Statin Dose Research Articles

Effect of high dose statin preloading on TIMI flow in patients presenting with ST-Elevation Myocardial Infarction undergoing Primary Percutaneous Coronary Intervention

Abstract Aim and objectives The aim of this study was to assess the impact of high intensity statins used prior to primary PCI in patients presenting with acute STEMI (ST-elevation Myocardial Infarction) on myocardial perfusion and in-hospital MACE (major adverse cardiac events). Patients and Methods The study included 170 patients who presented with acute STEMI to the cardiology department of Ain Shams university hospitals and underwent primary PCI (percutaneous coronary intervention). They were divided into two groups where the first group received high intensity statins (40-80mg of atorvastatin or 20-40mg of rosuvastatin) besides guideline recommended therapy before primary PCI and the 2nd group served as a control group and received guideline recommended therapy, and high intensity statins after going back to the coronary care unit after primary PCI. Post interventional thrombolysis in myocardial infarction (TIMI) flow grade and myocardial blush grade (MBG) were recorded and ST-segment resolution was measured. Results The majority of patients in both groups had the LAD as the culprit vessel for their presentation. In the control group there were 4 patients with TIMI I flow and MBG I, 13 with TIMI II flow and MBG II and 68 with TIMI III flow and MBG III. Meanwhile in the cases group there was 1 patient with TIMI I flow and MBG I, 3 with TIMI II flow and MBG II and 81 with TIMI III flow and MBG III. This difference was statistically significant with a P value of 0.010. There were 34 patients in the cases group who showed complete ST-segment resolution (40%) vs 19 patients (22.4%) in the control group which was statistically significant with a P value of 0.013. In addition, ejection fraction measured by M-mode had values of Mean+-SD of 45.91 ± 5.49 in cases group vs 43.01 ± 8.80 in control group which was statistically significant with a P value of 0.011. There was not a statistically significant difference between the two groups regarding in-hospital death of all causes and stroke after primary PCI. Conclusion High intensity statin loading before primary PCI resulted in improved post-procedural TIMI flow, MBG, complete ST-segment resolution and ejection fraction as measured by M-mode but did not decrease incidence of in-hospital MACE.

Effects of Statin Therapy and Dose on Cardiovascular and Limb Outcomes in Peripheral Arterial Disease: A Systematic Review and Meta-analysis

Statin therapy is indicated in patients with peripheral arterial disease (PAD). National Institute for Health and Care Excellence guidelines suggest the use of “high intensity” statins, although evidence with PAD specific data are lacking. The effect of statin therapy and dose on outcomes in PAD is investigated. Studies measuring statin use in PAD patients and outcomes were identified based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. The EMBASE and MEDLINE databases were interrogated from January 1957 until February 2020. Twenty-two observational cohort studies and two randomised control trials were included (n = 268 611). Pooled estimates of dichotomous outcome data were calculated using the odds/hazard ratios (OR/HR) and 95% confidence interval (CI). Meta-analysis was conducted using the inverse variance or Mantel–Haenszel method. Outcomes included all cause mortality (ACM), cardiovascular mortality (CVM), major adverse cardiac events (MACE), and amputation. Subgroup analysis was performed on studies comparing patients taking high dose vs. combined low and moderate doses of statins. The GRADE criteria assessed the quality of evidence for outcomes. Statin therapy (vs. no statins) was significantly protective for ACM: OR 0.68 (95% CI 0.60 – 0.76) (number needed to treat [NNT] = 48), HR 0.74 (95% CI 0.70 – 0.78) (NNT = 10 – 91); MACE: OR 0.84 (95% CI 0.78 – 0.92) (NNT = 53), HR 0.78 (95% CI 0.65 – 0.93) (NNT = 167); and amputations: OR 0.59 (95% CI 0.33 – 1.07) (NNT = 333), HR 0.74 (95% CI 0.62 – 0.89) (NNT = 50). High doses of statins (vs. combined low and moderate doses) were significantly better protective against ACM OR 0.69 (95% CI 0.43 – 1.09) (NNT = 17), HR 0.74 (95% CI 0.62 – 0.89) (NNT = 16 – 200) but work less significantly for MACE OR 0.77 (95% CI 0.49 – 1.21) (NNT = 25). Amputations were less frequent in patients on high doses HR 0.78 (95% CI 0.69 – 0.90) (NNT = 53 – 1 000). Higher dosing of statins confers a significant improvement in patient outcomes, especially ACM and amputations, although the quality of the evidence was variable. Such findings require confirmation in larger, PAD specific trials.

