Patients Receiving Statin Therapy Research Articles

Comorbidity neural network model for personalised recommendations in cardiometabolic risk factor management: towards early precision medicine in routine clinical practice

Abstract Background and Aims Hypertension and hypercholesterolaemia often develop in tandem to confer a risk of cardiovascular disease that may be more than additive. The present study explored early comorbid therapeutic intervention, i.e., beyond individual disease silos, while minimising data bias to provide clinical decision support tools that are portable across clinics. Methods A neural network was created to reproduce UK national clinical guidelines with an accuracy higher than 95%. Relying on real-world evidence from the UK primary care Clinical Practice Research Datalink electronic health record resource, a transfer learning methodology was then applied to achieve recommended risk factor goal attainment after two years. Shapley values derived from game theory were used to define similar digital twin cohorts, and to evaluate individualised recommendations that deviated from national clinical guidelines by rejecting a no-benefit hypothesis retrospectively in a classical proportion test. The methodology was ported to an independent hold-out dataset with anonymized records from six primary care clinics in the South of England. Results The adult patient population (n=469,496, mean+SD age 61+11yr; M 56% vs F 44%; primary 84% vs secondary prevention 16%) included 101,255 diagnosed for hypertension and 112,180 for cholesterol management. While a majority of the 52,504 therapeutic decisions in a test set agree with single morbidity guidelines, for 4639 deviations from the guidance, a significant minority was identified for whom alternative therapy was recommended. Rejecting a no-clinical benefit hypothesis at the 95% confidence level in a retrospective analysis, 1367 decisions showed statistically significant better outcomes over guidelines, for example by escalating anti-hypertensive therapies for patients receiving statin therapy (1085) or by complementing anti-hypertensive therapy with a statin (158). Similar findings were obtained when tested in a hold-out dataset with 13,725 decisions for 6531 patients. Conclusions The results support the contention that machine learning can identify patient subgroups for whom comorbid intervention deviating from clinical guidelines may be appropriate. A novel aspect of the study is the demonstration of clinically portable and actionable application of machine learning in the context of comorbid cardiometabolic diseases. The results represent practical steps towards personalised precision medicine for cardiovascular comorbidity in routine clinical practice.

Three decades of lipid-lowering therapy in type 2 diabetic patients with angiographically proven stable coronary artery disease

Abstract Lipid-lowering therapy (LLT) is key to reducing the burden of macrovascular diabetes complications. Here, we aim to assess long-term trends in LLT and LDL-C levels among patients with type 2 diabetes (T2DM) with angiographically proven coronary artery disease (CAD). We investigated T2DM patients (n=590), who were referred to elective coronary angiography and were diagnosed with CAD in one of three observational cohort studies (OS) spanning 25 years: OS1: 1999-2000 (n=190); OS2: 2005-2008 (n=241); OS3: 2022-2023 (n=159). These studies were conducted at the same cardiology unit of a tertiary care hospital in Central Europe. The proportion of patients receiving statin therapy (C10AA and C10AB) increased significantly from 57.9% in OS1 to 64.3% in OS2 and 78.6% in OS3 (ptrend<0.001). Further, there was an increase in patients receiving high-intensity statin therapy, rising from none in OS1 to 8.5% in OS2 and 73.4% in OS3 (ptrend<0.001). The proportion of patients receiving more than one LLT compound also increased (OS1: 2.1%; OS2: 2.1%; OS3: 35.2%; ptrend<0.001). Use of ezetimibe (C10AX09) increased (OS1: 0.0%; OS2: 1.2%; OS3: 39.0%; ptrend<0.001) and fibrate use (C10AB) decreased (OS1: 5.3%; OS2: 3.3%; OS3: 0.6%; ptrend=0.015). Newly approved compounds (C10AX13 - C10AX16) were prescribed for 3.8% of patients in OS3. Among statin combination therapies, ezetimibe was predominantly used (93.5%). Mean LDL-C levels declined significantly from 123±38 mg/dL (OS1) to 115±39 mg/dL (OS2) and 77±38 mg/dL (OS3; ptrend<0.001). However, only 2.2% of patients in OS1, 2.5% in OS2 and 32.1% in OS3 reached an LDL-C target of <55 mg/dL (ptrend<0.001). This analysis suggests an upward trend in treatment intensity and a substantial improvement in LDL-C levels among T2DM patients with CAD. However, the majority of these patients still does not reach their LDL-C target.

Association between Estimated Small Dense Low-Density Lipoprotein Cholesterol and Occurrence of New Lesions after Percutaneous Coronary Intervention in Japanese Patients with Stable Angina and Receiving Statin Therapy.

