Background: The effect of alirocumab, a PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor, on coronary plaque burden in patients with familial hypercholesterolemia has not been addressed. Our aim was to assess changes in coronary plaque burden and its characteristics after treatment with alirocumab by quantification and characterization of atherosclerotic plaque throughout the coronary tree on the basis of a noninvasive analysis of coronary computed tomographic angiography in asymptomatic subjects with familial hypercholesterolemia receiving optimized and stable treatment with maximum tolerated statin dose with or without ezetimibe. Methods: This study is a phase IV, open-label, multicenter, single-arm clinical trial to assess changes in coronary plaque burden and its characteristics after 78 weeks of treatment with alirocumab in patients with familial hypercholesterolemia without clinical atherosclerotic cardiovascular disease. Participants underwent an initial coronary computed tomographic angiography at baseline and another at 78 weeks. Every patient received 150 mg of alirocumab subcutaneiously every 14 days in addition to high-intensity statin therapy. The main outcome was the change on coronary plaque burden and its characteristics by quantification and characterization of atherosclerotic plaque throughout the coronary tree on the basis of analysis of coronary computed tomographic angiography. Results: The study was completed by 104 patients. The median age was 53.3 (46.2–59.4) years. Of these patients, 54 were women (51.9%). Median low-density lipoprotein cholesterol was 138.9 (117.5–175.3) mg/dL at entry and 45.0 (36.0–65.0) mg/dL at follow-up ( P <0.001). Coronary plaque burden changed from 34.6% (32.5%–36.8%) at entry to 30.4% (27.4%–33.4%) at follow-up ( P <0.001). A significant change in the characteristics of the coronary atherosclerosis was also found: an increase in the proportion of calcified (+0.3%; P <0.001) and mainly fibrous (+6.2%; P <0.001) plaque, accompanied by a decrease in the percentage of fibro-fatty (–3.9%; P <0.001) and necrotic plaque (–0.6%; P <0.001). Conclusions: Treatment with alirocumab in addition to high-intensity statin therapy resulted in significant regression of coronary plaque burden and plaque stabilization on coronary computed tomographic angiography over 78 weeks in these groups of patients with familial hypercholesterolemia without clinical atherosclerotic cardiovascular disease. ARCHITECT (Effect of Alirocumab on Atherosclerotic Plaque Volume, Architecture and Composition) could link and explain ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) results. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT05465278.

BACKGROUND: Intensive lipid-lowering therapy may induce coronary atherosclerosis regression. Nevertheless, the factors underlying the effect of lipid-lowering therapy on disease regression remain poorly characterized. Our aim was to determine which characteristics of atherosclerotic plaque are associated with a greater reduction in coronary plaque burden (PB) after treatment with alirocumab in patients with familial hypercholesterolemia. METHODS: The ARCHITECT study (Effect of Alirocumab on Atherosclerotic Plaque Volume, Architecture and Composition) is a phase IV, open-label, multicenter, single-arm clinical trial to assess the effect of the treatment with alirocumab for 78 weeks on the coronary atherosclerotic PB and its characteristics in subjects with familial hypercholesterolemia without clinical atherosclerotic cardiovascular disease. Participants underwent a coronary computed tomographic angiography at baseline and a final one at 78 weeks. Every patient received alirocumab 150 mg subcutaneously every 14 days in addition to high-intensity statin therapy. RESULTS: One hundred and four patients were enrolled. Median age was 53.3 (46.2–59.4) years and 54 were women (51.9%). The global coronary PB changed from 34.6% (32.5%–36.8%) at entry to 30.4% (27.4%–33.4%) at follow-up, which is −4.6% (−7.7% to −1.9%; P <0.001) reduction. A decrease in the percentage of unstable core (fibro-fatty+necrotic plaque; from 14.1 [7.9–22.3] to 8.0 [6.4–10.6]; −6.6%; P <0.001) was found. A greater PB (β, 0.36 [0.13–0.59]; P =0.002) and a higher proportion of unstable core (β, 0.15 [0.08–0.22]; P <0.001) were significantly related to PB regression. CONCLUSIONS: Treatment with alirocumab in addition to high-intensity statin therapy might produce a greater PB regression in patients with familial hypercholesterolemia with higher baseline PB and in those with larger unstable core. Further studies are needed to corroborate the hypothesis raised by these results. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT05465278.

