Statin Dose Research Articles

Association between statin exposure and short-term mortality in patients with high-grade acute-on-chronic liver failure

Background & AimsAcute-on-chronic liver failure (ACLF) carries a high short-term mortality for patients with cirrhosis. Prior literature suggests that statin exposure may reduce the likelihood of ACLF events. However, it is unclear if statin exposure is associated with ACLF-related mortality. This study sought to determine the association between statin use and short-term mortality among patients hospitalised with ACLF. MethodsThis was a retrospective cohort study of Veterans Health Administration (VHA) patients diagnosed with cirrhosis between 2008 and 2021 and hospitalised with high-grade (2 or 3) ACLF. Patients were stratified into those with and without continuous statin exposure for at least 90 days prior to hospitalisation. Multivariable logistic regression models were created to determine the adjusted association between statin exposure and 28-day and 90-day mortality. Categorical statin dose exposure, converted to simvastatin equivalents, was also explored. ResultsA total of 11,731 patients with cirrhosis hospitalised with Grade 2 or 3 ACLF were included in the analytic cohort, 26% of whom had statin exposure. In adjusted logistic regression models, statin use was associated with 18% lower odds of ACLF-related 28-day mortality (odds ratio [OR] 0.82, 95% CI 0.73–0.93, p = 0.001) and 24% lower odds of 90-day mortality (OR 0.76, 95% CI 0.68–0.86, p <0.001). Increasing statin dose exposure was also associated with further reductions in 90-day mortality (e.g. OR 0.81, 95% CI 0.70–0.93 for 10–40 mg vs. 0 mg and OR 0.72, 95% CI 0.60–0.87 for 80 mg vs. 0 mg, p <0.001). ConclusionsIn this large, retrospective cohort study, statin exposure before high-grade ACLF hospitalisation was associated with reduced odds of 28-day and 90-day mortality in patients with cirrhosis. A statin dose-dependent reduction in 90-day ACLF-related mortality was also observed. Impact and ImplicationsStatins have been identified as a class of medications with potential beneficial effects for patients with cirrhosis. In this large, retrospective cohort study of patients with cirrhosis who seek care at the Veterans Health Administration, statin use was associated with a decrease in short term (28-day and 90-day) mortality as a result of acute-on-chronic liver failure. Future prospective studies are needed to further clarify the relative safety and efficacy of statin therapy in reducing morbidity and mortality associated with acute-on-chronic liver failure in patients with cirrhosis.

Myocardial infarction in patients with severe beta thalassaemia: a case series

BackgroundCardiac disease remains a dominant if not the most important cause of morbidity and mortality in patients with thalassaemia, particularly in those with thalassaemia major. Myocardial infarction and coronary artery disease however are rarely reported.Case presentationsThree older patients with three distinct thalassaemia syndromes presented with acute coronary syndrome. Two were heavily transfused whilst the other was a minimally transfused patient. Both heavily transfused patients had ST-elevation myocardial infarctions (STEMI) while the minimally transfused patient had unstable angina. Coronary angiogram (CA) was normal in two patients. One patient who developed a STEMI had a 50% plaque. All three were managed as standard ACS, although the aetiology appeared non-atherogenic.ConclusionsThe exact etiology of the presentation, remains a mystery and therefore the rational use of thrombolytic therapy, carrying out angiogram in the primary setting, using and continuing antiplatelet and high dose statins all remains unclear in this sub group of patients.

Plain language summary of results from ORION-10 and ORION-11: two studies to learn how well inclisiran works in people with high cholesterol.

This is a summary of the article describing the results of the ORION-10 and ORION-11 studies, which was published in the New England Journal of Medicine in April 2020. The studies included adult participants with atherosclerotic cardiovascular disease (ASCVD). ASCVD happens when the blood vessels that carry blood from the heart to other areas of the body are blocked by fatty build-up (plaque) causing a heart attack, stroke, or other problems. High levels of low-density lipoprotein cholesterol (LDL cholesterol) in the blood can cause this fatty build-up. ORION-11 also included participants who were at high risk for ASCVD due to other conditions or high cholesterol that runs in the family. To help researchers understand whether a medicine called inclisiran could help to lower LDL (bad) cholesterol in participants with ASCVD, or at risk of having ASCVD, who had high cholesterol and were taking the highest dose of statins recommended for them. In the ORION-10 and ORION-11 studies, around half of the participants received inclisiran and around half received a placebo (a placebo looks like the study treatment but has no medicine in it) in addition to their usual cholesterol-lowering treatment. Participants in each study received 4 injections of their assigned treatment: at the start, at 3months, and then every 6months. LDL cholesterol was lowered by about 50% more in the inclisiran group compared with the placebo group. This lowering of LDL cholesterol was consistent throughout both studies. Adverse events (medical problems) were similar between treatment groups. Participants in the inclisiran group had more reactions where the injections were given than the placebo group, but these were mostly mild and only lasted a few days. Based on the results of these studies, inclisiran was approved by the United States Food and Drug Administration (FDA) as a treatment option for use with statins to reduce LDL cholesterol in people with ASCVD. Clinical Trial Registration: NCT03399370 (ORION-10), NCT03400800 (ORION-11) (ClinicalTrials.gov).

