bluuebunny/crossref_metadata_2025_split huggingface dataset:
First 5-year TAVR/TAVI Outcomes from the South African SHARE-TAVI national registry and the influence of malignancy on late outcomes
Authors: Schaafsma E , Weich H , Scherman J , Ntsekhe M 
Published: October 2022

Abstract

Introduction
The South African (SA) national prospective multicentre observational SHARE-TAVI registry aims to provide local outcomes data on all TAVIs in State & Private sectors, to support local evidence-based policy evaluations, comparing outcomes to international data & identifying local variations.

Method
All 20 implant centres voluntarily capture all-comers data into the web-based registry. 2266 patients from 1 Sept 2014 to 28 Feb 2022 had pre-TAVI clinical evaluations and 1502 proceeded to TAVI & had procedural data & complications (VARC2 criteria), 30d & annual follow up recorded. The 5-yr cohort of 289 patients have clinical history and profile similar to international data (Table 1).

Results
Procedural success of 93.43% and 1-year mortality of 15.92% in the 5-yr cohort (STS score 8.85%) are similar to reported international data in early TAVI programmes. All-cause mortality at 5-years is 44.3% (in PARTNER 1 – 67.8%, PARTNER 2.0 – 46.0%), and the greatest proportion of non-cardiac mortality (38.5%) occurs in period &gt;1–2yr post-TAVI (lowest proportion 29.4% in &gt;3–4yr period). Outcomes measures in a more recent 2020 patient cohort (n=219, success 98.63% and 1-yr mortality 8.85%, STS risk score 5.51%) have improved compared to the 5-yr cohort.
Patients with “Prior or current malignancy” (POCM) at TAVI evaluation have increased mortality in both the 1-yr outcome (n=637) cohort, 18.7% 1-yr mortality vs 9.3% in those without POCM, and same trend in the 2-year outcome cohort n=443 (28.0% 2-year mortality vs 12.8% without malignancy). Frail patients with POCM in the 2-yr cohort have substantially higher mortality at 2 years, 34.8% than frail patients without POCM 15.9%
At evaluation 66% of patients are NYHA class III+IV, post-TAVI only 5.9% at 30d & 8.8% at 1-year, at 1-year 30% of patients have maintained improvement by 2 or 3 NYHA classes.

Conclusion
5-yr outcomes in SA are comparable to international data, and procedural outcomes have improved further as to be expected with maturation of the programme and technology. The NYHA class distribution at 1-yr shows improvements which should translate into improved quality of life, future studies should include patient self-reported quality of life assessments to verify this benefit. Malignancy, even if prior, may predict poorer outcomes in the longer term, possibly due to reported higher frailty in these patients. Amongst other factors, prior or current malignancy may be considered relevant when assessing patients for futility for TAVI in SA's severely constrained healthcare resource environment.

Funding Acknowledgement
Type of funding sources: Other. Main funding source(s): Educational and Research Grants from SA Heart Association and Medtronic, Edwards Life Sciences
Cost-effectiveness of icosapent ethyl for primary and secondary cardiovascular prevention in the UK
Authors: Michaeli D T , Michaeli J C , Boch T , Michaeli T 
Published: October 2022

Abstract

Background
Treatment with icosapent ethyl reduces the risk of major adverse cardiovascular events by 25% in patients with hypertriglyceridemia compared to placebo as demonstrated by The Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial (REDUCE-IT).

Objective
To assess the cost-effectiveness of icosapent ethyl, the purified eicosapentaenoic acid ethyl ester, in combination with statins compared to statin monotherapy for primary and secondary cardiovascular prevention from the perspective of England's National Health Service (NHS).

Methods
A Markov model simulated the progression of cardiovascular diseases and acute events, including myocardial infarction, stroke, angina, and coronary revascularization, in dyslipidaemia patients. The model was populated with cardiovascular outcome data derived from the REDUCE-IT trial. Cost and utility data were extracted from peer-reviewed literature. The incremental cost-effectiveness ratio (ICER) is reported per quality-adjusted life year (QALY) gained in 2021 Great Britain Pounds (£). Univariate, scenario, willingness-to-pay, and probabilistic sensitivity analyses were conducted to assess the robustness of results.

