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Twice-weekly topical calcipotriene/betamethasone dipropionate foam as proactive management of plaque psoriasis increases time in remission and is well tolerated over 52 weeks (PSO-LONG trial).
Lebwohl, M, Kircik, L, Lacour, JP, Liljedahl, M, Lynde, C, Mørch, MH, Papp, KA, Perrot, JL, Gold, LS, Takhar, A, et al
Journal of the American Academy of Dermatology. 2021;(5):1269-1277
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Abstract
BACKGROUND Topical psoriasis treatment relies on a reactive rather than a long-term proactive approach to disease relapse. OBJECTIVE Assess long-term efficacy and safety of proactive psoriasis management with twice-weekly calcipotriene 0.005%/betamethasone dipropionate 0.064% (Cal/BD) foam. METHODS Phase III trial (NCT02899962) included a 4-week open-label lead-in phase (Cal/BD foam once daily) and a 52-week, randomized, double-blind, maintenance phase. A total of 545 patients achieved treatment success (physician's global assessment "clear"/"almost clear," ≥2-grade improvement from baseline) and were randomized to proactive management (Cal/BD foam; n = 272) or reactive management (vehicle foam; n = 273) twice-weekly, with rescue treatment of Cal/BD foam once daily for 4 weeks upon relapse. Primary endpoint was time to first relapse (physician's global assessment "mild" or higher). RESULTS A total of 251 randomized patients (46.1%) completed the trial. Median time to first relapse was 56 days (proactive) and 30 days (reactive). Patients in the proactive group had an additional 41 days in remission compared with the reactive group over 1 year (P < .001). Number of relapses per year of exposure was 3.1 (proactive) and 4.8 (reactive). Cal/BD foam was well tolerated. LIMITATIONS Maintenance phase dropout rate (53.9%) was within the expected range but provides challenges in statistical analysis. CONCLUSION Long-term proactive management with Cal/BD foam demonstrated superior efficacy vs reactive management.
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Hydroxychloroquine to Prevent Recurrent Congenital Heart Block in Fetuses of Anti-SSA/Ro-Positive Mothers.
Izmirly, P, Kim, M, Friedman, DM, Costedoat-Chalumeau, N, Clancy, R, Copel, JA, Phoon, CKL, Cuneo, BF, Cohen, RE, Robins, K, et al
Journal of the American College of Cardiology. 2020;(3):292-302
Abstract
BACKGROUND Experimental and clinical evidence support the role of macrophage Toll-like receptor signaling in maternal anti-SSA/Ro-mediated congenital heart block (CHB). OBJECTIVES Hydroxychloroquine (HCQ), an orally administered Toll-like receptor antagonist widely used in lupus including during pregnancy, was evaluated for efficacy in reducing the historical 18% recurrence rate of CHB. METHODS This multicenter, open-label, single-arm, 2-stage clinical trial was designed using Simon's optimal approach. Anti-SSA/Ro-positive mothers with a previous pregnancy complicated by CHB were recruited (n = 19 Stage 1; n = 35 Stage 2). Patients received 400 mg daily of HCQ prior to completion of gestational week 10, which was maintained through pregnancy. The primary outcome was 2° or 3° CHB any time during pregnancy, and secondary outcomes included isolated endocardial fibroelastosis, 1° CHB at birth and skin rash. RESULTS By intention-to-treat (ITT) analysis, 4 of 54 evaluable pregnancies resulted in a primary outcome (7.4%; 90% confidence interval: 3.4% to 15.9%). Because 9 mothers took potentially confounding medications (fluorinated glucocorticoids and/or intravenous immunoglobulin) after enrollment but prior to a primary outcome, to evaluate HCQ alone, 9 additional mothers were recruited and followed the identical protocol. In the per-protocol analysis restricted to pregnancies exposed to HCQ alone, 4 of 54 (7.4%) fetuses developed a primary outcome as in the ITT. Secondary outcomes included mild endocardial fibroelastosis (n = 1) and cutaneous neonatal lupus (n = 4). CONCLUSIONS These prospective data support that HCQ significantly reduces the recurrence of CHB below the historical rate by >50%, suggesting that this drug should be prescribed for secondary prevention of fetal cardiac disease in anti-SSA/Ro-exposed pregnancies. (Preventive Approach to Congenital Heart Block With Hydroxychloroquine [PATCH]; NCT01379573).
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Changes in plasma lipids predict pravastatin efficacy in secondary prevention.
