Recurrent venous thromboembolism and bleeding with extended anticoagulation: the VTE-PREDICT risk score

Aims Deciding to stop or continue anticoagulation for venous thromboembolism (VTE) after initial treatment is challenging, as individual risks of recurrence and bleeding are heterogeneous. The present study aimed to develop and externally validate models for predicting 5-year risks of recurrence and bleeding in patients with VTE without cancer who completed at least 3 months of initial treatment, which can be used to estimate individual absolute benefits and harms of extended anticoagulation. Methods and results Competing risk-adjusted models were derived to predict recurrent VTE and clinically relevant bleeding (non-major and major) using 14 readily available patient characteristics. The models were derived from combined individual patient data from the Bleeding Risk Study, Hokusai-VTE, PREFER-VTE, RE-MEDY, and RE-SONATE (n = 15,141, 220 recurrences, 189 bleeding events). External validity was assessed in the Danish VTE cohort, EINSTEIN-CHOICE, GARFIELD-VTE, MEGA, and Tromsø studies (n = 59 257, 2283 recurrences, 3335 bleeding events). Absolute treatment effects were estimated by combining the models with hazard ratios from trials and meta-analyses. External validation in different settings showed agreement between predicted and observed risks up to 5 years, with C-statistics ranging from 0.48–0.71 (recurrence) and 0.61–0.68 (bleeding). In the Danish VTE cohort, 5-year risks ranged from 4% to 19% for recurrent VTE and 1% –19% for bleeding. Conclusion The VTE-PREDICT risk score can be applied to estimate the effect of extended anticoagulant treatment for individual patients with VTE and to support shared decision-making

Estimating individual lifetime risk of incident cardiovascular events in adults with type 2 diabetes: an update and geographical calibration of the DIAbetes Lifetime perspective model (DIAL2)

Background: The 2021 ESC cardiovascular disease (CVD) prevention guidelines recommend the use of (lifetime) risk prediction models to aid decisions regarding intensified preventive treatment options in adults with type 2 diabetes, e.g. the DIAbetes Lifetime perspective model (DIAL model). The aim of this study was to update the DIAL-model using contemporary and representative registry data (DIAL2) and to systematically calibrate the model for use in other European countries. Methods and Results: The DIAL2 model was derived in 467,856 people with type 2 diabetes without a history of CVD from the Swedish National Diabetes Register, with a median follow-up of 7.3 years (IQR 4.0-10.6 years) and comprising 63,824 CVD (including fatal CVD, nonfatal stroke and nonfatal myocardial infarction) events and 66,048 non-CVD mortality events. The model was systematically recalibrated to Europe’s low and moderate risk region using contemporary incidence data and mean risk factor distributions. The recalibrated DIAL2 model was externally validated in 218,267 individuals with type 2 diabetes from the Scottish Care Information – Diabetes (SCID) and Clinical Practice Research Datalink (CPRD). In these individuals, 43,074 CVD events and 27,115 non-CVD fatal events were observed. The DIAL2 model discriminated well, with C-indices of 0.732 (95%CI 0.726-0.739) in CPRD and 0.700 (95%CI 0.691-0.709) in SCID. Interpretation: The recalibrated DIAL2 model provides a useful tool for the prediction of CVD-free life expectancy and lifetime CVD risk for people with type 2 diabetes without previous CVD in the European low and moderate risk regions. These long-term individualized measures of CVD risk are well suited for shared decision making in clinical practice as recommended by the 2021 CVD ESC prevention guidelines

An alternative approach identified optimal risk thresholds for treatment indication: an illustration in coronary heart disease.

Treatment thresholds based on risk predictions can be optimized by considering various health (economic) outcomes and performing marginal analyses, but this is rarely performed. We demonstrate a general approach to identify treatment thresholds optimizing individual health (economic) outcomes, illustrated for statin treatment based on 10-year coronary heart disease (CHD) risk predicted by the Framingham risk score

An alternative approach identified optimal risk thresholds for treatment indication: an illustration in coronary heart disease.

