High-intensity Statin Therapy Research Articles

Effects of high-intensity statin therapy on steroid hormones and vitamin D in type 2 diabetic men: A prospective self-controlled study.

The study aimed to assess the effect of high-intensity statin therapy on testicular and adrenal steroids and vitamin D levels in type 2 diabetic men. A prospective study, conducted between March 2021 and July 2022, including 60 men with type 2 diabetes, aged 40-65 years, statin-free, and in whom treatment with high-intensity statin was indicated. The patients had two visits, before and 6 months after a daily intake of 40 mg of atorvastatin. During each visit, they underwent a clinical examination, and a fasting blood sample was collected for biological and hormonal measurements. There was a significant increase in the prevalence of decreased libido (from 22% to 47%, p = 0.001) and a significant decrease in the frequency of sexual intercourse (from 4 [1-8] to 3 [0-4] per month, p = 0.005). The median ADAM's score significantly increased (from 4 [2-7] to 6 [3-8], p = 0.000). Twenty-two percent of the patients developed gynecomastia. The median total, bioavailable and free testosterone significantly decreased from 15.1 (11.4-17.4), 6.3 (5.0-7.8), and 0.27 (0.22-0.33) nmol/L to 12.7 (10.7-15.9), 5.7 (4.4-7.0), and 0.24 (0.19-0.30) nmol/L, respectively, with no change in FSH and LH levels. Three patients (5%) developed hypogonadism (testosterone <8 nmol/L). There was a significant decrease in DHEAS from 4.5 (2.8-6.1) to 3.8 μmol/L (2.6-5.6) and no change in cortisol and vitamin D levels. High-intensity statin therapy decreased androgen levels in type 2 diabetic men with significant clinical impact.

An audit to review the prescribing and monitoring of high-intensity statin therapy in acute coronary syndrome patients

Abstract Introduction High-intensity statin therapy (HIST) is recommended as secondary prevention following an acute coronary syndrome (ACS). Prior to initiating a statin, a baseline liver function test (LFT) and lipid profile are required, which should be repeated in primary care after 3 months for safety purposes and to measure efficacy. Targets to measure efficacy are defined as part of local, national[1] and European guidance.[2] Aim To investigate if a National Health Service (NHS) Health Board are compliant with current guidance on the prescribing and monitoring of HIST in ACS patients. Methods A retrospective audit of all new ACS diagnoses in the NHS Ayrshire &amp; Arran in June 2022 was undertaken using inpatient prescribing data. The Clinical Portal system was used to obtain LFT and lipid profile results and these were recorded in Microsoft Excel for analysis. Results The patient cohort (n=57) was 58% male, with a mean age of 69 years. LFTs were measured in 96.5% patients on admission and 84.2% at follow-up. Conclusion HIST with Atorvastatin 80mg was initiated in most cases (84.2%), with appropriate clinical exceptions. HIST appeared effective with 78.9% of patients achieving a 40% reduction in non-HDL cholesterol and 63% of patients achieving an LDL-C target of &amp;lt;1.8mmol/L. These results highlight the need for clinical review at 3 months to optimise lipid lowering therapy as 37% of patients had not met an LDL-C target of &amp;lt;1.8mmol/L. Interpretation of this data is limited by small sample size due to limited allocation of time for data collection and by the fact that not all patients had both baseline and follow-up lipid profiles taken so it cannot be determined if they met treatment targets (n=38). There is a need for the NHS Health Board to improve lipid profile monitoring of HIST as although LFTs were measured in 96.5% patients on admission and 84.2% at follow-up, only 73.7% had a baseline lipid profile and 47.4% at follow-up. As both are measured using the same blood sample, it is suggested that targeted clinician education regarding lipid profile requesting alongside LFTs could significantly improve adherence to audit standards.

Treatment patterns and adherence to lipid-lowering drugs during eight-year follow-up after a coronary heart disease event