Abstract P357: Gender Disparities in Utilization of Statins in Patients With Cancer and Atherosclerotic Cardiovascular Disease: Results From Houston Methodist Learning Health System Outpatient Registry

Background: Gender disparities in utilization of statins have been reported across patients with cardiovascular disease, however these patterns remain unknown amongst cancer patients. We sought to evaluate gender differences in statin use amongst cancer patients with atherosclerotic cardiovascular disease (ASCVD) using data from a large US healthcare system. Methods: Houston Methodist Learning Health System Outpatient Registry was utilized to obtain data of adult population between 2016 to 2022. All patients with a cancer and ASCVD diagnosis listed on their problems list using the ICD-10 CM codes were included. Statin use and dose were identified in the database using ATC codes, and this information was recorded based on medication reconciliation reviews with patients at each clinical encounter. Multivariate logistic regression analysis and chi-square test were utilized to compare statin use between the two genders. Results: A total of 16,926 patients with cancer and ASCVD were included (41.6% women). Women with cancer and ASCVD reported lower statin use (63.9% vs 73.7%; p&lt;0.01) and lower high-intensity statin use (27.5% vs 37.2%; p&lt;0.01) compared with men. Women with cancer and ASCVD were also less likely to have LDL-C&lt;70mg/dL (25.8% vs 35.2%; p&lt;0.01) compared with men. Consistent results were observed even after adjusting for demographic and cardiovascular risk factors (any statin OR 0.68 [0.63, 0.72]; high-intensity statin OR 0.66 [0.61, 0.70]). These disparities persisted across age (&lt;65, ≥65 years) and racial/ethnic (NHW, Hispanics, NHB, Asian/Other) strata. Conclusion: Although statins can potentially ameliorate risk of adverse cardiovascular events in patients with cancer, significant gender disparities exist in utilization of statins among US patients with cancer and established ASCVD, with women less likely to have guideline defined goal of LDL&lt;70 mg/dL and receive any and high-intensity statin therapy across age and racial/ethnic subgroups.

Abstract P107: Utilization of Statins in Patients With versus Without Cancer and Atherosclerotic Cardiovascular Disease

Background: Patients with cancer and concomitant atherosclerotic cardiovascular disease (ASCVD) have an increased risk of cardiovascular mortality compared with general population. Accordingly, optimal utilization of statins remains crucial to curtail adverse cardiovascular events in this high-risk cohort. We sought to compare the demographic burden and utilization of statins in ASCVD patients with cancer versus without cancer. Methods: Houston Methodist Learning Health System Outpatient Registry is an EMR-linked registry which was queried for adult patients with established ASCVD (2016-2022). International Classification of Diseases 10 th Revision Clinical Modification codes (ICD 10-CM) were utilized to ascertain ASCVD and cancer diagnosis. ATC codes were used to identify statin use and dose in the database, and this information was recorded based on medication reconciliation reviews with patients during every clinical encounter. Results: A total of 97,819 patients with ASCVD were included in this analysis of which 16,926 patients (17.3%) had a concurrent cancer diagnosis. Patients with ASCVD and cancer reported lower utilization of any statin (69.6% vs 71.2%) and high-intensity statin (33.2% vs 37.6%) compared with patients without cancer. Consistent results were observed across gender, age and racial strata with the exception of Hispanics and NHB, where ASCVD patients with cancer reported increased utilization of any statin compared with patients without cancer. Interestingly, patients with ASCVD and cancer were more likely to have LDL&lt;70mg/dL compared with ASCVD patients without cancer (41.1% vs 36.2%) across gender, age and racial strata. Conclusion: Albeit higher risk of adverse cardiovascular events, utilization of statins, particularly high-intensity statins remains suboptimal in cancer patients with established ASCVD. Considering the underlying cardiovascular risk patients with cancer and concomitant ASCVD may derive the greatest benefit from intensive LDL-C lowering therapies.

