[Effectiveness of the CNIC polypill in secondary cardiovascular prevention in the subgroup of patients of the NEPTUNO study using atorvastatin doses of 20 mg]. / Efectividad de la polipíldora CNIC en prevención cardiovascular secundaria en el subgrupo de pacientes del estudio NEPTUNO con dosis de atorvastatina de 20 mg.

Objective: To analyse the incidence and risk of recurrent major adverse cardiovascular events (MACE), level of risk factor control, treatment persistence and cost of the CNIC polypill version containing acetylsalicylic acid (ASA) 100 mg, atorvastatin 20 mg (A20), and ramipril 2.5, 5.0 or 10 mg in secondary cardiovascular prevention patients. Method: Subanalysis of the observational, retrospective, multicentre, NEPTUNO study in patients treated for two years with the CNIC polypill A20, the same monocomponents as single drugs, equipotent drugs, and other therapies. Results: 922 patients were included in each group. The risk of recurrent MACE was lower among CNIC A20 polypill users than all others (21%, 23% and 26% increased risk among the monocomponents, equipotent or other therapy cohorts, respectively; p < 0.05). The magnitude of the mean change in low-density lipoprotein cholesterol and blood pressure, as well as the increase in the proportion of patients achieving target goals, was also greater among patients treated with the CNIC A20 polypill than in any of the other cohorts (all p < 0.001). Treatment persistence was significantly higher in patients treated with the CNIC A20 polypill (p < 0.001) and was a less costly strategy than any other therapeutic option. Conclusions: In patients in secondary cardiovascular prevention, the CNIC A20 polypill (ASA 100 mg, atorvastatin 20 mg, and ramipril 2.5, 5.0 or 10 mg) constitutes a valid therapeutic option with similar benefits and outcomes to the version of the polypill with atorvastatin 40 mg.

Objetivo: Analizar la incidencia y el riesgo de eventos adversos cardiovasculares mayores (MACE) recurrentes, el nivel de control de factores de riesgo, la persistencia al tratamiento y el coste de la versión de la polipíldora CNIC que contiene 100 mg de ácido acetilsalicílico (AAS), 20 mg de atorvastatina (A20) y 2.5/5.0 ó 10 mg de ramipril en pacientes en prevención cardiovascular secundaria. Método: Subanálisis del estudio observacional, retrospectivo y multicéntrico NEPTUNO en pacientes tratados durante 2 años con la polipíldora CNIC A20, los mismos monocomponentes por separado, medicamentos equipotentes uotras terapias. Resultados: Se incluyeron 922 pacientes en cada grupo. El riesgo de sufrir un MACE recurrente en el grupode polipíldora CNIC A20 fue menor que en todas las demás cohortes (21%, 23% y 26% de aumento del riesgo en las cohortesde monocomponentes, equipotentes u otras terapias, respectivamente; p < 0.05). La magnitud del cambio en el colesterol unidoa lipoproteínas de baja densidad y la presión arterial, así como el incremento en la proporción de pacientes que alcanzaron losobjetivos establecidos, fueron mayores en los pacientes tratados con la polipíldora CNIC A20 que en cualquiera de las otrascohortes (p < 0.001). La persistencia al tratamiento fue mayor en los pacientes tratados con la polipíldora CNIC A20 (p < 0.001)y esta estrategia resultó ser menos costosa que cualquier otra opción terapéutica. Conclusiones: En pacientes en prevencióncardiovascular secundaria, la polipíldora CNIC A20 (AAS 100 mg; atorvastatina 20 mg; ramipril 2.5/5.0 ó 10 mg) constituye unaopción terapéutica válida con beneficios y resultados similares a la versión de la polipíldora con 40 mg de atorvastatina.

Classification tree obtained by artificial intelligence for the prediction of heart failure after acute coronary syndromes. / Árboles de clasificación obtenidos mediante inteligencia artificial para la predicción de insuficiencia cardiaca tras el síndrome coronario agudo.

