Safety Of Statins Research Articles

Efficacy and safety of moderate-intensity statin with ezetimibe combination therapy in patients after percutaneous coronary intervention: a post-hoc analysis of the RACING trial

Moderate-intensity statin role with ezetimibe combination therapy following percutaneous coronary intervention (PCI) has not been thoroughly investigated, particularly compared to high-intensity statin monotherapy. We aimed to investigate the effect of ezetimibe combination with moderate-intensity statin in patients with atherosclerotic cardiovascular disease following PCI. This was a post-hoc analysis of a subset of patients who underwent PCI in the RACING trial. At 26 centres in South Korea, patients with atherosclerotic cardiovascular disease (ASCVD) were randomly assigned to receive either moderate-intensity statin with ezetimibe combination therapy (rosuvastatin 10mg with ezetimibe 10mg) or high-intensity statin monotherapy (rosuvastatin 20mg). The prespecified endpoints of the RACING trial were used. The primary endpoint was the 3-year composite of cardiovascular death, major cardiovascular events, and nonfatal stroke. Event rates between the two groups were compared using log-rank tests, and hazard ratios (HR) with 95% confidence intervals (CI) were estimated using Cox regression analysis. Consistent with the RACING trial, the primary and secondary efficacy endpoints were evaluated using an intention-to-treatment approach, and the safety endpoints were assessed in the safety population. The RACING trial was registered at ClinicalTrials.gov (NCT03044665). Between Feb 14, 2017, and Dec 18, 2018, 3780 participants were enrolled in the RACING trial. Prior history of PCI was found in 2497 patients (67%, median 64 years, 79% male), and was associated with higher rates of the primary endpoint (hazard ratio [HR], 1.34; 95% confidence interval [CI], 1.06-1.69; p=0.014). Among patients with prior PCI, moderate-intensity statin therapy with ezetimibe combination versus high-intensity statin therapy did not increase the risk of the primary endpoint (HR, 0.95; 95% CI, 0.74-1.24; p=0.781). The proportion of patients with low-density lipoprotein cholesterol (LDL-C) <70mg/dL at 1, 2, and 3 years was 74%, 76%, and 73%, respectively, in the combination therapy group, and was significantly higher than that in the high-intensity statin monotherapy group (57%, 62%, and 59%, respectively, all p<0.001). Discontinuation of lipid-lowering drugs occurred less frequently in the combination group (4.2% vs. 7.6%, p=0.001). The effects of ezetimibe combination therapy observed in the RACING trial were consistently preserved among patients with ASCVD following PCI. Ezetimibe combination could be considered as a suitable therapeutic strategy to achieve strict control of LDL-C and reduce drug intolerance in patients who underwent PCI. Hanmi Pharmaceutical, Seoul, South Korea.

Safety and efficacy of statin treatment in very elderly patients / Segurança e eficácia do tratamento com estatinas em pacientes muito idosos

Abstract&#x0D; Introduction and objectives: The treatment of dyslipidemia over 75 years old is not well elucidated, due to the non-inclusion in large randomized clinical trials. Elderly people develop atherosclerosis more often and the worldwide population shows greater longevity. To evaluate the efficacy and safety of statin in very elderly people. Methods: The patients were divided into two groups: over 75 years (very elderly) and up to 75 years (control group). We evaluated: coronary artery disease (CAD); stroke; clearance of creatinine; creatine phosphokinase (CPK) and transaminase (ALT, AST) levels; lipid profile; type, dosage, and time using a statin. Results: The sample of 120 patients, 53,2% male, age 74.1 (±11.1) years, 82.3 very elderly, and 64.9 years in the control group. The total cholesterol, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein (HDL-C) in very elderly and control were 162 and 166 (p=ns), 84 and 90 (p=ns), 52.5 and 47 mg/dL (p=0.07), respectively. CAD and stroke, respectively 52.5 and 78.8% (p=0.007), and 18.6 and 7.7% (p=0.09). The time using a statin and the number of drugs taken were the same in the groups. The CPK and ALT levels were 97 and 110 (p=ns) and 16.5 and 20 U/L (p=0.004), respectively. There was no statin dose reduction in the elderly group despite the higher proportion of clinical comorbidities or renal dysfunction. Conclusions: The statin treatment in very elderly patients is effective and safe. The increased risk of CAD and stroke in elderly people corroborate the importance of statin use in this age group.

