Abstract: There are limited data on health status instruments in patients with peripheral artery disease and cardiovascular and limb events. We evaluated the relationship between health status changes and cardiovascular and limb events. Methods and Results In an analysis of the EUCLID (Examining Use of Ticagrelor in Symptomatic Peripheral Artery Disease) trial, we examined the characteristics of 13 801 patients by tertile of health status instrument scores collected in the trial (EuroQol 5‐Dimensions [EQ‐5D], EQ visual analog scale [VAS] , and peripheral artery questionnaire). We assessed the association between the baseline health status measurements and major adverse cardiovascular events, major adverse limb events, and lower‐extremity revascularization procedures during trial follow‐up and the association between 12‐month health status change scores and subsequent end points during follow‐up. There were 13 217 (95%) patients with EQ‐5D scores, 13 533 (98%) with VAS scores, and 4431 (32%) with peripheral artery questionnaire scores. Patients in the lowest baseline EQ‐5D tertile (0 to 〈 0.69) were more likely to be female with severe claudication compared with the highest tertile (0.79–1.0; P 〈 0.01). Patients in the lowest VAS (0–60) and peripheral artery questionnaire (0–49) tertiles had lower ankle–brachial indices compared with the highest tertiles (80–100 and 76–108, respectively; P 〈 0.01). There was a significant association between baseline EQ‐5D, VAS, and peripheral artery questionnaire scores and adjusted major adverse cardiovascular events, major adverse limb events, and lower‐extremity revascularization ( P 〈 0.05). Improved EQ‐5D and VAS scores over 12 months were associated with reduced risk of subsequent major adverse cardiovascular events or lower‐extremity revascularization (all P 〈 0.01). Conclusions Although health status instruments are rarely used in clinical practice, these measures are associated with outcomes, including major adverse cardiovascular events, major adverse limb events, and lower‐extremity revascularization. Further research is needed to determine the relationship between changes in these instruments, revascularization, and outcomes.

Abstract: Background: EXSCEL was a multinational, randomized, blinded, placebo-controlled, pragmatic CV outcome trial of once-weekly exenatide on the background of usual care. We report exenatide’s impact on estimated glomerular filtration rate (eGFR), new macroalbuminuria and 2 renal composites from a prespecified analysis plan. Methods: Opportunistic local laboratory data were collected. Overall least squares mean difference (LSMD) eGFR (95% confidence interval [95% CI]) was calculated for 13844 patients with baseline and ≥1 follow-up value. Effect on new macroalbuminuria was estimated with a Cox regression model. Effects on renal composites were estimated with interval censored time to event models, with and without covariate adjustment (demographics and disease characteristics). Results: Intention-to-treat analyses showed no significant difference in eGFR levels with exenatide (LSMD +0.21 [-0.27, 0.70] mL/min.1.73m2, p=0.39). New macroalbuminuria occurred in 2.2% and 2.5% of the exenatide and placebo groups (p=0.19). There was a 15% lower renal composite 2 adjusted risk with exenatide (p=0.027) (Table). Conclusions: A composite of 40% eGFR decline, renal replacement, renal death or new macroalbuminuria was significantly reduced in an adjusted analysis by the addition of exenatide in a broad range of people with type 2 diabetes. Other renal outcomes were numerically but not statistically improved with exenatide. Disclosure M. Bethel: Research Support; Self; AstraZeneca, Merck Sharp & Dohme Corp., Merck Serono. Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Consultant; Self; Novo Nordisk Inc.. Advisory Panel; Self; AstraZeneca. Other Relationship; Self; Sanofi. Consultant; Self; Theracos, Inc.. Research Support; Self; GlaxoSmithKline plc. R.J. Mentz: Research Support; Self; AstraZeneca, GlaxoSmithKline plc., Merck & Co., Inc.. P. Merrill: None. J.B. Buse: Other Relationship; Self; ADOCIA, AstraZeneca, Dexcom, Inc., Elcelyx Therapeutics, Inc., Eli Lilly and Company, Fractyl Laboratories, Inc., Intarcia Therapeutics, Inc., Lexicon Pharmaceuticals, Inc., Metavention, NovaTarg, Novo Nordisk A/S, Sanofi, VTV Therapeutics. Research Support; Self; Boehringer Ingelheim GmbH, Johnson & Johnson Services, Inc., Theracos, Inc.. Other Relationship; Self; Shenzhen Hightide Biopharmaceutical, Ltd.. Research Support; Self; National Heart, Lung, and Blood Institute, National Center for Advancing Translational Sciences. Other Relationship; Self; National Institute of Diabetes and Digestive and Kidney Diseases, American Diabetes Association. Research Support; Self; Patient-Centered Outcomes Research Institute. Other Relationship; Self; National Institute of Environmental Health Sciences. J.C. Chan: Consultant; Self; Bayer AG. Other Relationship; Self; Bayer AG. Consultant; Self; Sanofi. Other Relationship; Self; Sanofi, Eli Lilly and Company, Amgen Inc.. Consultant; Self; AstraZeneca, Merck & Co., Inc., Pfizer Inc.. Other Relationship; Self; Pfizer Inc.. Board Member; Self; Asia Diabetes Foundation. Stock/Shareholder; Self; GemVCare. Other Relationship; Self; Merck Sharp & Dohme Corp.. Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Novartis AG, Eli Lilly and Company. S.G. Goodman: Research Support; Self; Amgen Inc.. Consultant; Self; Amgen Inc.. Research Support; Self; AstraZeneca. Consultant; Self; AstraZeneca. Research Support; Self; Bayer AG. Consultant; Self; Bayer AG. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Research Support; Self; Bristol-Myers Squibb Company. Consultant; Self; Bristol-Myers Squibb Company. Research Support; Self; Eli Lilly and Company. Consultant; Self; Eli Lilly and Company. Research Support; Self; GlaxoSmithKline plc.. Consultant; Self; Merck & Co., Inc., Novartis Pharmaceuticals Corporation. Research Support; Self; Pfizer Inc.. Consultant; Self; Pfizer Inc.. Research Support; Self; Sanofi. Consultant; Self; Sanofi. Research Support; Self; Regeneron Pharmaceuticals, Inc.. Consultant; Self; Regeneron Pharmaceuticals, Inc.. Research Support; Self; CSL Behring. N. Iqbal: Employee; Self; AstraZeneca. N. Jakuboniene: None. B.G. Katona: Employee; Self; AstraZeneca. Y. Lokhnygina: None. R.D. Lopes: Consultant; Self; Bayer AG, Boehringer Ingelheim GmbH. Other Relationship; Self; Bristol-Myers Squibb Company. Consultant; Self; Daiichi Sankyo Company, Limited. Other Relationship; Self; GlaxoSmithKline plc., Medtronic. Consultant; Self; Merck & Co., Inc.. Other Relationship; Self; Pfizer Inc.. A.P. Maggioni: None. P.K. Ohman: Employee; Self; AstraZeneca. N.R. Poulter: Advisory Panel; Self; AstraZeneca, Novo Nordisk A/S, Amgen Inc.. Research Support; Self; Servier. Speaker's Bureau; Self; AstraZeneca, Novo Nordisk A/S, Amgen Inc., Servier. Other Relationship; Self; International Society of Hypertension. A. Ramachandran: None. T. Tankova: None. B. Zinman: Consultant; Self; Novo Nordisk A/S, Boehringer Ingelheim Pharmaceuticals, Inc., AstraZeneca, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Sanofi, Merck & Co., Inc., Abbott. A.F. Hernandez: Research Support; Self; AstraZeneca, GlaxoSmithKline plc., Merck & Co., Inc.. Consultant; Self; Bayer AG, Boehringer Ingelheim Pharmaceuticals, Inc.. Research Support; Self; Janssen Pharmaceuticals, Inc., Novartis Pharmaceuticals Corporation. R.R. Holman: Research Support; Self; AstraZeneca, Merck & Co., Inc., Bayer AG. Advisory Panel; Self; Elcelyx Therapeutics, Inc., Novartis AG, Novo Nordisk A/S. Other Relationship; Self; Bayer AG. Advisory Panel; Self; Merck & Co., Inc.. Other Relationship; Self; AstraZeneca.