Abstract P628: The Right Dose for the Right Patient - High Intensity Rosuvastatin Dosing in Patients With Chronic Kidney Disease

Introduction: The utilization of high intensity statins for lipid lowering therapy has revolutionized our approach to decreasing the incidence of myocardial infarction. In February 2003, rosuvastatin was approved by the FDA for use at dosages ranging from 5mg to 40mg daily, with lower doses recommended for patients with reduced glomerular filtration rates (GFRs). Prescribing patterns of rosuvastatin for patients with chronic kidney disease (CKD), notably those with a GFR &lt; 30 mL/min/1.73m 2 , is largely unstudied. Methods: A single center retrospective study of all admitted patients with a chart diagnosis of chronic kidney disease (CKD) over the course of one year was performed. Data on inpatient rosuvastatin orders and overall statin selection was collected and analyzed. Results: Between 10/1/2021-10/1/2022, a total of 5359 patients were admitted with the diagnosis of CKD. In this cohort, 62% (n = 3325) had a prescription for a statin placed for continuation of outpatient care or new initiation of lipid lowering therapy. Most patients were on atorvastatin (69.4%, n = 2310) or rosuvastatin (20.9%, n = 695). Among inpatients with CKD, a total of 1465 inpatient rosuvastatin orders were placed. Almost 32% (n = 468) of these patients had an eGFR &lt;30 mL/min/1.73m 2 . Of this cohort, 48% (n = 223) were prescribed doses of 20mg or 40mg rosuvastatin daily, which is above the FDA recommended dose for this population ( Figure 1 ). Conclusions: A large percentage of patients on lipid lowering therapies have CKD, and data regarding renal outcomes associated with high doses of statins in this population are limited. In this large single center study, we found that nearly half of patients with eGFR &lt;30 mL/min/1.73m 2 were on inappropriately high doses of rosuvastatin when considering their kidney function. Further research into long term outcomes and rosuvastatin dosing in this patient population is needed.

Abstract P432: Statin Initiation for Primary Prevention and Dose Intensity According to Age in the Women’s Health Initiative

Introduction: Over 50% of US adults older than 75 live free of atherosclerotic cardiovascular disease (ASCVD) and diabetes (DM), yet data on incident statin use among this population are lacking. Our objective was to assess statin initiation by age among the Women’s Health Initiative cohort free of ASCVD and DM at baseline (1993). Hypothesis: Statin initiation is higher at older ages and differs by race/ethnicity. Methods: Exclusions were statin use at baseline, known ASCVD, DM, and no follow-up after baseline. Self-reported medication use was assessed in 1996 and 2008. Specific statin and dose prescribed at the time of initiation were identified using National Drug Codes and determined statin intensity, defined by the ACC/AHA guidelines. We estimated the adjusted association between age group (&lt;65, 65-74, and ≥75) and statin initiation and assessed for heterogeneity by race/ethnicity. We also assessed statin dose at the time of initiation. Results: Over 12 years of follow-up, 27% of 99,631 women free of ASCVD and DM at baseline initiated a statin; initiation was lower with older age (Table). This association remained after adjustment for ASCVD risk factors and did not differ by race/ethnicity (p for interaction &gt;0.5). Moderate intensity dose was most common at statin initiation overall, and moderate and high intensity dose were both lower with older age. Conclusion: Of women free of ASCVD and DM, women older than 75 were least likely to start a statin and most likely to start low intensity statin therapy at initiation than younger women. We identified a potential clinical gap for investigation: whether lower overall use of statins and lower intensity statin therapy among older women are associated with preventable ASCVD.

Bempedoic Acid for Lipid Management in the Indian Population: An Expert Opinion.

