Safety and Efficacy of Intensified Antiplatelet Therapy in Patients Undergoing Neuroendovascular Procedures.

INTRODUCTION: The purpose of this study was to evaluate safety and efficacy of intensified antiplatelet therapy guided by VerifyNow assay P2Y12 reaction unit (PRU) reported values in patients undergoing neuroendovascular procedures. METHODS: An observational, retrospective review was conducted at a single academic tertiary referral center and comprehensive stroke center from December 1, 2012, to August 31, 2014. The primary objective was to determine the prevalence of thromboembolic complications stratified by preprocedural PRU values. Secondary outcomes were assessed by investigating whether the goal PRU value of 190 or less is sufficient to reduce thromboembolic complications on the day of the procedure, and 30- and 90-day postprocedure. RESULTS: There was no statistically significant difference in the overall rate of complications in the two groups (two events in the group with preprocedural PRU values of 190 or more versus seven events in the group with preprocedural PRU values of less than 190, p = 0.668). Furthermore, the rates of thromboembolic events by 90 days were not significantly different in the two groups (one event in the group with preprocedural PRU ≥ 190 versus four events in patients with preprocedural PRU < 190, p = 1). Similarly, there was no statistically significant difference in the rate of hemorrhagic events in the two groups by 90-day postprocedure (one versus three events, p = 0.558). CONCLUSION: The observed rate of thromboembolic and hemorrhagic complications in patients with preprocedural PRU values of less than 190 was not significantly different from the rate observed in patients with preprocedural PRU values of greater than 190. Sources of funding: No external funding used.

Safety and efficacy of repeated doses of 14.6 or 23.4 % hypertonic saline for refractory intracranial hypertension.

BACKGROUND: The efficacy of administering single bolus doses of 14.6 or 23.4 % hypertonic saline (HTS) to treat refractory intracranial hypertension has been demonstrated in the literature and has emerged as an important therapeutic option in treating these patients. However, many institutions lack experience with this therapy and there are few published studies evaluating the safety of repeated bolus dosing of HTS. METHODS: A retrospective review of patients admitted between January 2008 and July 2012 was conducted to evaluate the use of repeated dosing of HTS in patients with refractory intracranial hypertension. The primary objective was to evaluate the safety of repeated dosing of HTS assessed by documented adverse effects such as central pontine myelinolysis (CPM) and severe fluctuations in serum sodium concentrations. Secondary objectives were to evaluate the efficacy of repeated dosing HTS in reducing intracranial pressure (ICP) and to compare the dose-response relationship of 14.6 and 23.4 % doses. RESULTS: Fifty-five patients were included for evaluation, each receiving an average of 8.9 (range 2-61) doses of HTS. A statistically significant increase in mean serum sodium concentration occurred with the administration of HTS (p < 0.0001). No cases of CPM were identified. The use of HTS was found to be effective based on decreases in ICP after administration (p < 0.0001, mean ICP reduction: 10.1 mmHg, range 3-23.6 mmHg). The efficacy of 23.4 % saline in decreasing ICP was not found to be significantly different than 14.6 % saline (p = 0.23). CONCLUSIONS: Repeat bolus dosing of 14.6 or 23.4 % HTS appears to be relatively safe and effective for treating refractory intracranial hypertension assuming there is frequent electrolyte monitoring and concomitant fluid management.

Safety and efficacy of ticagrelor for neuroendovascular procedures. A single center initial experience.

INTRODUCTION: Although platelet response testing is controversial, up to one-third of neuroendovascular patients are 'resistant' to clopidogrel and are at risk for in stent thrombotic complications and may require alternative antiplatelet therapy. Ticagrelor is a new reversible ADP P2Y12 platelet receptor inhibitor with no known resistance. We describe the clinical experience with ticagrelor for neuroendovascular procedures as an alternative in clopidogrel P2Y12 platelet resistant patients. METHODS: We reviewed our cerebrovascular database for all patients who were non-responders to clopidogrel, defined as P2Y12% inhibition <30%, despite repeat clopidogrel loading dose of at least 600 mg, and who were then administered ticagrelor. RESULTS: 18 patients were non-responders to clopidogrel; 10 (56%) were men, eight (44%) were women, with a median age of 61 years (range 38-84). All patients received loading doses of at least 600 mg of clopidogrel and showed P2Y12 levels below 20% prior to ticagrelor administration. Patients were loaded with 180 mg of ticagrelor, and all but one patient showed an initial P2Y12 response above 60%. 11 patients underwent stenting, two underwent coiling, and five underwent treatment by pipeline embolization device. No patient experienced any adverse effects in the postoperative period related to the use of ticagrelor. CONCLUSIONS: Ticagrelor offers an effective alternative to clopidogrel non-responders. All of our patients showed immediate platelet inhibition after a loading dose of 180 mg of ticagrelor, with no adverse effects. The cost of medication, patient compliance (twice a day doses), and reversible inhibition should be taken into consideration when using ticagrelor.