Is it Time for Single-Pill Combinations in Dyslipidemia?

Despite the availability of lipid-lowering therapies (LLTs) that are safe and effective, the overall rate of low-density lipoprotein cholesterol (LDL-C) control at a population level in real-life studies is low. Higher-intensity treatment, earlier intervention, and longer-term treatment have all been shown to improve outcomes. However, in clinical practice, actual exposure to LLT is a product of the duration and intensity of, and adherence to, the treatment. To increase exposure to LLTs, the European Society of Cardiology guidelines recommended a stepwise optimization of LLTs by increasing statin intensity to the maximally tolerated dose, with subsequent addition of ezetimibe and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. Evidence from randomized controlled trials performed in a range of patients suggested that adding ezetimibe to statins rather than doubling the statin dose resulted in significantly more patients at LDL-C goal and significantly fewer patients discontinuing treatment because of adverse events. In addition, data showed that combination treatments effectively increased exposure to LLT. Despite these data and recommendations, optimization of LLT is often limited to increasing statin dose. Therapeutic inertia and poor treatment adherence are significant and prevalent barriers to increasing treatment exposure. They are known to be influenced by pill burden and complexity of treatment. Single-pill combinations provide a strategic approach that supports the intensification of treatment without increasing pill burden or treatment complexity. Single-pill combinations, compared with free associations, have been shown to increase the adherence to LLT and the percentage of patients at LDL-C goal.

Lipid-lowering therapy in special situations

The review is devoted to the use of lipid-lowering medicines in certain categories of patients, especially those with acute coronary syndrome, stroke, chronic heart failure, valvular heart disease, atherosclerosis of the central and peripheral arteries, chronic kidney disease, as well as in persons undergoing percutaneous coronary intervention. It is noted that all patients with acute coronary syndrome without any contraindications or intolerance are advised to start (or continue) high-dose statin therapy as early as possible, regardless of the initial values ​​of low-density lipoprotein cholesterol. If the target level of low density lipoproteins is not reached after 4-6 weeks of using the maximum tolerated dose of statins, a combination with ezetimibe is recommended, and if this combination is not effective enough, the addition of a proprotein convertase inhibitor subtilisin / kexin type 9 is needed. Strategy of short pre-treatment or loading (in the case of prior therapy) with high doses of statins should be considered for elective percutaneous coronary intervention or acute coronary syndrome without ST-segment elevation. The use of statins to lower cholesterol levels is not indicated in patients with heart failure unless otherwise indicated. Lipid-lowering therapy for atherosclerotic lesions of the carotid arteries significantly reduces the risk of stroke. Recommendations for the treatment of dyslipidemia in organ transplant patients are comparable to those used for patients at high or very high risk of cardiovascular disease, although more attention needs to be paid to the causes of lipid abnormalities and possible side effects associated with drug interactions.

Design and rationale of the EVOCATION trial: A prospective, randomized, exploratory study comparing the effect of evolocumab on coronary microvascular function after percutaneous coronary intervention in patients with stable coronary artery disease