Lipid-lowering is a central theme in the management of patients with atherosclerotic cardiovascular disease (ASCVD)and heterozygous familial hypercholesterolemia (HeFH), with statins being currently used as the first-line lipid-lowering agent (LLAs). Bempedoic acid (BA) has been recently approved for lipid management in ASCVD/HeFH patients. This expert opinion paper brings out the essential conceptto assess the current place of BA in the Indian population. Here we highlight that the majority of the patients with clinical ASCVD may not be receiving the optimal dose of statin, thereby failing to achieve their lipid targets. The addition of BA to statin results in a significant reduction in low-density lipoprotein cholesterol (LDL-C) along with substantial reductions in non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B (ApoB), and high-sensitivity C-reactive protein (hsCRP) levels. For patients who do not achieve LDL-C targets, BA can be an effective add-on alternative to choose among non-statin LLAs. BA is a good choice for statin-intolerant cases, especially in combination with ezetimibe. Given the lack of effect of worsening hyperglycemia or any increase in the occurrence of new-onset diabetes, BA can be used without hesitation in patients with diabetes. The small risk of hyperuricemia could be mitigated with appropriate patient selection and monitoring of serum uric acid levels in patients at high risk of hyperuricemia. We believe BA is an excellent non-statin therapy that is efficacious, well-tolerated, and cost-effective for lipid management in ASCVD, HeFH, and statin-intolerant patients in India.

Does statin use affect amyloid beta deposition and brain metabolism?

There are contradictory findings regarding the effect of statin drugs on amyloid β (Aβ) deposition as one of the main hallmarks of Alzheimer's disease (AD), along with tau pathology. We aimed to longitudinally investigate the therapeutic and preventive role of statin drugs by examining the brain Aβ deposition and metabolism rate in AD, mild cognitive impairment (MCI), and healthy controls (HC). The data of 828 subjects including 178 HC, 492 MCI, and 158 AD individuals were obtained from ADNI. The baseline and longitudinal [18 F] AV45 and 18-fluorodeoxyglucose (FDG) PET standard uptake value ratio (SUVR) measures were investigated among statin users and non-users. Our results showed that there is no significant difference in baseline Aβ deposition and metabolism rate between statin users and non-users among HC, MCI, and AD subjects. While there was no significant effect of statin on metabolism rate, there was a significant difference in Aβ deposition change after 4 years (from baseline) between statin users and non-users within HC subjects (p= 0.011). The change of Aβ deposition at 4 years from baseline was -2.0± 6.3% for statin users and 1.4± 4.7% for non-users. There was no significant association between statin duration use with baseline and longitudinal Aβ deposition and metabolism rate. However, statin dosage was significantly associated with Aβ deposition in 2 years (r= -0.412, p= 0.021) in the HC group. Moreover, our analysis showed a significant correlation between total statin exposure (duration×dosage) and Aβ deposition in 2 years visit (r= -0.198, p= 0.037) in HC subjects. Furthermore, we investigated the longitudinal changes within each group of statin users and non-users separately in linear mixed models. Our findings showed that there are no significant changes in AV45 and FDG SUVR among both groups. The present longitudinal analysis revealed that using statins might be beneficial in slowing down or stabilizing the Aβ deposition due to aging in subjects without cognitive impairment. However, once the clinical symptoms of cognitive impairment appear, statins fail to slow down Aβ deposition. Overall, our findings revealed that statin users might have slower Aβ aggregation than non-users.

Use of an Uncertainty Profile to Validate High-Performance Liquid Chromatography (HPLC) for the Simultaneous Determination of Statins in Synthetic Pharmaceutical Products

Here is reported a full validation of a high-performance liquid chromatography (HPLC) method for the determination of statins in a pharmaceutical product using the uncertainty profile. In addition, the uncertainty estimates based on the β-content, γ-confidence tolerance intervals are compared to those using the β-expectation tolerance interval via a graphical comparison. The results are useful in elucidating the applicability and flexibility of the uncertainty profile, which allows the analyst to choose the desired proportion of the results with a well-determined uncertainty. This approach allowed the determination of the validity of the statin assays. Four of the five statin dosages were shown to be accurate by demonstrating that more than 90% of the outcomes were compliant; however, rosuvastatin’s dosage was valid only by ensuring an 80% compliance rate. The uncertainty profile is a widely applicable strategy that may be used to evaluate analytical methods and compute the uncertainty in order to confirm suitability for use while providing reliable results.

Statin Treatment Intensity, Discontinuation, and Long-Term Outcome in Patients With Acute Myocardial Infarction and Impaired Kidney Function.

