Clinical Research in Cardiology最新文献

Background: Heart failure (HF), including heart failure with reduced ejection fraction (HFrEF), remains a major public health issue with increasing disease burden. Recent advances, particularly data on sodium-glucose cotransporter-2 inhibitors (SGLT2i), have shifted HFrEF treatment paradigms based on strong evidence from randomised-controlled trials (RCTs). There is a lack of data reflecting HFrEF patient outcomes in relation to SGLT2i treatment in a real-world environment.

Methods: The ongoing H²-registry, initiated in 2021, collects real-world data on hospitalised HF patients in Germany. We analysed HFrEF patients (left ventricular ejection fraction, LVEF ≤ 40%) enrolled until 30-11-2024, stratified by SGLT2i treatment status at index hospital discharge and during follow-up (FU). We assessed baseline characteristics, predictors of SGLT2i use, and 12-month outcomes.

Results: Of 810 HFrEF patients (513 SGLT2i, 297 no-SGLT2i), the median age was 70 years, and 23% were female. Baseline characteristics were comparable between groups. Median LVEF was 30%, and 39% had type 2 diabetes. Use of renin-angiotensin-aldosterone system inhibitors, beta-blockers, and mineralocorticoid receptor antagonists (MRA) was more common in the SGLT2i group. Patients treated with SGLT2i at baseline had significantly lower all-cause mortality during FU in unadjusted time-to-event analyses (HR [95% CI] 0.53 [0.33-0.88]; p = 0.012). However, in multivariate analyses, only MRA treatment was independently associated with reduced mortality risk during FU (HR [95% CI] 0.41 [0.23-0.74]; p = 0.003). In a sub-cohort of patients being continuously treated with an SGLT2i during FU, the observed effect of SGLT2i was more pronounced (unadjusted HR [95% CI] 0.46 [0.28-0.77], p = 0.0023), and continuous SGLT2i treatment was significantly associated with lower all-cause mortality in multivariate analyses (adjusted HR [95% CI] 0.54 [0.30-0.99], p = 0.046).

Conclusion: In this prospective German HF registry, SGLT2i treatment was significantly associated with reduced all-cause mortality in HFrEF patients only with continuous use during FU. Treatment with MRA was independently associated with lower all-cause mortality in all performed analyses. These findings add to the available body of evidence regarding the real-world effectiveness of SGLT2i in HFrEF.

Trial registration: NCT04844944.

Background: The European Society of Cardiology regularly updates its clinical practice guidelines. However, it is not well established whether guideline changes have significant effects on actual clinical practice. Therefore, we retrospectively analyzed lipid-lowering therapy at discharge after acute coronary syndrome (ACS) in a 1-year period before and a 1-year period after publication of the 2019 ESC/EAS Guidelines for the management of dyslipidaemias, respectively.

Methods and results: In total, we included 691 patients who were discharged alive after AMI. A total of 354 patients were treated in the period before, and 337 after the guideline change. After the guideline change, the proportion of patients discharged on high-dose statin was higher (89.3% vs 80.5%; p = 0.001) and ezetimibe was prescribed more often (31.2% vs 5.9%; p < 0.00001) resulting in more patients being discharged on high-intensity treatment (92.9% vs. 81.6%; p < 0.0001). Median on-treatment LDL-cholesterol was significantly higher in the period before (65 [IQR 47 to 90] mg/dL) than after the publication of the 2019 guidelines (48 [IQR 35 to 69] mg/dL; p < 0.0001). The LDL-C goal of < 55 mg/dL would have been reached by 37.5% patients in the earlier period and was reached by 62.9% in the later period (p < 0.0001).

Conclusions: The update of the 2019 ESC/EAS Guidelines for the management of dyslipidaemias was associated with a significant improvement in the prescription of high-dose statin and ezetimibe in patients after ACS. The change of the guidelines rapidly translated into clinical practice resulting in improved risk factor control in patients at very high risk.

Background: Heart failure (HF) is a heterogeneous clinical syndrome affecting a growing global population. Due to the high incidence of cardiovascular risk factors, a large proportion of the Western population is at risk for heart failure. Oxidative stress and inflammation play a crucial role in the pathophysiology of heart failure with preserved ejection fraction (HFpEF). While previous studies have demonstrated an association between dysfunctional HDL and heart failure, the specific link between oxidized HDL and HF remains unexplored.

Methods: In this cross-sectional observational study, the antioxidant function of HDL was assessed in 366 patients with suspected heart failure. HFpEF assessment was conducted according to current guidelines. A validated cell-free biochemical assay was used to determine reduced HDL antioxidant function as assessed by increased HDL-lipid peroxide content (HDL_ox), normalized by HDL-C levels and the mean value of a pooled serum control from healthy participants (nHDL_ox; no units). Results were expressed as median with interquartile range (IQR).

Results: Participants with HFpEF (n = 88) had 15% higher mean relative levels of nHDL_ox than those without heart failure (n = 180). Using a basic multivariate model adjusted for age, sex, eGFR and a full multivariate model (adjusted for diabetes, hypertension, atrial fibrillation, LDL cholesterol, hsCRP, and coronary artery disease), nHDL_ox was an independent predictor for HFpEF (p < 0.05). An increase in 1-SD in nHDL_ox was associated with a 67% increased risk for HFpEF if compared with participants without heart failure (p = 0.02).

