The potential for improved outcomes in the prevention and therapy of diabetic kidney disease through 'stacking' of drugs from different classes.

Aggressive therapy of diabetic kidney disease (DKD) can not only slow the progression of DKD to renal failure but, if utilized at an early enough stage of DKD, can also stabilize and/or reverse the decline in renal function. The currently recognized standard of therapy for DKD is blockade of the renin-angiotensin system with angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs). However, unless utilized at a very early stage, monotherapy with these drugs in DKD will only prevent or slow the progression of DKD and will neither stabilize nor reverse the progression of DKD to renal decompensation. Recently, the addition of a sodium-glucose cotransporter-2 inhibitor and/or a mineralocorticoid receptor blocker to ACE inhibitors or ARBs has been clearly shown to further decelerate the decline in renal function. The use of glucagon-like peptide-1 (GLP-1) agonists shown promise in decelerating the progression of DKD. Other drugs that may aid in the deceleration the progression of DKD are dipeptidyl peptidase-4 inhibitors, pentoxifylline, statins, and vasodilating beta blockers. Therefore, aggressive therapy with combinations of these drugs (stacking) should improve the preservation of renal function in DKD.

Sex differences in cardiologic medication provision for adults with coronary heart disease: an analysis of health claims data from 2018 to 2020 in Saxony-Anhalt, Germany.

BACKGROUND: Coronary heart diseases (CHDs) have experienced the largest increase worldwide as a cause of death, accounting for 16% of all deaths. In Saxony-Anhalt, a federal state in Germany, both CHD morbidity and acute myocardial infarction mortality rates are particularly high. Several risk factors associated with CHDs have been studied in Saxony-Anhalt, but sex differences in service use and medication have not been investigated. This study therefore aimed to investigate sex differences in the quality and quantity of cardiological care provided to adults with CHD. METHODS: This study used health claims data from 2018 to 2020 to analyse the utilisation of healthcare services and adherence to medication-related guideline recommendations in primary and specialist care. The sample included 133,661 individuals with CHD from a major statutory health insurance company (Germany). RESULTS: Almost all CHD patients (> 99%) received continuous primary care. Continuous cardiologist utilisation was lower for females than for males, with 15.0% and 22.2%, respectively, and sporadic utilisation showed greater differences, with 33.5% of females and 43.4% of males seeking sporadic cardiologist consultations. Additionally, 43.1% of the identified CHD patients participated in disease management programmes (DMPs). The study also examined the impact of DMP participation and cardiologist care on medication uptake and revealed that sex differences in medication uptake, except for statin use, were mitigated by these factors. Statins were prescribed to 42.9% of the CHD patients eligible for statin prescription in accordance with the QiSA indicator for statin prescription eligibility. However, there were significant sex differences in statin utilisation. Female CHD patients were less likely to use statins (35.2%) than male CHD patients were (50.1%). The difference in statin utilisation persisted after adjustment for DMP participation and cardiologist consultation. CONCLUSIONS: This study highlights sex differences in the utilisation of cardiological healthcare services for patients with CHD in the Saxony-Anhalt cohort. These findings underscore the continuing need for interventions to reduce sex inequalities in accessing healthcare and providing health care for patients with CHD. Factors at the health care system, patient, and physician levels should be further investigated to eventually improve statin prescription in people with CHD, especially women.

Statin loading before coronary artery bypass grafting: a randomized trial.

