bluuebunny/crossref_metadata_2025 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

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

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

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<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<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

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<0.001), and lower PEDSR:PLDSR ratio (1.18±0.46 vs 1.53±0.61, p<0.001). PEDSR:PLDSR was moderately correlated with E:A (r=0.495, p<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

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<0.0001) and 10-year follow-up (71.1% vs. 65.2%; HR 1.34; CI 1.30–1.39; p<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<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

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<0.001), had lower hemoglobin level (12.8 [11.2–14.0] vs 13.8 [12.8–15.0], P<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<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<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<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 >50% (HR 5.0, 95% CI 2.5–10.1, P<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<0.001) as well as in cancer group (53.9%/year versus 24.9%/year, P<0.05) as compared to those treated with statins (Figure 1). No statin use (HR 2.3, 95% CI 1.8–3.0, P<0.001), an active cancer (HR 2.3, 95% CI 1.8–3.0, P<0.001), patient's age (HR 2.3, 95% CI 1.8–2.9, P<0.001, per year) and anemia (HR 1.7, 95% CI 1.4–2.1, P<0.001) independently increased long-term mortality while no coronary artery stenosis >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<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

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

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

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.
The gender gap in prescription pattern of sodium-glucose cotransporter 2 inhibitors in patients with type 2 diabetes
Authors: Hammer A , Hofer F , Kazem N , Koller L , Steinacher E , Niessner A , Sulzgruber P
Published: October 2022

Background

The major benefit of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in type 2 diabetes mellitus (T2DM) on cardiovascular outcome has been undoubtably proven in several landmark trials and different populations. In consideration of emerging evidence that there are clinically relevant gender-related differences in the course of T2DM and subsequent cardiovascular outcomes, it is unknown if SGLT2i therapy is gender independent utilized in clinical practice. In this regard, real-world data are needed to determine whether there is a gender gap in SGLT2i prescription and if this influences long-term outcome.

Methods

Patients with T2DM admitted to a tertiary academic center between 01/2014 and 04/2020 were identified through a search of electronic health records. Data on antidiabetic therapy was acquired at discharge, and were screened for SGLT2i prescription. Subsequently, the entire cohort was prospectively followed.

Results

In total, 812 patients (median age 70 years, 29.7% female) were included in the present analysis. Only 17.3% of the study population received an SGLT2i. In direct comparison between sexes, females show lower rates of SGLT2i prescription (11,2% vs. 19,8%, p=0.003), despite comparable patient characteristics. Furthermore, males show a significantly higher probability of SGLT2i prescription, illustrated as an adjusted odds ratio of 2.59 (CI 95% 1.29–5.19; p=0.008). During a median follow-up time of 2.3 years, a total of 142 patients died due to cardiovascular causes – corresponding to 103 (18.0%) male and 39 (16.2%) female participants. Females who did not receive a SGLT2i showed higher rates of chronic kidney disease (CKD, 25.2% vs. 7.4%, p=0.039) and greater levels of proBNP (2092 pg/ml (IQR: 738–5279) vs. 825 pg/ml (IQR: 298–2479), p=0.011) as compared to non-SGLT2i females.

Conclusion

Despite clear evidence on the beneficial effect of SGLT2i, the present data suggest a gender-gap in SGLT2i prescription and thus missed potential in female patients. The most common reason for not prescribing a SGLT2i in females was the presence of CKD. However, SGLT2i (i.e. Empagliflozin) are approved to use in individuals with a glomerular filtration rate (GFR) as low as ≥20ml/min, and therefore more awareness has to be raised, that SGLT2i are feasible to prescribe in such vulnerable patients with present cardiovascular comorbidities, to achieve a benefit as shown in several landmark trials. Additionally, more attention is needed to address this gender-gap and ensure that both sexes receive equal attention, in terms of state of the art T2DM therapy to reduce mortality and morbidity.