BACKGROUND: Coronary heart disease is the leading cause of heart failure (HF), and tools are needed to identify patients with a higher probability of developing HF after an acute coronary syndrome (ACS). Artificial intelligence (AI) has proven to be useful in identifying variables related to the development of cardiovascular complications. METHODS: We included all consecutive patients discharged after ACS in two Spanish centers between 2006 and 2017. Clinical data were collected and patients were followed up for a median of 53months. Decision tree models were created by the model-based recursive partitioning algorithm. RESULTS: The cohort consisted of 7,097 patients with a median follow-up of 53months (interquartile range: 18-77). The readmission rate for HF was 13.6% (964 patients). Eight relevant variables were identified to predict HF hospitalization time: HF at index hospitalization, diabetes, atrial fibrillation, glomerular filtration rate, age, Charlson index, hemoglobin, and left ventricular ejection fraction. The decision tree model provided 15 clinical risk patterns with significantly different HF readmission rates. CONCLUSIONS: The decision tree model, obtained by AI, identified 8 leading variables capable of predicting HF and generated 15 differentiated clinical patterns with respect to the probability of being hospitalized for HF. An electronic application was created and made available for free.

Lp(a) Levels in Relatives of Patients with Acute Coronary Syndrome and Elevated Lp(a): HER(a) Study.

Background: Lipoprotein(a) [Lp(a)] is a proatherogenic particle associated with increased cardiovascular risk. It is mainly genetically determined; so, the aim of our study is to evaluate the levels of Lp(a) in the relatives of a prospective cohort of patients who have suffered from an acute coronary syndrome (ACS) with Lp(a) ≥ 50 mg/dL. Methods: We conducted a multicenter prospective study, in which consecutive patients who had suffered from an ACS and presented Lp(a) ≥ 50 mg/dL and their first-degree relatives were included. Results: We included 413 subjects, of which 56.4% were relatives of the patients. Family history of early ischemic heart disease was present in 57.5%, and only 20.6% were receiving statin treatment. The family cohort was younger (37.5 vs. 59.1 years; p < 0.001), and 4% had ischemic heart disease and fewer cardiovascular risk factors. Mean Lp(a) levels were 64.9 mg/dL, 59.4% had levels ≥ 50 mg/dL, and 16.1% had levels ≥ 100 mg/dL. When comparing the patients with respect to their relatives, the mean level of Lp(a) was lower but without significant differences regarding the levels of LDLc, ApoB, and non-HDL. However, relatives with Lp(a) ≥ 50 mg/dL, had values similar to the group of patients with ACS (96.8 vs. 103.8 mg/dL; p = 0.18). No differences were found in Lp(a) levels in relatives based on the other lipid parameters. Conclusions: Overall, 59.4% of the first-degree relatives of patients who suffered from an ACS with Lp(a) ≥ 50 mg/dL also had elevated levels. Relatives with elevated Lp(a) had similar levels as patients.

The CNIC-polypill (acetylsalicylic acid, atorvastatin, and ramipril), an effective and cost-saving secondary prevention strategy compared with other therapeutic options in patients with ischaemic heart disease.

Aims: The retrospective NEPTUNO study evaluated the effectiveness of the Centro Nacional de Investigaciones Cardiovasculares (CNIC)-polypill (including acetylsalicylic acid, ramipril, and atorvastatin) vs. other therapeutic approaches in secondary prevention for cardiovascular (CV) disease. In this substudy, the focus was on the subgroup of patients with ischaemic heart disease (IHD). Methods and results: Patients on four strategies: CNIC-polypill, its monocomponents as loose medications, equipotent medications, and other therapies. The primary endpoint was the incidence of recurrent major adverse CV events (MACEs) after 2 years. After matching, 1080 patients were included in each cohort. The CNIC-polypill cohort had a significantly lower incidence of recurrent MACE compared with monocomponents, equipotent drugs, and other therapies cohorts (16.1 vs. 24, 24.4, and 24.3%, respectively; P < 0.001). The hazard ratios (HRs) for recurrent MACE were higher in monocomponents (HR = 1.12; P = 0.042), equipotent drugs (HR = 1.14; P = 0.031), and other therapies cohorts (HR = 1.17; P = 0.016) compared with the CNIC-polypill, with a number needed to treat of 12 patients to prevent a MACE. The CNIC-polypill demonstrated a greater reduction in LDL cholesterol (LDL-c; -56.1 vs. -43.6, -33.3, and -33.2% in the monocomponents, equipotent drugs, and other therapies, respectively; P < 0.001) and systolic blood pressure (-13.7 vs. -11.5, -10.6, and -9.1% in the CNIC-polypill, monocomponents, equipotent drugs, and other therapies, respectively; P < 0.001) compared with other cohorts. The CNIC-polypill intervention was less costly and more effective than any other therapeutic option, with €2317-€2407 cost savings per event prevented. Conclusion: In IHD, the CNIC-polypill exemplifies a guideline-recommended secondary prevention treatment linked to better outcomes and cost saving compared with other therapeutic options.

