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Profile of patients diagnosed with acute venous thromboembolism in routine practice according to age and renal function: RE-COVERY DVT/PE study.
Ageno, W, Casella, IB, Chee, KH, Schellong, S, Schulman, S, Singer, DE, Desch, M, Tang, W, Voccia, I, Zint, K, et al
Journal of thrombosis and thrombolysis. 2021;(3):561-570
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Abstract
In randomized clinical trials (RCTs) of nonvitamin K antagonist oral anticoagulants (NOACs) for acute venous thromboembolism (VTE), ~ 12-13% of patients were elderly and ~ 26% had mild-to-moderate renal impairment. Observational studies are not restricted by the selection and treatment criteria of RCTs. In this ancillary analysis of the RE-COVERY DVT/PE global observational study, we aimed to describe patient characteristics, comorbidities, and anticoagulant therapy for subgroups of age (< or ≥ 75 years) and renal impairment (creatinine clearance [CrCl; estimated with Cockcroft-Gault formula] < 30 [severe], 30 to < 50 [moderate], 50 to < 80 [mild], ≥ 80 [normal] mL/min). Of 6095 eligible patients, 25.3% were aged ≥ 75 years; 38.2% (1605/4203 with CrCl values) had mild-to-moderate renal impairment. Comorbidities were more common in older patients (73.9% aged ≥ 75 vs. 58.1% < 75 years) and in those with mild or moderate versus no renal impairment (75.9%, 80.9%, and 59.3%, respectively). At hospital discharge or 14 days after diagnosis (whichever was later), most patients (53.7% and 55.1%, respectively) in both age groups received NOACs; 20.8% and 23.4%, respectively, received vitamin K antagonists, 19.0% and 21.8% parenteral therapy, 2.3% and 3.8% other anticoagulant treatments. Use of NOACs decreased with worsening renal impairment (none 58.5%, moderate 49.6%, severe 25.7%) and, in younger versus older patients with moderate renal impairment (33.1% vs. 56.1%). In routine practice, there are more elderly and renally impaired patients with VTE than represented in RCTs. Decreasing renal function, but not older age, was associated with less NOAC use. Clinical Trial Registration: http://www.clinicaltrials.gov . Unique identifier: NCT02596230. Decreasing renal function, particularly in the subgroup with CrCl < 30 mL/min, but not older age, was associated with less use of nonvitamin K antagonist oral anticoagulants (NOACs). Nevertheless, more than half of the older patients with moderate renal impairment received a NOAC as their oral anticoagulant.
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Non-Adherence to Antihypertensive Guidelines in Patients with Asymptomatic Carotid Stenosis.
Haley, W, Shawl, F, Charles Sternbergh, W, Turan, TN, Barrett, K, Voeks, J, Brott, T, Meschia, JF
Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association. 2021;(8):105918
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IMPORTANCE Hypertension and carotid stenosis are both risk factors for stroke, but the presence of carotid stenosis might dampen enthusiasm for tight control of hypertension because of concerns for hypoperfusion. OBJECTIVE To determine the extent to which there are opportunities to potentially improve pharmacotherapy for hypertension in patients known to have asymptomatic high-grade carotid stenosis. DESIGN We examined anti-hypertensive medication prescription and adherence to evidence-based hypertension treatment guidelines in a cross-sectional analysis of baseline data of patients enrolled in a clinical trial. SETTING The Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial (CREST-2) is a multicenter prospective randomized open blinded end-point clinical trial of intensive medical management with or without revascularization by endarterectomy or stenting for asymptomatic high-grade carotid stenosis. PARTICIPANTS 1479 participants (38.6% female; mean age 69.8 years) from 132 clinical centers enrolled in the CREST-2 trial as of April 6, 2020 who were taking ≥1 antihypertensive drug at baseline. EXPOSURES Pharmacotherapy for hypertension. MAIN OUTCOME Adherence to evidence-based guidelines for treating hypertension. RESULTS Of 1458 participants with complete data, 26% were on one, 31% on 2, and 43% on ≥3 antihypertensive medications at trial entry. Thirty-two percent of participants were prescribed thiazide; 74%, angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB); 38%, calcium channel blocker (CCB); 56%, a beta blocker; 11%, loop diuretic; and 27%, other. Of those prescribed a single antihypertensive medication, the proportion prescribed thiazide was 5%; ACEI or ARB, 55%, and CCB, 11%. The prevalence of guideline-adherent regimens was 34% (95% CI, 31-36%). CONCLUSIONS AND RELEVANCE In a diverse cohort with severe carotid disease and hypertension, non-adherence to hypertension guidelines was common. All preferred classes of antihypertensive drug were under-prescribed. Using staged iterative guideline-based care for hypertension, CREST-2 will characterize drug tolerance and stroke rates under these conditions. TRIAL REGISTRATION ClinicalTrials.gov Number NCT02089217.