AIMS: Evidence suggests that a high-dose statin loading before a percutaneous coronary revascularization improves outcomes in patients receiving long-term statins. This study aimed to analyse the effects of such an additional statin therapy before surgical revascularization. METHODS AND RESULTS: This investigator-initiated, randomized, double-blind, and placebo-controlled trial was conducted from November 2012 to April 2019 at 14 centres in Germany. Adult patients (n = 2635) with a long-term statin treatment (≥30 days) who were scheduled for isolated coronary artery bypass grafting (CABG) were randomly assigned to receive a statin-loading therapy or placebo at 12 and 2 h prior to surgery using a web-based system. The primary outcome of major adverse cardiac and cerebrovascular events (MACCE) was a composite consisting of all-cause mortality, myocardial infarction (MI), and a cerebrovascular event occuring within 30 days after surgery. Key secondary endpoints included a composite of cardiac death and MI, myocardial injury, and death within 12 months. Non-statistically relevant differences were found in the modified intention-to-treat analysis (2406 patients; 1203 per group) between the statin (13.9%) and placebo groups (14.9%) for the primary outcome [odds ratio (OR) 0.93, 95% confidence interval (CI) 0.74-1.18; P = 0.562] or any of its individual components. Secondary endpoints including cardiac death and MI (12.1% vs. 13.5%; OR 0.88, 95% CI 0.69-1.12; P = 0.300), the area under the troponin T-release curve (median 0.398 vs. 0.394 ng/ml, P = 0.333), and death at 12 months (3.1% vs. 2.9%; P = 0.825) were comparable between treatment arms. CONCLUSION: Additional statin loading before CABG failed to reduce the rate of MACCE occuring within 30 days of surgery.

Medium-intensity statin with ezetimibe versus high-intensity statin in acute ischemic cerebrovascular disease (MESIA): A randomized clinical trial.

BACKGROUND: High-risk stroke patients are recommended to receive high-intensity statin therapy to reduce the risk of stroke recurrence. However, doubling the dosage of statin drugs did not increase the achievement rate of LDL-C target or provide additional clinical benefits, but significantly increased the risk of adverse reactions. Statins and ezetimibe work through different mechanisms and the combined use of statins and ezetimibe significantly improves outcomes with comparable safety profiles. We tested the hypothesis that moderate-intensity statin with ezetimibe may offer advantages over the conventional high-intensity statin regimen in terms of efficacy and safety. METHODS: We conducted a randomized controlled trial. Eligible participants were aged 18 years or older with acute ischemic cerebrovascular disease. We randomly assigned (1:1) participants within the acute phase of ischemic stroke, i.e., within 1 week after the onset of mild ischemic stroke (NIHSS score ≤ 5), within 1 month for severe cases (NIHSS score ≥ 16), and within 2 weeks for the rest, as well as patients with TIA within 1 week of symptom onset, to receive either moderate-intensity statin with ezetimibe (either 10-20 mg atorvastatin calcium tablets plus a 10 mg ezetimibe tablet, or 5-10 mg rosuvastatin calcium tablets once per day plus a 10 mg ezetimibe tablet once per day) or high-intensity statin (40 mg atorvastatin calcium tablets or 20 mg rosuvastatin calcium tablets once per day) for 3 months. Randomization was performed using a random number table method. The primary efficacy outcome was the level and achievement rate of LDL-C after 3 months of treatment, specifically LDL-C ≤ 1.8 mmol/L or a reduction in LDL-C ≥ 50 %. The secondary outcome was the incidence of new stroke or transient ischemic attack (TIA) within 3 months. The safety outcome was liver and renal function tests, and the occurrence of statin-related muscle events within 3 months. FINDINGS: This trial took place between March 15, 2022, and March 7, 2023. Among 382 patients screened, 150 patients were randomly assigned to receive either medium-intensity statins with ezetimibe (n = 75) or high-intensity statins (n = 75). Median age was 60.0 years (IQR 52.75-70.25); 49 (36.6 %) were women and 85 (63.4 %) were men. The target achievement of LDL-C at 3 months occurred in 62 (89.86 %) of 69 patients in the medium-intensity statin with ezetimibe group and 46 (70.77 %) of 65 patients in the high-intensity statin group (P=0.005, OR=0.273, 95 % CI: 0.106, 0.705). The reduction magnitude of LDL-C in moderate-intensity statin with ezetimibe group was significantly higher (-56.540 % vs -47.995 %, P=0.001). Moderate-intensity statin with ezetimibe group showing a trend of a greater reduction in LDL-C absolute value than high-intensity statin group but without statistical significance (-1.77±0.90 vs -1.50±0.89, P=0.077). New AIS or TIA within 3 months, liver and renal function tests, and the occurrence of statin-related muscle events within 3 months were also statistically insignificant. Multivariate logistic regression analysis showed that both gender and lipid-lowering regimen as independent risk factors influencing the rate of LDL-C achievement in individuals diagnosed with acute ischemic cerebrovascular disease, but only lipid-lowering regimen had predictive value. INTERPRETATION: Compared to guideline-recommended high-intensity statin therapy, moderate-intensity statin with ezetimibe further improved the achievement rate of LDL-C in patients with acute ischemic cerebrovascular disease, with a higher reduction magnitude in LDL-C. In terms of safety, there was no significant difference between the two regimens, suggesting that moderate-intensity statin with ezetimibe can also be considered as an initial treatment option for patients with acute ischemic cerebrovascular disease.

