bluuebunny/crossref_metadata_2025_split huggingface dataset:
High long-term persistence to evolocumab treatment regimens in European clinical practice: analysis of the HEYMANS registry
Authors: Ray K K , Perrone-Filardi P , Ebenbichler C , Vogt A , Bridges I , Sibartie M , Dhalwani N N 
Published: October 2022

Abstract

Background
Lipid-lowering treatments (LLTs) require both adherence and persistence to the treatment regimen long-term to maximise treatment benefits. Small molecules require self-medication daily but therapies such as evolocumab are labelled for self-medication every 2 weeks or monthly. Limited data exist concerning the long-term persistence to evolocumab in routine clinical practice.

Purpose
Using data from the HEYMANS registry, the objective of this analysis was to evaluate persistence and discontinuation of evolocumab in Europe.

Methods
HEYMANS was a prospective registry including adults initiating evolocumab treatment in routine clinical practice in 12 European countries between August 2015 and June 2020. Originally designed to have up to 12 months of follow-up, the protocol was amended (February 2018) to extend follow-up for up to 30 months. Patients yet to complete 12 months follow-up at this date, were followed up for up to 30 months. Therefore, we analysed evolocumab discontinuation separately for the two time periods: 0–12 months (all), 12–30 months (subset).

Results
Of the 1951 total patients, 30 patients discontinued participation in the study before 12 months (evolocumab use still ongoing at study discontinuation). Therefore, evolocumab use status was determined for 1921 patients at 12 months. Of these, 1781 (92.7%), remained on evolocumab at 12 months of follow-up (Figure). At 12 months, LDL-C levels were reduced from baseline by a median of 58% (Q1, Q3: 41%, 69%). In total, 1136 patients were eligible for extended follow up after protocol amendment. Of these, 137 patients discontinued study participation before 30 months of follow-up (with evolocumab ongoing). Therefore, evolocumab use status was determined in 999 patients, of whom, 92.2% (921) remained on evolocumab treatment at 30 months of follow-up (Figure). The reductions in LDL-C levels seen at 12 months were sustained throughout the study, with patients continuing to achieve median LDL-C reductions of 58% (Q1, Q3: 42%, 70%) from baseline at 30 months of follow-up.

Conclusions
In this real-world study, representative of European practice, of patients who entered the extension phase, the proportion of patients who remained on evolocumab up to 30 months exceeded 90%, and treatment was associated with sustained LDL-C reductions. These data suggest that the self-administration regimen of evolocumab is both feasible and acceptable in general populations, providing long-term sustained, reductions in LDL-C with likely associated health benefits.

Funding Acknowledgement
Type of funding sources: Private company. Main funding source(s): Amgen (Europe) GmbH
Evolocumab treatment is associated with early and sustained reductions in low-density cholesterol (LDL-C) over 30 months: final results from the pan-European observational HEYMANS registry
Authors: Ray K K , Perrone-Filardi P , Ebenbichler C , Vogt A , Bridges I , Sibartie M , Dhalwani N N 
Published: October 2022

Abstract

Background
Variability in LDL-C control at a population level associates with worse CV outcomes. This could in part be related to variations in patient adherence to self-administration regimens or variability in the response to a given therapy. Potent therapies such as PCSK9 inhibitors (PCSK9i) reduce cardiovascular events but some have questioned whether these therapies, which require dosing every 2 weeks, can offer sustained population level control of LDL-C.

Purpose
Using data from the HEYMANS registry, the objective of these analyses was to evaluate, at a population level, various metrics of variability in LDL-C reduction over time with evolocumab treatment.

Methods
HEYMANS was a prospective registry including adults initiating evolocumab treatment in clinical practice in 12 European countries between August 2015 to June 2020. Patient data were collected for ≤6 months before evolocumab initiation (baseline) and ≤30 months post initiation. LDL-C measurements were collected per clinical practice. At each 3-month time point in the study, we analysed median (and 95% CI) reductions in LDL-C, and the proportion of patients achieving ≥30% and ≥50% reductions in LDL-C from baseline.

Results
Data from 1951 patients were included in this final analysis (62% male, mean age 60 years, median baseline LDL-C 3.98 [Q1–Q3 3.17–5.07]) mmol/L). Most patients (85%) were receiving evolocumab for secondary prevention, with 40% not on oral LLT of whom the majority reported a history of statin intolerance. There was a median of 4 (Q1, Q3: 2, 6) LDL-C measurements per patient during follow-up. Within 3 months of initiating evolocumab treatment, LDL-C levels had reduced by a median of 58% and this reduction was maintained over 30 months (Figure 1). Among patients with an LDL-C value, ∼85% achieved a ≥30% reduction at each follow-up throughout the study, and ∼63% achieved a ≥50% reduction at each visit (Figure 2).

