bluuebunny/crossref_metadata_2025_split huggingface dataset:
First clinical experiences with inclisiran in real world setting
Authors: Galema-Boers J M H , Mulder J W C M , Steward K , Roeters Van Lennep J E 
Published: November 2023

Abstract

Background
Inclisiran is the first-in-class small interfering RNA (siRNA) PCSK9 inhibitor. In clinical trials, inclisiran showed effective and sustained LDL-C reduction of approximately 50%. However, data about the efficacy and safety in clinical setting are scarce. We aim to investigate the efficacy and safety in clinical practice.

Methods
Registry of all consecutive patients who started with inclisiran at a lipid clinic of a university hospital. Patients were eligible if they fulfilled reimbursement criteria in the Netherlands; very high risk patients with FH and/or ASCVD and not on target LDL-C levels despite maximally tolerated oral lipid lowering medication. Patients were included if they started with inclisiran as first line (group 1) or switched from PCSK9 monoclonal antibody (mAbs) to inclisiran (group 2). LDL-C levels were measured 3 months after administration of inclisiran initiation. Median change of LDL-C levels was calculated on an individual and group level.

Results
We analysed 50 patients (26 women, 33 patients with FH), median [25th percentile; 75th percentile] age of 64 [52; 68] years. Patients who newly started Inclisiran (group 1) showed a LDL-C decrease of 39 [-50; -33]%. Patients who used statins as co-medication had a higher median LDL-C decrease compared to those without statin use (45% vs. 38%). However, patients who switched from mAbs to Inclisiran (group 2) had an increase in LDL-C of +41 [+3; +97]% (figure 1).
Almost half of the patients (42%) experienced a mild burning sensation. During follow-up 6 patients (12%) reported side effects as abdominal complains, dizziness, fatigue and flu-like symptoms in the first week after administration. One patient stopped treatment because of perceived side effects like fatigue and myalgia.

Conclusions
Our initial experience of inclisiran in a clinical setting showed slightly less reduction in LDL-C levels compared to clinical trials but a similar safety profile. Moreover, patients who switched from PCSK9 mAbs to inclisiran showed an increase in LDL-C levels implying that inclisiran is less potent in LDL-C reduction compared to PCSk9 mAbs.Figure 1Waterfallplot LDL-C change
Association between preeclampsia and long-term risk of arrhythmias
Authors: Havers-Borgersen E , Stahl A , Johansen M , Joens C , Koeber L , Fosboel E L 
Published: November 2023

Abstract

Background
Preeclampsia (PE), a pregnancy-induced hypertensive disorder, affects 4-5% of pregnancies worldwide. It is well known that hypertension is associated with increased risk of arrhythmias; however, data on the association between PE and arrhythmias are sparse and there is a lack of knowledge on the long-term risk of arrhythmias.

Purpose
To compare the incidence of arrhythmias following preeclamptic and normotensive pregnancies.

Methods
In this observational cohort study, we identified all primiparous women without history of arrhythmias who gave birth in Denmark from 1997 to 2016 using Danish nationwide registries. The women were stratified on whether they developed PE during their primiparous pregnancy and were followed from primiparous pregnancy to incident arrhythmia, emigration, death, or end of study (December 31, 2018). The comparative risks of arrhythmias were assessed in cause-specific Cox regression analyses adjusted for known arrhythmogenic risk factors including obesity, smoking, hypertension, coronary artery disease, cardiomyopathy, congenital heart disease, thyroid disease, diabetes, and alcohol abuse.