Low-density lipoprotein cholesterol (LDL-C) is considered the most important risk factor for coronary artery disease (CAD). Although lipid-lowering therapy using high-intensity statins for patients with stable CAD is one of the cornerstones of medication therapy, there is still a risk of residual cardiovascular events, even after controlling for LDL-C. Recently, attention has focused on the association between small dense LDL-C as a residual risk factor for CAD, and it has been reported that a formula can be used to calculate the small LDL-C. We investigated the association between estimated small dense LDL-C (Esd LDL-C) and the occurrence of new lesions with myocardial ischemia 2 years after percutaneous coronary intervention (PCI) in 537 patients with stable angina who underwent PCI. In this study, all patients had been prescribed statins. This study was based on previously reported data regarding the relationship between non-high-density lipoprotein cholesterol levels and stable angina pectoris after PCI. Revascularization, including new lesions and in-stent restenosis, and new lesions appeared in 130 and 90 patients, respectively, 2 years after PCI. Age, diabetes mellitus (DM), LDL-C, and Esd LDL-C were associated with the occurrence of revascularization and new lesions 2 years after PCI. Multivariate logistic regression analysis models revealed that Esd LDL-C [odds ratio (OR) 1.03, 95% confidence interval (CI) 1.004-1.048, p = 0.020; and OR 1.03, 95% CI 1.009-1.057, p = 0.007, respectively] were associated with the revascularization and occurrence of new lesions 2 years after PCI. As well as total cholesterol and LDL-C, Esd LDL-C was an independent risk factor for the revascularization and occurrence of new lesions 2 years after PCI for stable angina in Japanese patients receiving statin therapy. In patients with stable angina who are on lipid-lowering therapy with statins, calculating the Esd LDL-C may provide useful information for predicting revascularization and the occurrence of new lesions.

Transporter Genes and statin-induced Hepatotoxicity.

Hepatotoxicity has emerged as a major cause of statin treatment interruption. Although organic anion-transporting polypeptide 1B1 (SLCO1B1), multidrug resistance protein 1 (ABCB1), and breast cancer resistance protein (ABCG2) have been identified as transporters of statins, knowledge of their role in statin-associated hepatotoxicity remains limited. Therefore, we aimed to conduct a comprehensive analysis to elucidate the association between hepatotoxicity and SLCO1B1, ABCB1, and ABCG2 polymorphisms. This study retrospectively analyzed prospectively collected samples. We selected 10 single nucleotide polymorphisms (SNPs) of SLCO1B1, 9 SNPs of ABCB1, and 12 SNPs of ABCG2. We developed two models for multivariable analyses (Model I: clinical factors only; Model II: both clinical and genetic factors), and the attributable risk (%) of variables in Model II was determined. Among 851 patients, 66 (7.8%) developed hepatotoxicity. In Model I, lipophilic statins, atrial fibrillation (Afib), and diabetes mellitus showed a significant association with hepatotoxicity. In Model II, lipophilic statins and Afib, SLCO1B1 rs11045818 A allele, SLCO1B1 rs4149035 T allele, and ABCG2 rs2622629 TT genotype were associated with higher hepatotoxicity risk. Among them, the SLCO1B1 rs11045818 A allele exhibited the highest attributable risk (93.2%). The area under the receiver operating characteristic curve in Model I was 0.62 (95% CI: 0.55-0.69), and it was increased to 0.71 in Model II (95% CI: 0.64-0.77). This study investigated the correlation between hepatotoxicity and polymorphisms of transporter genes in patients taking statins. The findings could help improve personalized treatments for patients receiving statin therapy.

Association between statin use and acute pulmonary embolism in intensive care unit patients with sepsis: a retrospective cohort study.

Acute pulmonary embolism (APE) is a life-threatening medical condition that is frequently encountered and associated with significant incidence and mortality rates, posing a substantial threat to patients' well-being and quality of life. Sepsis is prominent independent risk factor for the development of APE. Despite recent investigations indicating a reduced APE risk through statin therapy, its impact on patients with sepsis and APE remains unresolved. The Medical Information Mart for Intensive Care (MIMIC)-IV database was utilized to identify patients diagnosed with sepsis and APE, irrespective of statin treatment status, as part of this study. The primary study aim was to assess the risk of APE, which was analyzed using multivariate logistic regression models. The study encompassed a total of 16,633 participants, with an average age of 64.8 ± 16.2 years. Multivariate logistic regression revealed that septic patients receiving statin therapy in the intensive care unit (ICU) exhibited a 33% reduction in the risk of developing APE (OR = 0.67, 95% CI: 0.52-0.86, p < 0.001). The findings of further analyses, including stratification based on statin usage, dosage, and propensity score matching, consistently reinforced the hypothesis that administering statins to patients with sepsis effectively mitigates their potential APE risk. The results of the study provide compelling evidence in favor of administering statins to septic patients as a prophylactic measure against APE, given that statins may reduce the risk of developing APE, and their anti-APE effect appears to be dose-dependent. Nonetheless, future randomized controlled trials are needed to validate these results.