Impact of Long-Term Antithrombotic and Statin Therapy on the Clinical Outcome in Patients with Cavernous Malformations of the Central Nervous System: A Single-Center Case Series of 428 Patients

Introduction: Literature regarding the safety and efficacy of antithrombotic (antiplatelet or anticoagulant) therapy and statins in patients with cavernous malformations (CMs) of the central nervous system is sparse, resulting in uncertainty about its use in clinical practice. The aim of this study was to analyze the impact of antithrombotic therapy and statins on the risk of hemorrhage and focal neurological deficit in patients with CMs. Methods: The authors’ institutional database was screened for all patients with CMs of the central nervous system treated at their institution between 2006 and 2018. Patients with radiological and/or histological diagnosis of CMs, clinical baseline characteristics, available patient’s medication history, and follow-up data were included in this study. Time-to-event probability (hemorrhage or focal neurological deficit) as well as the number of events (hemorrhage or focal neurological deficit) during follow-up were assessed in patients who were categorized according to their medical treatment (antithrombotic therapy, statins, combined therapy, or no treatment). Results: Four hundred twenty-eight patients with CMs were eligible and included in the final analysis. Sixty-nine (16.1%) patients were on long-term antithrombotic therapy and 46 (10.6%) on long-term statins, of whom 31 patients were on a combination of both. The probability of experiencing first hemorrhage or focal neurological deficit was less likely in patients on antiplatelet therapy (HR 0.09, 95% CI 0.021–0.39, p = 0.001), anticoagulant therapy (HR 0.12, 95% CI 0.016–0.85, p = 0.034), or the combination thereof (HR 0.12, 95% CI 0.016–0.93, p = 0.043) compared to patients with no antithrombotic treatment. The number of hemorrhages and focal neurological deficits were significantly lower in patients on antithrombotic therapy compared to patients on no treatment during follow-up. In patients on statins alone, the time-to-event probability was comparable to that of patients on no treatment (HR 0.91, 95% CI 0.438–1.91, p = 0.812), and the number of events was similar to patients on no treatment. Conclusion: The results of our study provide further evidence that antithrombotic therapy alone or in combination with statins in patients with CMs of the central nervous system does not increase the risk of hemorrhage or focal neurological deficit but, on the contrary, may have some benefit.

Short-term safety and efficacy of escalating doses of atorvastatin for dyslipidemia in children with predialysis chronic kidney disease stage 2-5.

Dyslipidemia is a potentially modifiable risk factor in patients with chronic kidney disease (CKD). Information on the safety and efficacy of statins in pediatric CKD is limited. Patients with CKD stage 2-5 and aged 5-18years with low-density lipoprotein cholesterol (LDL-C) > 130mg/dL and/or non-high-density lipoprotein cholesterol (non-HDL-C) > 145mg/dL were enrolled from September 2019 to February 2021. All patients were administered atorvastatin 10mg/day, which was escalated to 20mg/day if LDL-C remained > 100mg/dL and/or non-HDL-C > 120mg/dL at 12weeks. Proportion of patients achieving target lipid levels (LDL-C ≤ 100mg/dL and non-HDL-C ≤ 120mg/dL) and adverse events were assessed at 24weeks. Of 31 patients enrolled, target lipid levels were achieved in 45.2% (95% CI 27.8-63.7%) at 24weeks; 22 patients required dose escalation to 20mg at 12weeks. There was no difference in median lipid level reduction with 10 (n = 9) versus 20mg/day (n = 22, P = 0.3). Higher baseline LDL-C (OR 1.06, 95% CI 1.00-1.11) and older age (OR 36.5, 95% CI 2.57-519.14) were independent predictors of failure to achieve target lipid levels with 10mg/day atorvastatin. None had persistent rise in AST/ALT > 3 times upper normal limit (UNL) or CPK > 10 times UNL. No differences were noted in adverse events due to atorvastatin 10 or 20mg/day. Atorvastatin (10-20mg/day) administered for 24weeks was safe and effectively reduced LDL-C and non-HDL-C in children with CKD stages 2-5. Patients with higher baseline LDL-C required higher doses to achieve the target. A higher resolution version of the Graphical abstract is available as Supplementary information.