Results
A total of 521,517 primiparous women with a median age of 28 years were included and 23,523 (4.5%) were diagnosed with PE. Women with versus without PE were of similar age but had a higher burden of comorbidities. During a median follow-up period of 10.2 years, women with PE were associated with higher absolute incidences of arrhythmias (Figure 1). No statistically significant association was found for the composite of cardiac arrest, ventricular arrhythmias, or ICD-implantation nor for the composite of advanced 2nd or 3rd degree atrioventricular block, sinoatrial dysfunction, or pacemaker-implantation. However, women with PE were associated with a significant increased risk of the composite of supraventricular tachyarrhythmias and extrasystoles (p&lt;0.01) and the composite of all included arrhythmias (p&lt;0.01). Factors associated with arrhythmias among women with PE included obesity (HR 1.40 (95%CI 1.03-1.91), coronary artery disease (HR 2.39 (95%CI 1.14-5.00), cardiomyopathy (HR 9.65 (95%CI 3.46-26.92), and congenital heart disease (HR 5.86 (95%CI 2.59-13.28).

Conclusion
Preeclamptic women were associated with a significantly higher rate of arrhythmias - mainly driven by supraventricular tachyarrhythmias and extrasystoles - than normotensive women. For the purpose of primary and secondary prevention, this finding suggests that women with a history of PE may benefit from evaluation of cardiovascular risk factors, screening of and education in prevention of cardiovascular disease.Figure 1
Therapeutic gaps in low-density lipoprotein cholesterol management have narrowed over time but remain wide: a wide study of 40,141 acute coronary syndrome patients from 2016 to 2021
Authors: Sun H , Lai A , Tan G M , Yan B 
Published: November 2023

Abstract

Background
There are significant therapeutic gaps in ‘real-word’ low-density lipoprotein cholesterol (LDL-C) management in very-high risk patients. Understanding these gaps is important for developing strategies to bridge these gaps.

Purpose
We aimed to evaluate trends and identify therapeutic gaps in LDL-C management in very-high risk patients.

Methods
We retrospectively analyzed consecutive patients admitted with a diagnosis of acute coronary syndrome (ACS) to 16 public hospitals in between 2016 and 2021. Baseline and 12-month lipid-lowering therapy (LLT) including statins, ezetimibe and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor and LDL-C levels were recorded. We evaluated trends-over-time in percentage achievement of guideline Class I recommendations including (i) in-hospital initiation of high-intensity LLT; (ii) lipid-profile at follow-up post discharge; (iii) achieve at least 50% reduction in LDL-C from baseline with a goal of (iv) LDL-C &lt;1.4 mmol/L.

Results
Of 40,141 ACS patients (mean age 71, male 66.5%), 61.2% were statin-naïve on admission. Baseline average LDL-C was 2.35 mmol/L (IQR 1.74 to 3.13 mmol/L). LLT prescription on discharge increased over time from 63.8% in 2016 to 96.2% in 2021. The use of high-intensity statins on discharge also increased over time from 24.7% to 53.7% but still suboptimal. The use of high-intensity statins increased significantly at 12-months (29.4% in 2016 and 59% in 2021) compared to on discharge (44.1% vs. 40.9% overall, p&lt;0.001). The use of combination LLT was very low (1.3%-3.8%). Up to 22% of patients did not have repeated lipid profile after discharge. Of patients who had follow-up lipid profile, the median LDL-C was 1.74 mmol/L with a median LDL-C reduction of 29%. Only 27.5% reached the LDL-C goal of &lt;1.4 mmol/L and 22.5% achieved at least 50% of LDL-C reduction. LDL-C reduction improved over time from 25.8% in 2016 to 31% in 2021, proportion of patients who reached LDL-C goal of &lt;1.4 mmol/L improved over time from 20.8% in 2016 to 28.7% in 2021, and proportion of patients who achieved at least 50% of LDL-C reduction improved over time from 18.5% in 2016 to 24.6% in 2021, respectively.