Clopidogrel Resistance by P2Y12 Platelet Function Testing in Patients Undergoing Neuroendovascular Procedures: Incidence of Ischemic and Hemorrhagic Complications.

PURPOSE: The purpose of the study was to assess clopidogrel resistance and whether "intensified" antiplatelet therapy guided by platelet inhibition tests during neuroendovascular procedures would reduce ischemic complications. METHODS: We conducted a retrospective review of patients at Mayo Clinic in Jacksonville, Florida, who underwent neuroendovascular (NV) procedures and had P2Y12 platelet function testing from October 1, 2009, to September 30, 2010. The primary end-point was to determine P2Y12 resistance to antiplatelet therapy in patients who underwent NV procedures. Secondary objectives included incidence of hemorrhagic and ischemic events and a correlation between resistance and genetic CYP2C19 testing. RESULTS: 160 patients underwent P2Y12 platelet function tests. Eighty-one patients (81/160, 50.6%) met inclusion criteria. Platelet function tests identified 64 patients (79%) as non-resistant (≥20% P2Y12 inhibition) and 17 (21%) as resistant (<20% inhibition) after initial clopidogrel loading. There was an increased rate of death when a complication occurred in the resistant group by 30 day (17% versus 3%; p=0.059) and 90 day follow-up (23% versus 4%; p=0.032). There was no significant association found between complication and loading dose (p=0.0721). CONCLUSIONS: 21% of patients undergoing NV procedures were resistant to clopidogrel. Intensifying antiplatelet therapy to achieve ≥20% inhibition on platelet function testing did not result in higher numbers of ischemic or hemorrhagic events, but there was a trend toward more death in the resistant group by 30 and 90 days of those experiencing complication(s). AUTHOR JUSTIFICATIONS: Jerah D. Nordeen, Pharm.D.: Primary author Alden V. Patel, Pharm.D.: Contributor of professional content, study design Robert M. Darracott, Pharm.D.: Contributor of professional content, study design Gretchen S. Johns, M.D.: Contributor of professional content, study design Philipp Taussky, M.D.: Contributor of professional content, study design Rabih G. Tawk, M.D.: Contributor of professional content, study design David A. Miller, M.D.: Contributor of professional content, study design William D. Freeman, M.D.: Contributor of professional content, study design Ricardo A. Hanel, MD, PhD: Contributor of professional content, study design. LIST OF ABBREVIATIONS: (NV)neuroendovascular(CYP)cytochrome P-450(PPI)proton pump inhibitors(PCI)percutaneous coronary intervention. LIST OF COMMERCIAL PRODUCTS: Aspirin (Acetylsalicylic Acid) (Bayer Corp, Morristown, NJ, USA) Clopidogrel (Plavix®) (Bristol Myers Squibb/Sanofi Pharmaceuticals, Princeton, NJ, USA) VerifyNow® (Accumetrics Inc., San Diego, CA, USA) Ticlopidine (Ticlid®) (Roche Laboratories, Basel, Switzerland) Prasugrel (Effient®) (Eli Lilly & Co., Indianapolis, IN, USA) Eptifibatide (Integrilin®) (Merck & Co., Inc., Whitehouse Station, NJ, USA) Abciximab (Reopro®) (Janssen Pharmaceuticals, Inc., Titusville, NJ, USA) Tirofiban (Aggrastat®) (MGI Pharma, Inc., Bloomington, MN, USA) Pantoprazole (Protonix®) (Pfizer Inc., New York, NY, USA) Omeprazole (Prilosec®) (Procter and Gamble Pharmaceuticals, Mason, OH, USA) Famotidine (Pepcid®) (McNeil Consumer & Specialty Pharmaceuticals, Fort Washington, PA, USA) Ticagrelor (Brilinta®) (AstraZeneca Pharmaceuticals, Wilmington, NC, USA).