Kidney Amyloidosis: Updates on Pathogenesis and Therapeutic Frontiers.

BACKGROUND: Amyloidosis includes a diverse group of rare diseases characterized by the misfolding of native or mutant proteins, leading to extracellular accumulation in various organs. While 42 proteins have been identified to date, their distribution differs between systemic and localized forms. SUMMARY: Mass spectrometry analysis of tissue samples in the USA shows immunoglobulin light chain (AL) amyloidosis as the most prevalent systemic type, followed by transthyretin (ATTR). Heart and kidney involvements are common. Although there are 14 recognized types of kidney-related amyloidosis, clinicopathologic studies in the USA have identified 11 types, with AL amyloidosis being the most prevalent cause of kidney involvement. KEY MESSAGES: This review focuses on AL, AA, and ATTR amyloidosis due to their common systemic presentations. Recent US-based clinicopathologic studies challenge conventional beliefs that toxicity is primarily driven by amyloid deposition and highlight the role of the complement pathway. Diagnostic methods, particularly mass spectrometry, are crucial for accurate typing. Treatment strategies vary depending on the underlying type, with AL amyloidosis primarily targeting plasma cell clones, AA amyloidosis addressing underlying inflammation with systemic therapies, and ATTR amyloidosis focusing on ATTR stabilization or gene silencing.

Blood lead levels in an endangered vulture decline following changes in hunting activity.

Lead ammunition stands out as one of the most pervasive pollutants affecting wildlife. Its impact on bird populations have spurred efforts for the phase-out of leaded gunshot in several countries, although with varying scopes and applications. Ongoing and future policy changes require data to assess the effectiveness of adopted measures, particularly in the current context of biodiversity loss. Here, we assessed the long-term changes in blood lead (Pb) levels of Egyptian vultures from the Canary Islands, Spain, which have been severely affected by Pb poisoning over the past two decades. During this period, the reduction in hunting pressure and changes in legislation regarding firearms usage for small game hunting likely contributed to a decrease in environmental Pb availability. As anticipated, our results show a reduction in Pb levels, especially after the ban on wild rabbit hunting with shotgun since 2010. This effect was stronger in the preadult fraction of the vulture population. However, we still observed elevated blood Pb levels above the background and clinical thresholds in 5.6% and 1.5% of individuals, respectively. Our results highlight the positive impact of reducing the availability of Pb from ammunition sources on individual health. Nonetheless, the continued use of Pb gunshot remains an important source of poisoning, even lethal, mainly affecting adult individuals. This poses a particular concern for long-lived birds, compounding by potential chronic effects associated with Pb bioaccumulation. Our findings align with recent studies indicating insufficient reductions in Pb levels among European birds of prey, attributed to limited policy changes and their uneven implementation. We anticipated further reductions in Pb levels among Egyptian vultures with expanded restrictions on hunting practices, including a blanket ban on Pb shot usage across all small game species.

The trends of interpersonal violence burden in Latin America, 1990 to 2019: secondary data analysis from the global burden of disease study.

OBJECTIVES: We aimed to analyse the trends of interpersonal violence (IV) in Latin America (LA) between 1990 and 2019 for females and males at a national level. STUDY DESIGN: Cross-sectional descriptive study. METHODS: Following the 2019 Global Burden of Disease study we report IV mortality, premature mortality, years lived with disability and disability-adjusted life-years (DALYs) in LA by sex. To estimate the DALYs trends, we conducted a Joinpoint regression analysis. RESULTS: Across all LA countries, IV burden was higher among males. Most of the IV burden was attributable to premature death, with a higher percentage in men than women. The burden of IV was most pronounced within the 15 to 39 age-groups in the majority of countries. Physical violence (PV) by firearm was the main cause of IV in LA, followed by PV by other means. Women in LA experienced at least twice as many sexual violence DALYs as men. IV in LA exhibited heterogeneous trends, with certain countries witnessing a significant decline in the IV DALYs rate, while others displayed a significant increase. CONCLUSIONS: Our results show the great heterogeneity of IV burden present in the region as the trends varied from one country to another. Policing and criminal justice institutions in LA have failed to reduce crime and violence. Thus, tailored preventive measures and public policies that account for the specific context and geographical areas where this phenomenon is prevalent are urgently needed.

Therapeutic Plasma Exchange: Core Curriculum 2023.

