neurolysis has been demonstrated to have prolonged benefit in 70%-90% of patients with various upper abdominal cancers, irrespective of technique utilized.

References: CT-guided celiac plexus neurolysis: a review of anatomy, indications, technique, and tips for successful treatment
 Tuberculosis care can present numerous challenges for patients including medication adherence, adverse drug effects and drug costs – in particular when metered out over the course of a standard six month regimen. Higher potency regimens based on rifapentine, a cyclopentyl derivative of rifampin, are being studied as one way of shortening treatment course. A recent phase 3 noninferiority trial published this year in NEJM evaluated 6 months of standard RIPE compared with either of two 4-month regimens (each with rifapentine daily [replacing rifampin]; one regimen with and one without moxifloxacin daily [replacing ethambutol]) with a primary efficacy outcome of tuberculosis-free survival at 12 months. The 4-month rifapentine-moxifloxacin regimen — but not the rifapentine regimen — met predefined noninferiority criteria. In addition, time to culture negativity was shorter in both rifapentine groups than the standard therapy group. Adverse events did not differ significantly among the three groups (although hyperbilirubinemia was more common in both rifapentine groups). Important considerations for the use of the shortened regimen include the high cost and limited availability of rifapentine, need to take rifapentine after meals to maximize absorption, availability of fluoroquinolone susceptibility testing, and monitoring for toxicity (eg, QT prolongation) in the setting of prolonged moxifloxacin administration. Still, the possibility of a shortened course of treatment for tuberculosis demonstrated in this noninferiority trial invites further studies to confirm these findings and offers the possibility of eventual change in treatment guidelines.

References: Four-Month Rifapentine Regimens with or without Moxifloxacin for Tuberculosis.