Design and validation of a new questionnaire with a gender perspective to measure medication adherence for secondary prevention of ischaemic heart disease: study protocol.

INTRODUCTION AND OBJECTIVES: Only about 50% of chronic patients in high-income countries adhere to their treatment. There are methods to measure medication adherence but none of them can be considered optimal. This study will aim to design and validate a questionnaire to measure medication adherence in patients with ischaemic heart disease using a direct method as a gold-standard adherence measure and taking into account the gender perspective. Moreover, the profile of low adherence in these patients will be determined. METHODS AND ANALYSIS: First study phase consists on the questionnaire design following the next steps: identification of the dimensions, definition of the target population, questionnaire items and order, response coding, questionnaire instructions, content validity by experts and understandability. In the second phase, a cross-sectional study will be performed to end the questionnaire development and validate it. Four hundred and forty patients (50% female) with acute coronary syndrome receiving treatment within the previous 12 months will be included. Patient will answer the initial questionnaire and adherence to aspirin and statin will be measured using a direct method (drug concentration analysis in blood) and other questionnaires. From the set of preselected questionnaire items, those most closely associated with the gold standard measure will be selected using multivariate statistics. ETHICS AND DISSEMINATION: All participants gave their written informed consent before participating in the study. The study protocol follows the recommendations of the Declaration of Helsinki and was approved by the ethics committees of the three participating centres. The results of this study will be displayed at national and international conferences and in peer-reviewed scientific journals.

Lipoprotein(a) and Long-Term Recurrent Infarction After an Acute Myocardial Infarction.

Lipoprotein(a) (Lp[a]) is an emerging risk factor for incident ischemic heart disease. However, its role in risk stratification in in-hospital survivors to an index acute myocardial infarction (AMI) is scarcer, especially for predicting the risk of long-term recurrent AMI. We aimed to assess the relation between Lp(a) and very long-term recurrent AMI after an index episode of AMI. It is a retrospective analysis that included 1,223 consecutive patients with an AMI discharged from October 2000 to June 2003 in a single-teaching center. Lp(a) was assessed during index admission in all cases. The relation between Lp(a) at discharge and total recurrent AMI was evaluated through negative binomial regression. The mean age of the patients was 67.0 ± 12.3 years, 379 (31.0%) were women, and 394 (32.2%) were diabetic. The index event was more frequently non-ST-segment elevation myocardial infarction (66.0%). The median Lp(a) was 28.8 (11.8 to 63.4) mg/100 ml. During a median follow-up of 9.9 (4.6 to 15.5) years, 813 (66.6%) deaths and 1,205 AMI in 532 patients (43.5%) occurred. Lp(a) values were not associated with an increased risk of long-term all-cause mortality (p = 0.934). However, they were positively and nonlinearly associated with an increased risk of total long-term reinfarction (p = 0.016). In the subgroup analysis, there was no evidence of a differential effect for the most prevalent subgroups. In conclusion, after an AMI, elevated Lp(a) values assessed during hospitalization were associated with an increased risk of recurrent reinfarction in the very long term. Further prospective studies are warranted to evaluate their clinical implications.

[Predictive validity of the risk SCORE model in a Mediterranean population with arterial hypertension]. / Validez en la predicción de riesgo de la escala SCORE en una población mediterránea con hipertensión arterial.

