Search

Abstract Background Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is one of the most efficient therapeutic options available to cure many hematological malignancies. However, severe complications derived from this procedure, including graft-versus-host disease (GVHD) and infections, can limit its success and negatively impact survival. Previous studies have shown that alterations in the microbiome are associated with the development of allo-HSCT-derived complications. However, most studies relied on single techniques that can only analyze a unique aspect of the microbiome, which hinders our ability to understand how microbiome alterations drive allo-HSCT-associated diseases. Results Here, we have applied multiple “omic” techniques (16S rRNA and shotgun sequencing, targeted and un-targeted metabolomics) in combination with machine learning approaches to define the most significant microbiome changes following allo-HSCT at multiple modalities (bacterial taxa, encoded functions, and derived metabolites). In addition, multivariate approaches were applied to study interactions among the various microbiome modalities (the interactome). Our results show that the microbiome of transplanted patients exhibits substantial changes in all studied modalities. These include depletion of beneficial microbes, mainly from the Clostridiales order, loss of their bacterial encoded functions required for the synthesis of key metabolites, and a reduction in metabolic end products such as short chain fatty acids (SCFAs). These changes were followed by an expansion of bacteria that frequently cause infections after allo-HSCT, including several Staphylococcus species, which benefit from the reduction of bacteriostatic SCFAs. Additionally, we found specific alterations in all microbiome modalities that distinguished those patients who subsequently developed GVHD, including depletion of anti-inflammatory commensals, protective reactive oxygen detoxifying enzymes, and immunoregulatory metabolites such as acetate or malonate. Moreover, extensive shifts in the homeostatic relationship between bacteria and their metabolic products (e.g., Faecalibacterium and butyrate) were detected mainly in patients who later developed GVHD. Conclusions We have identified specific microbiome changes at different modalities (microbial taxa, their encoded genes, and synthetized metabolites) and at the interface between them (the interactome) that precede the development of complications associated with allo-HSCT. These identified microbial features provide novel targets for the design of microbiome-based strategies to prevent diseases associated with stem cell transplantation. Video Abstract