Treatment thresholds based on risk predictions can be optimized by considering various health (economic) outcomes and performing marginal analyses, but this is rarely performed. We demonstrate a general approach to identify treatment thresholds optimizing individual health (economic) outcomes, illustrated for statin treatment based on 10-year coronary heart disease (CHD) risk predicted by the Framingham risk score

Cost-Effectiveness of Intensifying Lipid-Lowering Therapy With Statins Based on Individual Absolute Benefit in Coronary Artery Disease Patients

BACKGROUND: A validated prediction model estimates the absolute benefit of intensive versus standard lipid-lowering therapy (LLT) with statins on next major cardiovascular events for individual patients with coronary artery disease. We aimed to assess whether targeting intensive LLT therapy to coronary artery disease patients with the highest predicted absolute benefit is cost-effective compared to treating all with standard or all with intensive LLT. METHODS AND RESULTS: A lifetime Markov model was constructed for coronary artery disease patients (n=10 000) with mean age 61 years. Number of major cardiovascular events, (non) vascular death, costs, and quality-adjusted life years (QALYs) were estimated for the following strategies: (1) standard LLT for all (reference strategy); (2) intensive LLT for those with 5-year absolute major cardiovascular events risk reduction (ARR) ≥3%, ≥2.3%, or ≥1.5% (corresponding to ≥20%, ≥15%, or ≥10% 5-year major cardiovascular events risk); and (3) intensive LLT for all. With intensive LLT for those with ≥3% 5-year ARR (13% of patients), 380 QALYs were gained for €2423/QALY. Using a threshold of ≥2.3% ARR (26% of patients), 630 QALYs were gained for €5653/QALY. Using a threshold of ≥1.5% ARR (56% of patients), 1020 QALYs were gained for €10 960/QALY. By treating all intensively, 1410 QALYs were gained (0.14 QALY per patient) for €17 223/QALY. With benefit-based treatment, 0.16 to 0.17 QALY was gained per treated patient. CONCLUSIONS: Intensive LLT with statins for all coronary artery disease patients results in the highest overall QALY gain against acceptable costs. However, the number of QALYs gained with intensive LLT by statins in individual patients can be increased with selective benefit-based treatment. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00327691 and NCT00159835

Identifying treatment response to antihypertensives in patients with obesity-related hypertension

Abstract Background In patients with obesity-related hypertension (ORH), reaction to antihypertensive medication is likely influenced by patientcharacteristics. Methods Effects of aliskiren, moxonidine and hydrochlorothiazide on 24-h blood pressure (BP) were compared to placebo. Linear mixed effect models were used to analyze the effect of patient characteristics on BP levels and treatment response. Results Systolic BP response to aliskiren was higher in patients with a BMI > 30.7 kg/m2 compared to patients with a BMI ≤ 30.7 kg/m2 (−21 mmHg versus -4 mmHg). In patients with a hsCRP > 1.8 mg/L the systolic BP response to aliskiren was higher than in patients with a low hsCRP (−15 mmHg versus −7 mmHg). Hydrochlorothiazide (HCTZ) treatment effect on systolic BP was −13 mmHg when heart rate > 71 beats/min compared to -3 mmHg when heart rate was ≤ 71 beats/min. Conclusion In patients with ORH, BP response to aliskiren is positively related to BMI and hsCRP. Systolic BP response to HCTZ is positively related to heart rate and negatively to renin levels. Trial registration NCT01138423 . Registered June 4th, 2010

Cholesterolverlaging bij ouderen Starten, stoppen of doorgaan?