A Systematic Review of Statins for the Treatment of Nonalcoholic Steatohepatitis: Safety, Efficacy, and Mechanism of Action.

Nonalcoholic fatty liver disease (NAFLD) is the liver component of a cluster of conditions, while its subtype, nonalcoholic steatohepatitis (NASH), emerges as a potentially progressive liver disorder that harbors the risk of evolving into cirrhosis and culminating in hepatocellular carcinoma (HCC). NASH and cardiovascular disease (CVD) have common risk factors, but compared to liver-related causes, the most common cause of death in NASH patients is CVD. Within the pharmacological armamentarium, statins, celebrated for their lipid-modulating prowess, have now garnered attention for their expansive therapeutic potential in NASH. Evidence from a plethora of studies suggests that statins not only manifest anti-inflammatory and antifibrotic properties but also impart a multifaceted beneficial impact on hepatic health. In this review, we used "statin", "NAFLD", "NASH", and "CVD" as the major keywords and conducted a literature search using the PubMed and Web of Science databases to determine the safety and efficacy of statins in patients and animals with NASH and NAFLD, and the mechanism of statin therapy for NASH. Simultaneously, we reviewed the important role of the intestinal microbiota in statin therapy for NASH, as it is hoped that statins will provide new insights into modulating the harmful inflammatory microbiota in the gut and reducing systemic inflammation in NASH patients.

Association between Statin Use and Chemotherapy-Induced Cardiotoxicity: A Meta-Analysis.

Background: Chemotherapy-induced cardiac dysfunction (CIC) is a significant and concerning complication observed among cancer patients. Despite the demonstrated cardioprotective benefits of statins in various cardiovascular diseases, their effectiveness in mitigating CIC remains uncertain. Objective: This meta-analysis aims to comprehensively evaluate the potential cardioprotective role of statins in patients with CIC. Methods: A systematic literature search was conducted using PubMed, Embase, and Scopus databases to identify relevant articles published from inception until 10th May 2023. The outcomes were assessed using pooled odds ratio (OR) for categorical data and mean difference (MD) for continuous data, with corresponding 95% confidence intervals (95% CIs). Results: This meta-analysis comprised nine studies involving a total of 5532 patients, with 1904 in the statin group and 3628 in the non-statin group. The pooled analysis of primary outcome shows that patients who did not receive statin suffer a greater decline in the LVEF after chemotherapy compared to those who receive statin (MD, 3.55 (95% CI: 1.04-6.05), p = 0.01). Likewise, we observed a significantly higher final mean LVEF among chemotherapy patients with statin compared to the non-statin group of patients (MD, 2.08 (95% CI: 0.86-3.30), p > 0.001). Additionally, there was a lower risk of incident heart failure in the statin group compared to the non-statin group of patients (OR, 0.41 (95% CI: 0.27-0.62), p < 0.001). Lastly, the change in the mean difference for LVEDV was not statistically significant between the statin and non-statin groups (MD, 1.55 (95% CI: -5.22-8.33), p = 0.65). Conclusion: Among patients of CIC, statin use has shown cardioprotective benefits by improving left ventricular function and reducing the risk of heart failure.