Conclusion
Despite an increasing trend in the use of high-intensity statins and combination LLT over time, most patients did not reach guideline-recommended LDL-C target. Early up-titration of statin and addition of non-statin LLT may be required in the majority of patients.
Strike Early and Strike Strong: application of a strategy comprising first-line combination of high-intensity statins and ezetimibe for patients with acute myocardial infarction in routine practice
Authors: Schiele F , Monnin C , Bettinger C , Guillon B , Besutti M , Chatot M , Chopard R , Meneveau N 
Published: November 2023

Abstract

Aim
Rapid and intense LDL-c reduction for patients with acute myocardial infarction (AMI) using a systematic combination of high intensity statins and ezetimibe, dubbed "Strike Early and Strike Strong" (SESS), has been proposed in a position paper endorsed by ESC. The applicability of this strategy in routine practice, and the tolerance and biological efficacy of such lipid lowering treatment (LLT) are poorly documented.

Methods
Single-center, prospective, observational study including 500 consecutive patients admitted for AMI. Unless there was known intolerance, a SESS policy was advocated at admission for AMI, irrespective of baseline LDL-c. Actual discharge LLT, LDL-c level during follow-up (3 to 8 months) and the rate of patients at ESC LDL-c target were recorded. We considered LLT to be maintained when observed LDL-c level at follow-up (FU) was not 20% higher than that expected from baseline LDL- and LLT intensity at discharge.

Results
Between January 2020 and July 2021, 527 patients were included, 387(75%) were male, 110(22%) had diabetes, mean age was 63±12 years. Admission LDL-c was 127±44mg/dL, 431(78%) had no previous LLT. At discharge, 456 (97%) a high intensity statin, and combined with ezetiibe in 430/456(92%). The mean capacity of the discharge LLT to decrease LDL-c was 63±10%. 12-month FU with biology was available for 273 randomly selected patients. The combination of high intensity statins and ezetimibe was maintained in 87%, although ezetimibe was stopped in 9% and the statin dose was reduced in 15% (mainly reduction from atorvastatin 80 to 40 mg/day). As a result, capacity of the LLT to decrease LDL-c was reduced to 59±11%. Mean LDL-c was 53±33 mg/dL. ESC LDL-c therapeutic goals were reached in 53%: LDL-c&lt;55mg/dL in 62% and &gt;50% decrease in baseline LDL-c in 74%. Regarding the need for PCSK9 inhibitors, the rate was 14% for a threshold for prescription set at a LDL-c≥ 70mg/dL, and 7% for a threshold set at ≥100mg/dL. An LDL-c level &lt;30mg/dL was observed in 19%.

Conclusion
The SESS strategy before discharge after ACS is feasible in routine practice. At 12 months, LLT intensity was maintained in the majority of cases, yielding an average LDL-c level of 53±33 mg/dL, and 53% of patients at LDL-c goals.
The impact of statin intensity on long-term outcomes in elderly patients with acute myocardial infarction who have undergone percutaneous coronary intervention
Authors: Choe J , Lee S H , Ahn J H , Park J S , Lee H W , Oh J H , Choi J H , Lee H C , Cha K S , Jeong M H 
Published: November 2023

Abstract

Background
The data regarding long-term clinical outcomes according to statin intensity in elderly patients who have undergone percutaneous coronary intervention (PCI) for acute myocardial infarction (MI) is unclear.

Purpose
We aimed to investigate the long-term clinical benefit of high intensity statin versus moderate to low intensity statin in elderly patients underwent PCI for acute MI.

Methods
Among 13104 patients with acute MI who have undergone PCI in a nationwide, prospective, and real-world registry, 4294 elderly (defined as ≥70 years) patients prescribed statin at discharge were included. 1136 patients were prescribed with high intensity statin, and 3158 patients were prescribed with moderate to low intensity statin. The major adverse cardiac events (MACE; all-cause death, recurrent MI, any revascularization, stroke, readmission due to heart failure [HF], or definite/probable stent thrombosis [ST]) and the components of MACE were compared in multivariable Cox regression, propensity score (PS) matched, and underwent PS-adjusted analyses.