Funding Acknowledgement

Type of funding sources: None.
Adherence and discontinuation of sglt2-inhibitors and glp1-r agonists in patients with type 2 diabetes with and without cardiovascular disease
Authors: Malik M , Falkentoft A , Jensen J , Andersson C , Parveen S L , Koeber L , Schou M E M
Published: October 2022

Background

Sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucacon-like-peptide-1 receptor (GLP-1R) agonists are two novel therapies in type 2 diabetes (T2D) that are recommended in patients with manifestations of cardiovascular disease or high risk of cardiovascular disease due to their cardioprotective benefits. Despite the increasing use of these drugs, there is still limited knowledge on the adherence patterns and the risk of discontinuation, according to the presence or absence of different cardiovascular conditions.

Purpose

To investigate the adherence and estimate the risk of discontinuation of SGLT2 inhibitors and GLP1-R agonists in patients with T2D with and without cardiovascular disease.

Methods

From Danish nationwide registers, we included all individuals >40 years with T2D who redeemed the first prescription of a SGLT2 inhibitor or GLP1-R agonist, between December, 2012 and December, 2018. Patients were divided into subgroups according to the presence or absence of different cardiovascular conditions (heart failure, ischemic heart disease, peripheral artery disease, atrial fibrillation), at the time of inclusion. Adherence over the course of one year after initiation of treatment was estimated by the proportion of days covered (PDC) for each subgroup, and adherence was defined as PDC 80%. The risk of discontinuation was estimated using multivariable cause-specific Cox regression models, and was defined as a break in treatment of 90 days. The Aalen-Johansen estimator was used to account for censoring and competing risks. Patients were followed until date of emigration, death or study end (December 31, 2019).

Results

We included 24,061 patients with T2D who initiated treatment with a SGLT2 inhibitor, and 13,899 patients with T2D who initiated treatment with a GLP1-R agonist, for the first time between December 10, 2012 and December 31, 2018. Median age at inclusion was 62 years (IQR 54–70) and 40% were female. In the analyses, 67% of the patients treated with SGLT2 inhibitors were adherent to therapy throughout the first year, whereas the same proportion of patients, 67%, were adherent to therapy with GLP-1R agonists. Mean PDC was 77% (SD 33) and 79% (31) for patients in therapy with SGLT2 inhibitors and GLP1-R agonists, respectively. No significant difference was observed related to the presence or absence of cardiovascular disease (SGLT2 inhibitor: mean PDC 77 (33) vs. 77 (33), GLP1-R agonist: 78 (32) vs. 79 (31)).

Conclusions

In this nationwide cohort study, we found that patients with T2D who initiated therapy with a SGLT2 inhibitor and those who initiated therapy with a GLP1-R agonist were almost equally adherent to therapy throughout the first year. Adherence in both treatment groups did not differ according to the presence or absence of cardiovascular disease.

Funding Acknowledgement

Type of funding sources: None.
Frailty and outcomes in octogenarians with atrial fibrillation treated with edoxaban: ESCAPE study
Authors: Denas G , Zoppellaro G , Granziera S , Pagliani L , Iliceto S , Pengo V
Published: October 2022

Background

Frailty is associated with significant morbidity and mortality among elderly adults. Whether frailty predicts adverse outcomes in patients treated with oral anticoagulants for stroke prevention in atrial fibrillation remains uncertain.

Purpose

To examine the impact of frailty in clinical outcomes in elderly patients with non-valvular atrial fibrillation treated with edoxaban.

Methods

This is an observational prospective single centre cohort study enrolling consecutive naïve to anticoagulation patients of age ≥80 years starting oral anticoagulation with edoxaban for stroke prevention in non-valvular atrial fibrillation and followed up for 2 years. At baseline, all patients were evaluated for frailty, comorbidities, medications, and stroke and bleeding risk factors. Frailty was assessed using the Survey of Health Ageing and Retirement in Europe Frailty Index (SHARE-FI) tool, a validated frailty measure centred on health resource utilisation, with the cohort stratified into non-frail, pre-frail and frail. The clinical outcomes were the cumulative incidence of stroke/systemic embolism, major bleeding, and clinically relevant non-major bleeding (CRNMB), and individual components part of the composite outcome.