Results
For primary cardiovascular prevention, icosapent ethyl increased QALYs gained by 0.79 and costs by £15,421 compared to statin monotherapy (ICER: 19,485 £/QALY). For secondary prevention, the omega-3 fatty acid, icosapent ethyl, extended QALYs by 0.98 for patients at costs of £12,981 (ICER: 13,285 £/QALY). At the NHS' willingness-to-pay threshold of 25,000 £/QALY, there is 98% and 100% probability icosapent ethyl is cost-effective in primary and secondary prevention, respectively. Results remained robust under univariate, scenario, and probabilistic sensitivity analyses.

Conclusion
Icosapent ethyl is cost-effective for primary and secondary cardiovascular prevention at an annual price of £2,064 in the UK.

Funding Acknowledgement
Type of funding sources: None.
Benefit accrual with cardiovascular disease prevention and effects of discontinuation: a modelling study
Authors: Wu R , Williams C , Zhou J , Schlackow I , Emberson J , Reith C , Keech A , Robson J , Wilkinson K , Armitage J , Collins R , Gray A , Simes J , Baigent C , Mihaylova B 
Published: October 2022

Abstract

Background
Statin therapy reduces rates of heart attacks and strokes and improves survival in people at increased cardiovascular disease (CVD) risk. However, there is some uncertainty when to start and how long to persist with statin therapy so as to optimise benefits.

Purpose
To project the accrual of benefit with statin therapy in population groups by age at therapy initiation using a newly developed micro-simulation model.

Methods
Participants without previous CVD (N=44,412) and with previous CVD (N=13,061) at entry were randomly selected from the UK Biobank cohort, ensuring sufficient representation in respective categories by age, LDL cholesterol, diabetes and 10-year CVD risk categories (QRISK3 score, for those without previous CVD only). The CTT-UKB model, a CVD micro-simulation model [1], was used to predict subsequent survival and quality-adjusted life years (QALYs) of the participants using their characteristics at entry. Treatment with atorvastatin 40mg daily was used as an example to illustrate the effect of the therapy compared to no such therapy. Scenarios include: (1) lifelong preventive therapy, (2) preventive therapy stopped at 80 years of age, and (3) delayed initiation of preventive therapy by 5 years in participants under 45 years of age.

Results
Statin treatment benefits, measured in QALYs gained, accrue over lifetime. The majority of benefits accrue later in life. Men accumulate larger benefits and earlier than women (Figure 1A). The pattern of benefits accrual is similar for participants with and without previous CVD (data not shown). The higher the participants' CVD risk, the larger and earlier the benefits, with younger participants accruing larger benefits (Figure 1B). Compared with lifelong prevention, stopping treatment at 80 years of age leads to large reductions in overall benefits, especially in women and those at lower CVD risk. For example, compared to lifelong therapy, people without previous CVD who initiate therapy in their 50s, would lose 47% of QALYs benefit (if men), 66% (if women), 73% (if with CVD risk &lt;5%), and 35% (if with CVD risk ≥20%), respectively, if they stop treatment when they reach 80 years of age. Five-year delay of statin therapy initiation in people under 45 years of age reduces their benefits by about 4% on average, though the loss is somewhat larger in people at higher CVD risk (Figure 2).

Conclusion
Benefits from lifelong cardiovascular prevention accrue over peoples' lifespan with large share of benefits accruing at older age. Stopping treatment earlier substantially reduces benefits.

Funding Acknowledgement
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): UK NationalInstitute for Health Research (NIHR) Health Technology Assessment (HTA) Programme, UK Medical Research Council (MRC), and British Heart Foundation
Impact of cardiovascular events on primary and hospital care costs: findings from UK Biobank study
Authors: Zhou J , Wu R , Williams C , Emberson J , Reith C , Keech A , Robson J , Wilkinson K , Armitage J , Collins R , Gray A , Simes J , Baigent C , Mihaylova B 
Published: October 2022

Abstract

Background
Need for primary and secondary healthcare increases following cardiovascular disease (CVD) events but there is no data on comparative increases in costs.

Purpose
To estimate annual primary care and hospital inpatient costs associated with key CVD and other adverse events using the UK Biobank (UKB) individual participant data.