Jayawardana, KS, Mundra, PA, Giles, C, Barlow, CK, Nestel, PJ, Barnes, EH, Kirby, A, Thompson, P, Sullivan, DR, Alshehry, ZH, et al
JCI insight. 2019;(13)
Abstract
BACKGROUNDStatins have pleiotropic effects on lipid metabolism. The relationship between these effects and future cardiovascular events is unknown. We characterized the changes in lipids upon pravastatin treatment and defined the relationship with risk reduction for future cardiovascular events.METHODSPlasma lipids (n = 342) were measured in baseline and 1-year follow-up samples from a Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) study subcohort (n = 4991). The associations of changes in lipids with treatment and cardiovascular outcomes were investigated using linear and Cox regression. The effect of treatment on future cardiovascular outcomes was examined by the relative risk reduction (RRR).RESULTSPravastatin treatment was associated with changes in 206 lipids. Species containing arachidonic acid were positively associated while phosphatidylinositol species were negatively associated with pravastatin treatment. The RRR from pravastatin treatment for cardiovascular events decreased from 23.5% to 16.6% after adjustment for clinical risk factors and change in LDL-cholesterol (LDL-C) and to 3.0% after further adjustment for the change in the lipid ratio PI(36:2)/PC(38:4). Change in PI(36:2)/PC(38:4) mediated 58% of the treatment effect. Stratification of patients into quartiles of change in PI(36:2)/PC(38:4) indicated no benefit of pravastatin in the fourth quartile.CONCLUSIONThe change in PI(36:2)/PC(38:4) predicted benefit from pravastatin, independent of change in LDL-C, demonstrating its potential as a biomarker for monitoring the clinical benefit of statin treatment in secondary prevention.TRIAL REGISTRATIONAustralian New Zealand Clinical Trials Registry identifier ACTRN12616000535471.FUNDINGBristol-Myers Squibb; NHMRC grants 211086, 358395, and 1029754; NHMRC program grant 1149987; NHMRC fellowship 108026; and the Operational Infrastructure Support Program of the Victorian government of Australia.
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Edoxaban Management in Diagnostic and Therapeutic Procedures (EMIT-AF/VTE)-Trial design.
Colonna, P, von Heymann, C, Santamaria, A, Matsushita, Y, Unverdorben, M
Clinical cardiology. 2018;(9):1123-1129
Abstract
Non-vitamin K dependent oral anticoagulants (NOAC) are now widely used in patients with nonvalvular atrial fibrillation (NVAF) for stroke prevention and in patients with venous thromboembolism (VTE) for the treatment and secondary prevention of the disease. Among NOAC, edoxaban demonstrated noninferiority to warfarin for stroke prevention in NVAF and for VTE treatment, with superior safety. EMIT-AF/VTE (Edoxaban Management in Diagnostic and Therapeutic Procedures) (NCT02950168) is a multicenter, prospective, and noninterventional registry study designed to collect detailed information on the periprocedural management of patients with NVAF and VTE receiving edoxaban. The primary objective of EMIT-AF/VTE is to document the periprocedural management of patients receiving edoxaban and to collect data on safety and other outcomes in these patients. The primary safety outcome is the rate of major bleeding. Other assessments include the evaluation of efficacy outcomes, periprocedural dosing, and timing of edoxaban. The observation period will start 5 days prior to the procedure and end 30 days post-procedure. EMIT-AF/VTE will aim to prospectively enroll up to approximately 1400 procedures from Europe. Enrollment commenced in December 2016 and will be completed in July 2018. As of July 2018, before database lock and with several procedure forms still temporarily inserted, a preliminary number of 1204 patients have been enrolled, who underwent a total of 1453 procedures. The prospective EMIT-AF/VTE registry program will expand the knowledge of periprocedural management of patients with NVAF and VTE receiving edoxaban in clinical practice.
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Unfavourable risk factor control after coronary events in routine clinical practice.