Percutaneous coronary intervention (PCI) is a standard treatment in patients with stable coronary artery disease (CAD); however, periprocedural myocardial infarction (PMI) remains a common complication of PCI. Aggressive lipid-lowering therapy with statin has shown to reduce the incidence of PMI by preventing coronary microvascular dysfunction. It is unclear whether evolocumab, a potent lipid-lowering agent, could diminish microvascular damage after PCI. The EVOCATION trial (jRCTs051180022) is a multicenter, randomized, open-label, active-controlled, parallel-group, exploratory, investigator-initiated clinical study to evaluate whether pretreatment with evolocumab could decrease the index of microvascular resistance (IMR) after PCI in patients with stable CAD. This study population consists of 100 patients with stable CAD who will undergo PCI and have high low-density lipoprotein cholesterol levels despite administration of maximum tolerated dose of statins for at least 2 weeks. Eligible patients are randomized in a 1:1 ratio to receive either evolocumab 140 mg every 2 weeks in addition to standard of care treatment or standard of care treatment only for 2–6 weeks before PCI. The primary endpoint is IMR after PCI. The EVOCATION trial will evaluate whether pretreatment with evolocumab reduces periprocedural microvascular damage in patients with stable CAD undergoing PCI.

The Effects of Statin Dose, Lipophilicity, and Combination of Statins plus Ezetimibe on Circulating Oxidized Low-Density Lipoprotein Levels: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background Elevated plasma low-density lipoprotein cholesterol (LDL-C) is the main risk factor for atherosclerotic cardiovascular disease (ASCVD). Statins are the drugs of choice for decreasing LDL-C and are used for the prevention and management of ASCVD. Guidelines recommend that subjects with high and very high ASCVD risk should be treated with high-intensity statins or a combination of high-intensity statins and ezetimibe. The lipophilicity or hydrophilicity (solubility) of statins is considered to be important for at least some of their LDL-C lowering independent pleiotropic effects. Oxidative modification of LDL (ox-LDL) is considered to be the most important atherogenic modification of LDL and is supposed to play a crucial role in atherogenesis and ASCVD outcomes. Objective The aim of this systematic review and meta-analysis was to find out what are the effects of statin intensity, lipophilicity, and combination of statins plus ezetimibe on ox-LDL. Methods PubMed, Scopus, Embase, and Web of Science were searched from inception to February 5, 2021, for randomized controlled trials (RCTs). Two independent and blinded authors evaluated eligibility by screening the titles and abstracts of the studies. Risk of bias in the studies included in this meta-analysis was evaluated according to the Cochrane instructions. Meta-analysis was performed using Comprehensive Meta-Analysis (CMA) V2 software. Evaluation of funnel plot, Begg's rank correlation, and Egger's weighted regression tests were used to assess the presence of publication bias. Results Among the 1427 published studies identified by a systematic databases search, 20 RCTs were finally included in the systematic review and meta-analysis. A total of 1874 patients are included in this meta-analysis. This meta-analysis suggests that high-intensity statin treatment is associated with a significant decrease in circulating concentrations of ox-LDL when compared with low-to-moderate treatment (SMD: -0.675, 95% CI: -0.994, -0.357, p < 0.001; I2: 55.93%). There was no difference concerning ox-LDL concentration between treatments with hydrophilic and lipophilic statins (SMD: -0.129, 95% CI: -0.330, -0.071, p = 0.206; I2: 45.3%), but there was a significant reduction in circulating concentrations of ox-LDL associated with statin plus ezetimibe combination therapy when compared with statin monotherapy (SMD: -0.220, 95% CI: -0.369, -0.071, p = 0.004; I2: 0%). Conclusion High-dose statin or combination of statins with ezetmibe reduces plasma ox-LDL in comparison low-to-moderate intensity statin therapy alone. Statin lipophilicity is not associated with reduction in ox-LDL plasma concentrations.

Abstract P114: Statins, High-density Lipoprotein, And Acute Kidney Injury After Endovascular Aortic Repair