The Management of Hypercholesterolemia in Patients with Neuromuscular Disorder.

We describe and discuss the safety of statins and non-statin drugs in neuromuscular disorders (NMDs). We also propose a pragmatic model of care for the management of such cases. Patients with both NMD and hypercholesterolemia may be particularly disadvantaged owing to the toxic effects of cholesterol-lowering therapy and the inability to take medication. Specifically, the management of hypercholesterolemia in patients with NMD is complicated by the increased risk of statin-related myotoxicity and concerns that statins may aggravate or possibly induce the onset of a specific NMD. The most severe form of statin-related myotoxicity is immune-mediated necrotizing myopathy. Management of hypercholesterolemia in patients with NMDs include treating modifiable factors, consideration of toxicity risk of statin, use of non-statin lipid lowering agents, noting possible drug interactions, and careful monitoring.

Lipid Lowering Agent Prescription and LDL Target Achievement in ACS Patients in Jeddah, Saudi Arabia

Background: The safety and efficacy of statins administered early to patients after an acute coronary syndrome (ACS) diagnosis have been proven. This study aimed to estimate the prevalence of compliance with guideline recommendations for high-intensity dose statins and achievement of reduced low-density lipoprotein (LDL) levels among patients with ACS in Saudi Arabia. Methods: A cross-sectional study was conducted on 566 patients at King Abdulaziz University Hospital, Jeddah, Saudi Arabia. Data on the patient&amp;apos;s demographics, comorbidities, type of ACS, lipid profile at admission, statin type, statin use pattern, side effects, and if the patient achieved the low-density lipoprotein cholesterol (LDL-C) goal (70 mg/dl) or (3.9 mmol/l) after management were collected. Results: At admission, 34.1% had an LDL-C level below 100 mg/dl, 64.5% had total cholesterol below 200 mg/dl, 57.2% had an average triglyceride level, and 53.7% had high-density lipoprotein cholesterol below 40 mg/dl. Moreover, 91% of patients consumed high-potency statins, 99.1% had no statin side effects, and atorvastatin 20 mg was the most commonly used high-potency statin, followed by atorvastatin 40 mg. Approximately 83% of patients achieved the LDL-C goal (70 mg/dl) after management, and patients who had diabetes mellitus, familial hyperlipidemia, or obesity, who experienced no side effects of statins, who had ST-segment elevation myocardial infarction, had an LDL-C level of 160-189 mg/dl at admission and those who had a high total cholesterol level at admission had a significantly higher level of achieving the LDL-C goal. Conclusions: In patients with congenital heart disease, lipid management could be improved to reduce the risk of recurrent cardiovascular disease and recurring episodes.

Comparative Muscle Tolerability of Different Types and Intensities of Statins: A Network Meta-Analysis of Double-Blind Randomized Controlled Trials.