INTRODUCTION AND OBJECTIVES: Hypertension is the most prevalent risk factor globally. Calculation of cardiovascular risk in hypertensive patients before initiation of treatment is recommended. This study aimed to assess the predictive value and clinical utility of the SCORE scale in preventing cardiovascular events and all-cause mortality in patients with hypertension. METHODS: Patients with hypertension from the ESCARVAL-RISK cohort were included. Cardiovascular risk was calculated using the SCORE scale. All deaths and cardiovascular events were recorded during a 5-year follow-up period. Sensitivity, specificity and predictive values were calculated for different cut-off points and the effect of different risk factors on the diagnostic accuracy of SCORE charts were assessed. RESULTS: In a final cohort of 9834 patients, there were 555 cardiovascular events and 69 deaths. The recommended risk value for initiating drug treatment (5%) had a specificity of 92% for death and 91% for cardiovascular events, and a sensitivity of 20% for death and 22% for cardiovascular events. In addition, the scale classified 80.4% of patients who experienced a cardiovascular event and 78.3% of those who died as low risk. Age, body mass index, retinopathy and anticoagulant therapy were associated with reduced predictive ability of the SCORE scale, while being female was associated with better risk prediction. CONCLUSIONS: The predictive ability of the SCORE scale for cardiovascular disease and total mortality in patients with hypertension is limited.

Index and Repeat Ablation for Atrial Fibrillation in Older versus Younger Patients: A Propensity-Score Matching Analysis.

Catheter ablation is a well-established rhythm control therapy in atrial fibrillation (AF). Although the prevalence of AF increases dramatically with age, the prognosis and safety profile of index and repeat ablation procedures remain unclear in the older population. The primary endpoint of this study was to assess the arrhythmia recurrence, reablation and complication rates in older patients. Secondary endpoints were the identification of independent predictors of arrhythmia recurrence and reablation, including information on pulmonary vein (PV) reconnection and other atrial foci. Older (n=129, ≥70 years) and younger (n=129, <70 years) patients were compared using a propensity-score matching analysis based on age, gender, obesity, hypertension, dyslipidemia, diabetes mellitus, dilated left atrium, severe obstructive sleep apnea, cardiac disease, left systolic ventricular function, AF pattern and ablation technique. Arrhythmia recurrence and reablation were evaluated in both groups using a Cox regression analysis in order to identify predictors. During a 30-month follow-up period, there were no significant differences between older and younger patients in the arrhythmia-free survival (65.1% and 59.7%; log-rank test p=0.403) and complication (10.1% and 10.9%; p>0.999) rates after the index ablation. However, the reablation rate was significantly different (46.7% and 69.2%; p<0.05, respectively). In those patients who underwent reablation procedure (redo subgroups), there were no differences in the incidence of PV reconnection (38.1% redo-older and 27.8% redo-younger patients; p=0.556). However, the redo-older patients had lower reconnected PVs per patient (p<0.01) and lower atrial foci (2.3 and 3.7; p<0.01) than the redo-younger patients. A further important finding was that age was not an independent predictor of arrhythmia recurrence or reablation. Our data reveal that the AF index ablation in older patients had a similar efficacy and safety profile to younger patients. Therefore, age alone must not be considered a prognostic factor for AF ablation but the presence of limiting factors such as frailty and multiple comorbidities.

Risk factors for major adverse cardiovascular events in postmenopausal women: UK Biobank prospective cohort study.

BACKGROUND AND AIMS: Cardiovascular risk increases during menopause, so the medical and scientific community should consider women's specific risk factors to prevent cardiovascular disease. This study aims to assess the risk factors for the incidence of major adverse cardiovascular events (MACE) exclusive to postmenopausal women. METHODS: We conducted a prospective cohort study in postmenopausal women aged 40 years and older, who were included in the UK Biobank cohort between 2006 and 2010 and followed to 2021 (12 years). A total of 156,787 women were followed for a median of 12.5 years (nearly 2 million person-years), and MACE risk was assessed using Fine-Gray competing risk models. RESULTS: The cumulative incidence of cardiovascular morbidity and mortality was 1.2% (0.97 cases per 1000 women-years). Not having taken birth control pills, not having children, and early menarche (≤12 years) were independently associated with cardiovascular morbidity and mortality. CONCLUSIONS: Risk factors for cardiovascular disease that are specific to women include early menarche, not having taken oral contraceptives, and reproductive history, and this relationship is independent of classic cardiovascular risk factors.