Acute kidney injury (AKI) after endovascular aortic repair (EVAR) occurs in 20% of patients and is an independent predictor of death. Higher preoperative high-density lipoprotein (HDL) cholesterol concentration before revascularization of chronic limb ischemia is associated with a lower risk of AKI. Further, preoperative statin use has been shown to be associated with a decreased risk of AKI after EVAR. We hypothesized that both preoperative statin use and higher preoperative HDL are associated with a lower risk of AKI in patients undergoing EVAR. Charts from adult patients that underwent EVAR were selected using the ICD codes (n=251). Each chart was reviewed for demographic and medical information, preoperative and postoperative serum creatinine concentrations, and preoperative HDL concentration. One hundred and three patients had available statin medication, serum creatinine, and HDL concentrations. The associations between statin dose, HDL concentration and maximum serum creatinine change from baseline in the first 48 postoperative hours was assessed using multivariable linear regression models, adjusted for AKI risk factors. Preoperative HDL concentration was not correlated with preoperative statin dose (Pearson’s R=0.0515, p=0.57). Higher preoperative statin doses (atorvastatin equivalents) and higher preoperative HDL concentrations were associated with lower serum creatinine rise (p=0.042 and 0.002 respectively, Figure). When both preoperative statin dose and preoperative HDL concentration were included in the model, both variables lost significance, suggesting HDL may mediate the relationship between preoperative statin dose and postoperative AKI. Higher preoperative HDL concentrations and statin doses were associated with less postoperative AKI. Future work involves identifying the biological mechanism underlying these associations as a first step towards developing new therapies to prevent AKI following EVAR.

Pharmacodynamic effect of bempedoic acid and statin combinations: predictions from a dose-response model.

AimsMany patients are unable to achieve guideline-recommended LDL cholesterol (LDL-C) targets, despite taking maximally tolerated lipid-lowering therapy. Bempedoic acid, a competitive inhibitor of ATP citrate lyase, significantly lowers LDL-C with or without background statin therapy in diverse populations. Because pharmacodynamic interaction between statins and bempedoic acid is complex, a dose–response model was developed to predict LDL-C pharmacodynamics following administration of statins combined with bempedoic acid.Methods and resultsBempedoic acid and statin dosing and LDL-C data were pooled from 14 phase 1–3 clinical studies. Dose–response models were developed for bempedoic acid monotherapy and bempedoic acid–statin combinations using previously published statin parameters. Simulations were performed using these models to predict change in LDL-C levels following treatment with bempedoic acid combined with clinically relevant doses of atorvastatin, rosuvastatin, simvastatin, and pravastatin. Dose–response models predicted that combining bempedoic acid with the lowest statin dose of commonly used statins would achieve a similar degree of LDL-C lowering as quadrupling that statin dose; for example, the predicted LDL-C lowering was 54% with atorvastatin 80 mg compared with 54% with atorvastatin 20 mg + bempedoic acid 180 mg, and 42% with simvastatin 40 mg compared with 46% with simvastatin 10 mg + bempedoic acid 180 mg.ConclusionThese findings suggest bempedoic acid combined with lower statin doses offers similar LDL-C lowering compared with statin monotherapy at higher doses, potentially sparing patients requiring additional lipid-lowering therapies from the adverse events associated with higher statin doses.

The Effect of Statins on C-Reactive Protein in Stroke Patients: A Systematic Review of Clinical Trials.

Background Statins reportedly have anti-inflammatory effects aside from their lipid-lowering impact. We investigated the effects of statin therapy on the level of C-reactive protein (CRP) or highly sensitive CRP (hs-CRP), a liver-derived marker of systemic inflammation, among stroke patients. Methods An online search was performed in Scopus, PubMed/MEDLINE, ISI Web of Science, and Google Scholar up to November 2020 to recognize clinical trials investigating the effects of statins on the CRP level in stroke patients. Results Overall, nine studies (11 treatment arms) with 1659 participants met the inclusion criteria. Six out of 9 studies (8 out of 11 arms) were categorized as studies with a high-quality methodological approach using the Cochrane Collaboration's tool. Data from 5 treatment arms indicated a significant decrease in CRP concentration, and in one treatment arm, CRP concentration did not suggest any considerable alteration following statin therapy. Moreover, two treatment arms showed a significant reduction in hs-CRP concentration and three treatment arms revealed no significant alteration in hs-CRP concentration following statin therapy. Generally, results were heterogeneous and independent of the type of statin, statin dose, treatment duration, and changes in plasma low-density lipoprotein cholesterol concentration. Conclusion The results suggest that statin therapy could reduce and, therefore, could be considered in these patients as potential anti-inflammatory agents.