The benefits of statins for ischemic cardio-cerebrovascular diseases are well known. However, concerns around muscle adverse events still exist. We therefore aimed to compare the muscle safety of individual statins in adults. PubMed, Embase, Cochrane Central Register of Controlled Trials and Web of Science were searched to include double-blind randomized controlled trials (RCTs) comparing one statin with another or with control treatment. Pairwise meta-analyses and network meta-analyses were undertaken with Stata 14.0 software. Relative risk (RR) with 95% confidence intervals (CIs) was adopted for each outcome. A total of 83 RCTs were included. In the pairwise meta-analysis, statins were significantly associated with only a slight increase in muscle symptoms compared with control (RR=1.05; 95% CI=1.01-1.09). In the drug-level network meta-analyses, no statistically significant difference was found between individual statins in the incidence of muscle symptoms, myalgia, myopathy, rhabdomyolysis, creatine kinase (CK) >10 times the upper limit of normal (ULN) or discontinuation due to muscle adverse events. In the dose-level network meta-analyses, there were no statistically significant dose-dependent effects on any outcomes except that moderate-intensity statins had a higher incidence of muscle symptoms than control (RR=1.13; 95% CI=1.01-1.27). Moderate simvastatin (RR=6.57; 95% CI=1.26-34.41) and moderate pravastatin (RR=5.96; 95% CI=1.00-35.44) had a statistically significantly higher incidence of CK >10×ULN compared with moderate atorvastatin. Lipophilic statins and statins metabolized by liver cytochrome P450 3A4 were not associated with an increased risk of muscle adverse events. Statins may be generally safe on muscle. Moderate atorvastatin may be superior to equivalent simvastatin and pravastatin in muscle tolerability.

Abstract 13331: Low Statin Adherence Identified Across Diverse Populations in the All of Us Research Program

Introduction: Statins are a cornerstone of primary and secondary prevention of atherosclerotic cardiovascular disease (ASCVD), the leading cause of death in the US. Despite conclusive evidence to the efficacy and safety of statins, low adherence remains a public health challenge. Although patient, clinician, and health system barriers to statin adherence have been documented, the effect of national policies targeting prescription access remains largely understudied. This study sought to assess the effect of the 2016 US Preventive Services Task Force (USPSTF) recommendation of statins on racial/ethnic disparities in treatment adherence. Methods: Utilizing records of the novel All of Us Research Program, a dataset of historically underrepresented groups in health research, we compared statin use in adult ASCVD non-Hispanic White (NHW) patients before (2014-2016) and after (2017-2020) the USPSTF recommendation with Black and Hispanic patients. Statin use was measured as percent days covered (PDC). Trends were compared using a regression model with demographics and an indicator variable for the change in recommendation as covariates. Regression coefficients and p-values were analyzed to assess the effect of the policy. Results: The study included 94,883 unique statin prescription records belonging to a patient cohort of which 52% were female, 21% Black and 12% Hispanic, with a mean age of 61.93 years. There was poor statin adherence across all racial/ethinic subgroups (PDC &lt; 0.80). Following the policy, PDC increased 3.1% overall (p&lt;0.01), 12 percentage points in Black patients and no change in Hispanics with respect to NHW. Conclusion: Our results provide preliminary evidence that the 2016 USPSTF changes increased statin adherence, yet there were differential effects among racial/ethnic subgroups. To address population adherence disparities, more research is needed to inform policy that will facilitate access for underserved populations in the United States.

Abstract 14703: Short Term Safety and Efficacy of Escalating Doses of Atorvastatin for Dyslipidemia in Children With Predialysis Chronic Kidney Disease Stage 2-5

Introduction: Dyslipidemia is a potentially modifiable risk factor in patients with chronic kidney disease (CKD). Information on safety and efficacy of statins in pediatric CKD is limited. Methods: Patients with CKD stage 2-5, aged 5- 18 years with low density lipoprotein cholesterol (LDL-C) &gt;130mg/dL and/or non-high density lipoprotein cholesterol (non HDL-C) &gt;145mg/dL were enrolled from September 2019 to February 2021. All patients were administered atorvastatin 10 mg/day, and escalated to 20 mg/day if LDL-C&gt;100 mg/dL and/or non-HDL &gt;120mg/dL at 12 weeks. Proportion of patients achieving target lipid levels (LDL-C ≤100 mg/dL and non HDL-C ≤120mg/dL), change in lipid and adverse effects were assessed at 24 weeks. Wilcoxon sign rank test was used to assess percentage change in lipid. Results: Of the 31 patients enrolled, target lipid levels were achieved in 45.2% patients (95% CI 27.8%-63.7%) at 24-week; 22 patients required dose escalation to 20 mg at 12 weeks. There was no difference in median reduction in lipid levels with 10 mg/day (n=9) versus 20 mg/day (n=22; p=0.3). Higher baseline LDL-C (OR 1.06, 95% CI 1.00 to 1.11) and older age (OR 36.50 95% CI 2.57 to 519.14) were independent predictors of failure to achieve target lipid levels with 10 mg/day atorvastatin. None had persistent rise in AST/ALT &gt;3 times upper normal limit (UNL) or CPK &gt;10 times UNL. No differences were noted in the adverse effects of atorvastatin 10 mg/day and 20 mg/day. Conclusions: Atorvastatin (10-20 mg/day) administered for 24 weeks was safe and effectively reduced LDL-C and non HDL-C in children with CKD stage 2-5. Patients with higher baseline LDL-C required higher doses to achieve the target.