The efficacy of intensive lipid-lowering therapies on the reduction of LDLc and of major cardiovascular events.

BACKGROUND: Statins are the cornerstone of lipid-lowering therapy (LLT) for reduction of low-density lipoprotein cholesterol (LDLc) levels and high percentage of patients require LLT combinations or alternative treatments for adequate LDLc control. METHODS: We performed an intention-to-treat meta-analysis of published data of phase III trials evaluating LLT efficacy on major adverse cardiovascular events (MACE). The primary endpoint was MACE incidence, as reported in each trial, and secondary analyses included myocardial infarction, stroke and mortality. RESULTS: Eleven clinical trials and 135,688 patients were included; seven trials tested high intensity LLT and 4 LLT combinations. Intensive LLT reduced MACE risk by 15% (12.03% vs. 13.79%, HR: 0.85 95% CI 0.80-0.90; p<0.001). The number needed to treat was 56 patients. Meta-regression analyses showed a linear correlation between absolute LDLc reductions and the risk of MACE. Significant reductions in myocardial infarction (HR: 0.83, 95% CI 0.80-0.86) and stroke (HR: 0.81, 95% CI 0.75-0.87) were observed. Cardiovascular death rate was 3.32% in LLT treatment arm vs. 3.56% in controls, resulting in a HR: 0.94 (95% CI 0.88-0.99; p = 0.03); no effect on all-cause mortality was observed (HR: 0.97 95% CI 0.93-1.01; p = 0.09). The sensitivity analyses verified the lack of heterogeneity, except for MACE that was mainly driven by the divergent results of the 2 trials. Small study effect was detected for the assessment of mortality. CONCLUSIONS: Current evidence consistently supports the efficacy of available intensity LLT for LDLc decrease on MACE and cardiovascular mortality reduction.

Changes in circulating ApoJ-Glyc levels in patients with suspected acute coronary syndrome: The EDICA trial.

BACKGROUND: Myocardial ischemia induces intracellular accumulation of non-glycosylated apolipoprotein J that results in a reduction of circulating glycosylated ApoJ (ApoJ-Glyc). The latter has been suggested to be a marker of transient myocardial ischemia. OBJECTIVE: This proof-of-concept clinical study aimed to assess whether changes in circulating ApoJ-Glyc could detect myocardial ischemia in patients attending the emergency department (ED) with chest pain suggestive of acute coronary syndrome (ACS). METHODS: In suspected ACS patients, EDICA (Early Detection of Myocardial Ischemia in Suspected Acute Coronary Syndromes by ApoJ-Glyc a Novel Pathologically based Ischemia Biomarker), a multicentre, international, cohort study assessed changes in 2 glycosylated variants of ApoJ-Glyc, (ApoJ-GlycA2 and ApoJ-GlycA6), in serum samples obtained at ED admission (0 h), and 1 h and 3 h thereafter, blinded to the clinical diagnosis (i.e. STEMI, NSTEMI, unstable angina, non-ischemic). RESULTS: 404 patients were recruited; 291 were given a clinical diagnosis of "non-ischemic" chest pain and 113 were considered to have had an ischemic event. ApoJ-GlycA6 was lower on admission in ischemic compared with "non-ischemic" patients (66 [46-90] vs. 73 [56-95] µg/ml; P = 0.04). 74% of unstable angina patients (all with undetectable hs-Tn), had ischemic changes in ApoJ-Glyc at 0 h and 89% at 1 h. Initially low ApoJ-Glyc levels in 62 patients requiring coronary revascularization increased significantly after successful percutaneous intervention. CONCLUSIONS: Circulating ApoJ-Glyc concentrations decrease early in ED patients with myocardial ischemia compared with "non-ischemic" patients, even in the absence of troponin elevations. ApoJ-Glyc may be a useful marker of myocardial ischemia in the ED setting.