Conclusion: HDL antioxidant function is reduced in patients with HFpEF. Improving HDL function is a promising target for early heart failure treatment.

Background and aims: Sympathetic overactivation plays a critical role in the pathophysiology of various conditions, such as arterial hypertension, chronic kidney disease, coronary artery disease (CAD), diabetes, metabolic syndrome, and dyslipidemia. Initially developed for hypertension management, renal denervation (RDN) has also been associated with metabolic improvements. Preclinical studies in rodent models suggest that RDN may improve lipid profiles by reducing sympathetic activity. This study analyses the effect of RDN on lipid profiles in hypertensive patients with or without CAD.

Methods: This analysis includes 122 hypertensive patients with (n = 30) or without CAD (n = 92). All patients underwent radiofrequency, ultrasound, or alcohol-injection-based RDN. Fasting lipid profile, including total cholesterol, triglyceride, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and non-HDL levels was measured at baseline and 6 months after RDN in parallel to office and 24-h ambulatory blood pressure (BP).

Results: Six months after RDN, the total cohort showed significant lipid profile improvements. The total cholesterol levels decreased by 10.3 ± 26.3 mg/dL (p < 0.001), LDL by 7.0 ± 20.4 mg/dL (p < 0.001), and triglycerides by 30.7 ± 69.4 mg/dL (p < 0.001), while non-HDL cholesterol levels declined by 7.6 ± 26.3 mg/dL (p = 0.002). These changes were independent of BP reduction. In patients with CAD, total cholesterol levels declined by 21.7 ± 29.1 mg/dL (p < 0.001), triglycerides by 40.7 ± 80.0 mg/dL (p = 0.009), LDL by 15.2 ± 22.0 mg/dL (p < 0.001), HDL by 2.8 ± 4.7 mg/dL (p = 0.003), and non-HDL by 15.0 ± 34 .8 mg/dL (p = 0.021). Reductions in total cholesterol and LDL were greater in CAD than in non-CAD (p = 0.011 and p = 0.006).

Conclusion: We observed a significant improvement in lipid profiles in hypertensive patients with CAD after RDN. This improvement may represent an additive benefit of RDN in hypertensive patients with CAD.

In a cohort of patients with dyslipidemia at very high cardiovascular risk, we investigated differences in LDL-C lipid target achievement, clinical outcomes, and persistence rates between users and non-users of PCSK9 monoclonal antibodies (PCSK9-mAb) over a 3-year observation period. The prospective, multi-center observational study included 1695 patients with dyslipidemia. Eligible patients were adults with familial or non-familial hypercholesterolemia, mixed dyslipidemia, or other therapy-refractory lipid disorders in line with the G-BA reimbursement regulations. Treatment decisions, including PCSK9-mAb administration, were made at the discretion of the treating physician. At baseline, 804 (47.4%) patients received PCSK9-mAb therapy, and 891 (52.5%) did not. There were 42 (4.7%) new PCSK9-mAb receivers during the follow-up. Median propensity-score adjusted LDL-C levels in PCSK9-mAb non-receivers decreased over time from 106.0 to 68.4 mg/dL. LDL-C in PCSK9-mAb receivers dropped from 112.5 mg/dL at baseline to 58.0 mg/dL at 3 years, consistently outperforming non-receivers. Target LDL-C goal attainment (< 55mg/dL) after 3 years was higher in the PCSK9-mAb group (43.2% vs. 34.5%). Persistence with PCSK9-mAb therapy over 3 years since treatment initiation was high (91.5%). Higher discontinuation rates of PCSK9-mAb were associated with baseline statin intolerance (HR = 2.3, p = 0.012). The use of PCSK9-mAb was associated with numerically fewer cardiovascular events (9.3 versus 15.7 per 100 patient-years, p not significant) and lower hospitalization rates due to cardiovascular events compared to non-users (6.3 versus 12.4 per 100 patient years, p = 0.001). This study underscores the real-world efficacy and safety of PCSK9-mAb therapy in achieving sustained LDL-C reduction. Identifier: Clinicaltrials.gov NCT03110432.

Background: "Jena auf Ziel" ("JaZ") is a prospective cohort study in patients with ST-elevation myocardial infarction (STEMI). Early combination of a statin and ezetimibe was initiated on the day of admission and lipid-lowering therapy (LLT) was escalated during follow-up with bempedoic acid (BA) and PCSK9 inhibitors (PCSK9-I) to reach guideline-recommended LDL-cholesterol (LDL-C) levels. During the initial follow-up period of 12 months, all patients reached the recommended ESC/EAS LDL-C target for very high-risk patients of < 55 mg/dL.