Fixed Combination for the Treatment of Dyslipidaemia.

PURPOSE OF REVIEW: It is clear from epidemiological studies that patients at high and very-high risk of atherosclerotic cardiovascular diseases (ASCVD) risk do not reach lipid guideline-recommended targets. Thus, fixed-dose combinations of statins/ezetimibe, bempedoic acid/ezetimibe and statins/fibrates may represent a further armamentarium in the field of lipid-lowering approaches in these individuals. RECENT FINDINGS: The combination therapy of moderate-intensity statin with ezetimibe is not inferior to high-intensity statin monotherapy in reducing cardiovascular outcomes. Drug discontinuation or dose reduction is inferior with fixed-dose combination. The fixed-dose combination of bempedoic acid with ezetimibe is superior to bempedoic acid in monotherapy in lowering LDL-C and in reducing high-sensitivity C-reactive protein concentrations. The combination fenofibrate with atorvastatin is superior to monotherapies in lowering triglycerides. Lipid-lowering fixed-dose combinations may guarantee a higher therapy adherence, representing a better approach to control plasma lipids and thus ameliorate ASCVD burden. Additional studies will define the advantages on cardiovascular outcomes in high and very high-risk patients.

Protective Effects of Different Classes, Intensity, Cumulative Dose-Dependent of Statins Against Primary Ischemic Stroke in Patients with Type 2 Diabetes Mellitus.

PURPOSE OF REVIEW: The aim of this study is to investigate the protective effects of different statin classes, intensity, and cumulative dose-dependent against primary ischemic stroke in patients with T2DM. RECENT FINDINGS: The Cox hazards model was used to evaluate statin use on primary ischemic stroke. Case group: T2DM patients who received statins; control group: T2DM patients who received no statins during the follow-up. Adjusted hazard ratio (aHR) for primary ischemic stroke was 0.45 (95% CI: 0.44 to 0.46). Cox regression analysis showed significant reductions in primary ischemic stroke incidence in users of different statin classes. Corresponding aHRs (95% CI) were 0.09 to 0.79 for pitavastatin, rosuvastatin, atorvastatin, pravastatin, simvastatin, fluvastatin, and lovastatin. Multivariate analyses indicated significant reductions in primary ischemic stroke incidence for patients who received different cumulative defined daily doses (cDDDs) per year (cDDD-year). Corresponding aHRs (95% CI) were 0.17 to 0.77 for quartiles 4 to 1 of cDDD-years, respectively (P for trend < .0001). Optimal intensity daily dose of statin use was 0.89 DDD with the lowest aHR of primary ischemic stroke compared with other DDDs. Persistent statin use reduces the risk of primary ischemic stroke in T2DM patients. Higher cDDD-year values are associated with higher reductions in primary ischemic stroke risk in T2DM patients.

Prescribing statin therapy in physically (in)active individuals vs prescribing physical activity in statin-treated patients: A four-scenario practical approach.

Statins are among the most commonly prescribed medications worldwide. Statin-associated muscle symptoms (SAMS) represent a frequent statin-related adverse effect associated with statin discontinuation and increased cardiovascular disease (CVD) events. Emerging evidence indicate that the majority of SAMS might not be actually caused by statins, and the nocebo/drucebo effect (i.e. adverse effects caused by negative expectations) might also explain SAMS. Physical activity (PA) is a cornerstone in the management of CVD risk. However, evidence of increased creatine-kinase levels in statin-treated athletes exposed to a marathon has been generalized, at least to some extent, to the general population and other types of PA. This generalization is likely inappropriate and might induce fear around PA in statin users. In addition, the guidelines for lipid management focus on aerobic PA while the potential of reducing sedentary behavior and undertaking resistance training have been overlooked. The aim of this report is to provide a novel proposal for the concurrent prescription of statin therapy and PA addressing the most common and clinically relevant scenarios by simultaneously considering the different stages of statin therapy and the history of PA. These scenarios include i) statin therapy initiation in physically inactive patients, ii) PA/exercise initiation in statin-treated patients, iii) statin therapy initiation in physically active patients, and iv) statin therapy in athletes and very active individuals performing SAMS-risky activities.