A meta-analysis of randomized controlled trials of statin-based therapy in patients with COVID-19.

Previous observational studies and meta-analyses have suggested that statins could be beneficial in reducing the risk of adverse clinical outcomes. This study is the first to conduct a meta-analysis of recently published randomized controlled clinical trials investigating the potential therapeutic benefits of statins for COVID-19. A thorough search was conducted using databases such as PubMed and Embase until May 2023 to identify randomized controlled clinical trials investigating the use of statins in patients with COVID-19. Review Manager 5.4 was used to analyze the selected studies. Seven randomized controlled trials comprising a total of 2,370 patients were included in this study. Of these, 1,295 patients received statin therapy, while 1,075 received placebo or other drugs. All included studies were conducted on inpatients with an average age of 45 - 61 years, and the proportion of patients with diabetes and coronary heart disease was less than 30%. One study only included severely ill patients. Our results showed that statin treatment did not significantly reduce hospitalized patient mortality (11.5 vs. 13.4%, p = 0.94), the proportion of patients transferred to intensive care due to disease changes (14.2 vs. 11.2%, p = 0.41), or the proportion of patients requiring mechanical ventilation (5.3 vs. 7.9%, p = 0.71) compared to controls. However, the use of statins was associated with a slight increase in hospital stay. A critical appraisal of published randomized controlled trials on statin therapy in COVID-19 did not show any significant effect on mortality, the risk of transfer to intensive care, or mechanical ventilation.

Risk Factors for Vulnerable Plaque Detected Using Near-Infrared Spectroscopy in Patients Receiving Statin Therapy with No History of Coronary Artery Disease.

Residual risk of atherosclerosis remains high despite the use of lipid-lowering therapy with statins. Near-infrared spectroscopy intravascular ultrasound imaging (NIRS-IVUS) can identify vulnerable plaque via the detection of lipid-rich plaque. This study aimed to reveal the clinical characteristics of patients with vulnerable plaque despite statin therapy.NIRS-IVUS was used to determine the maximum 4 mm Lipid Core Burden Index (MaxLCBI4 mm) values of 38 de novo culprit lesions from 32 patients with acute coronary syndrome (53%) (mean age: 73.1 ± 13.1 years) who underwent percutaneous coronary intervention after a minimum 6 months of statin therapy for primary prevention. A patient with vulnerable plaque was defined as an individual presenting at least 1 target lesion with a vulnerable plaque (MaxLCBI4 mm > 400). Overall, the average low-density lipoprotein cholesterol (LDL-C) level was 95.5 ± 27.2 mg/dL. Patients in the vulnerable plaque group were younger and had higher LDL-C, triglycerides, and non-high-density lipoprotein cholesterol (HDL-C) levels than those in the non-vulnerable plaque group. The MaxLCBI4 mm was positively correlated with LDL-C (P = 0.0002), triglycerides (P = 0.0003), and non-HDL-C (P = 0.0001). In multivariate analysis, all 3 treatable lipid components failed to show an independent relationship with the patients with vulnerable plaque. Using receiver-operating characteristics curve analysis, the cutoff points for LDL-C, triglycerides, and non-HDL-C were determined to be 78 mg/dL, 108 mg/dL, and 111 mg/dL, respectively, at MaxLCBI4 mm > 400. In conclusion, this study supports a more comprehensive and aggressive lipid-lowering therapy for the primary prevention of coronary artery disease.

Impact of statin treatment and exposure on the risk of chronic allograft dysfunction in Chinese lung transplant recipients

PurposeChronic lung allograft dysfunction (CLAD) was a common complication following lung transplantation that contributed to long-term morbidity and mortality. Statin therapy had been suggested to attenuate recipient inflammation and immune response, potentially reducing the risk and severity of CLAD. This study aimed to evaluate the impact of statin use and in vivo exposure on the incidence of CLAD in lung transplant recipients (LTRs), as well as their effects on immune cells and inflammatory factors. MethodsA retrospective cohort study was conducted on patients who underwent lung transplantation between January 2017 and December 2020. The incidence of CLAD, as per the 2019 ISHLT criteria, was assessed as the clinical outcome. The plasma concentrations of statin were measured using a validated UPLC-MS/MS method, while inflammation marker levels were determined using ELISA kits. ResultsThe statin group exhibited a significantly lower rate of CLAD (P = 0.002). Patients receiving statin therapy showed lower CD4+ T-cell counts, total T-lymphocyte counts, and IL-6 levels (P = 0.017, P = 0.048, and P = 0.038, respectively). Among the CLAD groups, the atorvastatin level (2.51 ± 1.31 ng/ml) was significantly lower than that in the non-CLAD group (OR = 1.438, 95%CI (1.007–2.053), P = 0.046). ConclusionStatin therapy significantly reduced the incidence of CLAD, as well as immune cell counts and inflammatory cytokine levels in LTRs. Although the statin exposure was significantly lower in CLAD patients, it was not associated with the incidence of CLAD.