Statin dosage in patients with acute myocardial infarction (AMI) and concomitant kidney dysfunction is a clinical dilemma. We studied discontinuation during the first year after an AMI and long-term outcome in patients receiving high versus low-moderate intensity statin treatment, in relation to kidney function. For the intention-to-treat analysis (ITT-A), we included all patients admitted to Swedish coronary care units for a first AMI between 2005 and 2016 that survived in-hospital, had known creatinine, and initiated statin therapy (N = 112,727). High intensity was initiated in 38.7% and low-moderate in 61.3%. In patients with estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m 2 , 25% discontinued treatment the first year; however, the discontinuation rate was similar regardless of the statin intensity. After excluding patients who died, changed therapy, or were nonadherent during the first year, 84,705 remained for the on-treatment analysis (OT-A). Patients were followed for 12.6 (median 5.6) years. In patients with eGFR 30-59 mL/min, high-intensity statin was associated with lower risk for the composite death, reinfarction, or stroke both in ITT-A (hazard ratio [HR] 0.93; 95% confidence interval, 0.87-0.99) and OT-A (HR 0.90; 0.83-0.99); the interaction test for OT-A indicated no heterogeneity for the eGFR < 60 mL/min group ( P = 0.46). Similar associations were seen for all-cause mortality. We confirm that high-intensity statin treatment is associated with improved long-term outcome after AMI in patients with reduced kidney function. Most patients with reduced kidney function initiated on high-intensity statins are persistent after 1 year and equally persistent as patients initiated on low-moderate intensity.

Abstract TP196: Real Life Utility Of PCSK9 Inhibitors Following Ischemic Stroke

Introduction: Hyperlipidemia is a modifiable risk factor for stroke, with the magnitude of LDL-C reduction correlating to risk of recurrent ischemic stroke. A high-intensity statin is considered standard of care in addition to dietary modification. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are used if the LDL-C target is not achieved despite maximally tolerated statins with ezetimibe. We investigated the role for PCSK9 inhibitors in our ischemic stroke population. Methods: An IRB approved retrospective review of patients admitted for acute ischemic stroke between 2019 – 2020 was performed. We estimated the probability of benefit from PCSK9 treatment with the following criteria: LDL &gt; 190 regardless of treatment, LDL 161-190 on any dose statin therapy, and LDL 131-160 on high intensity statin therapy. Results: 774 patients with ischemic stroke were admitted during this time frame. Mean age 62.8 +/- 13.2 with 57% male (52% Black, 42% White). 584 (75%) of these patients had LDL above goal. One patient was on PCSK9 therapy on admission. Although the majority of our patients had uncontrolled cholesterol, only one additional patient would meet the strict prescription criteria for PCSK9 therapy of being adherent to maximal tolerated statin dose and ezetimibe with LDL above goal. Other potential patients with estimated benefit include LDL &gt;190 (20 patients), LDL 161-190 (16 patients), LDL 131-160 (13 patients). In total this amounts to 6.7% of stroke patients who we would expect to need PCSK9 inhibitors in the future. Conclusion: Using conservative projections, we estimate that about 1 in 14 patients with ischemic stroke could benefit from PCSK9 therapy. Achieving LDL targets more consistently is a promising approach to decreasing the recurrent stroke rate. Further prospective data evaluating outcomes after initiating PCSK9 inhibitor treatment are needed to validate these findings.

Atorvastatin Potentially Reduces Mycobacterial Severity through Its Action on Lipoarabinomannan and Drug Permeability in Granulomas.

The majority of preclinical research has shown that Mycobacterium tuberculosis can modify host lipids in various ways. To boost its intramacrophage survival, M. tuberculosis causes host lipids to build up, resulting in the development of lipid-laden foam cells. M. tuberculosis binds to and enters the macrophage via the cell membrane cholesterol. Aggregation of cholesterol in the cell wall of M. tuberculosis and an increase in vascularity at the granuloma site reduce the permeability of rifampicin and isoniazid concentrations. However, very few studies have assessed the effect of statins on drug penetration. Here, we used atorvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, to observe its effect on the bacterial burden by increasing the drug concentration at the infection site. We looked into how atorvastatin could be used in conjunction with first-line drugs to promote drug permeation. In this study, we detected an accumulation of drugs at the peripheral sites of the lungs and impaired drug distribution to the diseased sites. The efficacy of antituberculosis drugs, with atorvastatin as an adjunct, on the viability of M. tuberculosis cells was demonstrated. A nontoxic statin dosage established phenotypic and normal granuloma vasculature and showed an additive effect with rifampicin and isoniazid. Our data show that statins help to reduce the tuberculosis bacterial burden. Our findings reveal that the bacterial load is connected with impaired drug permeability resulting from lipid accumulation in the bacterial cell wall. Statin therapy combined with antituberculosis medications have the potential to improve treatment in tuberculosis patients. IMPORTANCE Mycobacterium tuberculosis binds to and enters the macrophage via the cell membrane cholesterol. M. tuberculosis limits phagosomal maturation and activation without engaging in phagocytosis. Aggregation of cholesterol in the cell wall of M. tuberculosis and an increase in the vascularity at the granuloma site reduce the permeability of rifampicin and isoniazid concentrations. However, very few studies have assessed the effect of statins on drug penetration, which can be increased through a reduction in cholesterol and vascularity. Herein, we used atorvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, to observe its effect on bacterial burden through increasing the drug concentration at the infection site. Our main research goal is to diminish mycobacterial dissemination and attenuate bacterial growth by increasing drug permeability.