Results
During a median follow-up of 998 days, MACE, all-cause death, and cardiac death occurred in 1297 patients (30.2%), 737 patients (17.2%), and 460 patients (10.7%), respectively. The risks of MACE (entire: 26.9% vs. 31.4%, hazard ratio [HR] 0.83, 95% confidence interval [CI] 0.73-0.95, p=0.005; PS-matched: n=2186, 25.3% vs. 30.8%, HR 0.79, 95% CI 0.67-0.94, p=0.008), all-cause death (entire: 14.4% vs. 18.1%, HR 0.78, 95% CI 0.65-0.93, p=0.005; PS-matched: 13.8% vs. 18.9%, HR 0.69, 95% CI 0.57-0.92, p=0.002), cardiac death (entire: 9.5% vs. 11.4%, HR 0.81, 95% CI 0.67-0.97, p=0.042; PS-matched: 8.7% vs. 11.3%, HR 0.77, 95% CI 0.61-0.96, p=0.031), and readmission due to HF (entire: 5.5% vs. 7.5%, HR 0.72, 95% CI 0.55-0.95, p=0.021; PS-matched: 5.7% vs. 8.1%, HR 0.78, 95% CI 0.59-0.96, p=0.017) were significantly decreased in the patients received high intensity statin compared to in those received moderate to low intensity statin. There were no significant differences in the risks of recurrent MI, any revascularization, stroke, and definite/probable ST between the groups. In patients ≥80 years, compared to the moderate to low intensity statin group, high intensity statin group had the reduced rates of MACE, all-cause death, cardiac death, recurrent MI, any revascularization, stroke, readmission due to HF, or definite/probable ST, but insignificantly.

Conclusions
From the nationwide registry, we noted that in elderly patients after PCI for acute MI the administration of high intensity statin versus moderate to low intensity statin was contributed to the improved long-term clinical outcomes.
The effect of proprotein convertase subtilisin/kexin type 9 inhibition on the plasma proteome: a SPIRE sub-study
Authors: Kraaijenhof J , Cornel J H , Opstal T S J , Gill D , Hovingh G K , Stroes E S G , Catapano A L , Koenig W , Ridker P M , Nurmohamed N S 
Published: November 2023

Abstract

Background
The plasma proteome is an intermediate phenotype for disease and is a tool to inform on pharmacological mechanisms of effect. For selective low-density lipoprotein cholesterol (LDL-C) lowering by proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition, multiple studies have demonstrated that its potent LDL-C lowering effect coincides with marked reductions in both cellular and arterial plaque inflammation, despite unaltered high-sensitivity C-reactive protein (hs-CRP) levels.

Purpose
In the present study, we set out to investigate potential anti-inflammatory effects of PCSK9 inhibition using plasma proteomics.

Methods
In 190 patients participating in the SPIRE-1/2 trials, 184 targeted proteins were measured at baseline and after 12 months of bococizumab treatment using the Cardiovascular II and III panels (Sweden). Of the included patients, 96 patients received placebo and 94 received 150mg of bococizumab, once every two weeks. Considering the development of auto-antibodies in some patients, patients with LDL-C reduction below 15% were excluded. The primary outcome was the fold change in protein levels after 12 months compared to baseline. The Benjamini-Hochberg method was used to adjust for multiple comparisons with a false discovery rate (FDR) of 5%. The findings were compared to the LoDoCo2 sub-study which used the same proteomic panels.

Results
In the placebo group, there was no significant change in any of the proteins. In the bococizumab group (n=77, mean age 62.2±9.7 years and 70 [91%] male), LDL-C levels were reduced from 114±41 mg/dL to 47±34 mg/dL (mean reduction 66±29 mg/dL) on top of statin therapy while there was a neutral effect on hs-CRP (median change 0.0 mg/L IQR [-0.8,1.1]). PCSK9 was the only protein with change upon treatment with bococizumab (24.4±11.0 vs. 15.0±10.7; PFDR=0.033; Figure 1A). In comparison, treatment of colchicine in the LoDoCo2 sub-study was associated with a significant change in 60 proteins (Figure 1B).