Relationship of Missed Statin Therapy and 10-Year Atherosclerotic Cardiovascular Disease Risk Score to Retear Rate After Arthroscopic Rotator Cuff Repair

Background: There is no practical consensus on managing cholesterol in patients with rotator cuff repair despite hyperlipidemia and statin therapy being well-known factors in rotator cuff healing. The 10-year atherosclerotic cardiovascular disease (ASCVD) risk score is a commonly used guideline to determine statin administration for hyperlipidemia. Purpose: To identify the relationship between retear and preoperative factors, including 10-year ASCVD risk score and statin administration status, and to compare clinical outcomes and retear rates between patients who are taking and not taking statins. Study Design: Case-control study; Level of evidence, 3. Methods: This study enrolled 182 patients with a symptomatic full-thickness rotator cuff tear who underwent arthroscopic repair. Serum lipid profile, 10-year ASCVD risk score, statin eligibility, and statin administration status were assessed. Patients were categorized into 2 groups based on magnetic resonance imaging to evaluate cuff integrity at postoperative 6 months: a healed group and a retear group. Radiographic and intraoperative factors related to retear were analyzed. Multiple regression analysis was performed to evaluate factors related to rotator cuff retear. For the subgroup analysis, patients eligible for statin therapy were divided into 2 subgroups according to administration status. Results: There were 149 (81.9%) patients in the healed group and 33 (18.1%) in the retear group. In the multiple regression analysis, missed statin therapy, 10-year ASCVD risk score, and fatty infiltration of the infraspinatus muscle were the independent factors related to retear. The cutoff value for 10-year ASCVD risk score was 11.85%, with a sensitivity of 0.75 and a specificity of 0.62. In the subgroup analysis of 104 patients eligible for statin therapy, 66 (63.5%; group 1) received statin therapy and 38 (36.5%; group 2) missed it. Group 2 showed a significantly higher retear rate than group 1 (36.8% vs 13.6%; P = .006). Conclusion: Missed statin therapy, 10-year ASCVD risk score, and fatty infiltration of the infraspinatus were the independent factors associated with rotator cuff retear. Patients who missed statin therapy showed a higher retear rate than patients receiving statin therapy. Optimal statin therapy for patients who undergo arthroscopic rotator cuff repair might improve repair integrity.

Highlights of Cardiovascular Disease Prevention Studies Presented at the 2023 American College of Cardiology Conference.

To summarize selected late-breaking science on cardiovascular (CV) disease prevention presented at the 2023 American College of Cardiology (ACC) conference. The CLEAR outcomes randomized control trial (RCT) compared bempedoic acid to placebo in patients at high-risk of cardiovascular disease (CVD) or prevalent CVD and statin intolerance for CV outcomes. The YELLOW III was a single-arm study that evaluated the effect of Evolocumab on coronary plaque characteristics in patients with stable coronary artery disease (CAD). A cohort evaluated the association between a self-reported low-carbohydrate high-fat (ketogenic) diet and serum lipid levels as compared to a standard diet. The LOADSTAR trial compared CV outcomes with targeted low-density lipoprotein cholesterol (LDL-C) approach vs. high-intensity statin in patients with CAD. The PCDS statin cluster randomized trial compared the effectiveness of an electronic reminder to the clinician on a high-intensity statin use among patients with a history of ASCVD as compared to no reminder. A prospective cohort study compared the extent of coronary atherosclerosis among lifelong endurance athletes and healthy non-athletes. A causal artificial intelligence study combined polygenic risk scores with data from large CV prevention RCTs to guide systolic blood pressure and LDL-C reduction targets to reach average CV risk. The ACCESS trial evaluated the impact of eliminating copayment for low-income older adults in Canada with chronic CV diseases on composite CV outcomes. A pooled analysis of 3 large RCTs evaluated the association between residual inflammatory risk and CV outcomes, as compared to residual elevated cholesterol risk in patients receiving statin therapy. A Phase 2B RCT compared the efficacy of an oral PCSK9i, MK-0616, in reducing LDL-C as compared to a placebo. The late-breaking clinical science presented at the 2023 conference of the ACC paves the way for an evidence-based alternative to statin therapy and provides data on several common clinical scenarios encountered in daily practice.

