The prognostic impact of renal function decline during hospitalization for myocardial infarction

Aim: We analyzed the mortality risk of myocardial infarction (MI) patients according to renal function, observed during hospitalization. Materials & methods: Patients hospitalized for MI between 2006 and 2018 were followed (n = 5659). We divided the sample into four groups by estimated glomerular filtration (eGFR) [ml/min]: normal functions (lowest eGFR during hospitalization >60); transiently moderate insufficiency (lowest eGFR >30 and ≤60, highest >60); permanently moderate insufficiency (highest eGFR >30 and ≤60); severe insufficiency (highest and lowest eGFR ≤30). Results: Permanently moderate renal insufficiency indicates increased 5-years all-cause mortality (hazard risk ratio: 2.27 [95% CIs: 1.87–2.75], p < 0.0001), but a similar risk was found in patients with the only transient decline of renal functions (hazard risk ratio: 2.08 [95% CIs: 1.70–2.55], p < 0.0001). Both moderate insufficiency subgroups (transient/permanent) did not statistically differ regarding mortality risk. Conclusion: Even just fluctuation of eGFR toward moderate insufficiency during hospitalization represents an important prognostic indicator in MI patients.

Apixaban in patients on hemodialysis: a single dose pharmacokinetics study

Background Apixaban, a direct oral anticoagulant inhibiting factor Xa, has been proven to reduce the risk of atrial fibrillation-related stroke and thrombo-embolism in patients with mild to moderate renal insufficiency. Patients on renal replacement therapy, however, were excluded from randomized controlled trials. Therefore, uncertainty remains concerning benefits, dosing and timing of intake in hemodialysis population. Methods We conducted a phase II pharmacokinetics study in which twenty-four patients on maintenance hemodialysis were given a single dose (2.5 mg or 5 mg) of apixaban, either 30 minutes before or immediately after dialysis on the mid-week dialysis day. Results Apixaban 5 mg resulted in higher AUC0-48 in comparison to 2.5 mg, although significance could only be reached for dosing pre-dialysis (2.5 mg vs. 5 mg, P = 0.008). In line, peak concentrations (Cmax) after dosing pre-dialysis were significantly higher in the 5 mg than in the 2.5 mg groups (P = 0.02). In addition, dialysis resulted in significant reduction of drug exposure. AUC0-48 pre-dialysis were on average 48 percent (2.5 mg) and 26 percent (5 mg) lower than the AUC0-48 post-dialysis, in line with Cmax. As a result, a dose of 2.5 mg post-dialysis and a dose of 5 mg pre-dialysis resulted in similar AUC0-48. In contrast, significant differences were found between the 5 mg group post-dialysis and the 2.5 mg group pre-dialysis (P = 0.013). Conclusions Our data suggest that exposure to apixaban in patients in maintenance hemodialysis is not only dependent on drug dose but also on timing of intake relative to the hemodialysis procedure

OP0297 EFFICACY AND SAFETY OF ROMOSOZUMAB AMONG POSTMENOPAUSAL WOMEN WITH OSTEOPOROSIS AND MILD-TO-MODERATE CHRONIC KIDNEY DISEASE