Conclusion
Here, we show that PCSK9 inhibition with bococizumab resulted in a highly selective reduction of PCSK9 plasma levels without robustly affecting other circulating proteins in the measured panels, implying PCSK9 inhibition lowers ASCVD risk via pure lipid lowering pathways. Our study reinforces the neutral systemic inflammatory effect of PCSK9 inhibition on top of statin therapy. The local effects on cellular and vascular inflammation by PCSK9 inhibition observed in earlier studies most likely reflect a direct consequence of a reduced cholesterol content in inflammatory cells and plaques, subsequently leading to a local anti-inflammatory effect. These findings support the combination of targeted anti-inflammatory therapies on top of potent LDL-C lowering in order to further reduce the residual inflammatory risk.
Efficacy, safety, adherence and persistence of PCSK9 inhibitors in clinical practice: a single country, multicenter, observational study (AT-TARGET-IT)
Authors: Gargiulo P , Basile C , Calabro' P , Catalano A , Merlini P A , Iannuzzo G , Ciccone M M , Paloscia L , Varbella F , Brunetti N D , Paolillo S , Marzano F , Indolfi C , Perrone-Filardi P 
Published: November 2023

Abstract

Background
PCSK9 inhibitors (PCSK9i) significantly decrease LDL cholesterol (LDL-C), either as monotherapy or in addition to the maximally tolerated dose of statin and/or ezetimibe. Yet, few data are available on efficacy and background lipid-lowering therapy (LLT) adjustment in patients treated with PCSK9i in real-world observations.

Purpose
AT-TARGET-IT is an Italian multicenter registry involving 9 Italian centers, designed to assess efficacy, adherence, and persistence of PCSK9i, as well as prescribing doctors’ behavior in patients with atherosclerotic cardiovascular disease (ASCVD) or familial hypercholesterolemia (FH).

Methods
From June through November 2021, we enrolled patients with PCSK9i first prescription from 6 months before inclusion through starting of PCSK9i use. Clinical and demographic characteristics, concomitant therapies, blood chemistry, were recorded at the time of first prescription and at the latest observation preceding inclusion in the study. Background therapy was assessed at baseline and during follow-up, evaluating treatment withdrawal, reduction of doses, or changes from statin-ezetimibe association to single drug therapy.

Results
798 patients were enrolled. The median reduction in LDL-C levels was 64.9%. After stratification for CV risk, 63.8% achieved LDL-C target; of them, 83.3% took LLTs at PCSK9i initiation and 16.7% did not (Figure 1). 760 patients (95.2%) showed high adherence to therapy, 13 (1.6%) partial adherence, and 25 (3.1%) poor adherence (Figure 2). At 6 months, 99.7% of patients enrolled in the study remained on therapy; there were 519 and 423 patients in the study with a follow-up of at least 12 and 18 months, respectively. Persistence in these groups was 98.1% and 97.5%, respectively. Overall, 3.5% of patients discontinued therapy. No differences in efficacy, adherence, and persistence were found between alirocumab and evolocumab.

Conclusion
PCSK9i are safe and effective in clinical practice, leading to very high adherence and persistence to therapy, and achievement of recommended LDL-C target in most patients, especially when used as combination therapy.Stratified LDL-C target achievementAdherence and persistence status
Effects of sodium-glucose cotransporter-2 inhibitors on cardiovascular outcomes in patients with atrial fibrillation and type 2 diabetes mellitus
Authors: Oh Y S , Choi Y , Kim S H , Kim S H , Park S Y , Kim H J 
Published: November 2023

Abstract

Background
A sodium-glucose cotransporter-2 inhibitor (SGLT2i) improves clinical outcomes in patients with type 2 diabetes (T2DM) and cardiovascular disease. Also use of SGLT2i was associated with a reduction of atrial fibrillation (AF) burden. We investigated the effect of SGLT2is on clinical outcomes in patients with T2DM and AF.