Background and aimsProper prescription and high adherence to intensive lipid lowering drugs (LLD) in patients with coronary heart disease (CHD) are crucial and strongly recommended. The aim of this study is to investigate long-term treatment patterns and adherence to LLD following hospitalization for a CHD event. MethodsPatients admitted to two Norwegian hospitals with a CHD event from 2011 to 2014 (N = 1094) attended clinical examination and completed a questionnaire, median 16 months later. Clinical data were linked to pharmacy dispensing data from 2010 to 2020. The proportions using high-intensity statin therapy (atorvastatin 40/80 mg or rosuvastatin 20/40 mg) and non-statin LLD after the CHD event were assessed. Adherence was evaluated by proportion of days covered (PDC) and gaps in treatment. ResultsMedian age at hospitalization was 63 (IQR 12) years, 21 % were female. Altogether, 1054 patients (96 %) were discharged with a statin prescription, while treatment was dispensed in 85 % within the following 90 days. During median 8 (SD 2.5) years follow-up, the proportion using high-intensity statin therapy ranged 62–68 %, whereas the use of ezetimibe increased from 4 to 26 %. PDC <0.8 was found in 22 % of statin users and 26 % of ezetimibe users. The proportions with a treatment gap exceeding 180 days were 22 % for statins and 28 % for ezetimibe. Smoking at hospitalization and negative affectivity were significantly associated with reduced statin adherence, regardless of adherence measure. ConclusionsIn this long-term follow-up of patients with CHD, less than 70 % used high-intensity statin therapy with only small changes over time, and only 25 % used additional treatment with ezetimibe. We identified factors associated with reduced statin adherence that may be target for interventions.

Statin treatment intensity and cerebral vasomotor reactivity response in patients with ischemic stroke.

Cerebral vasomotor reactivity (VMR) is vital for regulating brain blood flow and maintaining neurological function. Impaired cerebral VMR is linked to a higher risk of stroke and poor post-stroke outcomes. This study explores the relationship between statin treatment intensity and VMR in patients with ischemic stroke. Seventy-four consecutive patients (mean age 69.3 years, 59.4% male) with recent ischemic stroke were included. VMR levels were assessed 4 weeks after the index stroke using transcranial Doppler, measuring the breath-holding index (BHI) as an indicator of the percentage increase in middle cerebral artery blood flow (higher BHI signifies higher VMR). Multistep multivariable regression models, adjusted for demographic and cerebrovascular risk factors, were employed to examine the association between statin intensity treatment and BHI levels. Forty-one patients (55%) received high-intensity statins. Patients receiving high-intensity statins exhibited a mean BHI of 0.85, whereas those on low-intensity statins had a mean BHI of 0.67 (mean difference 0.18, 95% confidence interval: 0.13-0.22, p-value<.001). This significant difference persisted in the fully adjusted model (adjusted mean values: 0.84vs. 0.68, p-value:.008). No significant differences were observed in BHI values within patient groups on high-intensity or low-intensity statin therapy (all p-values>.05). Furthermore, no significant association was found between baseline low-density lipoprotein (LDL) levels and BHI. High-intensity statin treatment post-ischemic stroke is linked to elevated VMR independent of demographic and clinical characteristics, including baseline LDL level. Further research is needed to explore statin therapy's impact on preserving brain vascular function beyond lipid-lowering effects.

Pharmacist optimization of lipid therapy in patients with peripheral vascular disease.

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. American College of Cardiology/American Heart Association guidelines recommend high-intensity statin therapy and consideration for nonstatin therapy for patients with peripheral vascular disease (PVD); however, utilization rates remain suboptimal. The primary objective of this study was to determine whether pharmacist intervention for patients with PVD could improve the percentage of patients discharged on a high-intensity statin. The study used a single-center pre/post design and included patients with PVD who underwent peripheral bypass during their admission. Postintervention patients managed with an order set including a preselected consult for a pharmacy lipid protocol were compared to preintervention patients managed using the order set without the consult. The primary outcome was the percentage of patients discharged on a high-intensity statin. Secondary outcomes included intensification of statin therapy, the addition of ezetimibe, and referral to an outpatient lipid clinic. A total of 175 patients were included in the analysis, with 94 patients in the preintervention group and 81 patients in the postintervention group. The primary outcome met statistical significance, with an increase in the percentage of patients discharged on a high-intensity statin in the postintervention group (70.4%) compared to the preintervention group (38.3%) (P < 0.001; 95% confidence interval, 1.37-2.46). Secondary outcomes that met statistical significance included an increase in the percentage of patients with any increase in statin intensity (35.8% vs 20.2%; P = 0.02). The addition of a pharmacist consult led to an increase in the percentage of patients discharged on a high-intensity statin and an increase in overall statin intensification.