Statin initiation and all-cause mortality in incident statin-naïve dialysis patients

Background and aimsCardiovascular disease is the main cause of death in end-stage kidney disease (ESKD) patients. We aimed to explore the association between statin initiation after starting dialysis and all-cause mortality in statin-naïve ESKD patients. MethodsWe analyzed nationwide claims data of incident dialysis patients from 2010 to 2017 in South Korea. Patients who had previous cardiovascular events or were administered statins before dialysis were excluded. The study group included dialysis patients receiving statins within 1 year after dialysis initiation. The control group was organized after propensity-score matching with age, sex, time of dialysis initiation, and underlying diabetes mellitus and hypertension. The main outcomes were all-cause mortality and major cardiovascular events. ResultsWe included 1596 patients who started statin treatment and 1:1 matched statin-nonusers. During the 9438 person-year follow-up, 468 deaths and 264 major adverse cardiovascular events (MACEs) occurred. Statin initiation was associated with a reduced risk of all-cause mortality (adjusted hazard ratio (aHR) 0.72, 95% confidence interval (CI) 0.60–0.87, p = 0.001), but not with MACE incidence (aHR 1.06, 95% CI 0.83–1.36, p = 0.62). In particular, patients prescribed the recommended dosage of statins according to the Kidney Disease Improving Global Outcomes guidelines showed the lowest mortality risk (aHR 0.55, 95% CI 0.40–0.75, p < 0.001). ConclusionsStatin initiation was associated with lower risk of all-cause mortality in statin-naïve ESKD patients. As indication bias may be present in observational study setting, further prospective studies are warranted to validate the association of statin initiation with mortality in incident dialysis cases.

Statin gap in patients living with HIV: assessing dose appropriateness.

Patients living with HIV (PLWH) are predisposed to atherosclerotic cardiovascular disease (ASCVD), resulting in concomitant antiretroviral and statin use. A statin prescribing gap for PLWH has been reported, but appropriateness of statin selection and dosing (ASD) has not been described. This is a comparative, retrospective study reviewing ASD in PLWH vs. uninfected patients at two outpatient clinics within an academic medical centre. Adults >21years old indicated for statin therapy were included. The primary outcome was percentage of PLWH prescribed an appropriately dosed statin, accounting for clinical- and patient-related variables, compared with uninfected patients. The secondary outcome was to identify patient characteristics associated with inappropriately dosed statins. After propensity score matching, 879 PLWH and 879 uninfected patients were included for analysis. Fewer PLWH (27.8%, n=244) were prescribed an ASD compared with uninfected patients (40.5%, n=356, P<0.001). Similar rates of statin omission were seen in both populations (P=0.11). More PLWH received too low a dose compared with the uninfected population (P<0.0064). There were lower ASD rates in PLWH for subgroups of patients with clinical ASCVD (P=0.00013) and 10-year ASCVD risk ≥7.5% (P=0.00055), but not in patients with low-density lipoprotein cholesterol ≥190mg/dL or diabetes. Although a statin gap exists in both PLWH and uninfected patients, the clinical significance may be greater for PLWH given the increased risk of ASCVD. This study confirms a larger statin gap in PLWH, particularly when underdosing of statin medications is considered. Additional analysis is warranted to investigate reasons for the ASD gap and beneficial clinical interventions.

Potential therapeutic effect of thymoquinone and/or bee pollen on fluvastatin-induced hepatitis in rats