Introduction: Intradialytic hypertension (IDH) is a poorly understood phenomenon with no consensus on its definition, etiology, or related factors, and there is limited evidence on its consequences. Objective: To determine the prevalence of IDH according to different definitions in hemodialysis (HD) units, with different clinical practices and assessment of possible events after 18 months have passed. Materials and methods: A cross-sectional observational study was conducted in 2 HD units, including all prevalent patients from March 2021 to September 2022. We established 3 definitions of IDH: • Def 1: Mean arterial pressure (MAP) difference pre- and pos-HD >15 mmHg • Def 2: Systolic blood pressure (SBP) difference pre- and pos-HD >10 mmHg • Def 3: SBP difference >0 and ultrafiltration rate (UFR) >5 ml/kg/hIDH was considered present if the criterion was met in more than 50% of the 6 consecutive sessions (2 weeks) of follow-up. Personal history, medications, dialysis characteristics, and pre- and post-HD biochemical data were collected. Residual renal function (RRF) was considered as urine output >250 ml/24 h. At 18 months, the possible events of the group were analyzed. Results: We included 169 patients (68% men) with a mean age of 67.9 (14.2) years and a median HD duration of 34.5 (IQR 17.5–67.5) months. Of these, 94 come from one unit and 75 from the other. The prevalence of IDH was 8.3% according to Def 1, 27.2% according to Def 2, and 29.6% according to Def 3. Def 2 showed an association with a history of previous hypertension, use of renin-angiotensin system inhibitors (RASIs), and furosemide, as well as with patients with RRF. Def 3 showed an association only with coronary artery disease. There was an association with different prescriptions of dialysis fluids. Catecholaminergic hormones and aldosterone did not increase in patients with hypertension during the HD session. They did not present a higher incidence of cardiovascular events or mortality at 18 months. Conclusions: IDH has different prevalence rates depending on the definition used and the studied center. The future poses an important challenge: to determine which definition correlates with higher morbidity and mortality and the role of differences found in different HD units. Resumen: Introducción: La hipertensión arterial intradiálisis (HTAID) es un fenómeno poco conocido del que no existe consenso en su definición, ni datos sobre su etiología o factores relacionados, y hay poca evidencia sobre sus repercusiones. Objetivo: Definir la prevalencia según diferentes definiciones en dos unidades de hemodiálisis (HD), de dos hospitales diferentes, con distinta práctica clínica y valoración de posibles eventos después de haber pasado 18 meses. Material y métodos: Estudio observacional transversal realizado en 2 unidades de HD donde se incluyeron todos los pacientes prevalentes desde marzo 2021 hasta septiembre 2022. Establecimos 3 definiciones de HTAID: • Def 1: Diferencia de presión arterial media (PAM) pre- y pos-HD > 15 mmHg • Def 2: Diferencia de presión arterial sistólica (PAS) pre- y pos-HD > 10 mmHg • Def 3: Diferencia de PAS > 0 y UFR > 5 ml/kg/hConsideramos había HTAID si se cumplía el criterio en más del 50% de las 6 sesiones consecutivas (2 semanas) de seguimiento. Se recogieron antecedentes personales, medicamentos, características de diálisis y datos bioquímicos pre y post HD. Se consideró función renal residual (FRR) una diuresis >250 ml/24 h. Se analizó a los 18 meses los posibles eventos del grupo. Resultados: Incluimos 169 pacientes (68% hombres), con una edad media de 67,9 (14,2) años y una mediana de tiempo en HD de 34,5 (AIC 17,5–67,5) meses. De ellos 94 provienen de una unidad y 75 de la otra. La prevalencia de HTAID fue según Def1 (8,3%), Def 2 (27,2%) y Def3 (29,6%). Se evidencia una asociación en la Def2 con antecedente de HTA previa, uso de inhibidores del sistema renina angiotensina (ISRA) y furosemida y en los pacientes con FRR, en la Def3 solo asociación a coronariopatía. Existe asociación con las diferentes prescripciones de los líquidos de diálisis. No aumentaron las hormonas catecolaminérgicas y aldosterona en los pacientes con HTAID durante la sesión de HD. No presentaron mayor incidencia de eventos cardiovasculares o mortalidad a los 18 meses. Conclusiones: La HTAID tiene una prevalencia distinta tanto según la definición utilizada como la unidad estudiada. El futuro plantea un importante reto: conocer cuál de las definiciones determina una mayor implicación clínica y el papel que tienen las diferencias encontradas en las distintas unidades de HD.