Sverre, E, Peersen, K, Husebye, E, Gjertsen, E, Gullestad, L, Moum, T, Otterstad, JE, Dammen, T, Munkhaugen, J
BMC cardiovascular disorders. 2017;(1):40
Abstract
BACKGROUND Risk factor control after a coronary event in a recent European multi-centre study was inadequate. Patient selection from academic centres and low participation rate, however, may underscore failing risk factor control in routine clinical practice. Improved understanding of the patient factors that influence risk factor control is needed to improve secondary preventive strategies. The objective of the present paper was to determine control of the major risk factors in a coronary population from routine clinical practice, and how risk factor control was influenced by the study factors age, gender, number of coronary events, and time since the index event. METHODS A cross-sectional study determined risk factor control and its association with study factors in 1127 patients (83% participated) aged 18-80 years with acute myocardial infarction and/or revascularization identified from medical records. Study data were collected from a self-report questionnaire, clinical examination, and blood samples after 2-36 months (median 16) follow-up. RESULTS Twenty-one percent were current smokers at follow-up. Of those smoking at the index event 56% continued smoking. Obesity was found in 34%, and 60% were physically inactive. Although 93% were taking blood-pressure lowering agents and statins, 46% were still hypertensive and 57% had LDL cholesterol >1.8 mmol/L at follow-up. Suboptimal control of diabetes was found in 59%. The patients failed on average to control three of the six major risk factors, and patients with >1 coronary events (p < 0.001) showed the poorest overall control. A linear increase in smoking (p < 0.01) and obesity (p < 0.05) with increasing time since the event was observed. CONCLUSIONS The majority of coronary patients in a representative Norwegian population did not achieve risk factor control, and the poorest overall control was found in patients with several coronary events. New strategies for secondary prevention are clearly needed to improve risk factor control. Even modest advances will provide major health benefits. TRIAL REGISTRATION Registered at ClinicalTrials.gov (ID NCT02309255 ).
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Extended duration of anticoagulation with edoxaban in patients with venous thromboembolism: a post-hoc analysis of the Hokusai-VTE study.
Raskob, G, Ageno, W, Cohen, AT, Brekelmans, MP, Grosso, MA, Segers, A, Meyer, G, Verhamme, P, Wells, PS, Lin, M, et al
The Lancet. Haematology. 2016;(5):e228-36
Abstract
BACKGROUND There are few data on the relative efficacy and safety of direct oral anticoagulants, such as edoxaban, compared with vitamin K antagonists during extended therapy for venous thromboembolism. This analysis evaluates the risk-benefit of extended treatment for up to 12 months with edoxaban compared with warfarin among patients enrolled in the Hokusai-VTE study who continued therapy beyond 3 months. METHODS The Hokusai-VTE trial (NCT00986154) was a randomised, double-blind, event driven non-inferiority trial in 8292 patients comparing edoxaban with warfarin in the treatment of patients with acute venous thromboembolism. All patients were treated for at least 3 months and treatment was continued for up to 12 months. The outcomes at 12 months were documented in all patients irrespective of treatment duration. 3633 patients treated with edoxaban and 3594 treated with warfarin who completed 3 months of treatment were eligible for this analysis. The primary efficacy outcome was the incidence of adjudicated symptomatic recurrent venous thromboembolism evaluated for each of the time intervals of 3 months, greater than 3 months to 6 months, greater than 6 months to less than 12 months, and at 12 months, as well as the cumulative incidence occurring between 3 and 12 months. The principal safety outcome was the incidence of clinically relevant bleeding (composite of major or clinically relevant non-major bleeding). Both on-treatment and intention-to-treat analyses were done. FINDINGS In the on-treatment analysis, the incidence of recurrent venous thromboembolism at 3 months was 1·1% (0·8-1·4; 44 of 4118 patients) in the edoxaban-treated group versus 1·2% (0·9-1·6; 51 of 4122) in the warfarin-treated group; between greater than 3 months and 6 months, 0·7% (0·3-1·5; eight of 1076) versus 0·5% (0·2-1·1; five of 1084); between greater than 6 months and less than 12 months, 0·2% (0·0-0·8; two of 896) versus 0·8% (0·03-1·7; seven of 851); and at 12 months, <0·1% (0·0-0·3; one of 1661) versus 0·1% (0·0-0·4; two of 1659). In the on-treatment analysis, the cumulative incidence of recurrent venous thromboembolism between 3 and 12 months was 0·3% (95% CI 0·2-1·5; 11 of 3633 patients) in the edoxaban-treated group and 0·4% (0·2-1·7; 14 of 3594) in the warfarin-treated group (HR 0·78, 95% CI 0·36-1·72). The cumulative incidence of clinically relevant bleeding (major or non-major) between 3 and 12 months was 3·9% (95% CI 3·3-4·6; 143 of 3633 patients) in the edoxaban-treated group and 4·1% (3·5-4·8; 147 of 3594 patients) in the warfarin-treated group (HR 0·97, 95% CI 0·77-1·22); cumulative incidence of major bleeding was 0·3% (95% CI 0·2-0·5; 11 of 3633 patients) in the edoxaban-treated group and 0·7% (0·4-1·0; 24 of 3594 patients) in the warfarin-treated group (HR 0·45, 95% CI 0·22-0·92). Similar results were obtained in the intention-to-treat analysis. INTERPRETATION Extended treatment with edoxaban is effective and associated with less major bleeding than warfarin. Edoxaban once daily provides an attractive alternative to warfarin for patients with venous thromboembolism who require extended treatment for prevention of recurrent venous thromboembolism. FUNDING Daiichi Sankyo.