Methods
This was a retrospective study using a clinical data warehouse (CDW) constructed from 7 medical centers. We analyzed 11,043 patients with AF and T2DM. The patients were classified to the SGLT2i group and the control group according to the SGLT2i use. We performed 1:2 propensity score matching analysis. The primary endpoint was a composite of all-cause death or hospitalization due to heart failure events. The secondary endpoints were acute myocardial infarction, stroke, renal function decline and an initiation of dialysis.

Results
The propensity score matched population consisted of 467 patients in the SGLT2i group and 848 patients in the control group. During a mean follow up of 31.8 (± 21.0) months, the incidence of the primary endpoint was significantly lower in the SGLT2i group (9.6% vs. 16.9%, hazard ratio [HR] 0.624 [0.446 – 0.873]). SGLT2i was associated with reduced all-cause death (HR 0.292 [0.144 – 0.591]) and non-significantly lower risk of heart failure hospitalization (HR 0.734 [0.509 – 1.060]). There was no significant difference in the incidence of myocardial infarction, ischemic stroke, renal function decline and an initiation of dialysis between the two groups. In multivariate analysis, age, renal dysfunction, prior heart failure, and the absence of SGLT2i were independent predictors for the worse outcome.

Conclusion
SGLT2 inhibitor was associated with a lower incidence of all-cause mortality or heart failure hospitalization in patients with AF and T2DM.Freedom from the primary endpoint in the
Prescribing trends of sodium-glucose cotransporter 2 Inhibitors in patients with heart failure with preserved, mildly reduced and reduced ejection fraction
Authors: Hofer F , Hammer A , Steinacher E , Baumer U , Kazem N , Koller L , Richter B , Hengstenberg C , Sulzgruber P , Niessner A 
Published: November 2023

Abstract

Background
Numerous randomized controlled trials have evaluated the efficacy of SGLT2i and demonstrated decreased hospitalization rates for HF and a better cardiorenal outcome in diverse heart failure (HF) populations comprising HF patients with reduced (HFrEF), mildly reduced (HFmrEF) and preserved (HFpEF) ejection fraction. Since the beneficial effects of SGLT2i in HF patients are well known, real-world data on the clinical implementation of these agents following availability of CV outcome trial data seems of utmost importance.

Methods
We identified patients presenting with HF who were hospitalized at a university affiliated tertiary care center, between 01/2017 and 10/2022. All prescriptions of SGLT2i (dapagliflozin and empagliflozin) – including marketed fixed-dose combinations with other glucose-lowering drugs – were identified.

Results
In total, 2,673 patients with HF (median age 75, 39.9% female, 23.1% with diabetes) were included in the present analyses. Among the 2,637 patients with signs and symptoms suggestive of HF, 1086 (40.6%) had a documented left ventricular ejection fraction (LVEF) ≤ 40% (HFrEF), 445 (16.6%) a LVEF between 40-50% (HFmrEF) and 1142 (42.7%) a LVEF &gt; 50% (HFpEF). In the overall cohort, 382 (14.3%) patients received an SGLT2i. As shown in Figure 1, the prescription of SGLT2i significantly increased from the beginning to the end of the inclusion period. In detail, it climbed from 6.8% in 2017 to 56.6% in 2022 in the HFrEF group (p-trend &lt;0.001), from 3.3% to 49.2% in the HFmrEF group (p-trend &lt;0.001) and from 1.9% to a still very low 26.4% in the HFpEF group (p-trend &lt;0.001). While prescription of SGLT2i in HFrEF patients started to increase after the presentation of the DAPA-HF trial, the SGLT2i prescription in HFmrEF and HFpEF patients showed a marked rise after the presentation of the new HF ESC guidelines (2021) and the EMPEROR-Preserved trial.

Conclusion
The prescription of SGLT2i is constantly rising due to greater awareness among cardiologists and other specialists in internal medicine. Nevertheless, despite a growing evidence on the reduction of CV events by SGLT2i, our data show that there is still room for improvement in prescribing of these cardioprotective agents, especially in patients with HFpEF.Prescription trend of SGLT2i.