Resumen: Introducción: La hipertensión arterial intradiálisis (HTAID) es un fenómeno poco conocido del que no existe consenso en su definición, ni datos sobre su etiología o factores relacionados, y hay poca evidencia sobre sus repercusiones. Objetivo: Definir la prevalencia según diferentes definiciones en 2 unidades de hemodiálisis (HD), de 2 hospitales diferentes, con distinta práctica clínica y valoración de posibles eventos después de haber pasado 18 meses. Material y métodos: Estudio observacional transversal realizado en 2 unidades de HD donde se incluyeron todos los pacientes prevalentes desde marzo de 2021 hasta septiembre de 2022. Establecimos 3 definiciones de HTAID: - Def 1: Diferencia de presión arterial media (PAM) pre- y pos-HD > 15 mmHg. - Def 2: Diferencia de presión arterial sistólica (PAS) pre- y pos-HD > 10 mmHg. - Def 3: Diferencia de PAS > 0 y UFR > 5 ml/kg/h.Consideramos que había HTAID si se cumplía el criterio en más del 50% de las 6 sesiones consecutivas (2 semanas) de seguimiento. Se recogieron antecedentes personales, medicamentos, características de diálisis y datos bioquímicos pre- y pos-HD. Se consideró función renal residual (FRR) una diuresis > 250 ml/24 h. Se analizó a los 18 meses los posibles eventos del grupo. Resultados: Incluimos 169 pacientes (68% varones), con una edad media de 67,9 (14,2) años y una mediana de tiempo en HD de 34,5 (AIC 17,5-67,5) meses. De ellos, 94 provienen de una unidad y 75 de la otra. La prevalencia de HTAID fue según Def 1 (8,3%), Def 2 (27,2%) y Def 3 (29,6%). Se evidencia una asociación en la Def 2 con antecedente de HTA previa, uso de inhibidores del sistema renina angiotensina (ISRA) y furosemida y en los pacientes con FRR, en la Def 3 solo asociación a coronariopatía. Existe asociación con las diferentes prescripciones de los líquidos de diálisis. No aumentaron las hormonas catecolaminérgicas y aldosterona en los pacientes con HTAID durante la sesión de HD. No presentaron mayor incidencia de eventos cardiovasculares o mortalidad a los 18 meses. Conclusiones: La HTAID tiene una prevalencia distinta tanto según la definición utilizada como la unidad estudiada. El futuro plantea un importante reto: conocer cuál de las definiciones determina una mayor implicación clínica y el papel que tienen las diferencias encontradas en las distintas unidades de HD. Abstract: Introduction: Intradialytic hypertension (IDH) is a poorly understood phenomenon with no consensus on its definition, etiology, or related factors, and there is limited evidence on its consequences. Objective: To determine the prevalence of IDH according to different definitions in hemodialysis (HD) units, with different clinical practices and assessment of possible events after 18 months have passed. Materials and methods: A cross-sectional observational study was conducted in two HD units, including all prevalent patients from March 2021 to September 2022. We established three definitions of IDH: Def 1: Mean arterial pressure (MAP) difference pre- and pos-HD > 15 mmHg. Def 2: Systolic blood pressure (SBP) difference pre- and pos-HD > 10 mmHg. Def 3: SBP difference >0 and ultrafiltration rate (UFR) > 5 ml/kg/h.IDH was considered present if the criterion was met in more than 50% of the six consecutive sessions (2 weeks) of follow-up. Personal history, medications, dialysis characteristics, and pre- and post-HD biochemical data were collected. Residual renal function (RRF) was considered as urine output >250 ml/24 h. At 18 months, the possible events of the group were analyzed. Results: We included 169 patients (68% men) with a mean age of 67.9 (14.2) years and a median HD duration of 34.5 (IQR: 17.5-67.5) months. Of these, 94 come from one unit and 75 from the other. The prevalence of IDH was 8.3% according to Def 1, 27.2% according to Def 2, and 29.6% according to Def 3. Def 2 showed an association with a history of previous hypertension, use of renin-angiotensin system inhibitors (RASIs), and furosemide, as well as with patients with RRF. Def 3 showed an association only with coronary artery disease. There was an association with different prescriptions of dialysis fluids. Catecholaminergic hormones and aldosterone did not increase in patients with hypertension during the HD session. They did not present a higher incidence of cardiovascular events or mortality at 18 months. Conclusions: IDH has different prevalence rates depending on the definition used and the studied center. The future poses an important challenge: to determine which definition correlates with higher morbidity and mortality and the role of differences found in different HD units.

Abstract We compared outcomes of adult patients with secondary acute myeloid leukemia (sAML) versus de novo AML after non-T-depleted haploidentical stem cell transplant (HaploSCT) with post-transplant cyclophosphamide (PTCy). Seventeen hundred and eleven AML patients (sAML-231, de novo-1480) in first complete remission transplanted from 2010 to 2021, were included. Patients with de novo AML were younger, median age 55.8 versus 60.8 years, p

Multidrug-resistant Enterobacteriaceae (MRE) represent a major threat for patients’ health. Here, the authors describe how cooperation between gut commensal bacteria (Lactobacillus spp. And Clostridiales) restrict MRE colonization in mice and patients