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[Secondary prevention in patients with superficial urothelial carcinoma].
Schnöller, TJ, Zengerling, F, Hirning, C, Jentzmik, F
Der Urologe. Ausg. A. 2015;(7):992-7
Abstract
BACKGROUND Urothelial cancer is the 4th most common cancer in men and the 7th most common malignancy in women in Germany. 95 % of all tumors of the urinary bladder are urothelial carcinomas. At the time of diagnosis approximately 80 % of these carcinomas are not invasive. The affection is often multicentric. Approximately 10-15 % of the tumors develop into muscle-invasive growth. In this prospective study, we analyzed measures patients independently took to reduce their risk of bladder cancer recurrence. MATERIALS AND METHODS During the period January 2012 to December 2013, we surveyed a total of 97 patients with superficial transitional cell carcinoma (pTa). The question was how far the diagnosis of urothelial cancer has changed their lives, eating and drinking habits or whether follow-up consultations had been carried out regularly. Furthermore, we recorded whether they accepted psychological care or had autonomously adopted prophylactic measures, as well as changed their smoking habits, if they had smoked. RESULTS Of the 97 patients questioned, there were 79 men and 18 women (56 smokers and 41 nonsmokers). The median age was 71 years (range 36-96 years). For 22 patients (22.7 %), the diagnosis resulted in no changes. In 33 patients the changes were small (44 %), moderate in 20 (26.7 %), in 14 (18.6 %) strong and very strong in 8 (10.7 %). A total of 25 patients (25.8 %) changed their eating habits. In all, 49 patients changed their drinking habits; 48 patients claimed to drink more (> 2.0 L/day). One patient reduced his drinking amount. Regarding smoking, 40 patients (71.4 %) had stopped and 7 (12.5 %) reduced consumption, while 6 patients (10.7 %) had not changed their smoking habits. Overall, 44 patients (45.4 %) changed their physical activity: 11 (25 %) exercised more, 8 (18.1 %) less. Only 3 patients (3.1 %) used psycho-oncological care and 39 (40.2 %) patients used supportive/complementary medicine measures of favorablly influence their disease (mistletoe therapy, vitamin supplements). In addition, 22 patients (22.7 %) sought advice from their physician. However, 45.4 % of all patients did not believe in the success of their measures taken. CONCLUSION Of all patients diagnosed with urothelial carcinoma, 77.3 % reported a change in their living habits and they were willing to take specific steps, such as giving up smoking, being more physically active, changing drinking and eating habits in order to positively influence their disease. However, almost half of the patients (45.4 %) did not believe in a resounding success of their measures taken.
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Improving Adherence to Secondary Stroke Prevention Strategies Through Motivational Interviewing: Randomized Controlled Trial.
Barker-Collo, S, Krishnamurthi, R, Witt, E, Feigin, V, Jones, A, McPherson, K, Starkey, N, Parag, V, Jiang, Y, Barber, PA, et al
Stroke. 2015;(12):3451-8
Abstract
BACKGROUND AND PURPOSE Stroke recurrence rates are high (20%-25%) and have not declined over past 3 decades. This study tested effectiveness of motivational interviewing (MI) for reducing stroke recurrence, measured by improving adherence to recommended medication and lifestyle changes compared with usual care. METHODS Single-blind, prospective phase III randomized controlled trial of 386 people with stroke assigned to either MI treatment (4 sessions at 28 days, 3, 6, and 9 months post stroke) or usual care; with outcomes assessed at 28 days, 3, 6, 9, and 12 months post stroke. Primary outcomes were change in systolic blood pressure and low-density lipoprotein cholesterol levels as indicators of adherence at 12 months. Secondary outcomes included self-reported adherence, new stroke, or coronary heart disease events (both fatal and nonfatal); quality of life (Short Form-36); and mood (Hospital Anxiety and Depression Scale). RESULTS MI did not significantly change measures of blood pressure (mean difference in change, -0.2.35 [95% confidence interval, -6.16 to 1.47]) or cholesterol (mean difference in change, -0.0.12 [95% confidence interval, -0.30 to 0.06]). However, it had positive effects on self-reported medication adherence at 6 months (1.979; 95% confidence interval, 0.98-3.98; P=0.0557) and 9 months (4.295; 95% confidence interval, 1.56-11.84; P=0.0049) post stroke. Improvement across other measures was also observed, but the differences between MI and usual care groups were not statistically significant. CONCLUSIONS MI improved self-reported medication adherence. All other effects were nonsignificant, though in the direction of a treatment effect. Further study is required to determine whether MI leads to improvement in other important areas of functioning (eg, caregiver burden). CLINICAL TRIAL REGISTRATION URL: http://www.anzctr.org.au. Unique identifier: ACTRN-12610000715077.