Conclusions
In European clinical practice, evolocumab treatment was associated with early and sustained reductions in LDL-C of over 30 months, with limited variability in LDL-C reductions at a population level. Within 3 months of treatment, evolocumab was associated with ∼58% reduction in LDL-C levels that was maintained throughout the study. These data should reassure the clinical community that meaningful, consistent additional reductions in LDL-C can be achieved with use of evolocumab. As greater use of combination therapies is required to achieve lower LDL-C goals, expanding the use of PCSK9i could provide improvements in population level control of LDL-C in European clinical practice.

Funding Acknowledgement
Type of funding sources: Private company. Main funding source(s): Amgen (Europe) GmbH
Impact of high-intensity statin therapy on glycemic control post-acute coronary syndrome using real-world data
Authors: Rahhal A , Mahfouz A , Khir F , Abdelghani M , Alkhalaila O , Aljundi A , Ashour A , Alahmad Y , Alyafei S , Arabi A 
Published: October 2022

Abstract

Background
Statins use has been linked with increased risk of new onset diabetes and impaired glycemic control in the JUPITER trial and meta-analyses of randomized controlled trials. Nevertheless, the evidence is scarce in the real-world clinical settings, particularly among those receiving high-intensity statin post-acute coronary syndrome (ACS).

Methods
We conducted a retrospective observational study to determine the impact of statin use post-ACS on glycosylated hemoglobin (HbA1c) and the incidence of diabetes. The study included adults admitted with ACS between January 1, 2017 and December 31, 2018 and newly started on a high-intensity statin (rosuvastatin or atorvastatin). The outcomes assessed within 12 months of statin initiation were: (a) HbA1c before and after statin use among diabetic and non-diabetic patients; (b) incidence of diabetes. Paired sample t-test was used to compare HbA1c values pre and post statin use.

Results
Of the 1,253 patients included, 627 received rosuvastatin and 626 received atorvastatin following ACS. Most of the patients were Asian (77.3%), male (95.8%) with a median age of 51 years. The baseline HbA1c was 7.2±2.2% and 45% of the study population were diabetic at baseline. Among non-diabetic patients, statin use resulted in HbA1c increase from 5.7±0.7% to 6.0±0.8%, p&lt;0.001, while among diabetic patients who were receiving treatment for diabetes, HbA1c decreased from 8.8±1.9% to 7.8±1.9%, p&lt;0.001. New onset diabetes occurred in 41 (6%) of the non-diabetic patients, of whom 13 (1.9%) were receiving atorvastatin, while 28 (4.1%) were on rosuvastatin, p-value = 0.032. The use of both statins resulted in a significant increase of HbA1c among non-diabetic patients as demonstrated in Figure 1.

Conclusion
High intensity statin post-ACS was associated with increased HbA1c among non-diabetic patients. In particular, rosuvastatin significantly increased the new onset of diabetes compared to atorvastatin which might provide preference of atorvastatin use over rosuvastatin among non-diabetic patients post-acute coronary syndrome.

Funding Acknowledgement
Type of funding sources: None.
Unmasking early diastolic dysfunction in type 2 diabetes using the peak early-to-late diastolic strain rate ratio by cardiac MRI feature tracking
Authors: Yeo J L , Gulsin G S , Dattani A , Ayton S L , Bilak J M , Parke K S , Brady E M , McCann G P 
Published: October 2022

Abstract

Introduction
Type 2 diabetes (T2D) is associated with early alterations in left ventricular (LV) diastolic function, which precedes the development of heart failure. These may be quantified by cardiac MRI feature tracking, which permits a direct assessment of myocardial relaxation through calculation of diastolic strain rates. Previous studies have not fully exploited this technique by integrating early and late LV diastolic relaxation in asymptomatic adults with T2D.

Purpose
To explore whether the peak early-to-late diastolic strain rate ratio (PEDSR:PLDSR), derived from cardiac MRI feature tracking, could: 1) identify diastolic dysfunction in an asymptomatic cohort of adults with T2D, 2) compare this technique with conventional echocardiographic measures of diastolic function.