Objectives To estimate the readiness of Spanish National Health Service (NHS) hospitals to provide chimeric antigen receptor T cell (CAR-T), and to identify and quantify the different resources needed to provide CAR-T considering three scenarios defined by 10, 25 and 50 patients per centre per year.Design Targeted literature review and quantitative study using a questionnaire and telephone interviews. An algorithm was created to determine hospitals’ readiness based on their capacity and capability. All the requirements for quantification were assessed and validated by the steering committee, formed by members of the Spanish Group of Haematopoietic Transplantation and Cell Therapy. A weighting system (from 0 to 1) was established for capability quantification. For resources quantification, a scoring system was established, with 0 points representing the minimum and 3 points the maximum of additional resources that a hospital indicated necessary.Setting 40 Spanish hospital centres that perform allogeneic haematopoietic stem cell transplantation were invited to complete the questionnaire for capacity quantification, 28 of which provided valid responses. Nine hospitals participated in the interviews for resource quantification, eight of which had previously been designated by the Ministry of Health (MoH) to provide CAR-T.Outcome measure Current capacity of NHS Spanish sites to administer CAR-T under different theoretical scenarios with varying numbers of procedures, and the potential healthcare resources that would be needed to realise the theoretical capacity requirements.Results Four hospitals were optimally ready, 17 were somewhat ready and 7 were not ready. The actual extrapolated capacity of the currently designated MoH CAR-T sites would allow treatment of approximately 250 patients per year. Regarding healthcare resource needs, the numbers of haematologists, nurses and beds were the most important limiting factors, and those requiring further growth as patient numbers increased.Conclusions Increasing the number of CAR-T-qualified centres and/or increasing resources in the current designated sites are two potential strategies that should be considered to treat CAR-T-eligible patients in Spain.

Availability of haploidentical donors has broadened utilization of allogeneic hematopoietic cell transplantation (allo-HCT). Peripheral blood stem cells (PBSC) are being used with increased frequency in haploidentical allo-HCT. We evaluated extent of HLA disparity (2–3/8 versus 4/8 HLA antigen mismatches) on post-allograft outcomes when using T-cell replete PBSC from haploidentical donors for acute myeloid leukemia in first complete remission. Primary objectives entailed assessing cumulative incidence of grade 2–4 acute graft-versus-host disease (GVHD) and chronic GVHD (any grade). A total of 645 patients received a haploidentical allo-HCT from a donor with either 2–3 of 8 HLA antigen mismatches (n = 180) or with 4 of 8 HLA antigen mismatches (n = 465). Presence of 2–3 of 8 versus 4 of 8 HLA mismatches did not affect the incidence of acute GVHD (grade 2–4) and chronic GVHD (any grade). Overall survival (OS), leukemia-free survival (LFS) relapse incidence (RI), nonrelapse mortality and the composite endpoint of GVHD-free relapse-free survival were also similar among the groups. Pertaining to HLA-B leader matching effect, our analysis did not discern any difference in aforementioned post-allograft outcomes for this variable. However, in univariate analysis, absence of an antigen mismatch in HLA-DPB1 showed a trend for better OS. Notwithstanding inherent limitations associated with registry data, our results did not show an advantage of selecting a haploidentical donor with 2–3 of 8 HLA antigen mismatches over one with 4 of 8 HLA antigen mismatches when using PBSC as the cell source. Adverse cytogenetics remains a major adverse determinant of inferior OS and LFS and a higher RI. Using reduced-intensity conditioning yielded worse OS and LFS.

