Lipid-modifying Agents Research Articles

Maintenance immunosuppressive therapy in liver transplantation: results from CESIT study, an Italian retrospective cohort study

ObjectivesTo investigate the use of maintenance immunosuppressive treatments following liver transplantation and to compare their risk–benefit profiles in clinical practice.DesignRetrospective multicentrer cohort study.SettingFour Italian regions (Lombardy, Veneto, Lazio, Sardinia).MethodsData were...

Reversal of Atherosclerotic Plaque Growth and Vulnerability: Effects of Lipid-Modifying and Anti-Inflammatory Therapeutic Agents.

Atherosclerotic plaque development constitutes the primary substrate of coronary artery disease (CAD) and is the outcome of an intricate process involving endothelial damage, inflammation, and lipid retention. The clinical efficacy of many lipid-lowering therapies in patients with CAD has been well established. Over the past few decades, a substantial and significant advance regarding the use of invasive and non-invasive imaging modalities has been observed. Numerous studies have been conducted using these imaging techniques and have investigated the changes in morphology (e.g., atheroma volume) and composition (e.g., lipid burden, fibrous cap thickness, macrophage accumulation) at the plaque level that explain the improved clinical outcomes by various pharmacological interventions. Lipid-lowering agents, such as statins and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, demonstrate direct effects on plaque volume and composition that enhance plaque stabilization and/or regression beyond the reduction of low-density lipoproteins. An increasing amount of clinical research is also focused on the role of inflammation in plaque vulnerability and future adverse cardiac events. Consequently, there is a pressing need to explore therapeutic strategies that are capable of disrupting the inflammatory response as well as reducing atheroma burden and modifying high-risk plaque characteristics. This review provides a comprehensive analysis of the current evidence regarding the effects of traditional and novel therapeutic strategies targeting modification of the lipid profile and inflammatory processes on reversing plaque growth and attenuating vulnerable features, thereby promoting plaque stabilization and passivation.

Lipid-modifying agents and risk of all-cause, natural and suicide mortality in schizophrenia: nationwide cohort study.

Individuals with schizophrenia face high mortality risks. The effects of lipid-modifying agents on this risk remain understudied. This study was conducted to investigate the effects of lipid-modifying agents on mortality risk in people with schizophrenia. This nationwide cohort study collected the data of people with schizophrenia from Taiwan's National Health Insurance Research Database for the period between 1 January 2001 and 31 December 2019. Multivariable Cox proportional hazards regression with a time-dependent model was used to estimate the hazard ratio for mortality associated with each lipid-modifying agent. This study included 110 300 people with schizophrenia. Of them, 22 528 died (19 754 from natural causes and 1606 from suicide) during the study period, as confirmed using data from Taiwan's national mortality database. The use of lipid-modifying agents was associated with reduced risks of all-cause (adjusted hazard ratio [aHR]:0.37; P < 0.001) and natural (aHR:0.37; P < 0.001) mortality during a 5-year period. Among the lipid-modifying agents, statins and fibrates were associated with reduced risks of all-cause mortality (aHRs:0.37 and 0.39, respectively; P < 0.001 for both) and natural mortality (aHRs: 0.37 and 0.42, respectively; P < 0.001 for both). Notably, although our univariate analysis indicated an association between the use of lipid-modifying agents and a reduced risk of suicide mortality, the multivariate analysis revealed no significant association. Lipid-modifying agents, particularly statins and fibrates, reduce the risk of mortality in people with schizophrenia. Appropriate use of lipid-modifying agents may bridge the mortality gap between these individuals and the general population.

IJCM_104A: Polypharmacy and medication adherence among elderly population in a rural area of Ernakulam district, Kerala.