In ASCVD, moderate-intensity statin + ezetimibe was noninferior to high-intensity statin alone at 3 y.

Kim BK, Hong SJ, Lee YJ, et al. Long-term efficacy and safety of moderate-intensity statin with ezetimibe combination therapy versus high-intensity statin monotherapy in patients with atherosclerotic cardiovascular disease (RACING): a randomised, open-label, non-inferiority trial. Lancet. 202;400:380-90. 35863366.

Effectiveness and safety of statins on outcomes in patients with HIV infection: a systematic review and meta-analysis

Statins are hypolipidaemic in human immunodeficiency virus (HIV) positive individuals. However, their effect on all-cause mortality and rate of discontinuation is unclear. We conducted a systematic review to evaluate the impact of statins on all-cause mortality, discontinuation rates, and risk of adverse effects among HIV patients on highly active antiretroviral therapy (HAART). We searched four electronic databases from inception until October 2021 for trials and cohort studies evaluating the effects of statin treatment versus placebo in HIV patients. Forty-seven studies involving 91,594 patients were included. Statins were associated with significantly lower risk of discontinuation (RR, 0.701; 95% CI 0.508–0.967; p = 0.031). The risk of all-cause mortality (RR, 0.994; 95% CI 0.561–1.588; p = 0.827), any adverse effects (RR, 0.780; 95% CI 0.564–1.077; p = 0.131) and, diabetes mellitus (RR, 0.272; 95% CI 0.031–2.393; p = 0.241) with statin treatment were lower but not statistically significant compared to placebo/control. Statin treatment was associated with a trend of higher but statistically insignificant risk of myalgia (RR, 1.341; 95% CI 0.770–2.333; p = 0.299), elevated creatine kinase (RR, 1.101; 95% CI 0.457–2.651; p = 0.830) and liver enzyme activities (RR, 1.709; 95% CI 0.605–4.831; p = 0.312). Clinicians should consider the nocebo effect in the effective management of PLWH on statins, who present with common adverse effects such as myalgia and, elevated levels of creatine kinase and liver enzymes.

In Vitro Evidence of Statins' Protective Role against COVID-19 Hallmarks.

Despite the progressions in COVID-19 understanding, the optimization of patient-specific therapies remains a challenge. Statins, the most widely prescribed lipid-lowering drugs, received considerable attention due to their pleiotropic effects, encompassing lipid metabolism control and immunomodulatory and anti-thrombotic effects. In COVID-19 patients, statins improve clinical outcomes, reducing Intensive Care Unit admission, the onset of ARDS, and in-hospital death. However, the safety of statins in COVID-19 patients has been debated, mainly for statins’ ability to induce the expression of the ACE2 receptor, the main entry route of SARS-CoV-2. Unfortunately, the dynamic of statins’ mechanism in COVID-19 disease and prevention remains elusive. Using different in vitro models expressing different levels of ACE2 receptor, we investigated the role of lipophilic and hydrophilic statins on ACE2 receptor expression and subcellular localization. We demonstrated that the statin-mediated increase of ACE2 receptor expression does not necessarily coincide with its localization in lipid rafts domains, particularly after treatments with the lipophilic atorvastatin that disrupt lipid rafts’ integrity. Through a proteomic array, we analyzed the cytokine patterns demonstrating that statins inhibit the release of cytokines and factors involved in mild to severe COVID-19 cases. The results obtained provide additional information to dissect the mechanism underlying the protective effects of statin use in COVID-19.