The results of haploidentical stem cell transplantation (haploHCT) for patients with acute lymphoblastic leukemia (ALL) transplanted in active disease remain largely unknown. We retrospectively analyzed adult patients with R/R ALL who underwent haploHCT or matched sibling donor (MSD-HCT) as a first transplantation between 2012 and 2020. The analysis comprised 274 patients, 94 had a haploHCT, and 180 had an MSD-HCT. The median follow-up was 32 months. The median age was 33 (range 18–76) and 37 (18–76) years in the haplo- and MSD-HCT groups, respectively. Post-transplant cyclophosphamide (PTCy) was used in 88% of haploHCT and in 4% of the MSD-HCT group. Graft-versus-host disease grade III–IV was higher in haploHCT than in the MSD-HCT group (18% versus 9%; P = 0.042). The 2-year chronic (c) graft-versus-host disease rates were 17% versus 33% (hazard ratio [HR] = 0.56; P = 0.14), respectively. By multivariate analysis, relapse incidence, and leukemia-free survival were not significatively different between the transplant groups, while nonrelapse mortality (NRM) was significantly higher (25% versus 18% at 2 years; HR = 2.03; P = 0.042) and overall survival (OS) lower (22% versus 38% at 2 years; HR = 1.72; P = 0.009) in the haploHCT group compared with the MSD-HCT group. We conclude that the 2-year OS of R/R ALL patients undergoing MSD transplants is significantly better than in haploHCT with a higher NRM in the latter.

Real-world evidence comparing the efficacy of chimeric antigen receptor (CAR) T-cell therapy against that of the previous standard of care (SOC) for refractory large B-cell lymphoma (LBCL) is scarce. We retrospectively collected data from patients with LBCL according to SCHOLAR-1 criteria treated with commercial CAR T-cell therapy in Spain (204 patients included and 192 treated, 101 with axicabtagene ciloleucel [axi-cel], and 91 with tisagenlecleucel [tisa-cel]) and compared the results with a historical refractory population of patients (n = 81) obtained from the GELTAMO-IPI study. We observed superior efficacy for CAR-T therapy (for both axi-cel and tisa-cel) over pSOC, with longer progression-free survival (PFS) (median of 5.6 vs. 4–6 months, p ≤ 0.001) and overall survival (OS) (median of 15 vs. 8 months, p < 0.001), independently of other prognostic factors (HR: 0.59 (95% CI: 0.44–0.80); p < 0.001] for PFS, and 0.45 [(95% CI: 0.31–0.64)] for OS). Within the CAR-T cohort, axi-cel showed longer PFS (median of 7.3 versus 2.8 months, respectively, p = 0.027) and OS (58% versus 42% at 12 months, respectively, p = 0.048) than tisa-cel. These differences were maintained in the multivariable analysis. On the other hand, axi-cel was independently associated with a higher risk of severe cytokine release syndrome and neurotoxicity. Our results suggest that the efficacy of CAR-T cell therapy is superior to pSOC in the real-world setting. Furthermore, axi-cel could be superior in efficacy to tisa-cel, although more toxic, in this group of refractory patients according to SCHOLAR-1 criteria.

Axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) are CD19-targeted chimeric antigen receptor (CAR) T cells approved for relapsed/refractory (R/R) large B-cell lymphoma (LBCL). We performed a retrospective study to evaluate safety and efficacy of axi-cel and tisa-cel outside the setting of a clinical trial. Data from consecutive patients with R/R LBCL who underwent apheresis for axi-cel or tisa-cel were retrospectively collected from 12 Spanish centers. A total of 307 patients underwent apheresis for axi-cel (n=152) and tisa-cel (n=155) from November 2018 to August 2021, of which 261 (85%) received a CAR T infusion (88% and 82%, respectively). Median time from apheresis to infusion was 41 days for axi-cel and 52 days for tisa-cel (P=0.006). None of the baseline characteristics were significantly different between both cohorts. Both cytokine release syndrome and neurologic events (NE) were more frequent in the axi-cel group (88% vs. 73%, P=0.003, and 42% vs. 16%, P