From producing individual blood components for transfusion to the removal of pathogenic substances, apheresis is a cornerstone of modern medical therapies. The use of therapeutic plasma exchange (TPE), in which plasma and its soluble constituents are removed from the body in exchange for a replacement fluid, can be organ- and life-saving in many diseases. Given the notable similarities between TPE and hemodialysis, the nephrologist is often responsible for managing TPE. As such, one must be familiar with the technologies, approach to therapy, indications for use, and complications. TPE uses centrifugation or membrane separation technologies, with the latter able to be performed with certain hemodialysis machines familiar to the nephrologist. Furthermore, primary kidney diseases such as anti-glomerular basement membrane disease are frequently associated with autoantibodies, potentially making them ideal candidates for TPE. Nevertheless, the use of TPE in many kidney diseases is controversial because of the lack of supporting evidence. This review discusses TPE from the perspective of a nephrologist responsible for prescribing and managing TPE, as well as nephrologists engaged in the care of patients undergoing the procedure.

Updates on HIV and Kidney Disease.

PURPOSE OF REVIEW: With the advent of antiretroviral therapy, HIV infection has become a chronic disease in developed countries. RECENT FINDINGS: Non-HIV-driven risk factors for kidney disease, such as APOL1 risk variants and other genetic and environmental factors, have been discovered and are better described. Consequently, the field of HIV-associated kidney disease has evolved with greater attention given to traditional risk factors of CKD and antiretroviral treatment's nephrotoxicity. In this review, we explore risk factors of HIV-associated kidney disease, diagnostic tools, kidney pathology in HIV-positive individuals, and antiretroviral therapy-associated nephrotoxicity.

From screening to treatment: the new landscape of diabetic kidney disease.

Globally, diabetes mellitus is the leading cause of chronic kidney disease (CKD), and it is predicted to increase in the following years. Despite its high prevalence, CKD remains under diagnosed. In this BMC Medicine collection of articles on diabetic kidney disease (DKD), we place in context the importance of screening and early detection of DKD and the most accurate tools to monitor for optimal glycemic control in this his risk population. Further, we address this population's risk for severe complications such as stroke and all-cause mortality. We close this editorial by summarizing recent advances in management of this vulnerable population of patients with DKD, including guideline-directed medical therapy, novel treatments, and predictors of treatment failure.

Preliminary survey of the occurrence of mycotoxins in cereals and estimated exposure in a northwestern region of Mexico.

Mycotoxins have several toxicological implications. In the present study, we evaluate the presence of aflatoxin B1 (AFB1), ochratoxin A (OTA), and fumonisin (FB1) in paddy rice, polished rice, and maize from the fields and markets in Nayarit State (Mexico). The results indicated the presence of AFB1 in 21.21% of paddy rice samples and 11.11% of market maize samples. OTA was present in only 3.03% (one sample) of paddy rice samples. FB1 was detected in 87.50% and 88.88% of maize samples from field and market, respectively. The estimated human exposure was calculated for FB1 using the probable daily intake (PDI), which suggested that FB1 could contribute to the development of diseases through the consumption of contaminated maize. Positive samples indicated that some rice and maize samples were not suitable for human consumption. Further efforts are needed to continue monitoring mycotoxins and update national legislation on mycotoxins accordingly.

Violence in Colombia and Mexico: trend and impact on life expectancy of homicide mortality between 1998 and 2015.

OBJECTIVES: Colombia is considered one of the most violent countries in the world even though homicide mortality has decreased since 2002. Mexico's homicide rate has tripled since 2008, after a period of decreasing mortality; this fact has been compared with Colombia in the 1990s and defined as a 'Colombianization' of violence in Mexico. We analyzed and compared the trend and impact of homicide mortality in Colombia and Mexico between 1998 and 2015. STUDY DESIGN: Cross-sectional descriptive study. METHODS: We calculated the standardized mortality rates and the years of life lost using data from the National Institute of Statistics and Geography in Mexico and the National Management Department of Statistics in Colombia. We used the joinpoint regression analysis to identify significant changes in the mortality trend. RESULTS: During the 1990s, Colombia reached the highest homicide mortality rates in the world, but these rates have since decreased significantly. In Mexico, homicide mortality had a decreasing trend from 1998 to 2007; however, since 2008, the rate grew significantly, and although mortality tended to decrease after reaching its peak in 2011, a slight upturn was observed in 2015. CONCLUSIONS: We found that the trend in mortality in both countries has had certain similarities, such as the increase in mortality after the implementation of antidrug policies and the subsequent decrease; however, the political processes, the level of mortality reached, its impact on life expectancy, and its distribution by gender are dissimilar. We consider speaking of a 'Colombianization' of violence in Mexico to be inaccurate.