Optimizing therapy for cardiovascular diseases: proven organ-protective and preventive effects of pitavastatin and lercanidipine: A review

The article aims to systematize the available data on the current use of statins and calcium channel antagonists (CA) for cardiovascular disorders therapy and to analyze the results of clinical trials focused on pitavastatin and lercanidipine. The article addresses the safety and tolerability of statins and CA and their use in the treatment of various conditions. Pharmacological features, preventive and organ-protective effects of pitavastatin and lercanidipine are described. The publications from the MEDLINE/PubMed, Scopus, Cochrane Library, eLIBRARY, and Google Scholar databases over the past 25 years were analyzed. The evidence presented in the article warrants the more extensive use of statins and CA in the treatment of patients with cardiovascular disease.

Racial and ethnic differences in pharmacotherapy to prevent coronary artery disease and thrombotic events.

Awareness of racial/ethnic disparities represents a key challenge for healthcare systems that attempt to provide effective healthcare and to reduce existing inequalities in the use of and adherence to guideline-recommended cardiovascular drugs to improve clinical outcomes for cardiovascular disease (CVD). In this review, we describe important racial/ethnic differences between and within ethnic groups in the prevalence, risk factors, haemostatic factors, anti-inflammatory and endothelial markers, recurrence, and outcomes of CVD.We discuss important differences in the selection, doses, and response [efficacy and adverse drug reactions (ADRs)] in ethnically diverse patients treated with antithrombotics or lipid-lowering drugs. Differences in drug response are mainly related to racial/ethnic differences in the frequency of polymorphisms in genes encoding drug-metabolizing enzymes (DMEs) and drug transporters. These polymorphisms markedly influence the pharmacokinetics, dose requirements, and safety of warfarin, clopidogrel, and statins. This review aims to support a better understanding of the genetic differences between and among populations to identify patients who may experience an ADR or a lack of drug response, thus optimizing therapy and improving outcomes. The greater the understanding of the differences in the genetic variants of DMEs and transporters that determine the differences in the exposure, efficacy, and safety of cardiovascular drugs between races/ethnicities, the greater the probability that personalized medicine will become a reality.

Long-Term Preoperative Atorvastatin or Rosuvastatin Use in Adult Patients before CABG Does Not Increase Incidence of Postoperative Acute Kidney Injury: A Propensity Score-Matched Analysis.

Background: Acute kidney injury (AKI) is among the expected complications of cardiac surgery. Statins with pleiotropic anti-inflammatory and antioxidant effects may be effective in the prevention of AKI. However, the results of studies on the efficacy and safety of statins are varied and require further study. Methods: We conducted a retrospective cohort study to evaluate long-term preoperative intake of atorvastatin and rosuvastatin on the incidence of AKI, based on the “Kidney Disease: Improving Global Outcomes” (KDIGO) criteria in the early postoperative period after coronary artery bypass graft surgery (CABG). We performed propensity score matching to compare the findings in our study groups. The incidence of AKI was assessed on day 2 and day 4 after the surgery. Results: The analysis included 958 patients after CABG. After 1:1 individual matching, based on propensity score, the incidence of AKI was comparable both on day 2 after the surgery (7.4%) between the atorvastatin group and rosuvastatin group (6.5%) (OR: 1.182; 95%Cl 0.411–3.397; p = 0.794), and on postoperative day 4 between the atorvastatin group (3.7%) and the rosuvastatin group (4.6%) (OR: 0.723, 95%Cl 0.187–2.792; p = 0.739). Additionally, there were no statistically significant differences in terms of incidence of AKI after 1:1 individual matching, based on propensity score, between the rosuvastatin group and the control group both on postoperative day 2 (OR: 0.692; 95%Cl 0.252–1.899; p = 0.611) and day 4 (OR: 1.245; 95%Cl 0.525–2.953; p = 0.619); as well as between the atorvastatin group and the control group both on postoperative day 2 (OR: 0.549; 95%Cl 0.208–1.453; p = 0.240) and day 4 (OR: 0.580; 95%Cl 0.135–2.501; p = 0.497). Conclusion: Long-term statin use before CABG did not increase the incidence of postoperative AKI. Further, we revealed no difference in the incidence of post-CABG AKI between the atorvastatin and rosuvastatin groups.