BackgroundThe impact of glucagon-like peptide-1 receptor agonists on patients with heart failure has not been fully described. Our main objective was to evaluate the safety and clinical and glycemic efficacy of once-weekly semaglutide in obese patients with type 2 diabetes and heart failure.MethodsIn this observational, retrospective, real-world study, we enrolled outpatients with type 2 diabetes, obesity, and heart failure who started semaglutide and were followed-up on at 3, 6, and 12 months.ResultsA total of 136 patients were included. From baseline to 12 months, there was a significant improvement on the Kansas City Cardiomyopathy Questionnaire total symptom score (59.0 ± 24.1 vs 79.9 ± 28.4 points, p

BackgroundValproic acid (VPA) has shown beneficial effects in vitro against SARS-CoV-2 infection, but no study has analyzed its efficacy in the clinical setting.MethodsThis multicenter, retrospective study included 165 adult patients receiving VPA at the time of admission to hospital, and 330 controls matched for sex, age and date of admission. A number of clinical, outcome and laboratory parameters were recorded to evaluate differences between the two groups. Four major clinical endpoints were considered: development of lung infiltrates, in-hospital respiratory worsening, ICU admissions and death.ResultsVPA-treated patients had higher lymphocyte (PConclusionsVPA-treated patients seem to develop less serious COVID-19 than control patients, according to diverse clinical endpoints and laboratory markers.

Background and aimsObesity is linked to elevated levels of inflammatory serum markers such as C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNFa). Adiponectin and resistin are adipokines related to obesity. It has been described that adipose tissue presents a high production and secretion of these diverse pro-inflammatory molecules, which may have local effects on the physiology of fat cells as well as systemic effects on other organs. Our aim was to evaluate the impact that lifestyle modifications, by following a Mediterranean Diet (MedDiet) program and physical activity (PA) training, would have on inflammatory biomarkers and adipokine profile in a Metabolically Healthy Obese (MHO) elderly population from Malaga (Andalusia, Spain).Subjetcs and methodsSubjects aged ≥65 years (65 to 87 years old) with obesity (BMI ≥30 kg/m2) were included in this study if they met ≤1 of the following criteria: systolic blood pressure ≥130 mmHg and/or diastolic blood pressure ≥ 85 mmHg; triglycerides ≥150 mg/dL; HDL-C Results166 MHO elderly subjects, 40 (24.1%) male and 126 (75.9%) female (p < 0.0001), aged 71.7±5.2 years old (65 to 87 years old) were included in the study. After 12 months of intervention, only the waist circumference was significantly reduced in all the population (-2.5 cm, pConclusionHealthy aging is a multifactorial biological process in which lifestyle is essential. The presence of obesity in elderly metabolically healthy population is not a problem necessarily. Elderly MHO population who eat a MedDiet and practice regularly PA are capable to modulate their production of inflammatory cytokines (CRP, IL-6, TNFa) and adipokines profile (adiponectin, resistin), preventing other metabolic disorders.

(1) Background: Acute COVID-19 infections produce alterations in the skeletal muscle, leading to acute sarcopenia, but the medium- and long-term consequences are still unknown. The aim of this study was to evaluate: (1) body composition; (2) muscle strength and the prevalence of sarcopenia; and (3) the relationship between muscle strength with symptomatic and functional evolution in older patients affected by/recovered from COVID-19; (2) Methods: A prospective, longitudinal study of patients aged ≥65 years who had suffered from COVID-19 infection between 1 March and 31 May 2020, as confirmed by PCR or subsequent seroconversion. Persistent symptoms, as well as anthropometric, clinical, and analytical characteristics, were analyzed at 3 and 12 months after infection. The degree of sarcopenia was determined by dynamometry and with SARC-F; (3) Results: 106 participants, aged 76.8 ± 7 years, were included. At 3 months postinfection, a high percentage of sarcopenic patients was found, especially among women and in those with hospitalization. At 12 months postinfection, this percentage had decreased, coinciding with a functional and symptomatic recovery, and the normalization of inflammatory parameters, especially interleukin-6 (4.7 ± 11.6 pg/mL vs. 1.5 ± 2.4 pg/mL, p < 0.05). The improvement in muscle strength was accompanied by significant weight gain (71.9 ± 12.1 kg vs. 74.7 ± 12.7 kg, p < 0.001), but not by an increase in lean mass (49.6 ± 10 vs. 49.9 ± 10, p 0.29); (4) Conclusions: Older COVID-19 survivors presented a functional, clinical, and muscular recovery 12 months postinfection. Even so, it is necessary to carry out comprehensive follow-ups and assessments that include aspects of nutrition and physical activity.