Methods
Prospective cross-sectional study. People with T2D (n=253, mean age 63±7 years, 62% male, diabetes duration 11±8 years) without signs, symptoms or history of cardiovascular disease and non-diabetic controls (n=40, mean age 61±8 years, 63% male) underwent comprehensive phenotyping including echocardiography and cardiac MRI. The LV PEDSR:PLDSR was derived from cardiac MRI balanced steady-state free precession cine images using feature tracking. Correlations between circumferential PEDSR:PLDSR and echocardiography-derived E:A and E/e' were explored.

Results
Compared to controls, people with T2D had evidence of concentric LV remodelling, diastolic dysfunction, and diffuse myocardial fibrosis as demonstrated by increased LV mass/volume, E/e' ratio, and extracellular volume fraction, respectively (Table 1). People with T2D had lower PEDSR (0.87±0.23 vs 0.95±0.24 s–1, p=0.043), higher PLDSR (0.80±0.22 vs 0.67±0.16 s–1, p&lt;0.001), and lower PEDSR:PLDSR ratio (1.18±0.46 vs 1.53±0.61, p&lt;0.001). PEDSR:PLDSR was moderately correlated with E:A (r=0.495, p&lt;0.001) (Figure 1) but not E/e' (r=0.087, p=0.182).

Conclusions
Compared to people without diabetes, lower PEDSR:PLDSR in asymptomatic subjects with T2D highlights impaired myocardial relaxation in early diastole and greater dependence on atrial contraction for LV filling in this group. This novel MRI measure may be promising tool to assess global diastolic function in people undergoing cardiac MRI and especially useful in those with poor echocardiographic windows. The functional and prognostic significance of PEDSR:PLDSR warrants further assessment in longitudinal studies.

Funding Acknowledgement
Type of funding sources: Public Institution(s). Main funding source(s): National Institute for Health Research (NIHR) United Kingdom through a Research Professorship award (RP-2017-08-ST2-007).British Heart Foundation through a Clinical Research Training Fellowship (FS/16/47/32190).
Statin use and cardiovascular outcomes after myocardial infarction: a population-based case-control study
Authors: Kyto V , Saraste A , Tornio A 
Published: October 2022

Abstract

Background
Statin therapy is a cornerstone of secondary prevention after myocardial infarction (MI). However, many patients do not use statins.

Purpose
To study the impact of not using statin early after MI on adverse outcomes.

Methods
Consecutive MI patients admitted to 20 Finnish hospitals (n=64,401; median age 71) were retrospectively studied. Statin was not used by 17.1% within 90 days after MI discharge (exposure). Differences in baseline features, comorbidities, revascularization, and other evidence-based medications were balanced with propensity score matching, resulting in 10,051 pairs of patients with and without statin. Median follow-up was 5.9 years.

Results
High-risk patients used statins less frequently. Patients not using statin early after MI had higher all-cause mortality in 1-year (15.8% vs. 11.9%; HR 1.38; CI 1.30–1.46; p&lt;0.0001) and 10-year follow-up (71.1% vs. 65.2%; HR 1.34; CI 1.30–1.39; p&lt;0.0001). The number needed to harm by not using statin was 24.1 at 1-year and 9.5 at 10-years. The cumulative incidence of major adverse cardiovascular event was higher at 1- and 10-years in patients not using statins (sHR 1.15; p&lt;0.0001 for both). Cardiovascular death, new MI, and ischemic stroke were more frequent without early statin. A lack of statin was associated with outcomes regardless of sex, age, atrial fibrillation, dementia, diabetes, heart failure, revascularization, or usage of other evidence-based secondary preventive medications in subgroup analyses.

Conclusions
Lack of statin therapy after MI is associated with adverse outcomes across the spectrum of MI patients. Measures to improve timely statin use after MI are still needed.

Funding Acknowledgement
Type of funding sources: Foundation. Main funding source(s): Finnish Foundation for Cardiovascular Research, Paavo Nurmi Foundation
Use of statins in cancer patients following acute myocardial infarction and its impact on long-term clinical outcomes
Authors: Stepien K , Nowak K , Kachnic N , Horosin G , Walczak P , Nessler J , Zalewski J 
Published: October 2022

Abstract

Background
Statin use and its impact on long-term clinical outcomes in cancer patients following acute myocardial infarction (MI) remains insufficiently elucidated.

Purpose
We sought to analyze the prevalence of statins use in MI patients with cancer hospitalized in a tertiary cardio-oncology center and its influence on long-term mortality.

Methods
Of the 1,011 consecutive acute MI patients hospitalized between 2012 and 2017, cancer was found in 134 (13.3%) subjects including newly diagnosed cancer in 24 of them. All patients underwent coronary angiography. Within a median follow-up of 69.2 (37.8–79.9) months, a mortality rate, and its determinants were analyzed.