Clinical Benefit of Bempedoic Acid in Randomized Clinical Trials.

Bempedoic acid is a selective inhibitor of the adenosine triphosphate citrate lyase that reduces low-density lipoprotein cholesterol (LDLc) levels by 17% to 28%. Although the Evaluation of Major Cardiovascular Events in Patients With, or at High Risk for, Cardiovascular Disease Who Are Statin Intolerant Treated With Bempedoic Acid (CLEAR-OUTCOMES) trials demonstrated the efficacy on cardiovascular outcomes there is a controversy related to the possible net clinical benefit. Thereafter, we performed an intention-to-treat meta-analysis in line with recommendations from the Cochrane Collaboration and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The primary outcome of the metanalysis was the incidence of major adverse cardiovascular events, defined by each study protocol. Secondary outcomes for the analyses were myocardial infarction, stroke, myocardial revascularization, cardiovascular death, and all-cause death. Results of 4 clinical trials evaluated contained a total of 17,324 patients; 9,236 received bempedoic acid for a median of 46.6 months. The mean baseline LDLc was 129.4 (22.8) mg/100 ml and treatment was associated with a mean LDLc reduction of 26.0 (12.6) mg/100 ml. Treatment with bempedoic acid significantly reduced the incidence of major adverse cardiovascular events (hazard ratio [HR] 0.88, 95% confidence interval [CI] 0.81 to 0.96), myocardial infarction (HR 0.76, 95% CI 0.66 to 0.89) and myocardial revascularization (HR 0.82, 95% CI 0.73 to 0.92); the crude incidence of stroke, cardiovascular or all-cause mortality were lower in patients in the bempedoic acid groups although no significant risk reduction was observed. No heterogeneity was observed in any of the end points. In conclusion, the metanalysis of the 4 clinical trials currently available with bempedoic acid provides reliable evidence of its clinical benefit with no signs of heterogeneity or harm.

Effect of dapagliflozin on COVID-19 infection and risk of hospitalization.

BACKGROUND: Dapagliflozin has been proposed as a potential treatment for coronavirus disease 2019 (COVID-19) by reducing cytokine production and inflammation. However, there are limited data on its effectiveness. We aimed to evaluate the impact of dapagliflozin on COVID-19 severity (including hospitalization risk, ICU admission, in-hospital death and progression to severe COVID-19) and its potential on susceptibility to COVID-19 infection. METHODS: We conducted a population-based case-control study. For aim 1, we assessed COVID-19 severity in cases (positive PCR patients requiring hospitalization) and matched controls (negative PCR patients or positive PCR patients not requiring hospitalization). For aim 2, we compared positive PCR cases (hospitalized and non-hospitalized) with controls. Adjusted odds ratios (aORs) were calculated using a generalized linear mixed model. RESULTS: We analysed 86 602 subjects: 3060 were hospitalized cases, 26 757 were non-hospitalized cases and 56 785 were controls. Among the hospitalized COVID-19 patients, 228 were admitted to the ICU and 413 died. Dapagliflozin had no effect on the risk of hospitalization (aOR 0.98; 95% CI 0.65-1.48; P = 0.915), ICU admissions (aOR 1.21; 95% CI 0.34-4.25; P = 0.767) or in-hospital death (aOR 1.33; 95% CI 0.53-3.30; P = 0.543). Dapagliflozin reduced the risk of progression to severe COVID-19 by 35%, but this was not statistically significant (aOR 0.65; 95% CI 0.40-1.06; P = 0.086). Dapagliflozin was associated with a 30% increased risk of susceptibility to COVID-19 infection (aOR 1.31; 95% CI 1.05-1.62; P = 0.015). CONCLUSIONS: Use of dapagliflozin prior to SARS-CoV-2 infection was not associated with an increased risk of hospitalization, ICU admission, mortality or progression to severe COVID-19. However, it was associated with an increased risk of susceptibility to COVID-19 infection.

Cognitive Function with PCSK9 Inhibitors: A 24-Month Follow-Up Observational Prospective Study in the Real World-MEMOGAL Study.