Effects of statin therapy on diagnoses of new-onset diabetes and worsening glycaemia in large-scale randomised blinded statin trials: an individual participant data meta-analysis

Previous meta-analyses of summary data from randomised controlled trials have shown that statin therapy increases the risk of diabetes, but less is known about the size or timing of this effect, or who is at greatest risk. We aimed to address these gaps in knowledge through analysis of individual participant data from large, long-term, randomised, double-blind trials of statin therapy. We conducted a meta-analysis of individual participant data from randomised controlled trials of statin therapy that participated in the CTT Collaboration. All double-blind randomised controlled trials of statin therapy of at least 2 years' scheduled duration and with at least 1000 participants were eligible for inclusion in this meta-analysis. All recorded diabetes-related adverse events, treatments, and measures of glycaemia were sought from eligible trials. Meta-analyses assessed the effects of allocation to statin therapy on new-onset diabetes (defined by diabetes-related adverse events, use of new glucose-lowering medications, glucose concentrations, or HbA1c values) and on worsening glycaemia in people with diabetes (defined by complications of glucose control, increased use of glucose-lowering medication, or HbA1c increase of ≥0·5%). Standard inverse-variance-weighted meta-analyses of the effects on these outcomes were conducted according to a prespecified protocol. Of the trials participating in the CTT Collaboration, 19 trials compared statin versus placebo (123 940 participants, 25 701 [21%] with diabetes; median follow-up of 4·3 years), and four trials compared more versus less intensive statin therapy (30 724 participants, 5340 [17%] with diabetes, median follow-up of 4·9 years). Compared with placebo, allocation to low-intensity or moderate-intensity statin therapy resulted in a 10% proportional increase in new-onset diabetes (2420 of 39 179 participants assigned to receive a statin [1·3% per year] vs 2214 of 39 266 participants assigned to receive placebo [1·2% per year]; rate ratio [RR] 1·10, 95% CI 1·04-1·16), and allocation to high-intensity statin therapy resulted in a 36% proportional increase (1221 of 9935 participants assigned to receive a statin [4·8% per year] vs 905 of 9859 participants assigned to receive placebo [3·5% per year]; 1·36, 1·25-1·48). For each trial, the rate of new-onset diabetes among participants allocated to receive placebo depended mostly on the proportion of participants who had at least one follow-up HbA1c measurement; this proportion was much higher in the high-intensity than the low-intensity or moderate-intensity trials. Consequently, the main determinant of the magnitude of the absolute excesses in the two types of trial was the extent of HbA1c measurement rather than the proportional increase in risk associated with statin therapy. In participants without baseline diabetes, mean glucose increased by 0·04 mmol/L with both low-intensity or moderate-intensity (95% CI 0·03-0·05) and high-intensity statins (0·02-0·06), and mean HbA1c increased by 0·06% (0·00-0·12) with low-intensity or moderate-intensity statins and 0·08% (0·07-0·09) with high-intensity statins. Among those with a baseline measure of glycaemia, approximately 62% of new-onset diabetes cases were among participants who were already in the top quarter of the baseline distribution. The relative effects of statin therapy on new-onset diabetes were similar among different types of participants and over time. Among participants with baseline diabetes, the RRs for worsening glycaemia were 1·10 (1·06-1·14) for low-intensity or moderate-intensity statin therapy and 1·24 (1·06-1·44) for high-intensity statin therapy compared with placebo. Statins cause a moderate dose-dependent increase in new diagnoses of diabetes that is consistent with a small upwards shift in glycaemia, with the majority of new diagnoses of diabetes occurring in people with baseline glycaemic markers that are close to the diagnostic threshold for diabetes. Importantly, however, any theoretical adverse effects of statins on cardiovascular risk that might arise from these small increases in glycaemia (or, indeed, from any other mechanism) are already accounted for in the overall reduction in cardiovascular risk that is seen with statin therapy in these trials. These findings should further inform clinical guidelines regarding clinical management of people taking statin therapy. British Heart Foundation, UK Medical Research Council, and Australian National Health and Medical Research Council.

Lifetime effects and cost-effectiveness of standard and higher-intensity statin therapy across population categories in the UK: a microsimulation modelling study