Value of the clinical pharmacist interventions in the application of the American College of Cardiology (ACC/AHA) 2018 guideline for cholesterol management.

The study aims to examine the extent to which the updated ACC/AHA management of blood cholesterol guideline (2018) is implemented in practice and to assess the value of the clinical pharmacist interventions in improving physicians' adherence the guidelines recommendations. We utilized in this study an interventional before-after design. The study was conducted on 272 adult patients who visited the study site internal medicine clinics and were candidates for statin therapy based on the 2018 ACC/AHA guidelines for cholesterol management. Adherence to guideline recommendations was measured before and after clinical pharmacists' interventions by calculating the percentage of patients receiving statin therapy as per guideline recommendation, the type and intensity (moderate or high intensity) of statin therapy used, and the need for additional non-statin therapy. Adherence with guideline recommendations was significantly improved from 60.3% to 92.6% (X2 = 79.1, p = 0.0001) after clinical pharmacist interventions. Among patients who were on statin therapy, the percentage of those who were on proper statin intensity increased significantly from 47.6% to 94.4% (X2 = 72.5, p = 0.0001). The combination of statins with non-statin therapies such as ezetimibe and PCSK9 inhibitors increased from 8.5% to 30.6% (X2 = 95, p<0.0001) and from 0.0% to 1.6% (X2 = 6, p = 0.014), respectively. The use of other lipid-lowering agents was diminished from 14.6% to 3.2% (X2 = 19.2, p<0.0001). Collaboration between physicians and clinical pharmacists is a crucial strategy to improve patients' treatment and hence, achieve better health outcomes among patients suffering from dyslipidemia.

Association of lipid-lowering agent use and dry eye disease: A nationwide matched case-control study in Taiwan, 2002-2016.

The purpose of this study is to evaluate the association between lipid-lowering agent use and the risks of diagnosed dry eye disease (DED). This retrospective, case-control study included 780 786 patients who received lipid-lowering agents in 2002-2016, of which 17 409 were newly diagnosed with DED during a ≥2-year follow-up period. These patients were matched 1:4 with control participants for age, sex, and comorbidities. Separate odds ratios (OR) were calculated for DED and each of statin and fibrate use. Statin users had significantly higher odds of DED (adjusted OR=1.12; 95% confidence interval (CI)=1.08-1.16, p < 0.0001) than nonusers. Fibrate users did not show higher odds of DED than nonusers (adjusted OR=1.04; 95% CI=0.99-1.10, p=0.125). The lipophilic statin users did not show higher odds of DED compared with the hydrophilic statin users (adjusted OR=0.99, 95% CI=0.93-1.06, p=0.729). Among statin users, the odds of DED did not differ significantly between patients receiving statin therapy for >180 days vs. ≤90 days or patients receiving statin therapy for 91-180 days vs. ≤90 days (adjusted OR=1.00, p=0.922; adjusted OR=0.94, p=0.541, respectively). The odds of DED were not statistically different among patients receiving low-intensity, moderate-intensity, and high-intensity of statin therapy. Patients receiving statin therapy had a higher DED risk than patients not receiving statin therapy. The type of statin, the duration, and the intensity of statin use were not significantly associated with DED risks. Further studies are required to identify the relevant factors related to DED risks with statin.

Inflammation and cholesterol as predictors of cardiovascular events among patients receiving statin therapy: a collaborative analysis of three randomised trials