INTRODUCTION: The cognitive safety of monoclonal antibody proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) has been established in clinical trials, but not yet in real-world observational studies. We assessed the cognitive function in patients initiating PCSK9i, and differences in cognitive function domains, to analyze subgroups by the low-density lipoprotein cholesterol (LDL-C) achieved, and differences between alirocumab and evolocumab. METHODS: This has a multicenter, quasi-experimental design carried out in 12 Spanish hospitals from May 2020 to February 2023. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA). RESULTS: Among 158 patients followed for a median of 99 weeks, 52% were taking evolocumab and 48% alirocumab; the mean change from baseline in MoCA score at follow-up was + 0.28 [95% CI (- 0.17 to 0.73; p = 0.216)]. There were no significant differences in the secondary endpoints-the visuospatial/executive domain + 0.04 (p = 0.651), naming domain - 0.01 (p = 0.671), attention/memory domain + 0.01 (p = 0.945); language domain - 0.10 (p = 0.145), abstraction domain + 0.03 (p = 0.624), and orientation domain - 0.05 (p = 0.224)-but for delayed recall memory the mean change was statistically significant (improvement) + 0.44 (p = 0.001). Neither were there any differences in the three stratified subgroups according to lowest attained LDL-C level-0-54 mg/dL, 55-69 mg/dL and ≥ 70 mg/dL; p = 0.454-or between alirocumab and evolocumab arms. CONCLUSION: We did not find effect of monoclonal antibody PCSK9i on neurocognitive function over 24 months of treatment, either in global MoCA score or different cognitive domains. An improvement in delayed recall memory was shown. The study showed no differences in the cognitive function between the prespecified subgroups, even among patients who achieved very low levels of LDL-C. There were no differences between alirocumab and evolocumab. REGISTRATION: ClinicalTtrials.gov Identifier number NCT04319081.

Economic Burden Associated with the Treatment with a Cardiovascular Polypill in Secondary Prevention in Spain: Cost-Effectiveness Results of the NEPTUNO Study.

Purpose: The aim of this study was to estimate health-care resources utilization, costs and cost-effectiveness associated with the treatment with CNIC-Polypill as secondary prevention of atherosclerotic cardiovascular disease (ASCVD) compared to other treatments, in clinical practice in Spain. Patients and Methods: An observational, retrospective study was performed using medical records (economic results [healthcare perspective], NEPTUNO-study; BIG-PAC-database) of patients who initiated secondary prevention between 2015 and 2018. Patients were followed up to 2 years (maximum). Four cohorts were balanced with a propensity-score-matching (PSM): 1) CNIC-Polypill (aspirin+atorvastatin+ramipril), 2) Monocomponents (same separate drugs), 3) Equipotent (equipotent drugs) and 4) Other therapies ([OT], other cardiovascular drugs). Incidence of cardiovascular events, health-care resources utilization and healthcare and non-healthcare costs (2020 Euros) were compared. Incremental cost-effectiveness ratios per cardiovascular event avoided were estimated. Results: After PSM, 1614 patients were recruited in each study cohort. The accumulated incidence of cardiovascular events during the 24-month follow-up was lower in the CNIC-Polypill cohort vs the other cohorts (19.8% vs Monocomponents: 23.3%, Equipotent: 25.5% and OT: 26.8%; p<0.01). During the follow-up period, the CNIC-Polypill cohort also reduced the health-care resources utilization per patient compared to the other cohorts, particularly primary care visits (16.6 vs Monocomponents: 18.7, Equipotent: 18.9 and OT: 21.0; p<0.001) and hospitalization days (2.3 vs Monocomponents: 3.4, Equipotent: 3.7 and OT: 4.0; p<0.001). The treatment cost in the CNIC-Polypill cohort was lower than that in the other cohorts (€4668 vs Monocomponents: €5587; Equipotent: €5682 and OT: €6016; p<0.001) (Difference: -€919, -€1014 and -€1348, respectively). Due to the reduction of cardiovascular events and costs, the CNIC-Polypill is a dominant alternative compared to the other treatments. Conclusion: CNIC-Polypill reduces recurrent major cardiovascular events and costs, being a cost-saving strategy as secondary prevention of ASCVD.