Cardiovascular disease incidence and mortality have declined across developed economies and granular up-to-date cost-effectiveness evidence is required for treatments targeting large populations. To assess the health benefits and cost-effectiveness of standard and higher intensity statin therapy in the contemporary UK population 40-70 years old. A cardiovascular disease microsimulation model, developed using the Cholesterol Treatment Trialists' Collaboration data (117,896 participants; 5 years follow-up), and calibrated in the UK Biobank cohort (501,854 participants; 9 years follow-up), projected risks of myocardial infarction, stroke, coronary revascularization, diabetes, cancer and vascular and nonvascular death for all UK Biobank participants without and with statin treatment. Meta-analyses of trials and cohort studies informed statins' relative effects on cardiovascular events, incident diabetes, myopathy and rhabdomyolysis. UK healthcare perspective was taken (2020/2021 UK£) with costs per 28 tablets of £1.10 for standard (35%-45% LDL cholesterol (LDL-C) reduction) and £1.68 for higher intensity (≥45% LDL-C reduction) generic statin. Across categories by sex, age, LDL-C, and cardiovascular disease history/10-year cardiovascular risk, lifetime standard statin increased survival by 0.28-1.85 years (0.20-1.09 quality-adjusted life years (QALYs)), and higher intensity statin by further 0.06-0.40 years (0.03-0.20 QALYs) per person. Standard statin was cost-effective across all categories with incremental cost per QALY from £280 to £8530, with higher intensity statin cost-effective at higher cardiovascular risks and higher LDL-C levels. Stopping statin early reduced benefits and was not cost-effective. Lifetime low-cost statin therapy is cost-effective across all 40-70 years old in UK. Strengthening and widening statin treatment could cost-effectively improve population health. UK NIHR Health Technology Assessment Programme (17/140/02).

The importance of LDL-C lowering in atherosclerotic cardiovascular disease prevention: Lower for longer is better

Cumulative exposure to low-density lipoprotein cholesterol (LDL-C) is a key driver of atherosclerotic cardiovascular disease (ASCVD) risk. An armamentarium of therapies to achieve robust and sustained reduction in LDL-C can reduce ASCVD risk. The gold standard for LDL-C assessment is ultracentrifugation but in routine clinical practice LDL-C is usually calculated and the most accurate calculation is the Martin/Hopkins equation. For primary prevention, consideration of estimated ASCVD risk frames decision making regarding use of statins and other therapies, and tools such as risk enhancing factors and coronary artery calcium enable tailoring of risk assessment and decision making. In patients with diabetes, lipid lowering therapy is recommended in most patients to reduce ASCVD risk with an opportunity to tailor therapy based on other risk factors. Patients with primary hypercholesterolemia and familial hypercholesterolemia (FH) with baseline LDL-C greater than or equal to 190 mg/dL are at elevated risk, and LDL-C lowering with high-intensity statin therapy is often combined with non-statin therapies to prevent ASCVD. Secondary prevention of ASCVD, including in patients with prior myocardial infarction or stroke, requires intensive lipid lowering therapy and lifestyle modification approaches. There is no established LDL-C level below which benefit ceases or safety concerns arise. When further LDL-C lowering is required beyond lifestyle modifications and statin therapy, additional medications include oral ezetimibe and bempedoic acid, or injectables such as PCSK9 monoclonal antibodies or siRNA therapy. A novel agent that acts independently of hepatic LDL receptors is evinacumab, which is approved for patients with homozygous FH. Other emerging agents are targeted at Lp(a) and CETP. In light of the expanding lipid treatment landscape, this manuscript reviews the importance of early, intensive, and sustained LDL-C-lowering for primary and secondary prevention of ASCVD.

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

BackgroundHigh-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. MethodsWe 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. FindingsThis 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. InterpretationCompared 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.

Safety and Efficacy of PCSK9 Inhibitors in Patients with Acute Coronary Syndrome Who Underwent Coronary Artery Bypass Grafts: A Comparative Retrospective Analysis

Background. The in-hospital reduction in low-density lipoprotein cholesterol (LDL-C) levels following acute coronary syndrome (ACS) is recommended in the current clinical guidelines. However, the efficacy of proprotein convertase subtilisin–kexin type 9 (PCSK9) inhibitors in those patients undergoing coronary artery bypass graft (CABG) has never been demonstrated. Methods. From January 2022 to July 2023, we retrospectively analyzed 74 ACS patients characterized by higher LDL-C levels than guideline targets and who underwent coronary bypass surgery. In the first period (January 2022–January 2023), the patients increased their statin dosage and/or added Ezetimibe (Group STEZE, 43 patients). At a later time (February 2023–July 2023), the patients received not only statins and Ezetimibe but also Evolocumab 140 mg every 2 weeks starting as early as possible (Group STEVO, 31 patients). After one and three months post-discharge, the patients underwent clinical and laboratory controls with an evaluation of the efficacy lipid measurements and every adverse event. Results. The two groups did not differ in terms of preoperative risk factors and Euroscore II (STEVO: 2.14 ± 0.75 vs. STEZE: 2.05 ± 0.6, p = 0.29). Also, there was no difference between the groups in terms of ACS (ST-, Instable angina, or NSTE) and time of symptoms onset regarding total cholesterol, LDL-C, and HDL-C trends from the preprocedural period to 3-month follow-up, but there was a more significant reduction in LDL-C and total cholesterol in the STEVO group (p = 0.01 and p = 0.04, respectively) and no difference in HDL-C rise (p = 0.12). No deaths were reported. In three STEZE group patients, angina recurrence posed the need for percutaneous re-revascularization. No STEVO patients developed significant adverse events. The statistical difference in these serious events, 7% in STEZE vs. 0% in STEVO, was not significant (p = 0.26). Conclusions. Evolocumab initiated “as soon as possible” in ACS patients submitted to CABG with high-intensity statin therapy and Ezetimibe was well tolerated and resulted in a substantial and significant reduction in LDL-C levels at discharge, 1 month, and 3 months. This result is associated with a reduction but without a statistical difference between groups.