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Regional Variations in Alirocumab Dosing Patterns in Patients with Heterozygous Familial Hypercholesterolemia During an Open-Label Extension Study.
Langslet, G, Hovingh, GK, Guyton, JR, Baccara-Dinet, MT, Letierce, A, Manvelian, G, Farnier, M
Cardiovascular drugs and therapy. 2020;(4):515-523
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PURPOSE During the alirocumab open-label extension study ODYSSEY OLE (open-label extension; NCT01954394), physicians could adjust alirocumab dosing for enrolled patients, who were diagnosed with heterozygous familial hypercholesterolemia (HeFH) and who had completed previous phase III clinical trials with alirocumab. This post hoc analysis evaluated the differences in physician-patient dosing decisions between the regions of Western Europe, Eastern Europe, North America, and the rest of the world (ROW). METHODS Patients (n = 909) who received starting dose alirocumab 75 mg every 2 weeks (Q2W) during ODYSSEY OLE (patients from FH I, FH II, and LONG TERM parent studies) were included. Low-density lipoprotein cholesterol (LDL-C) levels were blinded until week 8; subsequently, LDL-C values were communicated to physicians. From week 12, dose adjustment from 75 to 150 mg Q2W, or vice versa, was possible. RESULTS Mean LDL-C values used for the decision to increase dose from 75 to 150 mg Q2W were higher in Eastern Europe (3.7 mmol/L; 144.0 mg/dL) and ROW (3.8 mmol/L; 145.2 mg/dL) compared with Western Europe (3.1 mmol/L; 118.6 mg/dL) and North America (3.3 mmol/L; 126.6 mg/dL). Irrespective of region, the mean LDL-C at the time of decision to maintain at 75 mg Q2W was approximately 1.8 mmol/L (70 mg/dL). During ODYSSEY OLE (median treatment duration of 131.7 weeks), alirocumab was shown to have no unexpected long-term safety concerns. CONCLUSIONS In this OLE study, the observed variations in clinical treatment decisions suggest that physicians may perceive the severity of HeFH and/or the treatment of HeFH differently depending on their region.
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Blood Pressure Targets Achievement According to 2018 ESC/ESH Guidelines in Three European Excellence Centers for Hypertension.
Tocci, G, Presta, V, Ferri, C, Redon, J, Volpe, M
High blood pressure & cardiovascular prevention : the official journal of the Italian Society of Hypertension. 2020;(1):51-59
Abstract
INTRODUCTION The most recent European guidelines on hypertension redefined office blood pressure (BP) treatment targets according to age strata and cardiovascular (CV) risk profile. AIM: To evaluate proportions of adult outpatients achieving office BP treatment targets recommended by current compared to previous hypertension guidelines. METHODS We extracted data from medical databases of adult outpatients followed in three excellence centers in hypertension (Rome, Italy; L'Aquila, Italy; Valencia, Spain). Office BP treatment targets were defined according to either 2013 ESH/ESC guidelines (< 140/90 mmHg in non-diabetic individuals aged 18-80 years, < 150/90 mmHg in those aged ≥ 80 years, and < 140/85 mmHg in diabetic individuals), or 2018 ESC/ESH guidelines: (< 130/80 mmHg in individuals aged 18-65 years, < 140/80 mmHg in those aged 65-79 and ≥ 80 years). SCORE risk was assessed in all patients. RESULTS From an overall sample of 14,229 adult subjects, 4049 (28.5%) resulted normotensive individuals, 3088 (21.7%) were untreated and 7092 (49.8%) treated hypertensive outpatients. Treated hypertensives showed significantly higher ESC score risk (8.3 ± 13.0% vs. 3.9 ± 8.4%; P < 0.001) and lower systolic/diastolic BP (140.6 ± 18.8/83.9 ± 11.5 vs. 148.3 ± 14.2/94.7 ± 10.1 mmHg; P < 0.001) than untreated hypertensives. Compared to previous guidelines, BP control significantly lowered in non-diabetic outpatients (n = 5847) of all age groups [18-65 years: (13.1% vs. 42.9%), 65-79 years (25.8% vs. 42.5%) and ≥ 80 years (29.1% vs. 66.0%); P < 0.001 for all comparisons]; similar reductions were observed in diabetic outpatients (n = 1245) [18-65 years (32.7% vs. 14.8%), 65-79 years (37.3% vs. 24.7%) and ≥ 80 years (47.1% vs. 27.9%); P < 0.001]. CONCLUSIONS According to the recommended new office BP treatment targets, the proportions of treated uncontrolled hypertensive patients substantially increased. These findings should prompt a tighter application of therapeutic recommendations and, thus, highlight the need for improving hypertension management and control strategies.