Results
Compared with non-cancer population, MI patients with cancer were older (73 [66–79] versus 68 [60–78] years, P&lt;0.001), had lower hemoglobin level (12.8 [11.2–14.0] vs 13.8 [12.8–15.0], P&lt;0.001), lower total cholesterol (4.1 [3.4–4.8] vs 4.4 [3.6–5.3], P=0.006) and lower HDL cholesterol (1.1 [0.9–1.4] vs 1.2 [1.0–1.6], P&lt;0.001), without significant differences in LDL cholesterol (2.5 [1.9–3.1] vs 2.6 [1.7–3.4], P=0.70). Statins were prescribed less frequently in MI patients with cancer as compared with non-cancer MI population (80.5% versus 92.1%, P&lt;0.001). Atorvastatin was the most frequent statin in both cancer and non-cancer groups (68.4% versus 75.1%, P=0.13). In cancer group simvastatin was more frequently (16.7% versus 5.9%, P&lt;0.001) while rosuvastatin was less frequently (8.8% versus 18.9%, P=0.007) prescribed than in non-cancer patients. The independent determinants of no use of statins were anemia (hazard ratio [HR] 2.3, 95% confidence interval [95% CI] 1.3–4.2, P=0.006), no coronary artery stenosis &gt;50% (HR 5.0, 95% CI 2.5–10.1, P&lt;0.001) and cancer (HR 1.9, 95% CI 1.01–3.7, P=0.049) but not LDL cholesterol. The mortality rates were significantly higher in MI patients not treated with statins, both in non-cancer population (29.5%/year versus 6.7%/year, P&lt;0.001) as well as in cancer group (53.9%/year versus 24.9%/year, P&lt;0.05) as compared to those treated with statins (Figure 1). No statin use (HR 2.3, 95% CI 1.8–3.0, P&lt;0.001), an active cancer (HR 2.3, 95% CI 1.8–3.0, P&lt;0.001), patient's age (HR 2.3, 95% CI 1.8–2.9, P&lt;0.001, per year) and anemia (HR 1.7, 95% CI 1.4–2.1, P&lt;0.001) independently increased long-term mortality while no coronary artery stenosis &gt;50% (HR 0.65, 95% CI 0.44–0.96, P=0.03) and better left ventricular ejection fraction (HR 0.97, 95% CI 0.96–0.98, P&lt;0.001, per 1%) improved long-term survival.

Conclusions
An active cancer, anemia and lack of significant coronary lesions were associated with no use of statins in patients following MI. By multivariable approach both no statins use in MI patients independently on an active malignancy were associated with unfavorable long-term outcomes.

Funding Acknowledgement
Type of funding sources: None.
The association between long-term statin use and cataract in both primary and secondary prevention of cardiovascular disease – a nationwide, cohort study on 597,605 cataract patients
Authors: Halili A , Bang C N B , Torp-Pedersen C T P 
Published: October 2022

Abstract

Background
The purpose of the present study was to determine the association between statin treatment duration and cataract in the entire Danish population.

Methods
We performed a population-based, nested case-control study with data over 25 years using national registries to identify cataract patients, who were matched with a control by age and gender. For each participant, we computed and categorized the statin treatment duration in never users, 1, 5, and 10 years by summation of all redeemed prescriptions. We performed conditional logistic regression analyses in subgroups of the participants according to history of either ischemic heart disease, diabetes, hypertension, or neither of these conditions.

Results
A total of 597.605 cataract patients were identified and each matched with a control, making an entire cohort of 1.195.210 participants. We identified 271.838 participants with ischemic heart disease, 79.703 participants had diabetes, 216.442 participants had hypertension, and 627.227 participants had neither of these conditions. The subgroups were each adjusted for co-morbidities, low-density lipoprotein cholesterol serum levels, and concomitant pharmacotherapy. We found no increased hazard of cataract with statin treatment duration at 1, 5, or 10 years compared to never using statins in either of the subgroups with ischemic heart disease, diabetes, or hypertension. There was, however, a statistically significant increased hazard of cataract in the subgroup without any known conditions at 1 year of statin use (1.14, 95%-CI [1.06:1.22]), 5 years (1.06, 95%-CI [1.00:1.12]), and 10 years (1.08, 95%-CI [1.01:1.15]). The median low-density lipoprotein level for the ischemic heart disease subgroup was 2.45 mmol/L, 2.20 mmol/L for the diabetes subgroup, 2.80 mmol/L for the hypertension subgroup, and 3.0 mmol/L for the subgroup without conditions.