Background: Polypharmacy is the concurrent use of multiple medications. Although there is no standard definition, polypharmacy is often defined as the routine use of five or more medications. This includes over-the-counter, prescription and/or traditional and complementary medicines used by a patient Objective: The aim of the study was to assess the prevalence of polypharmacy, describe the number and types of drugs used, and to determine medication adherence in elderly population Methodology: A cross sectional study was conducted among 364 elderly population residing in Vypin Block of Ernakulam district, Kerala by probability-proportional-to-size sampling. A semi structured questionnaire was administered by face-to-face interview to collect details on sociodemographic profile, regular medications and Morisky Medication-Taking Adherence Scale- MMAS (4-item) to assess medication adherence. The study participants were categorized into poor and good adherence based on MMAS score Results: More than half (53%) of the elderly were females, with a mean age of 69 ± 7 years. The prevalence of polypharmacy among the study population was 14.6% [95% CI, 11-18.2]. The most commonly used medications (35%) were oral blood glucose-lowering agents, followed by antihypertensive drugs and lipid-modifying agents. The vast majority (86.5%) had good medication adherence according to MMAS score. The independent determinants of medication adherence in our study were males (aOR=2.53 CI 1.09-5.08; p= 0.03) Christian religion (aOR=3.84 CI 1.43-10.34; p=0.008), staying along with family (aOR=8.15 CI 2.04-32.5; p=0.003), having polypharmacy (aOR=3.69 CI 1.54-2.82; p=0.003) and not having to pay for medications (aOR=3.4 CI 1.51- 7.64; p=0.003) were found statistically significant with medication adherence Conclusion: In order to improve medication adherence, the health care system should focus on women, those who stay alone and those who have to pay for medications

Predicting the risk of pancreatic cancer in women with new-onset diabetes mellitus.

People with new-onset diabetes mellitus (diabetes) could be a possible target population for pancreatic cancer surveillance. However, distinguishing diabetes caused by pancreatic cancer from type 2 diabetes remains challenging. We aimed to develop and validate a model to predict pancreatic cancer among women with new-onset diabetes. We conducted a retrospective cohort study among Australian women newly diagnosed with diabetes, using first prescription of anti-diabetic medications, sourced from administrative data, as a surrogate for the diagnosis of diabetes. The outcome was a diagnosis of pancreatic cancer within 3years of diabetes diagnosis. We used prescription medications, severity of diabetes (i.e., change/addition of medication within 2months after first medication), and age at diabetes diagnosis as potential predictors of pancreatic cancer. Among 99687 women aged ≥50years with new-onset diabetes, 602 (0.6%) were diagnosed with pancreatic cancer within 3years. The area under the receiver operating curve for the risk prediction model was 0.73. Age and diabetes severity were the two most influential predictors followed by beta-blockers, acid disorder drugs, and lipid-modifying agents. Using a risk threshold of 50%, sensitivity and specificity were 69% and the positive predictive value (PPV) was 1.3%. Our model doubled the PPV of pancreatic cancer in women with new-onset diabetes from 0.6% to 1.3%. Age and rapid progression of diabetes were important risk factors, and pancreatic cancer occurred more commonly in women without typical risk factors for type 2 diabetes. This model could prove valuable as an initial screening tool, especially as new biomarkers emerge.

Impact of COVID-19 Pandemic on Dispensing of Cardiovascular Drugs in Norway: An Interrupted Time Series Study

The COVID-19 pandemic resulted in changes in prescription patterns and fillings for certain medications, but little is known about its impact on the dispensing of cardiovascular drugs. Trends in dispensing of cardiovascular drugs before and during the pandemic were examined using a population-based cohort in Norway. Using interrupted time series analyses and considering March 1, 2020 as the interruption point, the impact of the pandemic on defined daily dose dispensing of prescribed cardiovascular drugs was estimated in a population of adults with and without pre-existing cardiovascular disease from January 2018 to December 2021. All data were analyzed in 2023. In a total of 4,053,957 adults, 690,910 (17.0%) had pre-existing cardiovascular disease. Prior to the pandemic, there was a significant monthly increase in any cardiovascular drug dispensing among those with pre-existing cardiovascular disease (0.30 defined daily dose per month per adult), including prescription of diuretics, calcium channel blockers, and lipid-modifying agents. After controlling for preinterruption trends, there was a slight decrease in level change immediately after the start of the pandemic (2.5 defined daily dose per month per adult) but an increase in the postinterruption trend (0.06 defined daily dose per month per adult) for dispensing of cardiovascular prescriptions, although these changes were not significant. Although the COVID-19 pandemic did not appear to result in significant changes in patterns of cardiovascular drug dispensing in Norway, continued access to cardiovascular drugs remains important to prevent further related morbidity.