Results

Among 160 patients who received edoxaban for stroke prevention in atrial fibrillation, 34% were frail, 20% pre-frail, 46% non-frail. The mean age of the cohort was 85±4 years and 58% were female. The mean CHA2DS2VASc score was 4±1. Mean Cockroft-Gault creatinine clearance (CrCl) was 52±17 mL/min, and edoxaban 30mg was administered to 59% of patients as per indications (weight ≤60 kg and/or, CrCl 15–50 ml/min). The follow up extended for 681±289 days. Primary endpoint occurred in 46 patients (28.7%; annualised rate 15.4%patient-years): 19 events occurred in non-frail, 9 in pre-frail, and 18 in frail patients (p=0.6). Stroke/systemic embolism occurred in 2.2%, major bleeding in 5.0%, and CRNM bleeding in 10.0% of patients. Frailty was not a predictor of the events part of the composite outcome (non-frail 5.4% vs pre-frail 0% vs frail 1.9%, p=0.27; non-frail 5.4% vs pre-frail 9.4% vs frail 1.9%, p=0.29; and non-frail 13.5% vs pre-frail 3.1% vs frail 9.3%, p=0.25; for stroke/systemic embolism, major bleeding, and CRNMB, respectively). Cumulative rate of events (Figure) did not differ in frail versus the rest (non-frail and pre-frail) of patients (p=0.521).

Conclusions

Frailty status was not a predictor of events among the elderly with atrial fibrillation treated with edoxaban. Anticoagulation with edoxaban is feasible in octogenarians even if frail.

Funding Acknowledgement

Type of funding sources: None.
Prognostic utility of left ventricular global longitudinal strain in patients with systemic amyloidosis
Authors: Bhatia K , Aggarwal D , Ochoa-Jimenez R , Lopez P , Konje S , Argulian E
Published: October 2022

Background

Myocardial deposition of amyloid proteins results in restrictive cardiomyopathy. Left ventricular global longitudinal strain (GLS) has emerged as a sensitive measure for detecting subclinical cardiac dysfunction over traditional echocardiographic parameters. However, multiple studies have provided differing conclusions regarding prognostic utility of impaired GLS in patients with systemic amyloidosis.

Purpose

We conducted a systematic review and meta-analysis to evaluate whether impaired GLS was associated with increased mortality or major adverse cardiovascular events (MACE) in patients with systemic amyloidosis.

Methods

We performed a literature search of Embase, Medline and Web of Science databases to identify studies that reported the association of GLS with clinical outcomes in patients with systemic amyloidosis (light chain or TTR amyloidosis). Outcomes of interest included all-cause mortality and MACE, defined as a composite of death or heart transplant or heart failure hospitalization. Unadjusted and adjusted hazard ratio (uHR and aHR respectively) were pooled using a random effects model. Heterogeneity among the studies was assessed using the Higgins I2 value.

Results

Out of 2139 initial citations, 28 observational studies with a total of 2713 patients were included in the analysis. The mean age ranged between 58–78 years and 62% of the patients were male. Most patients had cardiac amyloidosis (83%) and light-chain amyloidosis accounted for 69% of cases. Mean follow-up ranged between 1 and 5 years. GLS was significantly higher (less negative) (mean difference (MD) −3.69 [−5.94, −1.44], I2=87, p<0.01) in non-survivors compared with survivors. Similarly, patients who experienced MACE had a significantly higher mean GLS (MD −3.22, [−5.21, −1.22,], I2=82, p<0.01]. The risk of both mortality and MACE increased significantly for every −1% increase in GLS. In unadjusted models, a GLS above the defined threshold value was associated with a significantly higher risk of mortality (uHR: 1.66 [1.22, 5.21], I2=85.2, p<0.01) and MACE (uHR: 2.24 [1.28, 3.92], I2=39, p<0.01). In multivariable models an increase in GLS by −1% was an independent predictor of mortality (aHR: 1.09 [1.01,1.16], I2=53, p=0.02) and MACE (aHR: 1.24 [1.14,1.36], I2=0, p<0.01).

Conclusion

In patient with amyloidosis, the baseline left ventricular GLS may help identify patients with a higher risk of mortality and MACE.