Methods
UKB participants with linked primary care data (192,983 participants) or hospital inpatient episodes data (all 501,807 participants) contributed data to this study. The three categories of primary care services (patient consultations, diagnostic and monitoring tests, prescription medications), and hospital episodes were costed (2020 UK£) using the NHS England reference costs. Annual primary care costs and, separately, annual hospital inpatient costs were modelled as functions of participant characteristics at entry (socio-demographic, clinical, prior diseases) and time-updated first occurrences of myocardial infarction, stroke, coronary revascularization, incident cancer, incident diabetes, vascular death and non-vascular death during follow-up (p-value &lt;0.01 in stepwise covariate selection). One-part generalized linear regression model (GLM) with Poisson distribution and identity link function was used for primary care costs, and two-part model was used for inpatient costs (part 1: logistic regression models probability of incurring costs; part 2: GLM with Poisson distribution and identity link function models costs conditional on incurring any). Separate models were fitted among participants with and without previous CVD at entry into UKB.

Results
Most adverse events were associated with excess primary care and hospital inpatient costs. Compared to people without previous CVD, people with previous CVD had on average larger excess primary care and hospital inpatient costs in years with myocardial infarction, stroke and vascular death; but similar excess costs in years with other events. Among both people without and with previous CVD, the excess annual primary care costs were less than 7% of the excess annual hospital inpatient costs for vascular events (Table). However, following diabetes diagnosis the excess annual primary care costs were higher than the excess annual hospital inpatient costs (Table).

Conclusions
These excess primary and hospital care costs associated with CVD events could inform assessments of interventions and policies to reduce CVD risks in UK.

Funding Acknowledgement
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): UK National Institute for Health Research (NIHR) Health Technology Assessment (HTA) Programme, UK Medical Research Council (MRC), British Heart Foundation
Dutch Nationwide Implementation Program for familial hypercholesterolemia case finding in children: a cost-effectiveness and return on investment analysis
Authors: Ademi Z , Norman R , Sijbrands E , Ference B A , Watts G F , Hutten B , Wiegman A 
Published: October 2022

Abstract

Background
The Netherlands is one of the few countries in the world that actively screen for familial hypercholesterolemia (FH).

Objectives
We investigated the return on investment (ROI) and cost-effectiveness of the Dutch nationwide implementation program for FH case-finding and preventive treatment in children compared to later detection and treatment from both a societal and healthcare perspective in the Netherlands.

Methods
Cascade case finding and early preventive treatment were modelled to simulate the progression of disease and costs of ten-year-olds suspected of having heterozygous FH (HeFH) over a lifetime. The model consisted of three health states: alive without coronary heart disease (CHD), alive with CHD, and dead. The decision was to compare the nationwide implementation program for FH cascade case-finding in children and immediate treatment with statins compared to “usual care” later detection and treatment. The prevalence of HeFH in this target population was 51.2% as per the Dutch Health Program for FH case-finding, and the sensitivity and specificity of testing was 100%. Contemporary Mendelian Randomisation Analysis data was used to quantify the risk of a first coronary heart disease event as a function of age and total lifetime exposure to low-density-lipoprotein cholesterol. Costs and outcome were sourced from the Dutch data and other published sources. ROI for the Dutch nationwide implementation program for FH case-finding and cost-effectiveness analyses using incremental cost-effectiveness ratios (ICERs) (cost per quality-adjusted life years (QALYs) gained), compared with current usual care were the main outcomes of interest. All future benefits and costs were discounted annually by 1.5% and 4% respectively.

Results
Over the lifetime horizon, the ROI for the Dutch nationwide implementation program for FH case-finding was €16.52 (i.e. every euro spent on the program resulted in a return of €16.52). From the societal perspective, the Dutch nationwide implementation program for FH case-finding and early treatment with statins was the dominant strategy (health improvement and cost saving) compared to usual care. From a healthcare perspective, the Dutch nationwide implementation program for FH case-finding and early treatment with statins would gain 2.64 QALYs per person, at an additional cost of €7,178 (both discounted). These equated to an ICER of €2,668 per QALY gained.

Conclusions
From the societal perspective, the the Dutch nationwide implementation program for FH case-finding represented excellent value for investment for Netherlands, being not only health saving but also cost saving form a societal perspective and cost effective from a healthcare perspective.

