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Effects of veverimer on serum bicarbonate and physical function in women with chronic kidney disease and metabolic acidosis: a subgroup analysis from a randomised, controlled trial.
Mathur, VS, Wesson, DE, Tangri, N, Li, E, Bushinsky, DA
BMC nephrology. 2022;(1):82
Abstract
BACKGROUND Globally, the prevalence of chronic kidney disease (CKD) is higher in women than in men; however, women have been historically under-represented in nephrology clinical trials. Metabolic acidosis increases risk of progressive loss of kidney function, causes bone demineralization and muscle protein catabolism, and may be more consequential in women given their lower bone and muscle mass. Veverimer, an investigational, non-absorbed polymer that binds and removes gastrointestinal hydrochloric acid, is being developed as treatment for metabolic acidosis. METHODS This was a Phase 3, multicenter, randomised, blinded, placebo-controlled trial in 196 patients with CKD (eGFR: 20-40 mL/min/1.73 m2) and metabolic acidosis who were treated for up to 1 year with veverimer or placebo. We present the findings from a pre-specified subgroup analysis evaluating the effects of veverimer on metabolic acidosis and physical function among women (N = 77) enrolled in this trial. RESULTS At week 52, women treated with veverimer had a greater increase in mean (± standard error) serum bicarbonate than the placebo group (5.4 [0.5] vs. 2.2 [0.6] mmol/L; P < 0.0001). Physical Function reported by patients on the Kidney Disease and Quality of Life - Physical Function Domain, a measure that includes items related to walking, stair climbing, carrying groceries and other activities improved significantly in women randomized to veverimer vs placebo (+ 13.2 vs. -5.2, respectively, P < 0.0031). Objectively measured performance time on the repeated chair stand test also improved significantly in the veverimer group vs. placebo (P = 0.0002). CONCLUSIONS Veverimer was effective in treating metabolic acidosis in women with CKD, and significantly improved how they felt and functioned. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT03390842 . Registered on January 4, 2018.
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Patiromer for Treatment of Hyperkalemia in the Emergency Department: A Pilot Study.
Rafique, Z, Liu, M, Staggers, KA, Minard, CG, Peacock, WF
Academic emergency medicine : official journal of the Society for Academic Emergency Medicine. 2020;(1):54-60
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BACKGROUND Hyperkalemia is common and potentially life threatening. Patiromer is a Food and Drug Administration (FDA)-cleared oral potassium binder effective in the chronic treatment of hyperkalemia. OBJECTIVE The objective was to investigate the potential efficacy and safety of oral patiromer in treating acute hyperkalemia in the emergency department (ED). METHODS This is a single-center, randomized, open-label convenience sample pilot study in an inner-city ED. Adult patients with end-stage renal disease and a serum potassium level of ≥ 6.0 mEq/L were randomized to standard of care (SOC) or one dose of 25.2 g oral patiromer plus SOC (PAT). Blood samples and electrocardiograms were collected at enrollment and at 1, 2, 4, and 6 hours thereafter. The primary outcome was the difference in potassium between groups at 6 hours. Secondary outcomes were the amount and number of times insulin and albuterol were given. RESULTS Thirty patients were included in the final analysis, 15 in each group. There were no differences in age, sex, or baseline serum potassium. There was no difference in mean serum potassium between SOC and PAT groups at 6 hours (6.32 mEq/L, confidence interval [CI] = 6.0 to 6.63 mEq/L vs. 5.81 mEq/L, CI = 5.48 to 6.14 mEq/L). However, 2 hours posttreatment the serum potassium of the PAT group was lower than SOC group (5.90 mEq/L, CI = 5.63 to 6.17 mEq/L vs. 6.51 mEq/L, CI = 6.25 to 6.78 mEq/L) and also 0.61 mEq/L lower than baseline. There were no differences in the amount or number of administrations of insulin or albuterol between groups, although the amount of albuterol used in the PAT group at 6 hours was lower but not significant (median, 0 mg vs. 12.5 mg; p = 0.097). There were no differences in adverse events between groups. CONCLUSION In this open-label pilot study of severe hyperkalemia, a single dose of 25.2 g of oral patiromer reduced serum potassium within 2 hours but did not show a difference at 6 hours. This is the first study showing that patiromer may have a role in the acute management of hyperkalemia; however, more rigorous studies are needed.
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Thin, Very Thin, or Ultrathin Strut Biodegradable or Durable Polymer-Coated Drug-Eluting Stents: 3-Year Outcomes of BIO-RESORT.