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Multiple myeloma treatment patterns and clinical outcomes in the Latin America Haemato-Oncology (HOLA) Observational Study, 2008-2016.
de Moraes Hungria, VT, Martínez-Baños, DM, Peñafiel, CR, Miguel, CE, Vela-Ojeda, J, Remaggi, G, Duarte, FB, Cao, C, Cugliari, MS, Santos, T, et al
British journal of haematology. 2020;(3):383-393
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Limited data are available regarding contemporary multiple myeloma (MM) treatment practices in Latin America. In this retrospective cohort study, medical records were reviewed for a multinational cohort of 1103 Latin American MM patients (median age, 61 years) diagnosed in 2008-2015 who initiated first-line therapy (LOT1). Of these patients, 33·9% underwent autologous stem cell transplantation (ASCT). During follow-up, 501 (45·4%) and 129 (11·7%) patients initiated second- (LOT2) and third-line therapy (LOT3), respectively. In the LOT1 setting, from 2008 to 2015, there was a decrease in the use of thalidomide-based therapy, from 66·7% to 42·6%, and chemotherapy from, 20·2% to 5·9%, whereas use of bortezomib-based therapy or bortezomib + thalidomide increased from 10·7% to 45·5%. Bortezomib-based therapy and bortezomib + thalidomide were more commonly used in ASCT patients and in private clinics. In non-ASCT and ASCT patients, median progression-free survival (PFS) was 15·0 and 31·1 months following LOT1 and 10·9 and 9·5 months following LOT2, respectively. PFS was generally longer in patients treated with bortezomib-based or thalidomide-based therapy versus chemotherapy. These data shed light on recent trends in the management of MM in Latin America. Slower uptake of newer therapies in public clinics and poor PFS among patients with relapsed MM point to areas of unmet therapeutic need in Latin America.
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Safety and effectiveness of tofogliflozin in Japanese patients with type 2 diabetes mellitus in real-world practice: Results of 12-month interim analysis of a long-term post-marketing surveillance study (J-STEP/LT).
Utsunomiya, K, Senda, M, Kakiuchi, S, Kameda, H, Tamura, M, Kurihara, Y, Gunji, R, Fujii, S, Kaku, K
Journal of diabetes investigation. 2020;(1):132-141
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AIMS/INTRODUCTION Due to the paucity of tofogliflozin data, we assessed the safety and effectiveness of tofogliflozin among Japanese patients with type 2 diabetes mellitus in the clinical setting, stratifying the patients by age, sex, estimated glomerular filtration (eGFR) rate and body mass index. We report the results of a 12-month interim analysis. MATERIALS AND METHODS This was a 3-year prospective, observational and multicenter post-marketing study (Japanese Study of tofogliflozin with type 2 diabetes mellitus Patients/Long Term). RESULTS Out of 6,897 patients enrolled, the safety and effectiveness analysis populations consisted of 6,712 and 6,449 patients, respectively. During 12 months, adverse drug reactions and their incidence were 9.12 and 0.88%, respectively. The incidence of hypoglycemia was 0.67%. Polyuria/pollakiuria occurred more frequently in patients aged ≥65 years than in patients aged <65 years. Women experienced higher rates of urinary tract and genital infection than men. The lowest eGFR subgroup experienced maximum volume depletion-related events. Cardiovascular and cerebrovascular disorders occurred in 0.55% of the patients. Glycated hemoglobin (HbA1c) and bodyweight significantly decreased by -0.76% and -2.73 kg, respectively, from baseline to the last observation carried forward (P < 0.0001). Except for the lowest eGFR subgroup, other eGFR subgroups showed significantly decreased HbA1c values. All eGFR subgroups showed significantly decreased bodyweight, and all body mass index subgroups showed significantly decreased HbA1c and bodyweight. CONCLUSIONS Our interim 12-month data suggest that tofogliflozin could be used safely and effectively in Japanese patients with type 2 diabetes mellitus, as tofogliflozin was well tolerated with low hypoglycemia risk, and significantly improved HbA1c and bodyweight.