How to Use Statins in Secondary Prevention of Atherosclerotic Diseases: from the Beneficial Early Initiation to the Potentially Unfavorable Discontinuation.

Statins, a class of lipid-lowering drugs, reduce morbidity and mortality in patients with established atherosclerosis-related cardiovascular disease. Early initiation of statin therapy after admission for acute coronary syndromes (ACS), stroke, or transient ischemic attack (TIA) is associated with improved cardiovascular outcomes. Moreover, high-dose statin treatment prior to coronary or carotid revascularization has been shown to reduce cardiovascular events in these patients. However, many patients may be undertreated, and a residual cardiovascular risk remains in current clinical practice. Despite the beneficial role of statins, their discontinuation rate among patients is still elevated leading to severe adverse cardiovascular events due to atherosclerotic plaque destabilization. In this review, we summarized the impact of statin treatment among patients, focusing on the initiation time-points as well as the potential harm derived by their discontinuation.

Does statin suppress oxaliplatin-induced peripheral neuropathy in patients with colorectal cancer? A single-center observational study.

BACKGROUND: Oxaliplatin-induced peripheral neuropathy (OIPN) is a common and dose-limiting toxicity that markedly limits the use of oxaliplatin and affects quality of life. Statins have been shown to exert neuroprotective effects in preclinical settings. The aim of the present study was to clarify whether statins prevented OIPN in patients with colorectal cancer (CRC) receiving adjuvant CAPOX therapy. METHODS: We examined 224 patients who received adjuvant CAPOX therapy for CRC between July 2010 and December 2021 at our hospital. Patients were divided into "Statin" and "Non-statin" groups based on statin use. Details on and the adverse events of adjuvant CAPOX therapy were examined in association with statin use. RESULTS: Thirty-one patients (14%) were treated with statins. There were no intergroup differences in the relative dose intensity or number of CAPOX cycles between the Statin and Non-statin groups. In total, 94% of patients in the Statin group and 95% of those in the Non-statin group developed OIPN (p=0.67). The severity of OIPN was similar between the two groups (p=0.89). The frequency of treatment delays in CAPOX did not significantly differ between the Statin and Non-statin groups (16% vs. 11%, p=0.45). CONCLUSIONS: The efficacy of statins to attenuate OIPN during adjuvant CAPOX therapy was not apparent in the current study. Further studies are needed to confirm the present results.

International practice patterns of dyslipidemia management in patients with chronic kidney disease under nephrology care: is it time to review guideline recommendations?

BACKGROUND: In contrast to guidelines related to lipid therapy in other areas, 2012 Kidney Disease Improving Global Outcomes (KDIGO) guidelines recommend conducting a lipid profile upon diagnosis of chronic kidney disease (CKD) and treating all patients older than 50 years without defining a target for lipid levels. We evaluated multinational practice patterns for lipid management in patients with advanced CKD under nephrology care. METHODS: We analyzed lipid-lowering therapy (LLT), LDL- cholesterol (LDL-C) levels, and nephrologist-specified LDL-C goal upper limits in adult patients with eGFR < 60 ml/min from nephrology clinics in Brazil, France, Germany, and the United States (2014-2019). Models were adjusted for CKD stage, country, cardiovascular risk indicators, sex, and age. RESULTS: LLT treatment differed significantly by country, from 51% in Germany to 61% in the US and France (p = 0.002) for statin monotherapy. For ezetimibe with or without statins, the prevalence was 0.3% in Brazil to 9% in France (< 0.001). Compared with patients not taking lipid-lowering therapy, LDL-C was lower among treated patients (p < 0.0001) and differed significantly by country (p < 0.0001). At the patient level, the LDL-C levels and statin prescription did not vary significantly by CKD stage (p = 0.09 LDL-C and p = 0.24 statin use). Between 7-23% of untreated patients in each country had LDL-C ≥ 160 mg/dL. Only 7-17% of nephrologists believed that LDL-C should be < 70 mg/dL. CONCLUSION: There is substantial variation in practice patterns regarding LLT across countries but not across CKD stages. Treated patients appear to benefit from LDL-C lowering, yet a significant proportion of hyperlipidemia patients under nephrologist care are not receiving treatment.