Buiten, RA, Ploumen, EH, Zocca, P, Doggen, CJM, Danse, PW, Schotborgh, CE, Scholte, M, van Houwelingen, KG, Stoel, MG, Hartmann, M, et al
JACC. Cardiovascular interventions. 2019;(17):1650-1660
Abstract
OBJECTIVES The aim of this study was to assess the 3-year safety and efficacy of treating all-comer patients with 3 contemporary drug-eluting stents (DES). BACKGROUND The BIO-RESORT (Comparison of Biodegradable Polymer and Durable Polymer Drug-Eluting Stents in an All Comers Population) (TWENTE III) randomized trial (NCT01674803) found similar 1-year safety and efficacy for the 2 biodegradable-polymer DES (i.e., ultrathin-strut cobalt-chromium Orsiro sirolimus-eluting stent [SES] and very-thin-strut platinum-chromium Synergy everolimus-eluting stent) compared with the durable-polymer thin-strut cobalt-chromium Resolute Integrity zotarolimus-eluting stent (ZES). Two-year follow-up suggested that the SES might reduce repeat revascularizations beyond 1 year compared with the ZES. METHODS A total of 3,514 all-comer patients were treated at 4 centers for coronary intervention. The main clinical endpoint, target vessel failure, was a composite of safety (cardiac death or target vessel-related myocardial infarction) and efficacy (target vessel revascularization). Secondary endpoints included the individual components of target vessel failure and stent thrombosis. RESULTS Three-year follow-up data were available for 3,393 of 3,514 patients (96.6%). Target vessel failure occurred in 8.5% with SES and 10.0% with ZES (plog rank = 0.22) and in 8.8% with everolimus-eluting stents (vs. ZES, plog rank = 0.32). Rates of cardiac death, target vessel myocardial infarction, and target vessel revascularization were similar between stent groups. Landmark analyses found no statistically significant between-stent difference in repeat revascularization between 1 and 3 years. Definite or probable stent thrombosis rates were low (SES, 1.1%; everolimus-eluting stent, 1.1%; ZES, 0.9%) and similar with all 3 DES. CONCLUSIONS Despite substantial differences in stent backbone and polymer coating, all 3 DES showed favorable 3-year safety and efficacy in all comers, without significant between-stent differences. Further follow-up is required to definitely answer the question of whether one stent might improve clinical outcomes at a later stage.
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Effect of Patiromer on Hyperkalemia Recurrence in Older Chronic Kidney Disease Patients Taking RAAS Inhibitors.
Weir, MR, Bushinsky, DA, Benton, WW, Woods, SD, Mayo, MR, Arthur, SP, Pitt, B, Bakris, GL
The American journal of medicine. 2018;(5):555-564.e3
Abstract
BACKGROUND Older people are predisposed to hyperkalemia because of impaired renal function, comorbid conditions, and polypharmacy. Renin-angiotensin-aldosterone system inhibitors (RAASi), which are recommended to treat chronic kidney disease and heart failure augment the risk. Patiromer, a nonabsorbed potassium binder, was shown in the phase 3 OPAL-HK study to decrease serum potassium in patients with chronic kidney disease taking RAASi. We studied the efficacy and safety of patiromer in a prespecified subgroup of patients aged ≥65 years from OPAL-HK. METHODS Chronic kidney disease patients with mild or moderate-to-severe hyperkalemia received patiromer, initially 8.4 g/d or 16.8 g/d, respectively, for 4 weeks (treatment phase, part A). Eligible patients entered an 8-week randomized withdrawal phase (part B) and continued patiromer or switched to placebo. RESULTS Mean ± standard error change in serum potassium from baseline to week 4 of part A (primary endpoint) in patients aged ≥65 years was -1.01 ± 0.05 mEq/L (P < .001); 97% achieved serum potassium 3.8-<5.1 mEq/L. The serum potassium increase during the first 4 weeks of part B was greater in patients taking placebo than in those taking patiromer (P < .001). Fewer patients taking patiromer (30%) than placebo (92%) developed recurrent hyperkalemia (serum potassium ≥5.1 mEq/L). Mild-to-moderate constipation occurred in 15% (part A) and 7% (part B) of patients aged ≥65 years. Serum potassium <3.5 mEq/L and serum magnesium <1.4 mg/dL were infrequent (4% each in patients aged ≥65 years in part A). CONCLUSIONS Patiromer reduced recurrent hyperkalemia and was well tolerated in older chronic kidney disease patients taking RAASi.