Abstract: In patients with symptomatic peripheral artery disease with a history of limb revascularization, the optimal antithrombotic regimen for long-term management is unknown. Methods: The EUCLID trial (Examining Use of Ticagrelor In PAD) randomized 13 885 patients with peripheral artery disease to treatment with ticagrelor 90 mg twice daily or clopidogrel 75 mg daily. Patients were enrolled based on an abnormal ankle-brachial index ≤0.80 or a previous lower extremity revascularization. This analysis focuses on the 7875 (57%) patients enrolled based on the previous lower extremity revascularization criterion. Patients could not be enrolled within 30 days of most recent revascularization, and patients with an indication for dual antiplatelet therapy were excluded. The primary efficacy end point was a composite of cardiovascular death, myocardial infarction, or ischemic stroke. The primary safety end point was major bleeding. Results: Patients with a previous revascularization had a mean age of 66 years, 73% were male, and the median baseline ankle-brachial index was 0.78. After adjustment for baseline characteristics, patients enrolled based on previous revascularization had similar rates of the primary composite end point (hazard ratio [HR] 1.10, 95% confidence interval [CI] 0.98–1.23, P =0.12) and statistically significantly higher rates of myocardial infarction (HR 1.29, 95% CI 1.08–1.55, P =0.005) and acute limb ischemia (HR 4.23, 95% CI 2.86–6.25, P 〈 0.001) when compared with patients enrolled based on ankle-brachial index criteria. No differences in ticagrelor- versus clopidogrel-treated patients were found for the primary efficacy end point (11.4% vs 11.3%; HR 1.01, 95% CI 0.88–1.15; P =0.90), all-cause mortality (9.2% vs 9.2%; HR 0.99, 95% CI 0.86–1.15; P =0.93), acute limb ischemia (2.5% vs 2.5%; HR 1.03, 95% CI 0.78–1.36; P =0.84), or major bleeding (1.9% vs 1.8%; HR 1.15, 95% CI 0.83–1.59; P =0.41). The median duration of follow-up was ≈30 months. Conclusions: After adjustment for baseline characteristics, patients enrolled based on previous revascularization for peripheral artery disease had higher rates of myocardial infarction and acute limb ischemia, with similar composite rates of cardiovascular death, myocardial infarction, and stroke when compared with patients enrolled based on the ankle-brachial index criterion. No significant differences were found between ticagrelor and clopidogrel for reduction of cardiovascular or acute limb events. Clinical Trial Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT01732822.

Abstract: To report a case of probable ceftriaxone-induced acute pancreatitis. CASE SUMMARY: A patient with a history of short-bowel syndrome on home total parenteral nutrition developed fever, chills, and right flank pain. She was diagnosed with gram-negative catheter sepsis and prescribed antibiotic therapy to be administered for four weeks. After completion of the first week of therapy, the antibiotic regimen was changed to intravenous injections of ceftriaxone to be given daily at home. Prior to discharge the patient developed acute abdominal pain, leukocytosis, jaundice, and markedly elevated lipase and amylase concentrations consistent with acute pancreatitis. The patient's condition improved upon discontinuation of the ceftriaxone and the remainder of her stay was uneventful. DISCUSSION: There is only one other case report in the literature of probable ceftriaxone-induced pancreatitis. Multiple other medications have been implicated in causing acute pancreatitis. The exact mechanism of this uncommon adverse effect of ceftriaxone is unknown. CONCLUSIONS: There was a temporal relationship between the development of this patient's signs and symptoms and the administration of ceftriaxone. We could not identify any other factors that may have been responsible for the development of her acute pancreatitis. Ceftriaxone should be considered as a possible etiologic agent in patients who present with acute abdominal pain and elevated lipase and amylase concentrations.

Abstract: Patients with chronic kidney disease may develop new or more severe anemia when treated with antiplatelet agents due to blood loss in conjunction with impaired erythropoiesis. Because anemia independently predicts limb amputation and mortality among patients with peripheral artery disease (PAD), we evaluated the relationship between estimated glomerular filtration rate (eGFR) and hemoglobin (Hb) levels in the EUCLID trial in which patients with symptomatic PAD were randomized to ticagrelor or clopidogrel. At baseline, 9025, 1870, and 1000 patients had eGFR ⩾ 60, 45–59, and 〈 45 mL/min/1.73 m 2 , respectively. The mean fall in Hb during the trial was 0.46 ± 1.68 g/dL and did not differ by baseline eGFR category, although Hb fall ⩾ 10% was more frequent among patients with lower eGFR ( p for trend 〈 0.0001). On-study treatment with iron, erythropoiesis-stimulating agents, and/or red blood cell transfusion was reported for 479 (5.3%), 165 (8.8%), and 129 (12.9%) patients in the three eGFR categories, respectively ( p for trend 〈 0.0001). After adjustment for baseline and post-randomization effects, those not receiving anemia treatment had a smaller reduction in Hb from baseline than those receiving anemia treatment ( p 〈 0.0001). Other determinants of Hb reduction included absence of on-study myocardial infarction, coronary or peripheral revascularization, residence outside North America, male sex, and baseline eGFR. We conclude that among patients with PAD treated with P2Y 12 inhibitors, lower baseline eGFR was associated with a greater reduction in Hb. ClinicalTrials.gov Identifier: NCT01732822