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[Results of complex lipid-lowering therapy in patients with a history of acute coronary syndrome].
Danio, G, Márk, L, Katona, A
Orvosi hetilap. 2011;(8):296-302
Abstract
UNLABELLED Authors aimed to assess how target values in serum lipid concentrations (LDL- and HDL-cholesterol, triglyceride) can be achieved in patients with a history of acute coronary syndrome during follow up in an outpatient cardiology clinic. METHODS 201 patients with a history of acute coronary syndrome were included and were followed up between January 1 and May 31, 2007.Authors analyzed serum lipid parameters of the patients and the lipid-lowering medications at the time of the first meeting and during follow up lasting two years. RESULTS During the enrollment visit only 26.4% of the patients had serum LDL cholesterol at target level, whereas high triglycerides and low HDL cholesterol levels were observed in 40.3% and 33.3% of the patients, respectively. Only 22 patients (10.9%) achieved the target levels in all three lipid parameters. Of the 201 patients, 179 patients participated in the follow up, and data obtained from these patients were analyzed. There was a positive trend toward better lipid parameters; 42.5% of the patients reached the desired LDL-cholesterol target value and 17.3% of the patients had HDL-cholesterol and triglycerides target values. CONCLUSIONS These findings are consistent with those published in the literature. Beside the currently used therapeutic options for achieving optimal LDL-cholesterol, efforts should be made to reduce the so-called "residual cardiovascular risk" with the use of a widespread application of combination therapy.
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Preventing recurrence of thromboembolic events through coordinated treatment in the District of Columbia.
Dromerick, AW, Gibbons, MC, Edwards, DF, Farr, DE, Giannetti, ML, Sánchez, B, Shara, NM, Fokar, A, Jayam-Trouth, A, Ovbiagele, B, et al
International journal of stroke : official journal of the International Stroke Society. 2011;(5):454-60
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Abstract
RATIONALE PROTECT DC examines whether stroke navigators can improve cardiovascular risk factors in urban underserved individuals newly hospitalized for stroke or ischemic attack. Within one-year of hospital discharge, up to one-third of patients no longer adhere to secondary prevention behaviors. Adherence rates are lower in minority-underserved groups, contributing to health disparities. In-hospital programs increase use of stroke prevention therapies but may not be as successful in underserved individuals. In these groups, low literacy, limited healthcare access, and sparse community resources may reduce adherence. Lay community health workers (navigators) improve adherence in other illnesses through education and assisting in overcoming barriers to achieving desired health behaviors and obtaining needed healthcare services. AIMS AND DESIGN PROTECT DC is a Phase II, single-blind, randomized, controlled trial comparing in-hospital education plus stroke navigators to usual care. Atherogenic ischemic stroke and transient ischemic attack survivors are recruited from Washington, DC hospitals. Navigators meet with participants during the index hospitalization, perform home visits, and meet by phone. They focus on stroke education, medication compliance, and overcoming practical barriers to adherence. The interventions are driven by the theories of reasoned action and planned behavior. STUDY OUTCOMES The primary dependent measure is a summary score of four objective measures of stroke risk factor control: systolic blood pressure, low-density lipoprotein, hemoglobin Hb A1C, and antiplatelet agent pill counts. Secondary outcomes include stroke knowledge, exercise, dietary modification, and smoking cessation. CONCLUSION PROTECT DC will determine whether a Phase III trial of stroke navigation for urban underserved individuals to improve adherence to secondary stroke prevention behaviors is warranted.