Conclusions
We did not find an association between statin use and cataract in patients with ischemic heart disease, diabetes, or hypertension, however, in patients without any of these conditions we found a moderate association with cataract.

Funding Acknowledgement
Type of funding sources: None.
Absolute treatment effects for the primary outcome and all-cause mortality in the cardiovascular outcome trials in type 2 diabetes: a meta-analysis of individual patient data
Authors: Kuss O , Akbulut C , Schlesinger S , Georgiev A , Kelm M , Roden M , Wolff G 
Published: October 2022

Abstract

Background and purpose
Treatment effects from the large cardiovascular outcome trials (CVOTs) in diabetes are almost exclusively communicated as hazard ratios, although reporting guidelines recommend to report treatment effects also on an absolute scale, e.g. as numbers needed to treat (NNT). We aimed to analyze NNT in CVOTs of novel oral antidiabetic drugs comparing dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, or sodium-glucose cotransporter-2 (SGLT2) inhibitors to placebo.

Methods and results
We extracted individual time-to-event information for the primary outcome and all-cause mortality from 19 CVOTs that compared DPP-4 inhibitors, GLP-1 receptor agonists, or SGLT2 inhibitors to placebo. We estimated Weibull models for each trial and outcome and derived monthly NNTs. NNTs were summarized across all trials and within drug-classes by random effects meta-analysis methods. Treatment effects in the CVOTs appear smaller if they are reported as NNTs: Overall, 60 (95%-CI: 40–124) patients have to be treated for 29 months (the median follow-up time across all trials) to avoid a single event of the primary outcome, and 101 (95%-CI: 69–191) patients have to be treated for 39 months to avoid a single death.

Conclusion
We found that the respective treatment effects of novel oral antidiabetic drugs look less impressive when communicated on an absolute scale, as numbers needed to treat. For a valid overall picture of the benefit of these drugs, trial authors should thus also report treatment effects on an absolute scale.

Funding Acknowledgement
Type of funding sources: None.
Absolute treatment effects of novel oral antidiabetic drugs on cardiovascular mortality and hospitalization for heart failure: a meta-analysis of digitalized individual patient outcomes
Authors: Wolff G , Lin Y , Akbulut C , Brockmeyer M , Parco C , Hoss A , Sokolowski A , Westenfeld R , Kelm M , Roden M , Schlesinger S , Kuss O 
Published: October 2022

Abstract

Background and purpose
Absolute treatment effects of novel oral antidiabetic drugs for cardiovascular outcomes have thus far not been comprehensively evaluated. We thus aimed to perform a meta-analysis of digitalized individual patient data.

Methods and results
Individual patient outcomes from Cardiovascular Outcome Trials (CVOTs) evaluating dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists and sodium glucose transporter 2 (SGLT2) inhibitors against placebo with time-to-event information for cardiovascular mortality (CM) and/or hospitalization for heart failure (HHF) endpoints were digitalized from Kaplan-Meier plots; Weibull regression models with random-effects meta-analysis were used to estimate numbers-needed-to-treat (NNT) and Meta-NNT with 95% confidence intervals (CI). Sixteen CVOTs reported time-to-event information (14 in primary diabetes, two in primary heart failure populations). Thirteen studies including 96,860 patients were meta-analyzed for CM: at the median follow-up of 30 months, Meta-NNTs were 178 (64 to ∞ to −223) for DPP-4 inhibitors, 261 (158 to 745) for GLP-1 receptor agonists and 118 (68 to 435) for SGLT2 inhibitors. Ten studies including 96,128 patients were meta-analyzed for HHF: at the median follow-up of 29 months, estimated Meta-NNTs were −644 (229 to ∞ to −134) for DPP-4 inhibitors, 441 (184 to ∞ to −1100) for GLP-1 receptor agonists and 126 (91 to 208) for SGLT2 inhibitors. SGLT2 inhibitors were especially effective for HHF in primary heart failure populations (Meta-NNT 25 (19 to 39)) vs. primary diabetes populations (Meta-NNT 233 (167 to 385)) at 16 months of follow-up.

Conclusion
We found modest treatment benefits of GLP-1 receptor agonists and SGLT2 inhibitors for CM and HHF in primary T2DM populations. In primary heart failure populations, however, SGLT2 inhibitor benefits were substantial and comparable to established heart failure medication.

Funding Acknowledgement
Type of funding sources: None.