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Evaluation of an individualized dose titration regimen of patiromer to prevent hyperkalaemia in patients with heart failure and chronic kidney disease.
Pitt, B, Bushinsky, DA, Kitzman, DW, Ruschitzka, F, Metra, M, Filippatos, G, Rossignol, P, Du Mond, C, Garza, D, Berman, L, et al
ESC heart failure. 2018;(3):257-266
Abstract
AIMS: Hyperkalaemia risk precludes optimal renin-angiotensin-aldosterone system inhibitor use in patients with heart failure (HF), particularly those with chronic kidney disease (CKD). Patiromer is a sodium-free, non-absorbed potassium (K+ )-binding polymer approved for the treatment of hyperkalaemia. In PEARL-HF, patiromer 25.2 g (fixed dose) prevented hyperkalaemia in HF patients with or without CKD initiating spironolactone. The current study evaluated the effectiveness of a lower starting dose of patiromer (16.4 g/day) followed by individualized titration in preventing hyperkalaemia and hypokalaemia when initiating spironolactone. METHODS AND RESULTS This open-label 8-week study enrolled 63 patients with CKD, serum K+ 4.3-5.1 mEq/L, and chronic HF, who, based on investigator opinion, should receive spironolactone. Eligible patients started spironolactone 25 mg/day and patiromer 16.8 g/day (divided into two doses), with patiromer titrated to maintain serum K+ 4.0-5.1 mEq/L. Mean (standard deviation) serum K+ was 4.78 (0.51) mEq/L at baseline; weekly values were 4.48-4.70 mEq/L during treatment. Serum K+ of 3.5-5.5 mEq/L at the end of study treatment (primary endpoint) was achieved by 57 (90.5%) patients; 53 (84.1%) had serum K+ 4.0-5.1 mEq/L. One patient (1.6%) developed hypokalaemia, and two patients (3.2%) developed hypomagnesaemia. Spironolactone was increased to 50 mg/day in all patients; 43 (68%) patients required one or more patiromer dose titration. Adverse events (AEs) occurred in 36 (57.1%) patients, with a low rate of discontinuations [four (6.3%) patients]. The most common AE was mild to moderate abdominal discomfort [four (6.3%) patients]. CONCLUSIONS In this open-label study, patiromer 16.8 g/day followed by individualized titration maintained serum K+ within the target range in the majority of patients with HF and CKD, all of whom were uptitrated to spironolactone 50 mg/day, patiromer was well tolerated, with a low incidence of hyperkalaemia, hypokalaemia, and hypomagnesaemia.
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Gastrointestinal tolerance of low FODMAP oral nutrition supplements in healthy human subjects: a randomized controlled trial.
Erickson, J, Korczak, R, Wang, Q, Slavin, J
Nutrition journal. 2017;(1):35
Abstract
BACKGROUND There has been increasing interest in utilizing a diet low in fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs) for the treatment of irritable bowel syndrome (IBS), a functional gastrointestinal disease. While studies have indicated that this diet can be effective at symptom reduction, it is a restrictive diet and patients may find it challenging to find low FODMAP products to meet their nutrient needs. The primary objective of this study was to assess the gastrointestinal (GI) tolerance of three low FODMAP oral nutrition supplements (ONS) in healthy adults. METHODS A double-blind randomized controlled crossover study was conducted in 21 healthy adults (19-32 years). Fasted subjects consumed one of four treatments at each visit, with a one week wash out period between visits. Each participant received all treatments. Treatments included three low FODMAP ONS formulas (A, B, and C) as well as a positive control consisting of 5 g fructooligosaccharides (FOS) mixed in lactose-free milk. Breath hydrogen was measured at baseline, 1, 2, 3, and 4 h post treatment consumption. Subjective GI symptom questionnaires were completed at baseline, 0.5, 1, 1.5, 2, 3, 4, 12, 24 and 48 h following treatment consumption. Mean breath hydrogen concentrations and baseline corrected area under the curve for both breath hydrogen and GI symptoms were analyzed and compared between treatments. Significance was determined at P < 0.05. RESULTS The positive control resulted in higher breath hydrogen response compared to all three of the low FODMAP ONS beverages at 3 and 4 h after consumption. There were no differences in GI symptom response between treatments. CONCLUSIONS All treatments were well tolerated in healthy participants. The low FODMAP formulas resulted in a lower breath hydrogen response compared to the positive control, and may be better tolerated in individuals with IBS. More research should be conducted to better understand the GI tolerance of low FODMAP ONS in individuals with IBS. TRIAL REGISTRATION The protocol for this study was registered on ClinicalTrials.gov in January 2016 (Clinical Trials ID: NCT02667184 ).