Bij ouderen kan het risico op hart- en vaatziekten (HVZ) gereduceerd worden door cholesterolverlaging. Bij ouderen bestaat echter een grote spreiding in de hoogte van het risico op HVZ. Concurrerende risico’s, tijd-tot-baat van de medicatie in relatie tot de levensverwachting en de kwetsbaarheid van de patiënt moeten worden meegewogen bij het besluit om een oudere patiënt al dan niet een cholesterolverlager voor te schrijven. Gebruik bij het schatten van het cardiovasculaire risico bij ouderen een individuele risicoscore die rekening houdt met concurrerende risico’s. Begin bij vitale ouderen zonder vaatlijden alleen met cholesterolverlagers als zij een hoog cardiovasculair risico hebben, bijvoorbeeld door diabetes mellitus of een zeer hoge bloeddruk. Er is geen plaats voor cholesterolverlagers bij kwetsbare ouderen zonder vaatlijden. Begin met een cholesterolverlager bij oudere patiënten met vaatlijden of continueer deze. Stop bij patiënten die hinderlijke bijwerkingen ondervinden of als de levensverwachting van de patiënt niet langer dan 1-2 jaar is

How to translate clinical trial results into gain in healthy life expectancy for individual patients

Treatment effects from randomised trials are typically expressed as numbers needed to treat to prevent one adverse disease event during a fixed time interval (eg, five or 10 years). In the actual patient, however, many diseases are chronically progressive, despite treatment. Examples are diabetic nephropathy, some types of malignancies, osteoporosis, and atherosclerosis. In these examples, the aim of treatment is not to prevent but to delay the occurrence of symptomatic disease. Thus the actual effect of treatment is gain in disease-free life expectancy

How to translate clinical trial results into gain in healthy life expectancy for individual patients

Liam Berkowitz, do Editors Weblog, escreveu ontem que a tecnologia do papel electrónico será possivelmente lançada em 2009. Trata-se, pois, de uma das mais excitantes inovações, acrescenta a notícia, citando Ryosuke Kuwata, vice-presidente da E Ink Corp. Se as empresas americanas estão a desenvolver modelos a partir da tecnologia japonesa, os jornais europeus começam a despertar para o facto.O vídeo abaixo terá cerca de dois anos e mostra uma espécie de papel electrónico, com um indivíduo com..

Estimating Bleeding Risk in Patients with Cancer-Associated Thrombosis: Evaluation of Existing Risk Scores and Development of a New Risk Score

Background Bleeding risk is highly relevant for treatment decisions in cancer-associated thrombosis (CAT). Several risk scores exist, but have never been validated in patients with CAT and are not recommended for practice. Objectives To compare methods of estimating clinically relevant (major and clinically relevant nonmajor) bleeding risk in patients with CAT: (1) existing risk scores for bleeding in venous thromboembolism, (2) pragmatic classification based on cancer type, and (3) new prediction model. Methods In a posthoc analysis of the Hokusai VTE Cancer study, a randomized trial comparing edoxaban with dalteparin for treatment of CAT, seven bleeding risk scores were externally validated (ACCP-VTE, HAS-BLED, Hokusai, Kuijer, Martinez, RIETE, and VTE-BLEED). The predictive performance of these scores was compared with a pragmatic classification based on cancer type (gastrointestinal; genitourinary; other) and a newly derived competing risk-adjusted prediction model based on clinical predictors for clinically relevant bleeding within 6 months after CAT diagnosis with nonbleeding-related mortality as the competing event ("CAT-BLEED"). Results Data of 1,046 patients (149 events) were analyzed. Predictive performance of existing risk scores was poor to moderate (C-statistics: 0.50-0.57; poor calibration). Internal validation of the pragmatic classification and "CAT-BLEED"showed moderate performance (respective C-statistics: 0.61; 95% confidence interval [CI]: 0.56-0.66, and 0.63; 95% CI 0.58-0.68; good calibration). Conclusion Existing risk scores for bleeding perform poorly after CAT. Pragmatic classification based on cancer type provides marginally better estimates of clinically relevant bleeding risk. Further improvement may be achieved with "CAT-BLEED", but this requires external validation in practice-based settings and with other DOACs and its clinical usefulness is yet to be demonstrated