Factors associated with mixed dementia vs Alzheimer disease in elderly Mexican adults. / Factores asociados a la demencia mixta en comparación con demencia tipo Alzheimer en adultos mayores mexicanos.

INTRODUCTION: Mixed dementia (DMix) refers to dementia resulting from Alzheimer disease in addition to cerebrovascular disease. The study objectives were to determine the clinical and imaging factors associated with Dmix and compare them to those associated with Alzheimer disease. MATERIAL AND METHODS: Cross-sectional study including 225 subjects aged 65 years and over from a memory clinic in a tertiary hospital in Mexico City. All patients underwent clinical, neuropsychological, and brain imaging studies. We included patients diagnosed with DMix or Alzheimer disease (AD). A multivariate analysis was used to determine factors associated with DMix. RESULTS: We studied 137 subjects diagnosed with Dmix. Compared to patients with AD, Dmix patients were older and more likely to present diabetes, hypertension, dyslipidaemia, and history of cerebrovascular disease (P<.05). The multivariate analysis showed that hypertension (OR 1.92, CI 1.62-28.82; P=.009), white matter disease (OR 3.61, CI 8.55-159.80; P<.001), and lacunar infarcts (OR 3.35, CI 1.97-412.34; P=.014) were associated with Dmix, whereas a history of successfully treated depression showed an inverse association (OR 0.11, CI 0.02-0-47; P=.004) CONCLUSIONS: DMix may be more frequent than AD. Risk factors such as advanced age and other potentially modifiable factors were associated with this type of dementia. Clinicians should understand and be able to define Dmix.

Genes from pUM505 plasmid contribute to Pseudomonas aeruginosa virulence.

The pUM505 plasmid was isolated from a clinical strain of Pseudomonas aeruginosa. This plasmid contains a genomic island with sequence similar to islands found in chromosomes of virulent P. aeruginosa clinical isolates. The objective of this work was to determine whether pUM505 increases the virulence of P. aeruginosa and to identify the genes responsible for this property. First, using the lettuce-leaf model, we found that pUM505 significantly increases the virulence of P. aeruginosa reference strain PAO1. pUM505 also increased the PAO1 virulence in a murine model and increased cytotoxicity of this strain toward HeLa cells. Thus, we generated a pUM505 gene library of 103 clones in the pUCP20 binary vector. The library was transferred to Escherichia coli TOP10 and P. aeruginosa PAO1 to identify genes. The lettuce-leaf model allowed us to identify three recombinant plasmids that increased the virulence of both E. coli and P. aeruginosa strains. These recombinant plasmids also increased the virulence of the PAO1 strain in mice and induced a cytotoxic effect in HeLa cells. Eleven genes were identified in the virulent transformants. Of these genes, only the pUM505 ORF 2 has homology with a gene previously implicated in virulence. These results indicate that pUM505 contains several genes that encode virulence factors, suggesting that the plasmid may contribute directly to bacterial virulence.

Treatment of Acute Kidney Injury: A Review of Current Approaches and Emerging Innovations.

Acute kidney injury (AKI) is a complex and life-threatening condition with multifactorial etiologies, ranging from ischemic injury to nephrotoxic exposures. Management is founded on treating the underlying cause of AKI, but supportive care-via fluid management, vasopressor therapy, kidney replacement therapy (KRT), and more-is also crucial. Blood pressure targets are often higher in AKI, and these can be achieved with fluids and vasopressors, some of which may be more kidney-protective than others. Initiation of KRT is controversial, and studies have not consistently demonstrated any benefit to early start dialysis. There are no targeted pharmacotherapies for AKI itself, but some do exist for complications of AKI; additionally, medications become a key aspect of AKI management because changes in renal function and dialysis support can lead to issues with both toxicities and underdosing. This review will cover existing literature on these and other aspects of AKI treatment. Additionally, this review aims to identify gaps and challenges and to offer recommendations for future research and clinical practice.

Real-Life Experience on the Effect of SGLT2 Inhibitors vs. Finerenone vs. Combination on Albuminuria in Chronic Kidney Disease.