Inflammation and hyperlipidaemia jointly contribute to atherothrombotic disease. However, when people are treated with intensive statin therapy, the relative contributions of inflammation and hyperlipidaemia to the risk of future cardiovascular events might change, which has implications for the choice of adjunctive cardiovascular therapeutics. We aimed to evaluate the relative importance of high-sensitivity C-reactive protein (CRP) and low-density lipoprotein cholesterol (LDLC) as determinants of risk for major adverse cardiovascular events, cardiovascular death, and all-cause-death among patients receiving statins. We did a collaborative analysis of patients with-or at high risk of-atherosclerotic disease, who were receiving contemporary statins and were participants in the multinational PROMINENT (NCT03071692), REDUCE-IT (NCT01492361), or STRENGTH (NCT02104817) trials. Quartiles of increasing baseline high-sensitivity CRP (a biomarker of residual inflammatory risk) and of increasing baseline LDLC (a biomarker of residual cholesterol risk) were assessed as predictors of future major adverse cardiovascular events, cardiovascular death, and all-cause death. Hazard ratios (HRs) for cardiovascular events and deaths were calculated across quartiles of high-sensitivity CRP and LDLC in analyses adjusted for age, gender, BMI, smoking status, blood pressure, previous history of cardiovascular disease, and randomised treatment group assignment. 31 245 patients were included in the analysis from the PROMINENT (n=9988), REDUCE-IT (n=8179), and STRENGTH (n=13 078) trials. The observed ranges for baseline high-sensitivity CRP and LDLC, and the relationships of each biomarker to subsequent cardiovascular event rates, were almost identical in the three trials. Residual inflammatory risk was significantly associated with incident major adverse cardiovascular events (highest high-sensitivity CRP quartile vs lowest high-sensitivity CRP quartile, adjusted HR 1·31, 95% CI 1·20-1·43; p<0·0001), cardiovascular mortality (2·68, 2·22-3·23; p<0·0001), and all-cause mortality (2·42, 2·12-2·77; p<0·0001). By contrast, the relationship of residual cholesterol risk was neutral for major adverse cardiovascular events (highest LDLC quartile vs lowest LDLC quartile, adjusted HR 1·07, 95% CI 0·98-1·17; p=0·11), and of low magnitude for cardiovascular death (1·27, 1·07-1·50; p=0·0086) and all-cause death (1·16, 1·03-1·32; p=0·025). Among patients receiving contemporary statins, inflammation assessed by high-sensitivity CRP was a stronger predictor for risk of future cardiovascular events and death than cholesterol assessed by LDLC. These data have implications for the selection of adjunctive treatments beyond statin therapy and suggest that combined use of aggressive lipid-lowering and inflammation-inhibiting therapies might be needed to further reduce atherosclerotic risk. Kowa Research Institute, Amarin, AstraZeneca.

Inflammation contributes to cardiovascular risk in patients receiving statin therapy

Inflammation contributes to cardiovascular risk in patients receiving statin therapy

Efficacy and safety of the use of alirocumab in real clinical practice

To evaluate the results of two-year use of alirokumab in Karelia Republic. The observation group consisted of 27 patients (17 patients with familial hypercholesterolemia, 10 patients with the history of myocardial infarction), mean age 53.4±4.3 years, 70.3% men, follow-up duration from one year to 2.5 years, 18 (66.6%) patients received therapy for more than 2 years. 19 patients received alirocumab at a dose of 75 mg/ml once every 2 weeks, eight - at a dose of 150 mg/ml once every 2 weeks. Before the start of therapy, the majority received maximally tolerated statin therapy, 10 patients received statin therapy in combination with ezetemibe, 3 patients received ezetemibe monotherapy due to statin intolerance. The target levels of LDL cholesterol were considered for very high risk patients less than 1.4 mmol/L, high risk - less than 1.8 mmol/L, extreme risk - less than 1 mmol/L. The reduction of LDL on therapy with alirocumab was 58%; target levels of LDL were achieved in 77.8%. The level of decrease in LDL cholesterol less than 50% was noted only in 7.4% of cases. Patients requiring a large dose of the drug were classified as very high risk, had higher cholesterol and LDL-C levels. The level of Lp(a) decrease on 29.7% by 6-12 months. No destabilization of coronary heart disease, new cases of stroke were registered. The inclusion of alirocumab in the treatment regimen contributed to the stable course of atherosclerosis-associated diseases, the achievement of LDL cholesterol targets in 77.8% of patients, was not accompanied by side effects during 2.5 years therapy.

Statin Therapy is Associated with Higher Risk of Diabetic Complications: A Population-Based Cohort Study

BackgroundData regarding diabetic complications with chronic statin use among Asian population is very limited. Hence, we investigated diabetic progression in diabetic patients receiving statin therapy by evaluating the association with acute and chronic diabetic complications. MethodsThis retrospective population-based cohort study included patients aged 40 years or older who were diagnosed with type-2 diabetes mellitus (T2DM) in Hong Kong between January 1st, 2009 and December 31st, 2009 and followed up till December 31st, 2019. Patients were divided into statin users and non-users, and propensity score matching (PSM) was performed based on demographics, prior comorbidities, and medications. The study outcomes were new-onset Diabetic Ketoacidosis/ Hyperosmolar Hyperglycaemic State (DKA/HHS), new diabetic ophthalmological, neurological, and renal complications. ResultsAfter 1:1 PSM, the study cohort consisted of 3,247 statin users (48.6% male, age 65.03±11.99 years, mean follow-up 5.68±2.39 years) and 3,247 (50.5% male, age 63.20±12.15 years, mean follow-up 5.78±2.34 years) matched statin non-users. Cox proportional hazards model analyses showed that statin therapy was associated with a higher risk of new diabetic renal complications (HR: 1.44, [1.21-1.71], p<0.001), new diabetic ophthalmological complications (HR: 1.44, [1.19-1.73], p<0.001), and new diabetic neurological complications (HR: 1.47, [1.09-1.96], p<0.01), although it was not associated with a higher risk of DKA/HHS (HR: 1.31, [95% CI, 0.89-1.94], p=0.167). The statistical significance of the associations was not maintained under sensitivity analysis which involved excluding patients with previous coronary heart disease. ConclusionAmongst T2DM patients, statin use was associated with higher risk of developing chronic diabetic complications after PSM with multiple adjustments.