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Safety and efficacy of tofogliflozin in Japanese patients with type 2 diabetes mellitus in real-world clinical practice: Results of 3-month interim analysis of a long-term post-marketing surveillance study (J-STEP/LT).
Utsunomiya, K, Senda, M, Kakiuchi, S, Kameda, H, Tamura, M, Kurihara, Y, Gunji, R, Fujii, S, Fujiwara, H, Kaku, K
Journal of diabetes investigation. 2019;(5):1272-1283
Abstract
AIMS/INTRODUCTION The present study analysis was carried out to evaluate the safety and efficacy of tofogliflozin, a sodium-glucose cotransporter 2 inhibitor, in Japanese patients with type 2 diabetes mellitus in real-world clinical practice. MATERIALS AND METHODS This was a 3-year non-interventional observational study of patients with type 2 diabetes mellitus newly administered tofogliflozin who were uncontrolled on current therapy. We carried out a 12-week interim analysis of tofogliflozin as part of 3-year post-marketing surveillance study. The incidence of adverse drug reactions was evaluated as a safety end-point. As efficacy end-points, glycated hemoglobin and bodyweight were evaluated. RESULTS A total of 6,897 patients were enrolled. Tofogliflozin significantly reduced mean changes from baseline glycated hemoglobin (-0.63%, P < 0.0001) and bodyweight (-2.02 kg, P < 0.0001). The change in glycated hemoglobin and bodyweight reductions in response to tofogliflozin was consistently observed in all body mass index subgroups. Adverse drug reactions occurred in 345 of 6,712 patients (5.14%). There was a low incidence of adverse drug reactions known to be associated with sodium-glucose cotransporter 2 inhibitors, and they were reported as non-serious. The incidences of polyuria/pollakiuria were higher in patients aged ≥65 years than <65 years, and were significantly different among estimated glomerular filtration rate subgroups. Urinary tract and genital infections occurred more frequently in women than in men. CONCLUSIONS Tofogliflozin was well tolerated, and no emerging new safety concerns were observed. Tofogliflozin significantly improved glycemic control with no impact on bodyweight gain. The short-term administration of tofogliflozin is considered to have a favorable benefit-risk profile in Japanese patients with type 2 diabetes mellitus.
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International, multicentre, observational study of fluid bolus therapy in neonates.
Keir, AK, Karam, O, Hodyl, N, Stark, MJ, Liley, HG, Shah, PS, Stanworth, SJ, ,
Journal of paediatrics and child health. 2019;(6):632-639
Abstract
AIM: To assess the prevalence, types and indications for fluid bolus therapy in neonates with haemodynamic compromise. METHODS This was a pragmatic, international, multicentre observational study in neonatal units across Australasia, Europe and North America with a predefined study period of 10-15 study days per participating neonatal unit between December 2015 and March 2017. Infants ≤28 days of age who received a fluid bolus for the management of haemodynamic compromise (≥10 mL/kg given at ≤6 h) were included. RESULTS A total of 163 neonates received a bolus over 8479 eligible patient days in 41 neonatal units. Prevalence of fluid bolus therapy varied between centres from 0 to 28.6% of admitted neonates per day, with a pooled prevalence rate of 1.5% (95% confidence interval 1.1-1.9%). The most common fluid used was 0.9% sodium chloride (129/163; 79%), and the volume of fluid administered was most commonly 10 mL/kg (115/163; 71%) over a median of 30 min (interquartile range 20-60). The most frequent indications were hypotension (n = 56; 34%), poor perfusion (n = 20; 12%) and metabolic acidosis (n = 20; 12%). Minimal or no clinical improvement was reported by clinicians in 66 of 163 cases (40%). CONCLUSIONS Wide international variations in types, indications and effects of fluid bolus administration in haemodynamically compromised neonates suggest uncertainty in the risk-benefit profile. This is likely to reflect the lack of robust evidence to support the efficacy of different fluid types, doses and appropriate indications. Together, these highlight a need for further clinically relevant studies.