Low-Density Lipoprotein Cholesterol Levels on Statins and Cardiovascular Event Risk in Stable Coronary Artery Disease - An Observation From the REAL-CAD Study.

The relationship between very low on-treatment low-density lipoprotein cholesterol (LDL-C) level and cardiovascular event risk is still unclear in patients receiving the same doses of statins. From the REAL-CAD study comparing high-dose (4 mg/day) with low-dose (1 mg/day) pitavastatin therapy in patients with stable coronary artery disease, 11,105 patients with acceptable statin adherence were divided into 3 groups according to the on-treatment LDL-C level at 6 months (<70 mg/dL, 70-100 mg/dL, and ≥100 mg/dL). The primary outcome measure was a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal ischemic stroke, or unstable angina requiring emergent admission. The adjusted risks of the LDL-C <70 mg/dL group relative to the LDL-C 70-100 mg/dL group (reference) was not significantly different for the primary outcome measure in both 1 mg/day and 4 mg/day strata (HR 0.84, 95% CI 0.58-1.18, P=0.32, and HR 1.25, 95% CI 0.88-1.79, P=0.22). The adjusted risk of the LDL-C ≥100 mg/dL group relative to the reference group was not significant for the primary outcome measure in the 1 mg/day stratum (HR 0.82, 95% CI 0.60-1.11, P=0.21), whereas it was highly significant in the 4 mg/day stratum (HR 3.32, 95% CI 2.08-5.17, P<0.001). A very low on-treatment LDL-C level (<70 mg/dL) was not associated with lower cardiovascular event risk compared with moderately low on-treatment LDL-C level (70-100 mg/dL) in patients receiving the same doses of statins.

Statin use in patients with type 2 diabetes has lower risk of hip fractures: A Taiwan national population-based study.

Type 2 diabetes mellitus (T2DM) frequently co-exists with osteoporosis and dyslipidemia. Statins have been commonly used in the treatment of dyslipidemia. Recent studies have indicated a therapeutic role of statins in decreasing the risk of osteoporosis and fractures, but conflicting results have been reported. This study investigated the association between statin use and hip fracture (HFx) risk among T2DM patients. A retrospective Taiwan population-based propensity-matched cohort study was performed using the Diabetes Mellitus Health Database from Taiwan National Health Insurance Research Database. Patients with newly diagnosed with T2DM between 2010 and 2014 were identified. Patients who previously used statins and had ever suffered HFx before the index date were excluded. HFx that occurred from 2010 to 2019 was collected to compute the cumulative rate of HFx. Hazard ratios (HRs) were calculated for the HFx risk according to the use or non-use of statins. To evaluate the dose-effect relationship of statins, sensitivity analyses were conducted. After propensity score matching for age and sex, 188,588 patients were identified as statin users and non-statin users. Statin use after T2DM diagnosis was associated with a decreased HFx risk with an adjusted HR (aHR) of 0.69 (P<0.001). A dose-effect relationship was identified. The aHRs for developing HFx were 1.29, 0.67, and 0.36 for patients who used 28-174, 175-447, and >447 cumulative defined daily doses of statins, respectively (P<0.001). Statin use in adults with T2DM showed a lower risk of HFx by demonstrating a dose-response relationship.

Physicians and pharmacists' clinical knowledge of statin therapy and monitoring parameters, and the barriers to guideline implementation in clinical practice.