Oreo Cookie Treatment Lowers LDL Cholesterol More Than High-Intensity Statin therapy in a Lean Mass Hyper-Responder on a Ketogenic Diet: A Curious Crossover Experiment.

Recent research has identified a unique population of 'Lean Mass Hyper-Responders' (LMHR) who exhibit increases in LDL cholesterol (LDL-C) in response to carbohydrate-restricted diets to levels ≥ 200 mg/dL, in association with HDL cholesterol ≥ 80 mg/dL and triglycerides ≤ 70 mg/dL. This triad of markers occurs primarily in lean metabolically healthy subjects, with the magnitude of increase in LDL-C inversely associated with body mass index. The lipid energy model has been proposed as one explanation for LMHR phenotype and posits that there is increased export and subsequent turnover of VLDL to LDL particles to meet systemic energy needs in the setting of hepatic glycogen depletion and low body fat. This single subject crossover experiment aimed to test the hypothesis that adding carbohydrates, in the form of Oreo cookies, to an LMHR subject on a ketogenic diet would reduce LDL-C levels by a similar, or greater, magnitude than high-intensity statin therapy. The study was designed as follows: after a 2-week run-in period on a standardized ketogenic diet, study arm 1 consisted of supplementation with 12 regular Oreo cookies, providing 100 g/d of additional carbohydrates for 16 days. Throughout this arm, ketosis was monitored and maintained at levels similar to the subject's standard ketogenic diet using supplemental exogenous d-β-hydroxybutyrate supplementation four times daily. Following the discontinuation of Oreo supplementation, the subject maintained a stable ketogenic diet for 3 months and documented a return to baseline weight and hypercholesterolemic status. During study arm 2, the subject received rosuvastatin 20 mg daily for 6 weeks. Lipid panels were drawn water-only fasted and weekly throughout the study. Baseline LDL-C was 384 mg/dL and reduced to 111 mg/dL (71% reduction) after Oreo supplementation. Following the washout period, LDL-C returned to 421 mg/dL, and was reduced to a nadir of 284 mg/dL with 20 mg rosuvastatin therapy (32.5% reduction). In conclusion, in this case study experiment, short-term Oreo supplementation lowered LDL-C more than 6 weeks of high-intensity statin therapy in an LMHR subject on a ketogenic diet. This dramatic metabolic demonstration, consistent with the lipid energy model, should provoke further research and not be seen as health advice.

Statin therapy after elective abdominal aortic aneurysm repair improves long-term survival.

Patients with abdominal aortic aneurysms are at high risk of cardiovascular events. Although statin therapy is indicated for most of these patients, no specific recommendation regarding the intensity of therapy exists. The aim of this study was to assess the possible effect of statin therapy on survival of patients undergoing abdominal aortic aneurysm repair and to investigate if high-intensity statin therapy was superior to low-moderate-intensity therapy. Data from nationwide Swedish registers on hospital admissions, operations, and medications for patients undergoing elective abdominal aortic aneurysm repair from 2006 to 2018 were collected. The effect of statin use was evaluated in three separate propensity score matched cohorts: perioperative mortality was analysed according to whether patients were on statins before abdominal aortic aneurysm repair or not; long-term survival was assessed according to whether patients were on statins during follow-up or not; and, for those on statins after surgery, long-term survival was analysed according to whether patients were on high-intensity or low-moderate-intensity statin therapy. Preoperative statin use did not reduce 90-day perioperative mortality (OR 0.99, 95% c.i. 0.77 to 1.28), whilst there was a marked benefit regarding long-term survival for postoperative statin users (HR 1.43, 95% c.i. 1.34 to 1.54). High-intensity statin therapy had no advantage over low-medium-intensity statin therapy with regards to long-term survival (HR 1.00, 95% c.i. 0.80 to 1.25). In this nationwide propensity score matched cohort study, preoperative statin treatment had no benefit regarding 90-day perioperative survival, but postoperative statin treatment markedly improved long-term survival. No additional benefit regarding high-dose statin treatment could be confirmed in this analysis.