Pitavastatin Compared with Differential Intervention Trial by Standard Therapy on Cardiovascular Events in Patients with Dyslipidemia on Chronic Hemodialysis (DIALYSIS): A Randomized Controlled Trial.

INTRODUCTION: Statin has been reported to reduce cardiovascular events. However, the comparative efficacy of statin with standard therapy on cardiovascular events has not been sufficiently reported in patients on chronic hemodialysis. Thus, this study aimed to compare the effects of pitavastatin and standard therapy on mortality and cardiovascular events in chronic hemodialysis patients with dyslipidemia in Japan. METHODS: Patients on chronic hemodialysis with dyslipidemia were randomized into pitavastatin-administered (pitavastatin group) or dietary therapy as standard therapy (control) group. Primary outcomes are all-cause mortality and myocardial infarction; secondary outcomes are cardiac arrest and fatal myocardial infarction. The composite outcomes included the incidence of coronary intervention, stroke, fracture, and hospitalization due to heart failure and unstable angina. The clinical outcome analyses used a logistic regression model to categorize the variables. A p value of <0.05 was considered statistically significant. RESULTS: This study included 848 patients (422 in the control group and 426 in the pitavastatin group) from 79 health facilities. The mean age of the patients was 60.1±10.3 years, and the dialysis period was 7.2±7.6 years. The mean observation period was 36.5 months. The low-density lipoprotein cholesterol level was significantly lower than the baseline value in the pitavastatin group after 12 months of trial (79.8±26.1 vs. 107.8±25.5 mg/dL, p < 0.001). Moreover, the total number of deaths was 85, of which 50 occurred in the control group and 35 in the pitavastatin group. In an analysis adjusted for confounding factors due to participant attributes, there was a significant difference between the control group and the pitavastatin group in the primary and composite endpoints (p = 0.007 and p = 0.022, respectively). CONCLUSION: Our study has demonstrated that aggressive intervention with pitavastatin is more effective than the standard (dietary) therapy for improving the clinical outcomes in patients with dyslipidemia on chronic hemodialysis.

Emerging Therapies for the Treatment of Atherosclerotic Cardiovascular Disease: From Bench to Bedside.

Primarily a consequence of sedentary lifestyle, atherosclerosis has already reached pandemic proportions, and with every year the burden of it is only increasing. As low-density lipoprotein cholesterol (LDL-C) represents a crucial factor in atherosclerosis formation and progression, stringent lipid-lowering therapy could conceivably be the key to preventing the unfavorable outcomes that arise as a consequence of atherosclerosis. The use of statins in lipid-lowering is often burdened by adverse events or is insufficient to prevent cardiovascular events as a monotherapy. Therefore, in the present review, the authors aimed to discuss the underlying mechanisms of dyslipidemia and associated atherosclerotic cardiovascular disease (ASCVD) and preclinical and clinical trials of novel therapeutic approaches to its treatment, some of which are still in the early stages of development. Apart from novel therapies, a novel change in perspective is needed. Specifically, the critical objective in the future management of ASCVD is to embrace emerging evidence in the field of atherosclerosis, because clinicians are often burden by common practice and personal experience, both of which have so far been shown to be futile in the setting of atherosclerosis.

New Ideas for the Prevention and Treatment of Preeclampsia and Their Molecular Inspirations.