Millions of individuals worldwide use statins, and their significant impact on cardiovascular disease (CVD) has been well-established. However, a lack of knowledge about the up-to-date guideline recommendations regarding statin therapy is a common barrier to implementation in clinical practice. Therefore, the present study aimed to assess the current clinical knowledge about statin therapy and its monitoring parameters. Also, we evaluated the barriers to cholesterol management guideline implementation in Yemen. This observational cross-sectional study was conducted over four months, from June/2021 to September/2021, in Sana'a, Yemen. A validated questionnaire was distributed face-to-face to 650 participants (350 physicians and 300 pharmacists). Physicians and pharmacists from governmental and private hospitals and those working in private clinics or community pharmacies were included in the study. A total of 496 participants filled out the survey, with 22 being excluded due to incomplete data. So, the study has an overall response rate of 72.9% (474). The majority of pharmacists (81.8%) and physicians (78.7%) could not identify the patient group that needed ASCVD risk assessment before statin therapy initiation. Although a significant proportion of respondents knew of the fact that high-intensity statins are recommended for patients with ASCVD (65.4%) and primary hypercholesterolemia (58.4%), the majority of physicians and pharmacists could not identify the high (61.6% and 66.7.3%, respectively) and moderate statin-intensity doses (72.2% and 68.6%, respectively). Only 21.9% of all respondents knew that atorvastatin and rosuvastatin can be administered at any time of the day. Similarly, a low overall rate of respondents (19.6%) knew that atorvastatin does not need dose adjustment in chronic kidney diseases, with a statistically significant difference in knowledge between physicians and pharmacists (12.5% vs. 25.6%, p <0.001, respectively). Notably, only 39.2% of participants were aware that statins are not safe to use during breastfeeding. Around half of respondents (52.3%) correctly identify the duration (4 to 12 weeks) at which LD-C measuring is recommended after therapy initiation or dose change. The lowest knowledge scores for respondents were related to statin-drug interactions. Age, experience, degree, and previous guideline exposure were all significantly associated with the knowledge scores (p <0.05). The four most perceived barriers to implementing cholesterol management guidelines were no audit on adherence to the guidelines in the workplace (73.4%), insufficient resources to adequately implement and follow up on the guideline's recommendations (73.6%), patient's financial status (75.7%), and lack of familiarity about the guideline's latest recommendations (63.3%). Physicians and pharmacists had suboptimal clinical knowledge regarding statin therapy, dose intensities, drug-drug interaction, contraindications, and monitoring parameters. Therefore, physicians' and pharmacists' educational interventions regarding the up-to-date recommendation about statins are recommended.

Systematic analysis of the experimental and clinical pharmacology of nicotinamide and prospects for the treatment of atherosclerosis

Nicotinamide (niacin) is a PP (Pellagra-Preventive) vitamer necessary for the synthesis of nicotinamide adenine dinucleotide (NAD). The NAD molecule is a coenzyme of proteins involved in the synthesis of ATP from fats and carbohydrates. For more than 50 years, nicotinamide has been used as an antihyperlipidemic agent and to improve blood microcirculation. The results of a systematic analysis of 70417 publications on the pharmacology of nicotinamide made it possible to clarify the molecular mechanisms of the vasoprotective action of nicotinamide (including anti-inflammatory action), to summarize the results of experimental and clinical studies of anti-atherosclerotic effects (including the treatment of steatohepatosis and counteraction to obesity) and the cardioprotective properties of nicotinamide. The prospects for the combined use of statins and nicotinamide are shown, which allows to reduce the dosage of statins.

Особенности сердечно-сосудистых нарушений у больных диабетической стопой

The purpose — to improve the effectiveness of treatment of diabetic foot patients with cardiovascular disorders. Material and methods. 782 patients with diabetic foot (DF) were under observation. 4 groups were identified: group 1 — VAC therapy was used; group 2 — ultrasonic cavitation; group 3 — modern dressings were used for treatment; group 4 — with a standard treatment. Low doses of statins were used (atorvastatin 10–20 mg/day or rosuvastatin 5–10 mg/day) in 213 patients (27.2%) and 89 patients (11.4%) received moderate or high doses of statins (atorvastatin 40–80 mg/day or rosuvastatin 20 mg/day) in combination with ursodeoxycholic acid (UDCA) preparations (750–1750 mg/day). Results. In the low-dose statin subgroup, the rate of low-density lipoprotein cholesterol levels reduction averaged 17.6 (5.6) % of the initial values; triglycerides, respectively, 12.3 (3.5) % of the initial values; that was statistically significantly lower than in the moderate/high dose statin plus UDCA subgroup of 32.9 (5.4) % and 18.7 (3.2) %, respectively, all p&lt;0.001. In group 1, the average duration of hospital stay and the percentage of postoperative complications were statistically significantly lower in patients who received lipid-lowering therapy (28.5 (3.6) days and 8.8 (2.9) %), compared with those who did not receive this treatment (34.0 (2.8) days and 13.1 (2.6) %); p &lt; 0.001. Similar differences in the length of hospital stay and the percentage of postoperative complications, depending on the lipid-lowering therapy, also occurred in groups 2, 3, and 4 (p &lt; 0.001). Conclusions. The use of lipid-lowering therapy, including moderate / high doses of statins in combination with UDCA, contributed to a decrease in the length of hospital stay and a decrease in the incidence of postoperative complications in all groups of patients with DF.