Long-term efficacy and safety of moderate-intensity statin with ezetimibe combination therapy versus high-intensity statin monotherapy in patients with atherosclerotic cardiovascular disease (RACING): a randomised, open-label, non-inferiority trial

Drug combinations rather than increasing doses of one drug can achieve greater efficacy and lower risks. Thus, as an alternative to high-intensity statin monotherapy, moderate-intensity statin with ezetimibe combination therapy can lower LDL cholesterol concentrations effectively while reducing adverse effects. However, evidence from randomised trials to compare long-term clinical outcomes is needed. In this randomised, open-label, non-inferiority trial, patients with atherosclerotic cardiovascular disease (ASCVD) at 26 clinical centres in South Korea were randomly assigned (1:1) to receive either moderate-intensity statin with ezetimibe combination therapy (rosuvastatin 10 mg with ezetimibe 10 mg) or high-intensity statin monotherapy (rosuvastatin 20 mg). The primary endpoint was the 3-year composite of cardiovascular death, major cardiovascular events, or non-fatal stroke, in the intention-to-treat population with a non-inferiority margin of 2·0%. This trial is registered with ClinicalTrials.gov, NCT03044665 and is complete. Between Feb 14, 2017, and Dec 18, 2018, 3780 patients were enrolled: 1894 patients to the combination therapy group and 1886 to the high-intensity statin monotherapy group. The primary endpoint occurred in 172 patients (9·1%) in the combination therapy group and 186 patients (9·9%) in the high-intensity statin monotherapy group (absolute difference -0·78%; 90% CI -2·39 to 0·83). LDL cholesterol concentrations of less than 70 mg/dL at 1, 2, and 3 years were observed in 73%, 75%, and 72% of patients in the combination therapy group, and 55%, 60%, and 58% of patients in the high-intensity statin monotherapy group (all p<0·0001). Discontinuation or dose reduction of the study drug by intolerance was observed in 88 patients (4·8%) and 150 patients (8·2%), respectively (p<0·0001). Among patients with ASCVD, moderate-intensity statin with ezetimibe combination therapy was non-inferior to high-intensity statin monotherapy for the 3-year composite outcomes with a higher proportion of patients with LDL cholesterol concentrations of less than 70 mg/dL and lower intolerance-related drug discontinuation or dose reduction. Hanmi Pharmaceutical.

Comparative efficacy and safety of statins for osteoporosis: a study protocol for a systematic review and network meta-analysis

IntroductionOsteoporosis (OP) is a prevalent skeletal disease with high mortality and morbidity, followed by acute and chronic back pain, severe spinal deformity and dysfunction. First-line drugs for OP work through...

Are Clinicians Aggressive Enough in Treating Diabetes-Related Hyperlipidemia in Youth?

Cardiovascular disease is the leading cause of death in patients with type 1 diabetes (T1D) and type 2 diabetes (T2D). Subclinical atherosclerotic changes are noted in youth with diabetes; therefore, timely identification and management of modifiable cardiovascular risk factors including hyperlipidemia is crucial. We review the current guidelines for hyperlipidemia screening and treatment in youth with T1D and T2D. We discuss the efficacy of non-pharmacological strategies including dietary modifications, exercise, and glycemic control and pharmacological therapy. We summarize reported rates of treatment of diabetes-related hyperlipidemia in youth. Hyperlipidemia is prevalent among youth with T1D and T2D. Vast majority of youth with diabetes-related hyperlipidemia do not receive lipid-lowering treatments. There are several factors that contribute to suboptimal management of hyperlipidemia in youth with diabetes including limited data on efficacy and safety of statins in youth with diabetes. We propose strategies to improve hyperlipidemia management including education of providers and patients, quality improvement methods, and electronic health record alerts. Additionally, further studies are warranted to examine the safety of statins in youth with diabetes, cost-benefit analysis to aggressive screening and treatment, and long-term effect for improving cardiovascular morbidity and mortality.