Methods: Twelve months after the index event, patients enrolled in "JaZ" had the option of either continuing with regular follow-ups in the outpatient lipid clinic of the university hospital Jena or transitioning to standard care by their general practitioners (GPs). Fifty-three patients (62%) stayed with the outpatient lipid clinic and 32 (38%) preferred treatment by their local GP. After 24 months, we analyzed differences in prescribed lipid-lowering drugs, LDL-C target attainment, LDL-C time on target, and major adverse cardiac events (MACEs = nonfatal ischemic cardiovascular events, admission for heart failure, nonfatal stroke) between groups.

Results: All 85 patients enrolled in the initial study were followed up for 24 months. The average LDL-C after 24 months was 1.47 ± 0.71 mmol/L in the total study population. Fifty-one patients (60%) of the entire cohort were still on LDL-C target of 1.4 mmol/L or below (outpatient lipid clinic group: 72.5% vs. GP group: 27.5%; p = 0.037). The average LDL-C in patients followed up in the outpatient lipid clinic was significantly lower compared to patients who were treated by GPs (1.2 ± 0.7 mmol/L vs. 2.1 ± 1.04 mmol/L; p < 0.01). Moreover, patients in the outpatient lipid clinic had a longer time on LDL-C targets compared to patients treated by GPs (82.4 ± 29.5% vs. 62.4 ± 36.6%; p < 0.01). The main cause of missed LDL-C targets was deprescribing of LLT by local GPs, surpassing non-adherence (2.1 ± 1.04 mmol/L vs. LDL-C: 1.52 ± 0.53 mmol/L; p < 0.01). Patients with MACE during follow-up were characterized by a shorter time on LDL-C targets compared to patients without MACE (58.1 ± 29.9% vs. 79.1 ± 28.1%; p = 0.048) and higher LDL-C levels at 24 months (2.04 ± 1.26 mmol/L vs. 1.27 ± 0.72 mmol/L; p < 0.01).

Conclusion: In this cohort of STEMI patients, a less intensive lipid-lowering strategy during a 2-year follow-up was associated with higher LDL-C levels and a higher incidence of MACE. Therefore, a regular follow-up in a specialized lipid outpatient clinic was superior to standard care treatment by general practitioners.

Objectives: We investigated changes in lipid-lowering drug prescriptions in Germany as a whole and in the 16 federal states over the last 13 years and their association with hospitalization rates for acute myocardial infarction.

Design: Ecological study.

Setting: Nationwide German hospitalization, Diagnosis-Related Groups Statistic.

Patients/participants: German population in the years 2010 through 2022.

Intervention: All prescriptions of lipid-lowering drugs in the years 2010 to 2022 by federal state in Germany.

Main outcome measures: Hospitalization rates for the treatment of transmural infarction per calendar year and federal state (STEMI = ST-elevation myocardial infarction).

Results: The age-standardized prescription rates of lipid-lowering drugs per 1000 person-years increased from 77.4 in 2010 to 145.2 in 2022 (reference population: Germany 2011). Within the same period, the STEMI hospitalization rate per 100,000 person-years decreased from 143.7 to 100.1. Based on the prescription and hospitalization rates of the 16 federal states, it is shown that the STEMI hospitalization rate decreased the more the prescription rate of lipid-lowering drugs in a federal state increased over time (beta = 0.38, 95% confidence interval - 0.64; - 0.12; adjusted explained variance 0.362).

Conclusion: Increasing prescription rates of lipid-lowering drugs have correlated with decreasing rates of hospitalized cases for STEMI in Germany in the last decade.

Aim: To evaluate the effects of lipid-lowering medications of different intensities on total, calcified, and non-calcified plaque volumes in patients undergoing serial cardiac computed tomography angiography (CCTA).

Methods: Individuals with chronic coronary syndromes from 11 centers were included in a retrospective registry. Total, calcified, and non-calcified plaque volumes were quantified and the relative difference in plaque volumes between baseline and follow-up CCTA was calculated. The intensity of lipid-lowering treatment was designated as low, moderate, or high, based on current recommendations.

Results: Of 216 patients (mean age 63.1 ± 9.7 years), undergoing serial CCTA (median timespan = 824.5 [IQR = 463.0-1323.0] days), 89 (41.2%) received no or low-intensity lipid-lowering medications, and 80 (37.0%) and 47 (21.8%) moderate- and high-intensity lipid-lowering agents, respectively. Progression of total and non-calcified plaque was attenuated in patients on moderate-/high- versus those on no/low-intensity treatment and arrested in patients treated with high-intensity statins or PCSK9 inhibitors (p < 0.001). Halted increase of non-calcified plaque was associated with LDL-cholesterol reduction (p < 0.001), whereas calcified plaque mass and Agatston score increased irrespective of the lipid-lowering treatment (p = NS). The intensity of lipid-lowering therapy robustly predicted attenuation of non-calcified plaque progression as a function of the time duration between the two CCTA scans, and this was independent of age and cardiovascular risk factors (HR = 3.83, 95% CI = 1.81-8.05, p < 0.001).

Conclusion: The LOCATE multi-center observational study shows that progression of non-calcified plaques, which have been previously described as precursors of acute coronary syndromes, can be attenuated with moderate-intensity, and arrested with high-intensity lipid-lowering therapy.

German clinical trials register: DRKS00031954.