The prevalence of type 2 diabetes mellitus (T2DM) is rising in the general population. This increase leads to higher cardiovascular risk, with cardiovascular diseases being the main cause of death in diabetic patients. New therapeutic weapons for diabetes mellitus are now available. Sodium-glucose cotransporter type 2 (SGLT2) inhibitors are novel drugs that are widely used due to their strong benefit in preventing hospitalization for decompensated heart failure and renal protection, limiting the deterioration of the glomerular filtration rate, independently of the presence of diabetes mellitus. These drugs have also shown benefit in the prevention of atherosclerotic cardiovascular events and cardiovascular mortality in diabetic patients with established cardiovascular disease. On the other hand, patients with T2DM usually present a high burden of associated comorbidities. Some of these entities are arterial hypertension, dyslipidemia, hyperuricemia, obesity, non-alcoholic fatty liver disease (NAFLD), polycystic ovary syndrome (PCOS), vascular aging, respiratory diseases, or osteoporosis and fractures. Healthcare professionals should treat these patients from an integral point of view, and not manage each pathology separately. Therefore, as potential mechanisms of SGLT2 inhibitors in metabolic diseases have not been fully reviewed, we conducted this review to know the current evidence of the use and effect of SGLT2 inhibitors on these metabolic diseases.

Peripheral arterial disease (PAD) is a highly prevalent atherosclerotic condition. In patients with PAD, the presence of intermittent claudication leads to a deterioration in quality of life. In addition, even in asymptomatic cases, patients with PAD are at high risk of cardiac or cerebrovascular events. Treatment of PAD is based on lifestyle modifications; regular exercise; smoking cessation; and control of cardiovascular risk factors, including hypercholesterolemia. A growing number of studies have shown that statins reduce cardiovascular risk and improve symptoms associated with PAD. Current guidelines recommend the use of statins in all patients with PAD in order to decrease cardiovascular events and mortality. However, the prescribing of statins in patients with PAD is lower than in those with coronary heart disease. This review provides relevant information from the literature that supports the use of statins in patients with PAD and shows their potential benefit in decreasing lower limb complications as well as cardiovascular morbidity and mortality.

Atherosclerotic cardiovascular diseases (ASCVD) are the leading cause of death worldwide. High levels of total cholesterol—and of low-density lipoprotein cholesterol in particular—are one of the main risk factors associated with ASCVD. Statins are first-line treatment for hypercholesterolemia and have been proven to reduce major vascular events in adults with and without underlying ASCVD. Findings in the literature show that statins reduce coronary and cerebrovascular morbidity and mortality in middle-aged people, but their benefits in older adults are not as well-established, especially in primary prevention. Furthermore, many particularities must be considered regarding their use in old subjects, such as age-related changes in pharmacokinetics and pharmacodynamics, comorbidities, polypharmacy, and frailty, which decrease the safety and efficacy of statins in this population. Myopathy and a possible higher risk of falling along with cognitive decline are classic concerns for physicians when considering statin use in the very old. Additionally, some studies suggest that the relative risk for coronary events and cardiovascular mortality associated with high levels of cholesterol decreases after age 70, making the role of statins unclear. On the other hand, ASCVD are one of the most important causes of disability in old subjects, so cardiovascular prevention is of particular interest in this population in order to preserve functional status. This review aims to gather the current available evidence on the efficacy and safety of statin use in very old patients in both primary and secondary prevention.