Preeclampsia (PE) is a pregnancy-specific disorder affecting 4-10% of all expectant women. It greatly increases the risk of maternal and foetal death. Although the main symptoms generally appear after week 20 of gestation, scientific studies indicate that the mechanism underpinning PE is initiated at the beginning of gestation. It is known that the pathomechanism of preeclampsia is strongly related to inflammation and oxidative stress, which influence placentation and provoke endothelial dysfunction in the mother. However, as of yet, no "key players" regulating all these processes have been discovered. This might be why current therapeutic strategies intended for prevention or treatment are not fully effective, and the only effective method to stop the disease is the premature induction of delivery, mostly by caesarean section. Therefore, there is a need for further research into new pharmacological strategies for the treatment and prevention of preeclampsia. This review presents new preventive methods and therapies for PE not yet recommended by obstetrical and gynaecological societies. As many of these therapies are in preclinical studies or under evaluation in clinical trials, this paper reports the molecular targets of the tested agents or methods.

The Effects of Statins on Cardiovascular and Inflammatory Biomarkers in Primary Prevention: A Systematic Review and Meta-Analysis.

BACKGROUND: Statins are well-established for their treatment of cardiovascular disease (CVD) due to their cholesterol-lowering effects and potential anti-inflammatory properties. Although previous systematic reviews demonstrate that statins reduce inflammatory biomarkers in the secondary prevention of CVD, none examine their effects on cardiac and inflammatory biomarkers in a primary prevention setting. METHODS: We conducted a systematic review and meta-analysis to examine the effects of statins on cardiovascular and inflammatory biomarkers among individuals without established CVD. The biomarkers included are: cardiac troponin, N-terminal pro B-type natriuretic peptide (NT-proBNP), C-reactive protein (CRP), tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), soluble vascular cell adhesion molecule (sVCAM), soluble intercellular adhesion molecule (sICAM), soluble E-selectin (sE-selectin) and endothelin-1 (ET-1). A literature search was performed through Ovid MEDLINE, Embase and CINAHL Plus for randomised controlled trials (RCTs) published up to June 2021. RESULTS: Overall, 35 RCTs with 26,521 participants were included in our meta-analysis. Data was pooled using random effects models presented as standardised mean differences (SMD) with 95% confidence intervals (CI). Combining 36 effect sizes from 29 RCTs, statin use resulted in a significant reduction in CRP levels (SMD -0.61; 95% CI -0.91, -0.32; P<0.001). This reduction was observed for both hydrophilic (SMD -0.39; 95% CI -0.62, -0.16; P<0.001) and lipophilic statins (SMD -0.65; 95% CI -1.01, -0.29; P<0.001). There were no significant changes in serum concentrations of cardiac troponin, NT-proBNP, TNF-α, IL-6, sVCAM, sICAM, sE-selectin and ET-1. CONCLUSION: This meta-analysis demonstrates that statin use reduces serum CRP levels in a primary prevention setting for CVD, with no clear effect on the other eight biomarkers studied.

Prescription of statins after acute coronary syndrome; a single-centre observational study.

There is limited information about the current use of high-intensity statins (HIS) after acute coronary syndrome (ACS) in Pakistani patients. We studied the prescription of HIS in patients admitted with ACS to Ittefaq Hospital, Lahore, Pakistan, from February 2019 to December 2019. Among the 411 patients, 221 (53.8%) patients underwent Percutaneous Coronary Intervention (PCI), 62 (15.1%) were referred for Coronary Artery Bypass Graft (CABG), and 128 (31.1%) were treated medically. Overall 408 (99.3%) patients were prescribed statins and 198 (48.2%) received HIS, with 45 (10.9%) patients receiving maximally allowed dose (Atorvastatin 80mg or Rosuvastatin 40mg). Patients treated with PCI were more likely to be prescribed HIS (73.3% vs 26.7%, p <0.001), while older patients (>75 years of age), those treated medically, and patients with severely reduced LV systolic function were significantly less likely to receive HIS (p <0.001). Our study, therefore, identifies a gap in implementation of guidelines for HIS use, particularly among the medically treated ACS patients.