Funding Acknowledgement
Type of funding sources: None.
Long-term effects of coronavirus disease 2019 on the cardiovascular system: the CV COVID-19 registry
Authors: Arevalos Rivas V , Ortega-Paz L , Fernandez-Rodriguez D , Jimenez-Diaz V A , Baneras Rius J , Campo G , Diaz J F , Scardino C , Rodriguez-Santamarta M , Gonzalo N , Perginotti A , Alfonso F , Amat-Santos I , Sabate M , Brugaletta S 
Published: October 2022

Abstract

Background
Patients with COVID-19 have an increased risk of cardiovascular adverse events during the acute phase. However, the long-term cardiovascular outcomes are unknown.

Objective
We aimed to determine the long-term effects of COVID-19 in the cardiovascular system.

Methods
This is a multicenter, observational, retrospective registry conducted at 17 centers in Spain and Italy. Consecutive patients older than 18 years who underwent a real-time reverse transcriptase-polymerase chain reaction (RT-PCR) for SARS-CoV2 in the participating institutions were included. Patients were classified into two groups, according to the results of the RT-PCR: COVID-19 positive or negative. The primary outcome was cardiovascular (CV) death at 1-year. The secondary outcomes included acute myocardial infarction, stroke, heart failure hospitalization, pulmonary embolism, and serious cardiac arrhythmias at 1-year. Outcomes were compared between the two groups. An independent clinical event committee adjudicated events.

Results
A total of 4427 patients were included, 3578 (80.8%) patients with COVID-19 and 849 (19.2%) without COVID-19. COVID-19 patients were older, had a higher rate of classical cardiovascular risk factors, except for active smoking, and had fewer comorbidities. At a median time of 13.5 (IQR 11.8–15.8) months, after an adjustment by baseline characteristics, there was no difference in CV death (1.4% vs. 1.1%; HR 1.03 [0.49–2.18]; p=0.941) between patients with COVID-19 and without. However, COVID-19 patients experienced higher rate of venous thromboembolism (VTE) (3.9% vs. 0.6%, HR 6.11 [2.46–15.16]; p=0.001), major bleeding (2.9% vs. 0.5%, HR 5.38 [1.95–14.84]; p=0.001), and serious cardiac arrhythmias (2.6% vs. 0.9%, HR 2.25 [1.07–4.73]; p=0.033). During follow-up, between discharge and end of follow-up, COVID-19 patients did not experience a higher risk of adverse cardiovascular outcomes (composite of CV death, any MI, ischemic stroke, systemic arterial thrombosis, VTE, heart failure hospitalization, or any serious arrhythmia) compared to patients without (HR 0.80; [0.53–1.21]; p=0.298).

Conclusions
At 1-year follow-up, COVID-19 was not associated with an increased risk of cardiovascular death but with a higher risk of VTE events, major bleeding, and serious cardiac arrhythmias. COVID-19 was not associated with a higher risk of adverse cardiovascular events during follow-up.

Funding Acknowledgement
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Carlos III Institute, Madrid, Spain
Causes of admission and mortality among patients admitted in 37 cardiology departments in 17 Sub-Saharan African countries: the FEBRUARY observatory (2016–2021) from African Research Network
Authors: Ali Toure I , Traore A K , Cavagna P , Damorou J M , Diao M , Dzudie A , N'Guetta R , Kouam Kouam C , Hermann Y , Limbole E , Gaye B , Toure C , Yameogo V , Jouven X , Antignac M 
Published: October 2022

Abstract

Background
Cardiovascular disease (CVD) is a major cause of death worldwide. At least two-third of CVD death occurs in low- (LIC) and middle-income (MIC) countries. An estimated 1 million deaths were attributable to CVD in sub-Saharan Africa (SSA) alone. Scarce data are available about the admission for CVD and outcome in cardiology department in SSA.

Purpose
To describe admission for CVD and outcome of hospitalization in 17 in SSA countries.

Methods
We conducted a transversal and longitudinal study in CV department of 37 hospitals from 23 cities in 17 SSA countries (10 low income: Niger, Guinea, Benin, Mali, Democratic Republic of the Congo, Tchad, Burkina Faso, Togo, Burundi, Ethiopia and 7 middle income: Cote d'Ivoire, Senegal, Cameroon, Congo, Soudan, Mauritania, Gabon). The February study was designed by a multidisciplinary collaborative team of epidemiologists, pharmacists and cardiologists from Africa and France. This ongoing observatory included all inpatients in February from each year since 2016.Data including socio-demographic and clinical characteristics, causes of admission, clinical, biological, complementary examinations, treatments, length of stay and discharge diagnosis were collected by the investigating physicians. All analyses were performed through scripts developed in the R software (4.0.3 (2020-10-10))