Statins Ticagrelor and Rhabdomyolysis: A Coincidence or a Drug Interaction?

Statins play a key role in the management of atherosclerotic cardiovascular disease for both primary and secondary prevention. However, their increasing usage has correspondingly led to a higher incidence of adverse effects, with muscle symptoms being the most common. An intriguing drug interaction exists between ticagrelor and high-intensity statins, which may exacerbate the adverse effects of statin-induced rhabdomyolysis, leading to significant consequences. This study was conducted to examine the profile of patients who have experienced statin-induced rhabdomyolysis while undergoing percutaneous transluminal coronary angioplasty (PTCA). This was an observational study that included 1,862 patients who underwent PTCA at our institute over the course of 1 year. Over a 1-year period, we encountered four patients who were being treated with high-intensity statin therapy following acute coronary syndrome. These patients presented with muscle weakness and kidney injury. A notable commonality among all patients was the co-prescription of ticagrelor. Two patients died, while the other 2 were successfully managed through hydration, electrolyte balance, dialysis, and alternative lipid management drugs. The concomitant use of ticagrelor and high-intensity statins should be carefully considered due to the additional risk of rhabdomyolysis and kidney injury. Future pharmacokinetic studies are needed to establish a causal relationship and predict potential drug interactions, which, if not avoided, could be fatal.

New possibilities for lipid level control using inclisiran — prospects for interaction between a cardiologist and a neurologist

Dyslipidemia is one of the most significant modifiable cardiovascular risk factors. The change in the modern paradigm for dyslipidemia treatment from high-intensity statin therapy to high-intensity lipid-lowering therapy makes it possible to more often use new drug classes to achieve the target level of low-density lipoprotein cholesterol. The article presents two case reports on the use of inclisiran as part of combination lipid-lowering therapy for secondary prevention in patients at very high cardiovascular risk. Based on the presented cases, following clinical aspects of the management of cardiovascular patients are discussed: the safety of achieving low-density lipoprotein cholesterol levels below 1 mmol/l in a patient with asymptomatic cerebral infarction, the need for adequate dyslipidemia treatment after revascularization, the strategic importance of prescribing lipid-lowering therapy in patients with cerebrovascular disease to reduce the cardiovascular risk, adherence to therapy as a significant aspect of effective dyslipidemia control.

POTENTIAL FOR PATHOGENETIC CORRECTION OF PROTEASE-ANTIPROTEASE SYSTEM IMBALANCE IN PATIENTS WITH COMORBIDITY OF STABLE ANGINA PECTORIS OF THE II-III FUNCTIONAL CLASS AND STAGE II-III CHRONIC OBSTRUCTIVE PULMONARY DISEASE

The aim of this study is to assess the clinical effectiveness of the therapy including exogenous L-arginine and statins under the comorbidity of stable angina pectoris of the II-III functional class and chronic obstructive pulmonary disease of the II-III stage.&#x0D; Materials and methods. The study included 50 patients with coronary heart disease and chronic obstructive pulmonary disease (mean age 57 years; male/female ratio 78/22%). In order to assess the clinical effectiveness of the therapy for combined cardiopulmonary pathology, the patients were randomized into 2 subgroups: subgroup 1 included 25 patients who took metabolitotropic medication under high-intensity statin therapy (the basic therapy included L-arginine and rosuvastatin as a hypolipidemic agent in a dose of 20 mg/day); subgroup 2 included 25 patients who received only basic therapy under moderately intensive statin therapy (daily doses of atorvastatin 20 mg, rosuvastatin 10 mg)). The groups were comparable in terms of gender distribution and demographic characteristics. Comparative analysis of smoking experience, initial smoking age and smoking history did not differ significantly between the groups. After 12±1 weeks, a control examination was carried out.&#x0D; Results. The analysis of the ratio of the MMP-9 activity level before and after the therapy showed that the level of MMP-9 expression decreased by 43.28% (p&lt;0.05) in the 1st subgroup and by 13.18% in the 2nd subgroup until the end of the therapy. TIMP activity after 12 weeks of the treatment was +33.11% (p&lt;0.05) and +11.27% for the 1st and 2nd subgroups respectively. The difference between subgroups 1 and 2 in the level of the CRP marker before and after the therapy was -45.65% (p&lt;0.05) and -9.09%, respectively. 76% of people from the 1st subgroup reached the target level of healthy people before the completion of the therapy that is significantly higher than the similar indicator in the 2nd subgroup (32%) at χ2=8.05, p&lt;0.01.&#x0D; Conclusions: The application of L-arginine alongside high-intensity statin therapy for patients presenting with stable angina pectoris of the II-III functional class and stage II-III chronic obstructive pulmonary disease (COPD) resulted in more notable positive changes in the modulation of protease-antiprotease status disorders. This was evidenced by a reduction in the heightened expression of MMP-9 and an increase in the level of TIMP during the course of treatment.