Statin and aspirin use in parasitic infections as a potential therapeutic strategy: A narrative review.

Infections, including zoonoses, constitute a threat to human health due to the spread of resistant pathogens. These diseases generate an inflammatory response controlled by a resolving mechanism involving specialized membrane lipid-derived molecules called lipoxins, resolvins, maresins, and protectins. The production of some of these molecules can be triggered by aspirin or statins. Thus, it is proposed that modulation of the host response could be a useful therapeutic strategy, contributing to the management of resistance to antiparasitic agents or preventing drift to chronic, host-damaging courses. Therefore, the present work presents the state of the art on the use of statins or aspirin for the experimental management of parasitic infections such as Chagas disease, leishmaniasis, toxoplasmosis or malaria. The methodology used was a narrative review covering original articles from the last seven years, 38 of which met the inclusion criteria. Based on the publications consulted, modulation of the resolution of inflammation using statins may be feasible as an adjuvant in the therapy of parasitic diseases. However, there was no strong experimental evidence on the use of aspirin; therefore, further studies are needed to evaluate its role inflammation resolution process in infectious diseases.

The role of statins in the prevention of preeclampsia.

Preeclampsia is a common hypertensive disorder of pregnancy associated with considerable neonatal and maternal morbidities and mortalities. However, the exact cause of preeclampsia remains unknown; it is generally accepted that abnormal placentation resulting in the release of soluble antiangiogenic factors, coupled with increased oxidative stress and inflammation, leads to systemic endothelial dysfunction and the clinical manifestations of the disease. Statins have been found to correct similar pathophysiological pathways that underlie the development of preeclampsia. Pravastatin, specifically, has been reported in various preclinical and clinical studies to reverse the pregnancy-specific angiogenic imbalance associated with preeclampsia, to restore global endothelial health, and to prevent oxidative and inflammatory injury. Human studies have found a favorable safety profile for pravastatin, and more recent evidence does not support the previous teratogenic concerns surrounding statins in pregnancy. With reassuring and positive findings from pilot studies and strong biological plausibility, statins should be investigated in large clinical randomized-controlled trials for the prevention of preeclampsia.

Trends in the use of oral anticoagulants, antiplatelets and statins in four European countries: a population-based study.

PURPOSE: To evaluate time trends in the prevalence of antithrombotic and statin use in four European countries. METHODS: Using population-based data from the United Kingdom, Denmark, Spain and Italy between 2010 and 2018, we calculated standardized annual prevalence proportions of antithrombotics and statin use, and changes in prevalence proportions (2018 vs. 2010). RESULTS: Prevalence proportion of statins increased from 24.8% to 24.6% (UK), 21.0% to 22.3% (Region of Southern Denmark [RSD]), 12.9% to 14.3% (Udine, Italy), and 20.3% to 23.2% (Spain). Prevalence proportions of antithrombotics declined in all four countries: 18.7% to 15.9% (UK; - 2.8% points), 18.9% to 18.1% (RSD; - 0.8% points), 17.7% to 16.6% (Udine; - 1.1% points) and 15.0% to 13.6% (Spain; - 1.4% points). These declines were driven by reductions in low-dose aspirin use: 15.3% to 8.9% (UK; - 6.4% points), 16.3% to 9.5% (RSD; - 6.8% points), 13.5% to 11.6% (Udine; - 1.9% points), and 10.2% to 8.8% (Spain; - 1.4% points). In the UK, low-dose aspirin use declined from 9.1% to 4.3% (- 4.8% points) for primary CVD prevention, and from 49.6% to 36.9% (- 12.7% points) for secondary prevention. Oral anticoagulant use gradually increased but did not fully account for the decrease in low-dose aspirin use. CONCLUSIONS: Antithrombotic use in the UK, RSD, Udine and Spain declined between 2010 and 2018, driven by a reduction in use of low-dose aspirin that is not completely explained by a gradual increase in OAC use. Use of statins remained constant in the UK, and increased gradually in the RSD, Udine and Spain.