Statin therapy may protect against acute kidney injury in patients hospitalized for interstitial SARS-CoV2 pneumonia

Background and aimsCOVID-19-associated acute kidney injury (AKI) represents an independent risk factor for all-cause in-hospital death in patients with COVID-19. Chronic statin therapy use is highly prevalent in individuals at risk for severe COVID-19. Our aim is to assess whether patients under treatment with statins have a lower risk of AKI and in-hospital mortality during hospitalization for interstitial SARS-CoV2 pneumonia. Methods and resultsOur study is a prospective observational study on 269 consecutive patients admitted for COVID-19 pneumonia at the Internal Medicine Unit of IRCCS Sant'Orsola Hospital in Bologna, Italy. We compared the clinical characteristics between patients receiving statin therapy (n = 65) and patients not treated with statins and we assessed if chronic statin use was associated with a reduced risk for AKI, all-cause mortality, admission to ICU, and disease severity. Statin use was associated with a significant reduction in the risk of developing AKI (OR 0.47, IC 0.23 to 0.95, p 0.036) after adjustment for age, sex, BMI, hypertension, diabetes, and chronic kidney disease (CKD). Additionally, statin use was associated with reduced C-reactive protein (CRP) levels (p 0.048) at hospital admission. No significant impact in risk of all-cause mortality (HR 1.98, IC 0.71 to 5.50, p 0.191) and ICU admission (HR 0.93, IC 0.52 to 1.65, p 0.801) was observed with statin use, after adjustment for age, sex, BMI, hypertension, diabetes, and CKD. ConclusionThe present study shows a potential beneficial effect of statins in COVID-19-associated AKI. Furthermore, patients treated with statins before hospital admission for COVID-19 may have lower systemic inflammation levels.

Association of Statin Therapy With Major Adverse Cardiovascular and Limb Outcomes in Patients With End-stage Kidney Disease and Peripheral Artery Disease Receiving Maintenance Dialysis

Controversy exists regarding whether statin therapy has benefits for patients with kidney failure, and the consequences of statin therapy for patients with kidney failure and concomitant peripheral artery disease (PAD) are particularly uncertain. To evaluate the association of statin therapy with cardiovascular (CV) and limb outcomes among patients with kidney failure and concomitant PAD and dyslipidemia who are receiving long-term maintenance dialysis. This retrospective cohort study used data from the Taiwan National Health Insurance Research Database. A total of 20 731 patients with kidney failure receiving long-term maintenance dialysis who were diagnosed with PAD and dyslipidemia between January 1, 2001, and December 31, 2013, were identified, and 10 767 patients met study criteria. Data were analyzed from June 8, 2021, to June 2, 2022. Primary outcomes were all-cause death and the composite of endovascular therapy (EVT) and amputation. Other outcomes of interest included CV events (CV death, acute myocardial infarction, ischemic stroke, and hospitalization for heart failure), major adverse limb events (new-onset claudication, new-onset critical limb ischemia, EVT, and nontraumatic amputation), and all-cause readmission. All outcomes were examined at 1 year and 3 years of follow-up. To minimize selection bias, propensity score matching on a 1:1 ratio was performed among patients receiving statin therapy (statin group) and patients not receiving statin therapy (nonstatin group). A defined daily dose (DDD) approach was used to evaluate whether the association of statin therapy with the risk of primary outcomes was dose dependent. Among 20 731 patients with kidney failure and concomitant PAD and dyslipidemia receiving long-term maintenance dialysis, 10 767 patients (5593 women [51.9%]; mean [SD] age, 68.5 [11.5] years; all of Taiwanese ethnicity) met the predetermined study criteria; of those, 3597 patients were receiving statin therapy, and 7170 were not. A total of 6470 patients (mean [SD] age, 66.4 [11.3] years; 3359 women [51.9%]) were included in the 1:1 propensity score-matched cohort, with 3235 patients in each group (statin and nonstatin). The incidence and risk of CV and all-cause death were significantly lower in the statin group vs the nonstatin group at 3 years of follow-up (CV death: 611 patients [18.9%] vs 685 patients [21.2%]; hazard ratio [HR], 0.86 [95% CI, 0.77-0.96]; P = .008; all-cause death: 1078 patients [33.3%] vs 1138 patients [35.2%]; HR, 0.92 [95% CI, 0.84-0.996]; P = .04). Statin use was also associated with a significantly lower incidence and risk of the composite adverse limb outcome of EVT and amputation at 3 years of follow-up (314 patients [9.7%] vs 361 patients [11.2%]; subdistribution HR, 0.85 [95% CI, 0.73-0.99]; P = .04). Results of subgroup analyses were consistent with those of the primary analysis across all subgroup variables. In the adjusted dose-response analysis, the risk reduction associated with statin use increased in a dose-dependent manner for both all-cause death (HR: 0.95 for DDD <0.50, 0.92 for DDD 0.50-0.99, 0.85 for DDD 1.00-1.49, and 0.79 for DDD ≥1.50; P = .002 for trend) and the composite outcome of EVT and amputation (subdistribution HR: 0.79 for DDD <0.50, 0.78 for DDD 0.50-0.99, 0.82 for DDD 1.00-1.49, and 0.58 for DDD ≥1.50; P = .002 for trend) compared with no statin therapy; however, not all findings in the DDD analysis were statistically significant. In this cohort study, statin therapy was associated with reductions in the risk of all-cause death, CV death, and the composite adverse limb outcome of EVT and amputation. These findings suggest that statin therapy may have protective CV and limb benefits for patients with kidney failure and concomitant PAD who are receiving long-term maintenance dialysis.