BACKGROUND: There have been several recent advances in the care of patients with chronic kidney disease (CKD), including the use of sodium glucose cotransporter 2 (SGLT2) inhibitors and selective mineralocorticoid receptor antagonists (MRAs). There are very few data reporting the outcomes of these treatments in real-world experience. The aim of this retrospective study is to report the effects of SGLT2 inhibitors, finerenone, and their combination in CKD patients in our community-based setting. METHODS: Ninety-eight patients with CKD with an estimated glomerular filtration rate (eGFR) between 25 and 90 mL/min per 1.73 m2 and a urine albumin-to-creatinine ratio (UACR) ≥ 30 mg/g were included. Patients were divided into three groups: two monotherapy groups of SGLT2 inhibitors or finerenone and a third combination group of therapy with SGLT2 inhibitors for the first 4 months and SGLT2 inhibitors and finerenone subsequently. The primary outcomes were the timing and percentage of patients achieving a >50% reduction in UACR from baseline. RESULTS: Group 1 comprised 52 patients on SGLT2i, group 2 had 22 patients on finerenone, and group 3 had 24 patients on combination therapy. The baseline median UACR and mean eGFR were 513 mg/g and 47.9 mL/min per 1.73 m2 in group 1, 548.0 mg/g and 50.5 mL/min per 1.73 m2 in group 2, and 800 mg/g and 60 mL/min per 1.73 m2 in group 3. At baseline, 71 (72.4%) patients were on the angiotensin-converting enzyme inhibitor (ACEi) or the angiotensin receptor blocker (ARB), and 78 (79.5%) patients had type 2 diabetes. After 8 months of follow-up, a >50% decrease in albuminuria was achieved in 96% of patients in group 3, compared to 50% in group 1 and 59% in group 2 (p-values were <0.01 and <0.01, respectively). There was a statistically but not clinically significant change in mean potassium levels in group 2 (+0.4 mmol/L) compared to either group 1 (0.0 mmol/L with p-value: <0.01) or group 3 (-0.01 mmol/L with p-value: <0.01). However, there was no difference in potassium levels when comparing groups 1 and 3. At the end of the follow-up, the average difference in eGFR was -3.4 (8.8), -5.3(10.1), and -7.8 (11.2) mL/min per 1.73 m2 in groups 1, 2, and 3, respectively, without a statistically significant difference between groups. CONCLUSIONS: In this real-world experience in our community setting, the combination of SGLT2 inhibitors and finerenone in our adult patients with CKD was associated with a very significant and clinically relevant reduction in UACR, without an increased risk of hyperkalemia. Combination therapy of SGLT2 inhibitor and finerenone regarding background use of ACEi/ARB is feasible and should be encouraged for further albuminuria reductions in CKD patients.

MGRN1 depletion promotes intercellular adhesion in melanoma by upregulation of E-cadherin and inhibition of CDC42.

Mahogunin Ring Finger 1 is an E3-ubiquitin ligase encoded by the color gene MGRN1. Our previous in vitro and in vivo studies demonstrated that Mgrn1 deletion in mouse melanoma cells induced cell differentiation and adhesion, and decreased cell motility and invasion on collagen I, and lung colonization in an in vivo model. Here, we investigated the role of MGRN1 on human melanoma cell morphology, adhesion and expression of genes/proteins involved in an EMT-like transition. We demonstrated that wild-type BRAF human melanoma cells adopted a clustering-like morphology on collagen I, with permanent MGRN1 abrogation resulting in bigger cell clusters. Enhanced intercellular adhesion was mostly mediated by induction of E-cadherin and higher co-localization with ß-catenin. Transcriptional upregulation of E-cadherin likely occurred through downregulation of the ZEB1 repressor. Finally, pulldown assays showed reduced activation of CDC42 in the absence of MGRN1, which was reverted after E-cadherin silencing. Overall, these findings highlight a new MGRN1-dependent pathway regulating melanoma cell shape, motility, and invasion potential.

[SEMERGEN positioning on approaching chronic heart failure in primary care]. / Posicionamiento SEMERGEN en el abordaje de la insuficiencia cardíaca crónica en atención primaria.