Evolution of More Aggressive LDL-Cholesterol Targets and Therapies for Cardiovascular Disease Prevention

Over the last half-century, discussions on the exact targets for low-density lipoprotein cholesterol (LDL-C) reduction have evolved towards a more aggressive approach with lower LDL-C targets, particularly for high-risk patients with pre-existing atherosclerotic cardiovascular disease (ASCVD). A wealth of cardiovascular outcome trials have shown the efficacy of statin therapy in general, as well as the incremental impact of high-intensity statin therapy in particular. More recent trials have further demonstrated the impact of non-statin therapies, including ezetimibe, proprotein convertase subtilisin/kexin type 9 inhibitors, and, most recently, bempedoic acid, on reducing ASCVD outcomes. The availability of these and other newer therapies has prompted clinicians to strive for lower LDL-C targets to address residual ASCVD risk after statin therapy. This paper will provide an overview of the historical trends in lipid management and therapeutics and review the current state of evidence for lower LDL-C targets in clinical guidelines and recommendations.

Association of health information technology-driven multidisciplinary approaches with low-density lipoprotein cholesterol target achievement in patients with an acute coronary syndrome

ObjectiveControlling of low-density lipoprotein cholesterol (LDL-C) in patients with acute coronary syndrome (ACS) remains a challenge. Health information technology (HIT) is increasingly being applied to close quality gaps in chronic illness care. The aim of this study was to perform a qualitative review of the association of implementing HIT on lipid management processes of care and LDL-C goal attainment in patients with ACS. MethodEligible patients with a discharge diagnosis of ACS from January 2018 to December 2021 at a tertiary medical center were retrospectively reviewed. An HIT system with a multidisciplinary approach including initiating high-intensity statin therapy, periodic laboratory follow-up, titration of lipid-lowering agents, patient education, patient-level and system-level interventions involving database monitoring and outreach by centralized care teams was introduced in October 2018. Electronical medical records including data on medications and laboratory findings at discharge and within 1 year were compared before and after implementing the HIT system. ResultsA total of 2001 ACS patients (average age 63 ± 12.7 years, 79.66 % men) were analyzed. The LDL-C < 70 mg/dL goal attainment rates (36.52 %, 53.57 %, 59.22 %, 62.18 % in 2018–2021) and medium serum LDL-C levels (80.5 mg/dL, 68 mg/dL, 65 mg/dL, 64 mg/dL in 2018–2021) significantly improved within 6 months (2018 as the reference, all p<0.001). The LDL-C attainment rate at 12 months also steadily increased (53.80 %, 61.82 %, 64.21 % in 2019–2021, p = 0.019). Most of the patients switched to a high-intensity statins regimen at discharge (0.57 %, 63.67 %, 72.41 %, 84.44 %, in 2018–2021, p<0.001 with 2018 as the reference), with low adverse event rates. The maintenance rates of high-intensity statin regimens at 12 months continued to improve (41.36 %, 49.04 %, 61.39 % in 2019–2021, p<0.001). ConclusionsEfforts to control LDL-C should be increased in ACS patients by initiating and intensifying statin treatment earlier. Our results confirmed that a team-based strategy with HIT improved LDL-C target achievement for most patients with ACS.

Comparative Analysis of High-Intensity versus Low-to-Moderate Intensity Statin Therapy in Patients Undergoing Rotational Atherectomy for Calcified Coronary Artery Disease.