Almost one third of patients do not achieve type 2 diabetes remission after bariatric surgery or are unable to sustain this effect long term. Our objective was to delve further into the dynamic responses of diabetes after bariatric surgery and to evaluate the “time-within-remission range” as a variable of metabolic control. A descriptive cohort study was done using a computerised multicentre and multidisciplinary registry. All data were adjusted by propensity score. A total of 1186 subjects with a follow-up of 4.5 ± 2.5 years were included. Type of surgery, diabetes remission, recurrence of diabetes, “time-within-remission range” and key predictors of diabetes outcomes were assessed. All patients (70% women, 51.4 ± 9.2 years old, body mass index (BMI) 46.3 ± 6.9 kg/m²) underwent primary bariatric procedures. “Time-within-remission range” were 83.3% (33.3–91.6) after gastric bypass, 68.7% (7.1–87.5) after sleeve gastrectomy and 90% (83.3–92.8) after malabsorptive techniques (p < 0.001 for all). Duration of diabetes, baseline HbA1c and insulin treatment were significantly negatively correlated with the “time-within-remission range”. The association of bariatric techniques with “time-within-remission range”, using gastric bypass as a reference, were: odds ratio (OR) 3.70 (2.34–5.84), p < 0.001 for malabsorptive techniques and OR 0.55 (0.40–0.75), p < 0.001 for sleeve gastrectomy. Characteristics of type 2 diabetes powerfully influence the outcomes of bariatric surgery. The “time-within-remission range” unveils a superiority of gastric bypass compared to sleeve gastrectomy.

Introduction: The interaction between corticosteroids and protease inhibitors (PIs) is a clearly described drug interaction. Several case series have been described.-Fluticasone is the one with the greatest potential risk of producing iatrogenic adrenal insufficiency given its pharmacokinetic characteristics. Clinical Case: 44-year-old woman diagnosed with HIV (human immunodeficiency virus) category B3 diagnosed in 1989; multiple antiretroviral treatments. Severe lipodystrophy Also HCV genotype IA. Bronchial asthma since 2000. A treatment with fluticasone 1 inh / 24h, salbutamol on demand, darunavir 800 mg / day and ritonavir 100 mg / day. He had known lipodystrophy since 2001 and the abdominal perimeter was controlled, showing an increase in it. Likewise, she presented progressive proximal weakness in the lower limbs, with increased hair, capillary fragility and alopecia, which is why she was referred to Endocrinology. Moderate hirsutism, muscle atrophy were observed and in the analytical study: normal FSH and LH. Testosterone 0.05 ng / ml (0.1–0.9), ACTH 1.0 pg / ml (7.2–63.3), Cortisol am 0.65 µg / dl (4.30–22.40). Urinary free cortisol 3.74 µg / 24h (36–137). A Synacten Test is performed: Basal 0.52; 30 min 2.33; 60 min 2.84 with ACTH 1 and a diagnosis of iatrogenic independent ACTH Cushing Syndrome associated with secondary adrenal insufficiency. With this diagnosis, he was referred to the pulmonology clinic for a change from inhaled corticosteroid to beclomethasone and replacement treatment with hydroaltenesone was started. Three months later, he was admitted for a fever after stopping hydroaltesone. It was restarted, antibiotic treatment was prescribed, and she was discharged home with a new regimen of antiretrovirals (raltegravir, tenofovir, and abacavir). Clinical Lesson: Fluticasone is a synthetic steroid that is cleared by the cytochrome P450 enzyme CYP3A4, which is inhibited or enhanced by a multitude of drugs, including ritonavir. As it is not metabolized, there is an increase in circulating levels, causing a decrease in ACTH secretion and therefore a suppression of the adrenal gland with its insufficiency and cushing syndrome. In our case and usually, the initial signs are difficult to detect due to their overlap with lipodystrophy associated with protease inhibitors. Although there is no agreement in the literature: the options are the replacement of fluticasone with another corticosteroid that is not a CYP3A4 substrate such as beclomethasone and the replacement of ritonavir with another antiretroviral (as in our case) or the reduction of the dose of fluticasone. It is recommended to avoid the initiation of fluticasone in patients receiving ritonavir. Substitution treatment with a progressive reduction in dose is performed with hydroaltesona. Most cases resolve in 9–12 months.