Heart failure (HF) is a public health problem that generates a large healthcare burden both in hospitals and in Primary Care (PC). The publication of numerous studies about HF in recent years has led to a paradigm shift in the approach to this syndrome, in which the work of PC teams is gaining greater prominence. The recent guidelines published by the European Society of Cardiology have fundamentally introduced changes in the management of patients with HF. The new proposed strategy, with drugs that reduce hospitalizations and slow the progression of the disease, should now be a priority for all professionals involved. This position document analyzes a proposal for an approach based on multidisciplinary teams with the leadership of family doctors, key to providing quality care throughout the entire process of the disease, from its prevention to the end of the life.

[Impact of an interactive web application on the improvement of cardiovascular risk factors control. Control-RCV project]. / Utilidad de una aplicación web interactiva en la mejora del control de los factores de riesgo cardiovascular. Proyecto Control-RCV.

OBJECTIVE: To ascertain the utility of an interactive web application in the improvement of cardiovascular (CV) risk control. METHODS: Observational study in which primary care physicians consecutively included high/very high CV risk patients with at least one of the following risk factors poorly controlled: hypertension, dyslipidemia or diabetes. After the introduction of data, the application generated a report comparing the recommended and the real targets. Then, the physicians could modify the therapeutic approach. The study consisted of 2 visits, at baseline and after 4-6 months. RESULTS: A total of 379 patients (66.4±9.0 years; 67.3% male; 67.5/32.5% with high/very high CV risk) were included. At baseline, most patients received recommendations about salt restriction (90.2%), diet (94.2%), and physical activity (94.5%). With regard to pharmacological treatments, 53.6% of patients were not taking fixed-dose combinations. Only 35.1% met always with treatment. In 95.8% of patients sanitary education was given, in 29.8% the polypill was prescribed and in 24.3% lifestyle changes were recommended. During the second visit, a significant improvement in lifestyle changes (less smoking and alcohol consumption, and more physical activity, salt restriction and diet), CV risk factors (less obesity, blood pressure, lipids, HbA1c), as well as CV risk reduction were observed. The therapeutic compliance also improved. CONCLUSIONS: The use of the application allows improving lifestyle and CV risk factors control, leading to a reduction of CV risk and an improvement of therapeutic compliance.

Evaluation of prophylaxis in primary prevention with acetylsalicylic acid in people with diabetes: A scoping review.

BACKGROUND: The efficacy and safety of acetylsalicylic acid (ASA) prophylaxis for the primary prevention of atherosclerotic cardiovascular disease (ACVD) remain controversial in people with diabetes (DM) without ACVD, because the possible increased risk of major bleeding could outweigh the potential reduction in the risk of mortality and of major adverse cardiovascular events (MACE) considered individually or together. OBJECTIVE: To evaluate the overall risk-benefit of ASA prophylaxis in primary prevention in people with DM and to compare the recommendations of the guidelines with the results of the meta-analyses (MA) and systematic reviews (SR). MATERIAL AND METHODS: We searched Medline, Google Scholar, Embase, and the Cochrane Library for SR and MA published from 2009 to 2020 which compared the effects of ASA prophylaxis versus placebo or control followed up for at least one year in people with DM without ACVD. Heterogeneity among the randomized clinical trials (RCT) included in the SR and MA was assessed. Cardiovascular outcomes of efficacy (all-cause mortality [ACM], cardiovascular mortality [CVM], myocardial infarction [MI], stroke and MACE) and of safety (major bleeding events [MBE], major gastrointestinal bleeding events [MGIBE], and intracranial and extracranial bleeding) were shown. RESULTS: The recommendations of 12 guidelines were evaluated. The results of 25 SR and MA that included a total of 20 RCT were assessed. None of the MA or SR showed that ASA prophylaxis decreased the risk of ACM, CVM or MI. Only two of the 19 SR and MA that evaluated ischemic stroke showed a decrease in the stroke risk (mean 20.0% [SD±5.7]), bordering on statistical significance. Almost half of the MA and SR showed, bordering on statistical significance, a risk reduction for the MACE composite endpoint (mean 10.5% [SD±3.3]). The significant increases in MGIBE risk ranged from 35% to 55%. The significant increases in the risk of MBE and extracraneal bleeding were 33.4% (SD±14.9) and 54.5% (SD±0.7) respectively. CONCLUSION: The overall risk-benefit assessment of ASA prophylaxis in primary prevention suggests that it should not be applied in people with DM.