Background:Osteoporosis and renal insufficiency are coexisting disease states in a substantial proportion of postmenopausal women. Since bisphosphonates are generally contraindicated in patients with estimated glomerular filtration rate (eGFR) <35 mL/min, it is important to evaluate other osteoporosis treatments in this setting.Objectives:To determine if baseline renal function affects the efficacy and safety of romosozumab.Methods:We performed post hoc analyses of two clinical trials of romosozumab in postmenopausal women with osteoporosis. In ARCH (NCT01631214), 4,093 patients were randomised 1:1 to romosozumab 210 mg monthly or alendronate 70 mg weekly for 12 months (mean age: 74.3 years; 96.1% with prevalent vertebral fractures [VFx]). In FRAME (NCT01575834), 7,180 patients were randomised 1:1 to romosozumab 210 mg or placebo monthly for 12 months (mean age: 70.9 years; 18.3% with prevalent VFx). For these analyses, patients were categorised by baseline eGFR (mL/min/1.73m2): normal renal function (eGFR ≥90), mild renal insufficiency (eGFR 60–89), or moderate renal insufficiency (eGFR 30–59). Least squares mean (LSM) percent change from baseline in bone mineral density (BMD) at the lumbar spine, total hip, and femoral neck; incidence of new VFx and adverse events (AEs); and changes in renal function were assessed for each eGFR category at Month 12 of the double-blind treatment period.Results:At baseline, most patients had mild/moderate renal insufficiency: 84% in ARCH, 88% in FRAME. In both studies, change from baseline in BMD was significantly higher in the romosozumab group across baseline eGFR categories (Figure). There was an interaction between BMD increase and renal function, and although BMD increase was not as large in women with impaired renal function, differences between romosozumab and control groups remained significant (Figure). In ARCH, among patients with eGFR ≥90, 60–89, and 30–59, the incidence of new VFx (romosozumab vs alendronate) at Month 12 was 3.3% vs 7.3%, 3.2% vs 3.9%, and 3.4% vs 6.2% in ARCH. In FRAME, the incidence of new VFx (romosozumab vs placebo) at Month 12 was 0.5% vs 3.0%, 0.4% vs 1.5%, and 0.6% vs 2.1%.In both studies, the incidences of AEs and serious AEs were similar in both treatment groups within and across eGFR categories. AEs of mild-to-moderate hypocalcaemia (investigator reported) occurred in two patients in ARCH (one romosozumab [eGFR 60–89] and one alendronate [eGFR ≥90]), and one patient in FRAME (romosozumab [eGFR 60–89]). Five patients in ARCH (all in the alendronate group) and 19 patients in FRAME (14 romosozumab, 5 placebo) had decreases in serum Ca levels (albumin adjusted); in the romosozumab group all were mild (<LLN–8.0 mg/dL) or moderate (<8.0–7.0 mg/dL). A similar percentage of patients in each group had changes in renal function over 12 months of treatment.Conclusion:The efficacy and safety of romosozumab vs alendronate or placebo was similar among postmenopausal women with osteoporosis and different levels of renal function.Acknowledgments:This study was funded by Amgen, Astellas and UCB Pharma. Editorial services were provided by Costello Medical.Disclosure of Interests:Paul Miller Grant/research support from: Amgen, Radius Health, Ultragenyx, Consultant of: Amgen, Radius Health, Jonathan Adachi Consultant of: Amgen, Speakers bureau: Amgen, Ben-Hur Albergaria Consultant of: Amgen Inc., Eli Lilly, Speakers bureau: Amgen Inc., Eli Lilly, Angela M Cheung Consultant of: Amgen, Eli Lilly, Arkadi Chines Shareholder of: Amgen Inc., Employee of: Amgen Inc., Evelien Gielen Consultant of: Amgen Inc., Takeda, Sandoz and UCB Pharma, Speakers bureau: Amgen Inc., Takeda, Sandoz and UCB Pharma, Bente Langdahl Grant/research support from: Amgen, NovoNordisk, Consultant of: Amgen Inc., Eli Lilly, UCB Pharma, Akimitsu Miyauchi Consultant of: Amgen Inc., Astellas BioPharma K.K., Teijin Pharma, Mary Oates Shareholder of: Amgen Inc., Employee of: Amgen Inc., Ian Reid Consultant of: Amgen Inc., Eli Lilly, Speakers bureau: Amgen Inc., Eli Lilly, Norma Ruiz Santiago Shareholder of: Amgen Inc., Employee of: Amgen Inc., Mark Vanderkelen Employee of: UCB Pharma, Wenjing Yang Shareholder of: Amgen Inc., Employee of: Amgen Inc., Zhigang Yu Shareholder of: Amgen Inc., Employee of: Amgen Inc.

Preventive Effects of Nicorandil Against Contrast-Induced Nephropathy in Patients With Moderate Renal Insufficiency Undergoing Percutaneous Coronary Intervention

We investigated the preventive effect of nicorandil on contrast-induced nephropathy (CIN) in patients with moderate renal insufficiency undergoing percutaneous coronary intervention (PCI). A total of 250 patients with a creatinine clearance (crCl) ≤60 mL/min undergoing PCI were randomly assigned to either a nicorandil group (nicorandil 10 mg 3 times/d and hydration; n = 125) or a control group (hydration only; n = 125). The first end point was the incidence of CIN defined as an increase in serum creatinine (Scr) levels by ≥0.5 mg/dL or ≥25% within 72 hours after exposure to the contrast medium. The secondary end points were (1) changes in Scr, blood urea nitrogen, and crCl and (2) the incidence of major adverse events during hospitalization. The incidence of CIN was 1.6% (2/125) in the nicorandil group and 9.6% (12/125) in the control group ( P = .011). There was no obvious difference in the incidence of major adverse events during hospitalization between the nicorandil and the control group (4.0% vs 4.8%, P = 1.000). Multivariate logistic regression analysis showed that nicorandil was a protective factor for CIN (odds ratios = 0.126, 95% confidence interval: −19.996 to −0.932, P = .012). Prophylactic administration of nicorandil may prevent against CIN in patients with moderate renal insufficiency undergoing PCI.

Medically Ill Patients with Moderate Renal Insufficiency Have More Thrombotic and Bleeding Events Than Those with Normal Renal Function: Insights from the Magellan and Mariner Trials of Extended Thrombprophylaxis