Results
Overall, 4360 patients were included in the February study. Men represented 56.4%. Mean of age was 56.7±16.8 years. The main cause of admission was heart failure (41.5%) followed by acute coronary syndrome (11.9%) and stroke (11%). Cause of admission varied significantly across countries (p&lt;0.01) and over the years (p&lt;0.01). Proportions of admission for heart failure varied from 20% in Ethiopia to 62% in Guinea. Mean of length of stay was 9.95±22.4 days. All causes of admission confounded, in-hospital mortality rate was 11% (N=423). Mortality rate differed significantly according to causes of admission (p&lt;0.01).Mortality rate among patients admitted for stroke, heart failure and acute coronary syndrome was respectively 18%, 12.3% and 9.5%. Overall, 31 (0.7%) were admitted for endocarditis and mortality rate among them was 20.8% (figure). Overall, mortality rate did not vary according to gender or over the years but was significantly different according to patient wealth index (p&lt;0.05), countries (p&lt;0.01) and level income countries (p&lt;0.01). Mortality rate was significantly higher in LIC.

Conclusion
Heart failure, acute coronary syndrome and stroke represent the two-third of causes of admission. Overall, mortality rate in cardiology departments in SSA reached 11%.

Funding Acknowledgement
Type of funding sources: None.
Accuracy of event rate and effect size estimation in major cardiovascular trials
Authors: Olivier C B , Struss L , Suennen N , Kaier K , Heger L A , Meerpohl J J , Mahaffey K W 
Published: October 2022

Abstract

Background
During the design of a randomized controlled trial (RCT), the estimation of the expected event rate (ER) and effect size (ES) of an intervention is an essential step to calculate the sample size, which determines the scope of the trial. Overestimation of ER and ES might lead to an underpowered trial design.

Objective
To evaluate the accuracy of the estimation of ER and ES in contemporary cardiovascular RCTs.

Methods
We searched “Medline” for cardiovascular RCTs published in the New England Journal of Medicine, The Journal of the American Medical Association, or The Lancet between 2010 and 2019. Only multicenter RCTs with a dichotomous primary endpoint and with not more than 2 study arms were included. Data were extracted from the original publication or the associated study protocol. For trials that tested superiority of an intervention, the effect size measurements hazard ratio, odds ratio, or risk ratio were summarized as the effect size ratio (ESR). To determine the accuracy of estimation, we compared the observed to the hypothesized ER and ESR, respectively. The association of the accuracy of estimation with trial characteristics was determined by linear regression.

Results
Of 875 identified publications, 374 underwent full review. After exclusion of trials with insufficiently reported data for this analysis, data from 344 trials were analyzed. 145 trials (42.2%) were industry sponsored, 122 (35.5%) were investigator-initiated with industry-co funding, and 77 (22.1%) with government or public funding. The majority (186; 54.1%) tested a drug as the intervention. 263 (76.5%) were designed to test for superiority of the intervention. The primary endpoint consisted of at least 2 components in 247 (71.8%) trials. The median estimated sample size was 2386 (interquartile range [IQR] 800, 6000).
The median observed event rate was 9.0% (IQR 4.3, 21.4%) and was significantly lower compared with the estimated ER (11.0% [IQR 6.0, 25.0%]; median deviation from estimation −6.9% [95% confidence interval, CI −10.0, −3.7%]; p&lt;0.001). 196 trials (61%) overestimated the event rate (Figure 1A). The overestimation was consistent across several subgroups (Figure 2A). The median observed ESR was 0.910 (IQR 0.740, 0.990) and was significantly higher compared with the estimated ESR (0.724 [IQR 0.600, 0.795]; median deviation from estimated effect size 26.0% [95% CI, 19.0, 33.0%]). 216 (82.1%) trials overestimated the effect size (Figure 1B). This overestimation was consistent across all analyzed subgroups (Figure 2B) and was less pronounced in trials with use of a composite primary outcome.

Conclusion
6 of 10 contemporary cardiovascular RCTs overestimated the event rate for the primary endpoint and 8 of 10 trials overestimated the effect sizes of an intervention. Overestimation may lead to inability to answer the trial hypothesis.

Funding Acknowledgement
Type of funding sources: None.