Nucleotide sequence of Pseudomonas aeruginosa conjugative plasmid pUM505 containing virulence and heavy-metal resistance genes.

We determined the complete nucleotide sequence of conjugative plasmid pUM505 isolated from a clinical strain of Pseudomonas aeruginosa. The plasmid had a length of 123,322bp and contained 138 complete coding regions, including 46% open reading frames encoding hypothetical proteins. pUM505 can be considered a hybrid plasmid because it presents two well-defined regions. The first region corresponded to a larger DNA segment with homology to a pathogenicity island from virulent Pseudomonas strains; this island in pUM505 was comprised of genes probably involved in virulence and genes encoding proteins implicated in replication, maintenance and plasmid transfer. Sequence analysis identified pil genes encoding a type IV secretion system, establishing pUM505 as a member of the family of IncI1 plasmids. Plasmid pUM505 also contained virB4/virD4 homologues, which are linked to virulence in other plasmids. The second region, smaller in length, contains inorganic mercury and chromate resistance gene clusters both flanked by putative mobile elements. Although no genes for antibiotic resistance were identified, when pUM505 was transferred to a recipient strain of P. aeruginosa it conferred resistance to the fluoroquinolone ciprofloxacin. pUM505 also conferred resistance to the superoxide radical generator paraquat. pUM505 could provide Pseudomonas strains with a wide variety of adaptive traits such as virulence, heavy-metal and antibiotic resistance and oxidative stress tolerance which can be selective factors for the distribution and prevalence of this plasmid in diverse environments, including hospitals and heavy metal contaminated soils.

[Utility of combined therapy in the prevention and treatment of the cardiovascular disease]. / Utilidad de la terapia combinada en la prevención y tratamiento de la enfermedad cardiovascular.

Although blood pressure control is crucial in patients with hypertension, current clinical practice guidelines recommend that the goal of treatment should be aimed at not only reducing blood pressure values but decreasing global cardiovascular risk. Available data suggest that blood pressure and LDL-cholesterol control rates, two of the most common cardiovascular risk factors, are low, not only in the primary care setting but also in specialists setting. Clinical trials, such as the Anglo-Scandanavian Cardiac Outcomes Trial (ASCOT), have demonstrated that the integration of a multifactorial approach through the treatment of different risk factors effectively reduces the risk of cardiovascular morbidity and mortality. The aim of this review was to update the current knowledge about the combined therapy of different risk factors in the hypertensive population.

[Clinical and economic consequences in patients initiating therapy with clopidogrel brand-name vs. generic: A real-life retrospective study]. / Consecuencias clínicas y económicas en pacientes que inician tratamiento con clopidogrel de marca vs. genérico: estudio retrospectivo de vida real.

OBJECTIVE: To evaluate the adherence to treatment, resource use, and costs in subjects initiating treatment with brand-name versus generic clopidogrel for acute coronary syndrome (ACS) and peripheral arterial disease (PAD). PATIENTS AND METHODS: Observational, retrospective study based on the medical records of patients aged ≥18 years who initiated treatment with clopidogrel (brand-name vs. generic) between 4 April 2015 and 31 March 2017. Four study groups were compared, and the follow-up was one year. The main measurements were: comorbidity, treatment adherence, medication possession ratio (MPR), resource use, and costs. The results were analysed using multivariate analysis. The level of statistical significance was P<.05. RESULTS: Four groups were compared: a) ACS: brand-name clopidogrel (N=1,067) vs. generic (N=3,504), and b) PAD: brand-name clopidogrel (N=425) vs. generic (N=994). In the ACS comparison (mean age: 69.7 years, 61.4% male), adherence (65.3% vs. 61.0%, P<.001), adjusted hazard ratio 0.85 and MPR (89.8% vs. 86.7%, P=.045) were more superior with brand-name clopidogrel than with the generic and with a lower mean cost per unit (€2,890 vs. €3,865, P=.001). In the PAD comparison, similar results were observed: persistence (64.7% vs. 58.9%, P=.039); adjusted hazard-ratio 0.86 and MPR (88.6% vs. 81.7%; P=.013) were more superior with brand-name clopidogrel than for the generic, with a lower mean cost per unit (€2,880 vs. €3,532, P=.044). CONCLUSIONS: There was better treatment adherence in patients initiating treatment with brand-name compared with generic clopidogrel for ACS and PAD, resulting in lower health costs for the Spanish National Health System.