Background: Hospitalized medically ill patients are at risk for venous thromboembolism (VTE) for at least 45 days after discharge. This observation prompted the MAGELLAN and MARINER trials, which evaluated the efficacy and safety of rivaroxaban for extended thromboprophylaxis. In MAGELLAN, rivaroxaban (10 mg once daily) started in hospital and continued for 35 days was compared with a 10±4 day course of enoxaparin (40 mg once daily) followed by placebo. In MARINER, a 45-day course of rivaroxaban (10 mg once daily for those with creatinine clearance [CrCl] ≥50ml/min and 7.5 mg once daily for those with CrCl 30-<50ml/min) started at discharge was compared with placebo. The goals of this analysis were: (i) to compare rates of VTE (total or symptomatic) and VTE related death and major or clinically relevant bleeding in patients with moderate renal insufficiency (CrCl 30-<50ml/min) and those with normal renal function (CrCL ≥50ml/min), and (ii) to determine if revised criteria for selecting patients for extended thromboprophylaxis are associated with reduced bleeding, particularly in those with moderate renal insufficiency. Methods: We evaluated key efficacy and safety outcomes in patients with moderate renal insufficiency and those with normal renal function from days 1 to 35 in the MAGELLAN study and in a MARINER-like subpopulation of MAGELLAN using the criteria defined a priori for patient exclusion used in the MARINER study. These criteria were: 1) active gastroduodenal ulcer within 3 months of randomization or currently symptomatic, 2) any bleeding within 3 months prior to randomization or during index hospitalization prior to randomization, 3) active cancer at randomization, 4) medical history of severe bronchiectasis or pulmonary cavitation, or 5) dual antiplatelet therapy at baseline. These criteria excluded approximately 20% of subjects in MAGELLAN at high risk of bleeding. Results: The rates of VTE and VTE related death in both the rivaroxaban and enoxaparin/placebo groups were approximately twofold higher in subjects with renal impairment than in those with normal renal function, but the relative risk reduction with rivaroxaban treatment (10mg) compared with enoxaparin/placebo was similar in both renal function subgroups. Rates of major and clinically relevant bleeding in the rivaroxaban group were approximately 50% higher in patients with renal impairment compared with those with normal renal function. In the MARINER like subpopulation, the relative risk reductions for efficacy outcomes were maintained in both renal subgroups, whereas the increase in major bleeding with rivaroxaban was reduced by approximately 50%. Conclusions: Medically-ill patients with renal impairment given extended thromboprophylaxis are at increased risk for both VTE and major bleeding. Use of the MARINER criteria to exclude patients at increased risk of bleeding appears to reduce the major bleeding risk without compromising the efficacy of 10mg daily of rivaroxaban. Figure Figure. Disclosures Weitz: Novartis: Honoraria; Servier: Honoraria; Janssen: Honoraria; Ionis: Consultancy, Honoraria; Daiichi-Sankyo: Honoraria; Bristol-Myers Squibb: Honoraria; Boehringer Ingelheim: Honoraria, Research Funding; Bayer: Honoraria. Raskob:Janssen: Consultancy; Bayer: Consultancy; BMS: Consultancy; Daiichi Sankyo: Consultancy; Boehringer Ingelheim: Consultancy; Eli Lilly: Consultancy; Pfizer: Consultancy, Honoraria; Novartis: Consultancy. Spyropoulos:Bayer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Colorado Prevention Center - ATLAS: Consultancy; Portola: Membership on an entity's Board of Directors or advisory committees; Boehringer Ingelheim: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Cohen:Aspen: Consultancy, Speakers Bureau; Bayer: Consultancy, Speakers Bureau; Boehringer Ingelheim: Consultancy, Speakers Bureau; BMS: Consultancy, Speakers Bureau; Daiichi Sankyo: Consultancy, Speakers Bureau; GSK: Consultancy, Speakers Bureau; Janssen: Speakers Bureau; Medscape: Consultancy, Speakers Bureau; Pfizer: Consultancy, Speakers Bureau; Portola: Consultancy, Speakers Bureau; AbbVie: Consultancy; ACI Clinical: Consultancy; Boston Scientific: Consultancy; CLS Behring: Consultancy; GLG: Consultancy; Guidepoint Global: Consultancy; Leo Pharma: Consultancy; McKinsey: Consultancy; Sanofi: Consultancy; Navigant: Consultancy; ONO: Consultancy; Takeda: Consultancy; Temasek Capital: Consultancy; TRN: Consultancy. Spiro:Bayer: Employment, Equity Ownership. De Sanctis:Bayer: Employment, Equity Ownership. Xu:Janssen Research and Development LLC: Employment, Equity Ownership. Suh:Janssen Research and Development LLC: Employment, Equity Ownership. Lu:Janssen Research and Development LLC: Employment. Lipardi:Janssen Research and Development LLC: Employment, Equity Ownership. Barnathan:Janssen Research and Development LLC: Employment, Equity Ownership.

Sugammadex: What to Know for Your Daily Practice

Sugammadex (Bridion) represents a class named muscle relaxant encapsulator. It can be used to reverse the neuromuscular blockade induced by rocuronium or vecuronium in case of general anesthesia. Its molecular weight is 2.178 g/mol, with a structure consisting in a ring of eight negative charges. It has no receptor interaction in human body and it is eliminated via kidney, being contraindicated in end-stage kidney disease patients. Sugammadex has few side effects but there are same case reports about allergic reactions. Only three drugs can actually interact with sugammadex: toremifene, flucloxacillin and fusidic acid. It can be used in elderly and pediatric patients, in morbidly obese patients, patients with hepatic insufficiency or mild and moderate renal insufficiency or in muscular disease. Despite its beneficial use, the high price remains its main issue.