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Outcomes of patients treated with durable polymer platinum-chromium everolimus-eluting stents: a meta-analysis of randomised trials.
Cassese, S, Ndrepepa, G, Byrne, RA, Kufner, S, Xhepa, E, de Waha, A, Rheude, T, Colleran, R, Giacoppo, D, Harada, Y, et al
EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology. 2017;(8):986-993
Abstract
AIMS: The durable polymer platinum-chromium everolimus-eluting stent (PtCr-EES) is a new-generation drug-eluting stent (DES) with a platinum-enriched metallic platform developed to improve the percutaneous treatment of patients with coronary artery disease. We sought to investigate the performance of durable polymer PtCr-EES versus other new-generation DES. METHODS AND RESULTS We undertook a meta-analysis of trials in which patients receiving percutaneous coronary intervention (PCI) were randomly assigned to durable polymer PtCr-EES versus other new-generation DES (other DES). Primary efficacy and safety outcomes were target lesion revascularisation (TLR) and definite/probable stent thrombosis (ST), respectively. Secondary outcomes were myocardial infarction (MI), target vessel revascularisation (TVR), death, cardiac death and longitudinal stent deformation (LSD). A total of 11,036 patients in seven trials received a PCI with either durable polymer PtCr-EES (n=6,613) or other DES (n=4,423). This latter group comprised patients treated with biolimus- (n=325), cobalt-chromium everolimus- (n=1,940) or zotarolimus-eluting stents (n=2,158). After a median follow-up of 12 months (interquartile range 12-24), durable polymer PtCr-EES displayed a risk of TLR (odds ratio 0.98, 95% confidence interval [CI]: 0.75-1.29; p=0.90) and definite/probable ST (0.89 [0.55-1.45]; p=0.63) comparable to that of other DES. However, the durable polymer PtCr-EES was associated with a higher risk of LSD (12.05 [1.60-90.71], p=0.02) compared to other DES. There was no significant difference with regard to other secondary outcomes nor was there heterogeneity across trials. CONCLUSIONS At one-year follow-up, the durable polymer PtCr-EES displays a performance comparable to that of other new-generation DES platforms.
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Randomised clinical trial: the efficacy of gut-directed hypnotherapy is similar to that of the low FODMAP diet for the treatment of irritable bowel syndrome.
Peters, SL, Yao, CK, Philpott, H, Yelland, GW, Muir, JG, Gibson, PR
Alimentary pharmacology & therapeutics. 2016;(5):447-59
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BACKGROUND A low fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) diet is effective in treating irritable bowel syndrome (IBS). AIM: To compare the effects of gut-directed hypnotherapy to the low FODMAP diet on gastrointestinal symptoms and psychological indices, and assess additive effects. METHODS Irritable bowel syndrome patients were randomised (computer-generated list), to receive hypnotherapy, diet or a combination. Primary end-point: change in overall gastrointestinal symptoms across the three groups from baseline to week 6. Secondary end-points: changes in psychological indices, and the durability of effects over 6 months. RESULTS Of 74 participants, 25 received hypnotherapy, 24 diet and 25 combination. There were no demographic differences at baseline across groups. Improvements in overall symptoms were observed from baseline to week 6 for hypnotherapy [mean difference (95% CI): -33 (-41 to -25)], diet [-30 (-42 to -19)] and combination [-36 (-45 to -27)] with no difference across groups (P = 0.67). This represented ≥20 mm improvement on visual analogue scale in 72%, 71% and 72%, respectively. This improvement relative to baseline symptoms was maintained 6 months post-treatment in 74%, 82% and 54%. Individual gastrointestinal symptoms similarly improved. Hypnotherapy resulted in superior improvements on psychological indices with mean change from baseline to 6 months in State Trait Personality Inventory trait anxiety of -4(95% CI -6 to -2) P < 0.0001; -1(-3 to 0.3) P = ns; and 0.3(-2 to 2) P = ns, and in trait depression of -3(-5 to -0.7) P = 0.011; -0.8(-2 to 0.2) P = ns; and 0.6(-2 to 3) P = ns, respectively. Groups improved similarly for QOL (all p ≤ 0.001). CONCLUSIONS Durable effects of gut-directed hypnotherapy are similar to those of the low FODMAP diet for relief of gastrointestinal symptoms. Hypnotherapy has superior efficacy to the diet on psychological indices. No additive effects were observed.