Funding Acknowledgement

Type of funding sources: None.
The use of warfarin as part of antithrombotic strategy after transcutaneous aortic valve replacement is not associated with better medium-term outcomes
Authors: Naser J , Gochanour B R , Scott C G , Luis S A , Greason K L , Crestanello J A , Gulati R , Eleid M F , Nkomo V T , Pislaru S V
Published: October 2022

Background

Bioprosthetic valve thrombosis is currently a well-recognized cause of bioprosthetic valve dysfunction. It was found to be associated with accelerated degeneration of the bioprosthesis with higher rates of valve re-replacement, even after treatment with anticoagulation. We hypothesized that the use of warfarin for three months after transcatheter aortic valve replacement (TAVR) protects against accelerated valve degeneration and is therefore associated with better outcomes compared to dual antiplatelet therapy (DAPT).

Methods

Consecutive adult patients who underwent TAVR in our clinic between 2012 and 2019 were identified retrospectively. Patients with atrial fibrillation were excluded. Subsequently, patients who received DAPT were propensity matched to up to 2 patients who received three months of warfarin as part of their anti-thrombotic regimen. Matching was performed for variables that were significantly different at baseline between the two groups and included diabetes mellitus, prior myocardial infarctions, chronic lung disease, peripheral arterial disease, hemoglobin at time of TAVR, kidney function [creatinine>2], use of angiotensin-converting enzyme inhibitors / angiotensin II receptor blockers, beta blockers, the Society of Thoracic Surgeons (STS) score [STS ≥8, STS 4–8, STS<4], and valve size. The two groups were then compared for outcomes of ischemic stroke, death, valve re-replacement/intervention, the composite endpoint of the aforementioned three outcomes, as well as the three-month outcome of hemorrhagic strokes. Kaplan Meier was used for outcome analysis, and discharge date was considered time zero. Patients who had their anti-thrombotic therapy interrupted were censored at that time point.

Results

A total of 1,373 patients who underwent TAVR were identified. Of these, 576 patients with atrial fibrillation were excluded. Baseline characteristics were compared between 633 patients who received three months of warfarin and 164 patients who received DAPT after TAVR. After matching the two groups, 435 patients were included in the final analysis [warfarin in 281, DAPT in 154; median time to last follow up 2.61 years], Table 1. There was no difference in matched (Figure 1) or unmatched analysis (not shown) in outcomes of ischemic stroke, death, valve re-replacement/intervention, their composite endpoint, or hemorrhagic strokes (p>0.05 for all).

Conclusion

Antithrombotic regimen including three months of warfarin after TAVR was not associated with better outcomes of ischemic strokes, deaths, and valve re-replacement/intervention or with increased risk of hemorrhagic strokes compared to DAPT.

Funding Acknowledgement

Type of funding sources: None.
Previous antithrombotic therapy does not have an impact on the in-hospital mortality of patients with upper gastrointestinal bleeding
Authors: Hozman M , Hassouna S , Grochol L , Waldauf P , Hracek T , Zborilova Pazdiorova B , Adamec S , Osmancik P
Published: October 2022

Background

The association between antithrombotic therapy due to concomitant cardiovascular disorders and the risk of gastrointestinal bleeding is well known; however, data regarding the influence of antithrombotics on outcomes and further management after a bleeding episode are scarce.

Purpose

This study was conducted to assess the impact of concomitant antithrombotic therapy and other variables on in-hospital and 6-month outcomes and to determine the re-initiation rate of the antithrombotic treatment after a bleeding event.

Methods

We retrospectively analysed all patients with upper gastrointestinal bleeding (UGB) who underwent urgent gastroscopy in 3 centres from 1 January 2019 to 31 December 2019. Demographic and medical data were collected from the electronic hospital database system.

Results

Among 333 patients (60% males, mean age 69±16 years), 44% were receiving antithrombotics. The in-hospital mortality rate was 12%, and the 6-months was 32%. In logistic regression we observed no association between antithrombotics and worse in-hospital outcomes. Haemorrhagic shock (OR 5.7, 95% CI 2.7 to 12.2; p<0.001), as well as a history of cancer (OR 2.7, 95% CI 1.1 to 6.9; p=0.03) and higher comorbidity (mean Charlson comorbidity index 5.6 vs. 6.9, OR 1.3, 95% CI 1.1 to 1.6; p=0.005) led to higher in-hospital mortality (tab. 1). In terms of 6-months outcomes, higher age (OR 1.03, 95% CI 1.00 to 1.05; p=0.02), higher comorbidity (OR 1.4, 95% CI 1.2 to 1.6; p<0.001), a history of cancer (OR 4.5, 95% CI 2.0 to 10.1; p<0.001) and a history of liver cirrhosis (OR 2.3, 95% CI 1.2 to 4.6; p=0.02) were associated with higher mortality. Other tested variables such as ischemic heart disease, heart failure or diabetes did not influence 6-month outcomes at statistically significant level (tab. 2). After a bleeding episode, antithrombotic treatment in patients with lasting indication from cardiovascular reasons was re-initiated in 81% of cases. One patient with atrial fibrillation was referred for a left atrial appendage closure.