Treatment Outcomes of the Acute Coronary Syndrome Among Patients Attending St. Paul Hospital.

Acute coronary syndrome (ACS) patients need intense therapy and diagnostic evaluation for improved treatment. In Ethiopia, where patient deaths and hospital stays are rising, the ACS treatment is thought to be not very effective. A retrospective cross-sectional study was conducted at St. Paul Hospital. The data were collected from patients medical records using a structured data abstraction checklist from 2018 to 2020. The data was entered, analyzed, and interpreted using SPSS version 24 software. Of 157 ACS patients, 69 (43.9%) had a STEMI diagnosis. Age was 63.69 years on average (SD: 8.23). The typical amount of time between the onsets of ACS symptoms to hospital presentation was 79.3 hours (3.3 days). For 104 (66.2%) patients, hypertension was the main risk factor for the development of ACS. Killip class III and IV patients made up about 3.8% of the ACS patients at St. Paul hospital. An EF of less than 40% was present in 36.3% of patients. Loading doses of aspirin (90.4%), anticoagulants (14%), beta-blockers (82.8%), statins (86%), clopidogrel (7.6%), and nitrates (2.5%) are among the medications taken inside hospitals. Of 157 ACS patients, 6 (3.8%) patients with medical records examined died while receiving treatment in the hospital, while 151 (96.2%) patients were discharged alive. STEMI was the most common diagnosis for ACS patients at St. Paul Hospital. The two main hospital events for these patients were CHF and cardiogenic shock.

Low-density lipoprotein cholesterol target achievement: How about low-income countries

Dylipidemias are a major cardiovascular risk factor especially for the LDLc. The control of low-density lipoprotein cholesterol (LDLc) level is one of the major targets in patients admitted for an acute coronary syndrome (ACS). It is in this sense that the latest European recommendations of 2019 about dyslipidemias fall into line. The objective of our work was to study the lipid profile after ACS and to assess the degree of applicability of the European recommendation in Tunisia. This was a prospective, multicentric, non-randomized study involving consecutive patients hospitalized for ACS in the cardiology departments of Abdrerrahman Mami Hospital, Mohamed Taher Maamouri Hospital and Internal Security Forces hospital in Tunisia between 26/10/2019 and 07/03/2020 and not on lipid lowering treatment; for whom a lipid assessment was carried out on admission and checked after four to six weeks of the ACS under high dose of statin. One hundred patients were included. The average age of our population was 58.7 ± 11.6 years and the sex ratio was 5.6. Obesity was prevalent in 15%, Diabetes in 35%, hypertension in 34% and smoking in 61% of cases. Our patients presented with an ST segment elevation myocardial infarction (STEMI) in 51% of cases. Initially, the mean total plasma cholesterol level was 1.72 ± 0.33 g/L; the mean plasma trigliceride level was 1.61 ± 1.1 g/L; for high-density lipoprotein cholesterol (HDLc) it was 0.38 ± 0.09 g/L and for LDLc it was 1.04 ± 0.26 g/L. All patients have received high doses of statins: 76% received 80 mg of atorvastatin, 15% received 40 mg of atorvastatin, 9% received 20 mg rosuvastatin. They all were blood tested four to six months later. The results showed a decrease of the cholesterol level by 27.5%, the triglyceride level by 20.6% and the LDLc level by 38.2% and an increase of HDLc level by 6.5%. A level of LDLc ≤ 0.55 g/L was achieved in 46% and a decrease by 50% or more was observed in 33%. The therapeutic target was reached in only 30% of cases. The only therapeutic alternative was the diet and lifestyle changes due to the unavailability of molecules recommended by the European society of cardiology in Tunisia. Our results demonstrate the difficulty of reaching the therapeutic target of LDLc after an ACS in Tunisia. Several factors can be identified, essentially the absence of medical products recommended in the second and third line by the ESC in Tunisia.