Patients With High Cardiovascular Risk as Candidates to Bempedoic Acid, After Treatment With Statins, Ezetimibe and PCSK9 Inhibitors: An Estimation and Cost-Effectiveness Analysis.

ABSTRACT: Low-density lipoprotein cholesterol (LDLc) is the lead effector of atherosclerosis and main treatment target. Bempedoic acid is a novel oral drug in the therapeutic armamentarium which is able to reduce LDLc. The objectives of this study were (1) to select the potential patients for administering bempedoic acid such as those with a very high cardiovascular risk in which objectives of LDLc were not achieved despite conventional treatment with PCSK9 inhibitors (PCSK9i) and/or statins and ezetimibe and (2) to estimate the cost-effectiveness of bempedoic acid in different scenarios. The methods used were a multicenter and retrospective study of 652 patients initiating treatment with any PCSK9 inhibitor in 17 different hospitals. Before and on-treatment LDLc cholesterol levels, medical treatments, clinical indication, and baseline characteristics were recorded. The results obtained from 443 subjects in secondary prevention were analyzed. The mean (±) LDLc level at baseline was 142.5 ± 46.4 mg/dL and 61.5 ± 40.5 mg/dL in the follow-up, with a reduction of 55.9% ( P < 0.0001); 71.6% of the patients reached the target of LDL < 55 mg/dL or >50% reduction. Of those patients treated with medium-intensity and low-intensity statins plus PCSK9 inhibitors (with or without ezetimibe), only 5.7% of them were able to reduce LDL below 55 mg/dL and the main LDLc reduction in this group was the lowest (42.9% on average). Patients with TG values >135 mg/dL represented 41.6% of the sample, of which approximately 10% of them were using fibrates. Assuming only LDLc reduction and the UK price, the incremental cost-effectiveness ratio was 88,359€; 83,117€; 82,378€; and 79,015€ for different discount rates. In conclusion, one-third of the patients could achieve the target LDL proposed in the 2019 ESC/EAS guidelines. Approximately 10% of them could also benefit from treating hypertriglyceridemia as indicated in the 2021 ESC guidelines on cardiovascular disease prevention. Patients with medium-intensity and low-intensity statins plus PCSK9i and ezetimibe would be the most benefited. Bempedoic acid could be a not cost-efficacy therapy in all the scenarios, but we need to wait for the CLEAR OUTCOMES Trial results.

Echocardiographic assessment of COVID19 sequelae in survivors with elevated cardiac biomarkers.

AIMS: We sought to determine, using advanced echocardiography, the prevalence and type of cardiovascular sequelae after COVID19 infection with marked elevation of cardiovascular biomarkers (CVB), and their prognostic implications. METHODS: All patients admitted from March 1st to May 25th, 2020 to a tertiary referral hospital were included. Those with cardiovascular diseases or dead during admission were excluded. Patients with hs-TnI > 45 ng/L, NT-proBNP>300 pg/mL, and D-dimer >8000 ng/mL were matched with COVID controls (three biomarkers within the normal range) based on intensive care requirements and age, and separately analyzed. RESULTS: From 2025 patients, 80 patients with significantly elevated CVB and 29 controls were finally included. No differences in baseline characteristics were observed among groups, but elevated CVB patients were sicker. Follow-up echocardiograms showed no differences among groups regarding LVEF and only slight differences between groups within the normal range. Hs-TnI patients had lower myocardial work and longitudinal strain. The presence of an abnormal echocardiogram was more frequent in the elevated CVB group compared to controls (23.8 vs 10.3%, P = 0.123) but mainly associated with mild abnormalities in deformation parameters. Management did not change in any case and no major cardiovascular events except deep vein thrombosis occurred after a median follow-up of 7 months. CONCLUSION: Minimal abnormalities in cardiac structure and function are observed in COVID19 survivors without previous cardiovascular diseases who presented a significant CVB rise at admission, with no impact on patient management or short-term prognosis. These results do not support a routine screening program after discharge in this population.

Global Geriatric Assessment and In-Hospital Bleeding Risk in Elderly Patients with Acute Coronary Syndromes: Insights from the LONGEVO-SCA Registry.

BACKGROUND: Bleeding risk scores have shown a limited predictive ability in elderly patients with acute coronary syndromes (ACS). No study explored the role of a comprehensive geriatric assessment to predict in-hospital bleeding in this clinical setting. METHODS: The prospective multicentre LONGEVO-SCA registry included 532 unselected patients with non-ST segment elevation ACS (NSTEACS) aged 80 years or older. Comorbidity (Charlson index), frailty (FRAIL scale), disability (Barthel index and Lawton-Brody index), cognitive status (Pfeiffer test) and nutritional risk (mini nutritional assessment-short form test) were assessed during hospitalization. CRUSADE score was prospectively calculated for each patient. In-hospital major bleeding was defined by the CRUSADE classification. The association between geriatric syndromes and in-hospital major bleeding was assessed by logistic regression method and the area under the receiver operating characteristic curves (AUC). RESULTS: Mean age was 84.3 years (SD 4.1), 61.7% male. Most patients had increased troponin levels (84%). Mean CRUSADE bleeding score was 41 (SD 13). A total of 416 patients (78%) underwent an invasive strategy, and major bleeding was observed in 37 cases (7%). The ability of the CRUSADE score for predicting major bleeding was modest (AUC 0.64). From all aging-related variables, only comorbidity (Charlson index) was independently associated with major bleeding (per point, odds ratio: 1.23, p = 0.021). The addition of comorbidity to CRUSADE score slightly improved the ability for predicting major bleeding (AUC: 0.68). CONCLUSION: Comorbidity was associated with major bleeding in very elderly patients with NSTEACS. The contribution of frailty, disability or nutritional risk for predicting in-hospital major bleeding was marginal.

An Easy Assessment of Frailty at Baseline Independently Predicts Prognosis in Very Elderly Patients With Acute Coronary Syndromes.

BACKGROUND: Information about the impact of frailty in patients with acute coronary syndromes (ACS) is scarce. No study has assessed the prognostic impact of frailty as measured by the FRAIL scale in very elderly patients with ACS. METHODS: The prospective multicenter LONGEVO-SCA registry included unselected patients with ACS aged 80 years or older. A comprehensive geriatric assessment was performed during hospitalization, including frailty assessment by the FRAIL scale. The primary endpoint was mortality at 6 months. RESULTS: A total of 532 patients were included. Mean age was 84.3 years, 61.7% male. Most patients had positive troponin levels (84%) and high GRACE risk score values (mean 165). A total of 205 patients were classified as prefrail (38.5%) and 145 as frail (27.3%). Frail and prefrail patients had a higher prevalence of comorbidities, lower left ventricle ejection fraction, and higher mean GRACE score value. A total of 63 patients (11.8%) were dead at 6 months. Both prefrailty and frailty were associated with higher 6-month mortality rates (P < .001). After adjusting for potential confounders, this association remained significant (hazard ratio [HR] 2.71; 95% confidence interval [CI] 1.09-6.73 for prefrailty and HR 2.99; 95% CI 1.20-7.44 for frailty, P = .024). The other independent predictors of mortality were age, Charlson Index, and GRACE risk score. CONCLUSIONS: The FRAIL scale is a simple tool that independently predicts mortality in unselected very elderly patients with ACS. The presence of prefrailty criteria also should be taken into account when performing risk stratification of these patients.