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Management of atrial fibrillation in the emergency room and in the cardiology ward: the BLITZ AF study.
Gulizia, MM, Cemin, R, Colivicchi, F, De Luca, L, Di Lenarda, A, Boriani, G, Di Pasquale, G, Nardi, F, Scherillo, M, Lucci, D, et al
Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology. 2019;(2):230-238
Abstract
AIMS: To assess the number of admissions to the emergency room (ER) of patients with atrial fibrillation (AF) or atrial flutter (af) and their subsequent management. To evaluate the clinical profile and the use of antithrombotics and antiarrhythmic therapy in patients with AF admitted to cardiology wards. METHODS AND RESULTS BLITZ-AF is a multicentre, observational study conducted in 154 centres on patients with AF/af. In each centre, data were collected, retrospectively for 4 weeks in ER and prospectively for 12 weeks in cardiology wards. In ER, there were 6275 admissions. Atrial fibrillation was the main diagnosis in 52.9% of the cases, af in 5.9%. Atrial fibrillation represented 1.0% of all ER admissions and 1.7% of all hospital admissions. A cardioversion has been performed in nearly 25% of the cases. Out of 4126 patients, 52.2% were admitted in cardiology ward; mean age was 74 ± 11 years, 41% were females. Patients with non-valvular AF were 3848 (93.3%); CHA2DS2-VASc score was ≥2 in 87.4%. Cardioversion was attempted in 38.8% of the patients. In-hospital mortality was 1.2%. At discharge, 42.6% of the patients were treated with vitamin K antagonists, 39.5% with direct oral anticoagulants, 13.6% with other antithrombotic drugs, and 4.2% did not take any antithrombotic agent. Rate control strategy was pursued in 47.2%, rhythm control in 44.0%, 45.6% were discharged in sinus rhythm. CONCLUSION Atrial fibrillation still represents a significant burden on health care system. Oral anticoagulant use increased over time even if compliance with guidelines, with respect to prevention of the risk of stroke, remains suboptimal.
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Medication Discontinuation in the IMPROVE-IT Trial.
Navar, AM, Roe, MT, White, JA, Cannon, CP, Lokhnygina, Y, Newby, LK, Giugliano, RP, Tershakovec, AM, Braunwald, E, Califf, RM, et al
Circulation. Cardiovascular quality and outcomes. 2019;(1):e005041
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BACKGROUND Although cholesterol-lowering medications can reduce the risk of recurrent cardiovascular events, premature discontinuation limits effectiveness. Discontinuation rates have not been systematically reported for lipid-lowering trials. METHODS AND RESULTS We evaluated medication discontinuation in IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial), which evaluated placebo+simvastatin versus ezetimibe+simvastatin in patients hospitalized with the acute coronary syndrome and followed longitudinally postdischarge. Reasons for discontinuation were evaluated from randomization through study end (median 71.9 [interquartile range 51.8-85.8] months). Kaplan-Meier (KM) discontinuation rates were evaluated at 30 days, 1 year, and through year 7, and compared by treatment arm and region, with Cox proportional hazards modeling used to evaluate predictors of discontinuation. Overall, 46.7% of subjects discontinued study medication (KM rate by study end 50.9% [95% CI, 50.1%-51.7%]). The risk of discontinuation was highest early in the trial but decreased with increasing time, with a terminal KM rate per 100 person-years of 8.4 (8.2-8.6) from years 1 to 7. Discontinuation was higher in the placebo+simvastatin versus ezetimibe+simvastatin arm (KM rate 52.0% versus 49.8%, P=0.049) and was highest in the United States (7-year KM rate 57.4%). In multivariable modeling, smoking, prior revascularization, hypertension, unstable angina, female sex, nonwhite race, and US location were associated with higher discontinuation rates. CONCLUSIONS Although discontinuation was highest early and stabilized to 8% per year, because of prolonged follow-up, most discontinuation occurred after year 1. Adding ezetimibe to statin therapy did not increase discontinuation risk. Geographic differences and patient-level factors should be considered in trial design and analysis. CLINICAL TRIAL REGISTRATION URL: https://www.clinicaltrials.gov . Unique identifier: NCT00202878.