(1) Background: Moderate-intensity statin therapy, when compared to high-intensity statin therapy in Asian populations, has shown no significant difference in cardiovascular prognosis in small studies. The aim of this study was to compare the prognosis of patients based on statin intensity following rotational atherectomy (RA) during high-complexity percutaneous coronary intervention (PCI). (2) Methods: The ROCK registry, a multicenter retrospective study, included patients who had undergone rotational atherectomy (RA) during percutaneous coronary intervention (PCI) at nine tertiary medical centers in South Korea between January 2010 and October 2019. The patients were divided into high-intensity statin (H-statin) and moderate/low-intensity statin (M/L-statin) therapy groups. The primary endpoint includes outcomes (cardiac death, target vessel myocardial infarction (MI), and target vessel revascularization (TVR)) within an 18-month follow-up period. (3) Results: In this registry, a total of 540 patients with 583 lesions were included. We excluded 39 lesions from the analysis due to the absence of statin usage. The H-statin group had 394 lesions and the M/L-statin group had 150 lesions. There were no significant differences in baseline characteristics, procedural adverse events without heart failure history, triglycerides, or medications between the two groups. The procedural success rate showed a significant difference between the two groups. Multivariate analysis did not show a significant association between M/L-statin therapy and an increased risk of the primary endpoint. In propensity score matching analysis, no significant difference was observed in the primary endpoint either. (4) Conclusions: In high-complex RA PCI, moderate/low-intensity statin therapy is not inferior to high-intensity statin therapy in Korea.

Effect of moderate-intensity statin with ezetimibe combination vs. high-intensity statin therapy according to sex in patients with atherosclerosis

We aimed to evaluate sex differences in the effects of moderate-intensity statin with ezetimibe combination therapy (rosuvastatin 10 mg plus ezetimibe) versus high-intensity statin (rosuvastatin 20 mg) monotherapy in patients with atherosclerotic cardiovascular disease (ASCVD). This was a sex-specific subgroup analysis of the RACING trial that evaluated the interaction between sex and treatment strategies for the primary outcome (composite of cardiovascular death, major cardiovascular events, or nonfatal stroke at 3 years). Of 3780 patients in the RACING trial, 954 (25.2%) were women. Regardless of sex, the effect of moderate-intensity statin with ezetimibe combination therapy on primary outcome compared with high-intensity statin monotherapy was similar (hazard ratio [HR] 0.98 [0.63–1.52] in women; HR 0.90 [0.71–1.14] in men). The rate of discontinuation or dose reduction of study drugs due to intolerance was lower in the ezetimibe combination group than in the high-intensity statin monotherapy group in both women (4.5% vs. 8.6%, P = 0.014) and men (4.8% vs. 8.0%, P < 0.001). LDL cholesterol levels of < 70 mg/dL at 1, 2, and 3 years were more frequently achieved in the ezetimibe combination group than in the high-intensity statin monotherapy group (all P < 0.001) in both sexes. There were no significant interactions between sex and treatment groups regarding the primary outcome, discontinuation, or dose reduction of study drugs, or the proportion of achievement of LDL cholesterol levels < 70 mg/dL. The effect of ezetimibe combination therapy for the 3-year composite outcomes was not different in both men and women. The benefits of ezetimibe combination therapy on LDL cholesterol lowering and drug tolerance were similarly observed regardless of sex.Trial registration: https://clinicaltrials.gov; Unique identifier: NCT03044665.

Coronary and Extra-coronary Subclinical Atherosclerosis to Guide Lipid-Lowering Therapy.

To discuss and review the technical considerations, fundamentals, and guideline-based indications for coronary artery calcium scoring, and the use of other non-invasive imaging modalities, such as extra-coronary calcification in cardiovascular risk prediction. The most robust evidence for the use of CAC scoring is in select individuals, 40-75 years of age, at borderline to intermediate 10-year ASCVD risk. Recent US recommendations support the use of CAC scoring in varying clinical scenarios. First, in adults with very high CAC scores (CAC ≥ 1000), the use of high-intensity statin therapy and, if necessary, guideline-based add-on LDL-C lowering therapies (ezetimibe, PCSK9-inhibitors) to achieve a ≥ 50% reduction in LDL-C and optimally an LDL-C < 70 mg/dL is recommended. In patients with a CAC score ≥ 100 at low risk of bleeding, the benefits of aspirin use may outweigh the risk of bleeding. Other applications of CAC scoring include risk estimation on non-contrast CT scans of the chest, risk prediction in younger patients (< 40 years of age), its value as a gatekeeper for the decision to perform nuclear stress testing, and to aid in risk stratification in patients presenting with low-risk chest pain. There is a correlation between extra-coronary calcification (e.g., breast arterial calcification, aortic calcification, and aortic valve calcification) and incident ASCVD events. However, its role in informing lipid management remains unclear. Identification of coronary calcium in selected patients is the single best non-invasive imaging modality to identify future ASCVD risk and inform lipid-lowering therapy decision-making.