Conclusions

Based on our observations, previous antithrombotic therapy does not worsen in-hospital outcomes in patients with UGB. Development of haemorrhagic shock during hospitalization predicted poor prognosis. Higher 6-month mortality was observed in older patients and patients with a history of liver cirrhosis. A history of cancer and higher comorbidity negatively affected the short- as well as long-term prognosis.

Funding Acknowledgement

Type of funding sources: None.
Myocardial deformation in athletes measured with feature tracking cardiovascular magnetic resonance
Authors: Silva C , Marcos-Carrion A , Garcia-Lopez M P , Lopez-Lereu M P , Monmeneu J V , Higueras L , Ferreira A M , Maceira A M
Published: October 2022

Background

Morphological changes of the heart associated with exercise are well studied. However, changes in myocardial mechanics of athlete's heart are less understood. The aim of this study was to analyze myocardial deformation parameters in athletes and controls, using feature tracking cardiac magnetic resonance (FT-CMR).

Methods

In a cohort of 73 athletes who had been submitted to CMR at 1.5T and 3 T (mean age 31±12 years, 69% males), we used CMR-FT to measure longitudinal, circumferential and radial strain and strain rates of both ventricles. Left ventricle (LV) longitudinal, circumferential and radial dyssynchrony index (L-SDI, C-SDI and R-CDI, respectively) was calculated as the standard deviation of the calculated time to peak strain percentages of the cardiac cycle with segmental strain analysis. We also measured these parameters in 73 age-matched healthy subjects.

Results

In comparison to the control subjects, athletes revealed lower left and right ventricle global longitudinal strain (−14.24% vs. −13.31%, p=0.03, and −18.12% vs. −15.95% p=0.01, respectively) and right ventricular (RV) global radial strain (19.28 vs 15.74, p<0.05) – Figure 1. There were no significant differences in LV global radial and circumferential strain. LV longitudinal, radial and circumferential systolic strain rate were also lower in athletes compared to controls (−0.69 s–1 vs. −0.78 s–1, p=0.04; 1.35 s–1 vs. 1.50 s–1, p=0.03: −0.92 s–1 vs −0.98 s–1, p=0.05, respectively). Regarding LV dyssynchrony index, we found no significant difference for L-SDI (10.76% vs. 10.72%, p=0.956), but athletes group showed lower C-SDI and R-SDI values (5.99% vs 4.84%, p=0.006, and 5.53% vs 4.47%, p=0.002).

Conclusion

Our study revealed attenuation of biventricular strain values and lower circumferential and radial LV dyssynchrony indexes in athletes, compared with healthy controls. We hypothesize that these differences may be related with exercise physiologic cardiac adaptations.

Funding Acknowledgement

Type of funding sources: None.
Influence of obesity on the safety and efficacy of antithrombotic therapy: a systematic review and meta-analysis
Authors: Rocha Darze B , Borges De Oliveira Q , Santos Viana M , Sahade Darze E , Fonteles Ritt L E
Published: October 2022

Background/Introduction

The prevalence of obesity has increased in recent decades and, considering its association with a higher risk of Venous Thromboembolism (VTE) and Acute Coronary Syndromes (ACS), it is necessary to establish an anticoagulation regimen suitable for this group of patients. The obese population is historically underrepresented in clinical trials, so the effect of obesity on the efficacy and safety of antithrombotic treatment is still uncertain.

Purpose

To evaluate the influence of obesity on the safety and efficacy of antithrombotic therapy in patients with ACS or VTE.