Background/Objectives: Cardiovascular disease remains a leading cause of mortality in Spain, with dyslipidemia being a major modifiable risk factor. Lipid-lowering therapy (LLT) is essential for cardiovascular risk reduction, but regional disparities in prescription patterns and LDL-C control persist. This study analyzes LLT prescription trends in Spain in 2019 and 2023, assessing temporal, demographic and regional differences. Methods: A retrospective observational study was conducted using the Spanish Primary Care Clinical Database (BDCAP), which contains 4.8 million anonymized primary care records. LLT prescriptions for primary prevention were analyzed by sex, age, community size, and employment status. Trends from 2019 to 2023 were evaluated, distinguishing between monotherapy and combination therapy. Results: In 2023, 5.8 million individuals received LLT for primary prevention (139.6 per 1000). Women had higher treatment rates than men after age 60. Treatment rates were highest in small communities and among retirees. The use of combination therapies almost doubled from 2019 to 2023, achieving better LDL-C control (56.4% vs. 41.5% with monotherapy, p < 0.001). Regional disparities were evident, with the lowest treatment rates in Cataluña and País Vasco and the highest in Galicia. Conclusion: LLT prescription patterns in Spain show remarkable socioeconomic and regional disparities. The increase in combination therapy suggests a shift towards more intensive lipid management. Standardized guidelines and targeted interventions are needed to ensure equitable and effective dyslipidemia treatment.

Introduction: Achieving LDL cholesterol (LDL-C) targets is critical in secondary cardiovascular prevention. Despite clinical guidelines promoting aggressive lipid-lowering strategies, many patients fail to reach recommended LDL-C levels. This study aimed to evaluate lipid profile management among secondary prevention patients in Spain using the Spanish Primary Care Clinical Database (BDCAP) registry. Methods: A repeated cross-sectional study was conducted using 2019–2023 data from the BDCAP. Patients with prior diagnoses of ischemic heart disease, stroke, or peripheral artery disease, and receiving lipid-lowering therapy, were included. Data on therapy type (monotherapy or combination therapy with lipid-lowering drugs), LDL-C serum levels, and demographic and socioeconomic factors were analyzed. Trends from 2019 to 2023 and regional differences were also explored. Results: In 2023, 1,565,429 patients received lipid-lowering drugs for secondary prevention (678.3 per 1000 attended), with higher rates in men. Combination therapy increased over time, from 88.9 to 191.1 per 1000 between 2019 and 2023. Regional disparities were notable, with treatment coverage ranging from 53.9% to 87.9%. Only 33.7% of treated patients achieved LDL-C < 70 mg/dL, and 65.6% achieved <100 mg/dL. Combination therapy was significantly more effective than monotherapy in reaching both LDL-C thresholds. Conclusions: Despite the growing use of combination lipid-lowering therapy, a substantial proportion of secondary prevention patients in Spain do not meet LDL-C targets. These findings highlight the need for more intensive lipid management strategies and improved adherence to clinical guidelines to optimize cardiovascular risk reduction.