Clinical Practice Variation of Statin Use in Pediatric Heart Transplantation

<h3>Purpose</h3> Universal initiation of statin therapy within 2 weeks of heart transplantation (HT) is a Class 1A recommendation in adults due to improved morbidity and mortality via reduction of coronary graft vasculopathy. Data regarding the benefit of statins in pediatric transplant patients is equivocal, although the safety and efficacy of statins in children with conditions including familial hyperlipidemias has now been well established. Previous work reported only 1/3 of pediatric transplant patients were prescribed a statin in the period before 2012. We sought to establish statin prescribing practices in a sample of U.S. pediatric HT recipients in the current era, hypothesizing that use of statins in pediatrics increases with age and has increased over time. <h3>Methods</h3> We performed a retrospective study of a geographically representative sample of U.S. children using the MarketScan® Commercial and Medicaid claims databases. The study population was children who underwent HT between the ages of 2 and 19 and had ≥3 years of continuous coverage from 1/1/2013-6/30/2018. We assessed the average age for initiation of statins and the probability of statin prescription by age. <h3>Results</h3> Of the 8.4 million children with available Marketscan data, 876 children (age: 9.8 ± 5.0 years, 54% male) underwent a HT prior to or during the study period. A higher proportion of HT recipients received Medicaid than commercial insurance coverage (56% vs. 44%, p<0.001). 35% (95% CI 32-38%) of HT recipients were on a statin, at an average age of 11.47 ± 4.6 years at the time of the first statin prescription. The earliest age of statin initiation was at 2 years. Likelihood of statin prescription increased with age (18% of those between 2-5 years, 25% between 6-10 years, and 47% in those over 13 years). <h3>Conclusion</h3> Only 1/3 of pediatric HT patients filled a prescription for a statin in this recent cohort, similar to historical rates. Younger children were less likely to receive statins, which may be related to lack of liquid formulation or lack of historical safety data in young children. However, only half of teenagers receive statins by age 19 which is contrary to current adult HT guidelines. This suggests that statin prescribing practices in children after HT should be a focus for improving adherence to national guidelines. Future work will look at effects of socioeconomic factors in statin prescribing patterns.

Statin Use in Patients With Chronic Liver Disease and Cirrhosis: Current Evidence and Future Directions.

Chronic liver disease (CLD) and its complications constitute a significant cause of mortality and morbidity worldwide. Most deaths are secondary to the decompensation of cirrhosis and evolution of portal hypertension (PHTN). Since disease progression reversal is hardly attainable after decompensated cirrhosis develops, it is essential to intervene early with a therapeutic agent or regimen that could prevent or slow disease evolution. Thus far, there has been no agreed-upon medication to help in the fight against the development of cirrhosis or its decompensation. While early data depicted statins as harmful agents for the liver, current evidence from preclinical and clinical studies suggests that they might have positive impact on CLD. Low-quality evidence supports the fact that statins reduce mortality in CLD. Moderate-quality evidence suggests that statins reduce the risk of hepatic decompensation, variceal bleeding, and mortality, especially among patients with compensated cirrhosis. Combining this data with the long track-record of safety and tolerability of statins and their potential benefits in hepatocellular carcinoma (HCC) risk reduction, hepatologists might soon rely on statins to achieve better outcomes in their CLD and cirrhotic patients without significant additional costs. This review describes the rationale behind the use of statins in patients with CLD and cirrhosis. It sheds light on the current preclinical and clinical studies that reflect beneficial effects of the use of different types and doses of statins in the treatment of patients with different types and stages of CLD and cirrhosis. It also emphasizes the need for designing and developing additional large prospective interventional randomized control trials (RCTs) to better evaluate the association between statin exposure and the risk of fibrosis progression and development of cirrhosis in patients with non-cirrhotic CLDs, the risk of progression of PHTN in patients with cirrhosis, and the mortality rates in patients with cirrhotic or non-cirrhotic CLDs.