Methods

This is a systematic review and meta-analysis, using the MEDLINE/PubMed, Scielo, Cochrane, EMBASE and Lilacs databases. Articles characterized as randomized, cohort or case-control studies that compared the occurrence of clinical outcomes (mortality or bleeding) between obese and non-obese patients using parenteral anticoagulants for the treatment of ACS or VTE were selected. To assess the risk of bias, the Cochrane Risk of Bias Tool and the Newcastle-Ottawa Scale were used. Statistical analysis was performed using Revman 5.4 software with relative risk and 95% CI as analytical parameters.

Results

Six articles, with a total of 40.939 patients, were eligible for this review, being 3 randomized clinical trials and 3 retrospective cohorts. Of the patients, 87.7% had ACS. The mortality rate was 2.6% (95% CI 2.2–3.0%) in obese patients and 3.6% (95% CI 3.3–4.0%) in non-obese patients, while the rate of major bleeding was 6.0% (95% CI 5.6–6.4%) in the obese group and 6.2% (95% CI 5.9–6.5%) in the non-obese group. The incidence of major bleeding was similar between groups with RR: 0.90, 95% CI: 0.77–1.04, p=0.14. The outcome incidence remained comparable when studies were analyzed separately by anticoagulant: enoxaparin (RR: 0.87, 95% CI, 0.70–1.08, p=0.21) or UFH (RR: 0.96, 95% CI, 0.79–1.17, p=0.67). The mortality rate, measured by only 2 studies, was lower in obese patients, with RR: 0.71, 95% CI 0.59–0.87, p=0.0007.

Conclusion

In patients treated for VTE or ACS, rates of thrombotic complications, death and bleeding were comparable between obese and non-obese patients, regardless of the antithrombotic used.

Funding Acknowledgement

Type of funding sources: None.
Protective effect of proton pump inhibitor against gastrointestinal bleeding in patients receiving oral anticoagulants: a systematic review and meta-analysis
Authors: Ahn H J , Lee S R , Choi E K , Rhee T M , Kwon S , Oh S , Gregory L I P
Published: October 2022

Background

The concurrent use of proton pump inhibitor (PPI) in oral anticoagulant (OAC) treated patients may be associated with a lower risk of gastrointestinal bleeding (GIB), but evidence is still conflicting according to individual OACs.

Purpose

We conducted a meta-analysis to estimate the risk of GIB in patients with OAC and PPI co-therapy.

Methods

A systematic search of PubMed, EMBASE, and Cochrane was performed for studies reporting GIB risk in OAC and PPI co-therapy. Primary outcomes were total GIB and major GIB events. We calculated pooled estimates of GIB risk by a random-effect meta-analysis and reported as odds ratios (OR) and 95% CI. Stratified analyses according to the origin of GIB, ethnic groups, individual OACs, and the presence of underlying GIB risk factors were performed.

Results

A total of 10 studies (1 randomized controlled study and 9 observational studies) and 1,970,931 patients who received OAC were included. OAC and PPI co-therapy were associated with a lower risk of total GIB, and major GIB; OR (95% CI) was 0.67 (0.62–0.74) for total GIB and 0.68 (0.63–0.75) for major GIB, respectively. Among total GIB, only the risk of upper GIB was lower with OAC and PPI co-therapy (OR 0.67, 95% CI 0.64–0.70). No difference in the lower risk of primary GIB outcomes of PPI co-therapy was observed between Asians and non-Asians (p-for-difference, total GIB=0.695, major GIB=0.748, respectively) and among individual OACs except for edoxaban. The protective effect of PPI on total GIB was more significant in high-risk patients, defined as those with concurrent medication of antiplatelets or non-steroidal anti-inflammatory drugs (OR 0.62, 95% CI 0.52–0.73) and presence of high bleeding risk factors such as previous GIB history, HAS-BLED score ≥3, or underlying gastrointestinal diseases. (OR 0.65, 95% CI 0.61–0.70).

Conclusion

In patients who receive OAC, the use of PPI co-therapy was associated with a lower risk of total GIB and major GIB irrespective of ethnic group and OAC type except for edoxaban. PPI co-therapy can be considered particularly in patients on concomitant NSAID and antiplatelet use or patients with high GIB risk factors.

Funding Acknowledgement

Type of funding sources: None.