PARAMETERS OF LIPID METABOLISM IN PATIENTS WITH CHRONIC KIDNEY DISEASE AND THYROID DYSFUNCTION

BACKGROUND . In CKD lipid metabolism disorders are associated with a high incidence of adverse outcomes. Dyslipidemia in patients with CKD is characterized by a decrease in HDL cholesterol, high triglyceride levels, and normal total cholesterol and LDL cholesterol levels. In CKD, a decrease in the functional activity of the thyroid gland (subclinical hypothyroidism) is often detected. THE AIM : to study the parameters of the lipid spectrum of blood in patients with different stages of chronic kidney disease and thyroid dysfunction. PATIENTS AND METHODS . A one-stage cross-sectional study of 457 patients with glomerulopathies without clinically significant diseases of the cardiovascular system with preserved ejection fraction (&gt; 55% according to Simpson method) according to echocardiography was carried out. To identify thyroid dysfunction, a screening determination of the level of TSH, free T4 was assessed. The parameters of the blood lipid spectrum and GFR were assessed in all patients. Parametric and nonparametric methods of statistical analysis were used. RESULTS . Advanced stages of CKD are characterized by the formation of atherogenic dyslipidemias. 13.1% of patients received statin therapy, the target values of the blood lipid spectrum on statin therapy were not achieved. In the group of patients with nephrotic syndrome, the parameters of the blood lipid spectrum were significantly worse. Most of the patients with CKD were outside the target values of the blood lipid spectrum. In patients with TSH&gt; 7.0 mIU / L, the content of TC, LDL, non-HDL was significantly higher than in the group of patients with normal thyroid function. CONCLUSION . Subclinical hypothyroidism contributes to the formation of atherogenic dyslipidemias in patients with CKD.

A propensity score-matched analysis of the impact of statin therapy on the outcomes of patients with non-small-cell lung cancer receiving anti-PD-1 monotherapy: a multicenter retrospective study.

BackgroundMany studies have recently reported the association of concomitant medications with the response and survival in patients with non-small-cell lung cancer (NSCLC) treated with cancer immunotherapy. However, the clinical impact of statin therapy on the outcome of cancer immunotherapy in patients with NSCLC is poorly understood.MethodsIn our database, we retrospectively identified and enrolled 390 patients with advanced or recurrent NSCLC who were treated with anti-programmed cell death-1 (PD-1) monotherapy in clinical practice between January 2016 and December 2019 at 3 medical centers in Japan to examine the clinical impact of statin therapy on the survival of patients with NSCLC receiving anti-PD-1 monotherapy. A propensity score-matched analysis was conducted to minimize the bias arising from the patients’ backgrounds.ResultsThe Kaplan–Meier curves of the propensity score-matched cohort showed that the overall survival (OS), but not the progression-free survival (PFS), was significantly longer in patients receiving statin therapy. However, a Cox regression analysis in the propensity score-matched cohort revealed that statin therapy was not an independent favorable prognostic factor, although it tended to be correlated with a favorable outcome.ConclusionsStatin therapy may be a combination tool for cancer immunotherapy in patients with NSCLC. These findings should be validated in further prospective studies with larger sample sizes.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12885-022-09385-8.