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Treatment with patiromer decreases aldosterone in patients with chronic kidney disease and hyperkalemia on renin-angiotensin system inhibitors.
Weir, MR, Bakris, GL, Gross, C, Mayo, MR, Garza, D, Stasiv, Y, Yuan, J, Berman, L, Williams, GH
Kidney international. 2016;(3):696-704
Abstract
Elevated serum aldosterone can be vasculotoxic and facilitate cardiorenal damage. Renin-angiotensin system inhibitors reduce serum aldosterone levels and/or block its effects but can cause hyperkalemia. Patiromer, a nonabsorbed potassium binder, decreases serum potassium in patients with chronic kidney disease on renin-angiotensin system inhibitors. Here we examined the effect of patiromer treatment on serum aldosterone, blood pressure, and albuminuria in patients with chronic kidney disease on renin-angiotensin system inhibitors with hyperkalemia (serum potassium 5.1-6.5 mEq/l). We analyzed data from the phase 3 OPAL-HK study (4-week initial treatment phase of 243 patients; 8-week randomized withdrawal phase of 107 patients). In the treatment phase, the (mean ± standard error) serum potassium was decreased concordantly with the serum aldosterone (-1.99 ± 0.51 ng/dl), systolic/diastolic blood pressure (-5.64 ± 1.04 mm Hg/-3.84 ± 0.69 mm Hg), and albumin-to-creatinine ratio (-203.7 ± 54.7 mg/g), all in a statistically significant manner. The change in the plasma renin activity (-0.44 ± 0.63 μg/l/hr) was not significant. In the withdrawal phase, mean aldosterone levels were sustained with patiromer (+0.23 ± 1.07 ng/dl) and significantly increased with placebo (+2.78 ± 1.25 ng/dl). Patients on patiromer had significant reductions in mean systolic/diastolic blood pressure (-6.70 ± 1.59/-2.15 ± 1.06 mm Hg), whereas those on placebo did not (-1.21 ± 1.89 mm Hg/+1.72 ± 1.26 mm Hg). Significant changes in plasma renin activity were found only in the placebo group (-3.90 ± 1.41 μg/l/hr). Thus, patiromer reduced serum potassium and aldosterone levels independent of plasma renin activity in patients with chronic kidney disease and hyperkalemia on renin-angiotensin system inhibitors.
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Nine-month angiographic and two-year clinical follow-up of novel biodegradable-polymer arsenic trioxide-eluting stent versus durable-polymer sirolimus-eluting stent for coronary artery disease.
Shen, L, Yang, W, Yin, JS, Liu, XB, Wu, YZ, Sun, AJ, Qian, JY, Ge, JB
Chinese medical journal. 2015;(6):768-73
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BACKGROUND Despite great reduction of in-stent restenosis, first-generation drug-eluting stents (DESs) have increased the risk of late stent thrombosis due to delayed endothelialization. Arsenic trioxide, a natural substance that could inhibit cell proliferation and induce cell apoptosis, seems to be a promising surrogate of sirolimus to improve DES performance. This randomized controlled trial was to evaluate the efficacy and safety of a novel arsenic trioxide-eluting stent (AES), compared with traditional sirolimus-eluting stent (SES). METHODS Patients with symptoms of angina pectoris were enrolled and randomized to AES or SES group. The primary endpoint was target vessel failure (TVF), and the second endpoint includes rates of all-cause death, cardiac death or myocardial infarction, target lesion revascularization (TLR) by telephone visit and late luminal loss (LLL) at 9-month by angiographic follow-up. RESULTS From July 2007 to 2009, 212 patients were enrolled and randomized 1:1 to receive either AES or SES. At 2 years of follow-up, TVF rate was similar between AES and SES group (6.67% vs. 5.83%, P = 0.980). Frequency of all-cause death was significantly lower in AES group (0 vs. 4.85%, P = 0.028). There was no significant difference between AES and SES in frequency of TLR and in-stent restenosis, but greater in-stent LLL was observed for AES group (0.29 ± 0.52 mm vs. 0.10 ± 0.25 mm, P = 0.008). CONCLUSIONS After 2 years of follow-up, AES demonstrated comparable efficacy and safety to SES for the treatment of de novo coronary artery lesions.