Hepatitis is one of earlier, but serious, signs of liver damage. High doses of statins for a long time can induce hepatitis. This study aimed to evaluate and compare the therapeutic potential of thymoquinone (TQ) and bee pollen (BP) on fluvastatin (F)-induced hepatitis in rats. Rats were randomly divided into: group 1 (G1, control), G2 (F, hepatitis), G3 (F + TQ), G4 (F + BP), and G5 (F + TQ + BP). Single treatment with TQ or BP relieved fluvastatin-induced hepatitis, with best effect for the combined therapy. TQ and/or BP treatment significantly (1) reduced serum levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma glutamyl transpeptidase, and total bilirubin, (2) decreased malondialdehyde levels and increased level of reduced glutathione, and activities of glutathione peroxidase and catalase in the liver, (3) improved liver histology with mild deposition of type I collagen, (4) increased mRNA levels of transforming growth factor beta 1, nuclear factor Kappa B, and cyclooxygenase 1 and 2, and (5) decreased tumor necrosis factor alpha and upregulated interleukin 10 protein in the liver. These data clearly highlight the ability of TQ and BP combined therapy to cause better ameliorative effects on fluvastatin-induced hepatitis than individual treatment by each alone.

Effectiveness of statin therapy and LDL-cholesterol target attainment rates according to 2016 and 2019 ESC/EAS dyslipidaemia guidelines in secondary prevention

Background and Aims: High intensity statin (HIS) therapy is widely recommended in secondary prevention after acute myocardial infarction (AMI). Recently, ESC/EAS 2019 dyslipidaemia guidelines have lowered the target LDL-C which necessitates the use of non-statin therapies more frequently. In this retrospective study, we investigated the rate of LDL-C target attainment in order to highlight the need of statin dose intensification and non-statin lipid lowering drug combinations.

Pharmacodynamic effect of bempedoic acid and statin combinations: Predictions from a dose-response model

Background and Aims: Many patients are unable to achieve guideline-recommended low-density lipoprotein cholesterol (LDL-C) targets, despite taking maximally tolerated lipid-lowering therapy. Bempedoic acid, a competitive inhibitor of ATP-citrate lyase, significantly lowers LDL-C levels with or without background statin therapy in diverse populations. LDL-C lowering with bempedoic acid–statin combinations in previously untreated patients has not been fully investigated. Because the pharmacodynamic interaction between statins and bempedoic acid is complex, a dose-response model was developed to predict LDL-C pharmacodynamics following administration of various statin doses combined with bempedoic acid.

Efecto en la vida real sobre el control de los factores de riesgo asociado al inicio con polipíldora cardiovascular a partir de fármacos equipotentes

ObjectiveThis work aims to analyze the impact of Spain's National Center for Cardiovascular Research (CNIC-Ferrer)’s cardiovascular (CV)-polypill on blood pressure (BP) and low-density lipoprotein cholesterol (cLDL) levels in patients in our healthcare area who previously took equipotent doses of statins and antihypertensives. Material and methodsAll patients in our healthcare area (Santiago de Compostela, Spain) who, as of December 31, 2019, had an active prescription for the CV-polypill (CNIC-Ferrer) since January 16, 2015 were registered. The index date was the start date of the CV-polypill prescription. The drugs the patient had previously received for dyslipidemia and hypertension were analyzed, classifying them by their equivalent potency to atorvastatin and ramipril. Changes in cLDL and BP were analyzed by means of Student's t-test for paired samples. ResultsWe analyzed 547 patients with a mean age of 71.5±11.5 years. The majority were men (60.6%). We observed a decrease in cLDL (−10.6 [95% CI: −7.0, −14.3], p<.001) in patients who started taking the CV-polypill who had previously taken equally potent doses of atorvastatin (n=471). We documented a reduction in systolic BP (−3.7 [95% CI: −0.4, −6.9], p=.029) in patients who had previously taken equally potent doses of ramipril (n=360). In 88 patients, the CV-polypill was started via equally potent doses of atorvastatin and ramipril, with a decrease in cLDL (−8.7 [95% CI: −3.8, −13.6], p=.001) and systolic BP (−3.6 [95% CI: −7.8, 0.5], p=.085). ConclusionsThe initiation of treatment with the CV-polypill in patients who previously received equally potent treatment with atorvastatin and ramipril was associated with a greater reduction in cLDL and systolic BP.

RE: Myocardial Injury After Noncardiac Surgery and Perioperative Atrial Fibrillation: From Evidence to Clinical Practice

In the perioperative medicine special issue, Borges et al. discussed aspects of myocardial injury after noncardiac surgery (MINS) care and recommend initiating aspirin and moderate-to-high dose statin in all patients diagnosed with MINS. One aspect of MINS management that was not discussed in the article was patients in whom MINS management might be different, such as with patients on dialysis. Borges et al. are not alone in this regard: the CCS perioperative guidelines do not mention any specific exclusions for the initiation of ASA and statin in patients diagnosed with MINS. However, there is insufficient evidence to recommend aspirin and statins in all patients with MINS, as exemplified by patients requiring dialysis.

Influencia del tratamiento con estatinas en una cohorte de pacientes ingresados por COVID-19

Aims and objectivesStatins have been proposed as potentially useful agents for modulating the host response in COVID-19. However, solid evidence-based recommendations are still lacking. Our aim was to study the association between statin use and clinical outcomes in a large cohort of hospitalized patients with SARS-CoV-2 infection, as well as the specific consequences of chronic treatment withdrawal during hospital admission. Material and methodsRetrospective observational study including 2191 hospitalized patients with confirmed SARS-CoV-2 infection. ResultsMean age was 68.0±17.8 years and 597 (27.3%) patients died during follow-up. A total of 827 patients (37.7% of the whole sample), received chronic treatment with statins. Even though they underwent more frequent admissions in critical care units, chronic treatment with statins was not independently associated with all-cause mortality [HR 0.95 (0.72-1.25)]. During the whole hospital admission, 371 patients (16.9%) received at least one dose of statin. Although these patients had a significantly worse clinical profile, both treatment with statins during admission [HR 1.03 (0.78-1.35)] and withdrawal of chronic statin treatment [HR 1.01 (0.78-1.30)] showed a neutral effect in mortality. However, patients treated with statins presented more frequently hepatic cytolysis, rhabdomyolysis and thrombotic/hemorrhagic events. ConclusionsIn this large cohort of hospitalized COVID-19 patients, statins were not independently associated with all-cause mortality during follow-up. Clinically relevant statin-associated adverse effects should be carefully monitored during hospital admission.

Statins for Prostate Cancer: When and How Much?

Statins have plausible biological effects against prostate cancer cells and are associated with improved disease-specific mortality. In current randomized placebo-controlled trial, low-dose atorvastatin caused no difference in relapses after radical prostatectomy in Asian men. Future trials should study higher statin doses at later disease stages with survival as the endpoint.See related article by Jeong et al., p. 5004.

Associations between statins and adverse events in primary prevention of cardiovascular disease: systematic review with pairwise, network, and dose-response meta-analyses

ObjectiveTo assess the associations between statins and adverse events in primary prevention of cardiovascular disease and to examine how the associations vary by type and dosage of statins.DesignSystematic review and...

Heterozygous familial hypercholesterolemia: prevalence and control rates

Introduction: Heterozygous familial hypercholesterolemia (heFH) is associated with a very high risk for cardiovascular events. Treatment with potent statins substantially reduces cardiovascular morbidity in these patients. Moreover, combination therapy with statins plus ezetimibe and/or proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors facilitates achievement of low-density lipoprotein cholesterol (LDL-C) targets in patients with heFH. However, heFH remains underdiagnosed and undertreated worldwide. Areas covered: In this review, we summarize current evidence on the prevalence and control rates of heFH. Accumulating data suggest that heFH is one of the most common hereditary metabolic disorders, affecting approximately 1 in every 300 individuals. However, only a small minority of patients with heFH achieve LDL-C targets, even in high-income countries and in subjects followed-up in specialized lipid clinics. Expert opinion: Given the underdiagnosis of heFH using cascade and opportunistic screening, wider, population-based screening strategies should be evaluated for their feasibility and cost-effectiveness if we aspire to timely diagnosis and therefore prevention of cardiovascular morbidity and mortality in this very high risk population. Overcoming inertia in uptitrating statin dose, adding ezetimibe and/or PCSK9 inhibitors along with more generous reimbursement for lipid-lowering agents in patients with heFH are essential for improving goal attainment rates.