Guideline-directed low-density lipoprotein cholesterol management following acute ischemic stroke: findings from Clalit health services

Abstract Background Patients with ischemic stroke are at high risk for future cardiovascular events and should be treated intensively with lipid-modifying agents. Combination lipid-lowering therapies are often needed to achieve updated (2019) guideline-directed treatment goals. However, real-world data on intensification of lipid-lowering therapies and attainment of low-density lipoprotein cholesterol (LDL-C) targets after ischemic stroke are limited. Methods Data from a single national health care service on patients hospitalized with acute ischemic stroke between Jan. 2020 and Feb. 2022. Included were 3027 patients surviving ≥1-year post-stroke, with documented LDL-C levels and lipid-lowering medications at 2 timepoints (&amp;lt;3 months and during 6-12 months post-discharge). Participants were classified according to preexisting stroke and/or coronary artery disease (CAD). Results LDL-C levels &amp;lt;70 mg/dL and &amp;lt;55 mg/dL were attained by 42.3% and 22.9% of patients early post-hospitalization, and in 49.5% and 27.1% during 6-12 months post-hospitalization, respectively. Attainment of guideline-recommended LDL-C goals was higher in those with preexisting cardiovascular disease. The use of combination lipid-lowering therapy (ezetimibe and/or PCSK9 inhibitor plus statin) increased between the 2 timepoints: from 2% to 3.2% in those without prior stroke and/or CAD, and from 5.4% to 7% in those with prior stroke and/or CAD. Conclusions Despite the advances in drug development and the availability of several mechanisms to lower cholesterol levels, the attainment of guideline-recommended LDL-C targets after acute ischemic stroke is suboptimal. Intensification of treatment with combination lipid-lowering therapies 6-12 months following hospitalization is uncommonly performed in clinical practice, even in those with preexisting cardiovascular disease.

Abstract 14710: The Landscape of Pharmacological Interventional Trials for the Treatment or Prevention of Coronary Artery Disease: Analysis of clinicaltrials.gov Listings From 2008 to 2022

Background: Coronary artery disease (CAD) has been the leading cause of death and disability over the past two decades. Aims: To systematically assess the characteristics and trends of clinical trials pertaining to the treatment or prevention of CAD. Methods: The analysis included studies that (1) were registered in the ClinicalTrials.gov database from 2008 to 2022; (2) involved ≥1 pharmacological intervention; and (3) were designed to treat or prevent CAD or its complications. Study records were downloaded on December 27, 2022 for screening and analysis. Pharmacological interventions were classified according to the World Health Organization Anatomical Therapeutic Chemical Classification System. Annual trends by the year of study registration were assessed with a two-sided Cochran-Armitage test. Results: A total of 1,619 trials were identified from a pool of 437,319 studies. There was a declining trend in the number of CAD trials (Figure A). The majority of trials (47.5%) were targeted to enroll ≤100 participants, while 39.4% targeted 101-1000 participants, 10.5% targeted 1001-5000 participants, and 2.6% were mega-trials (&gt;5000 participants). The distribution of study duration was as follows: ≤12 months (25.3%), 13-60 months (67.3%), and &gt;60 months (7.5%). Of note, the open-label design was more commonly employed in treatment trials (41.8% vs. 31.6%; p=0.02), while the parallel assignment was more frequently utilized in prevention trials (88.8% vs. 82.0%; p=0.03). In addition, declining trends in the proportions of phase 3 trials (p=0.0008; Figure B) and trials of lipid-modifying (p=0.0043) or anti-thrombotic agents (p=0.03; Figure C) were observed. Conclusion: Between 2008 and 2022, the clinical trial landscape of CAD diminished and was mainly shaped by studies with small to moderate sample sizes and short to intermediate follow-up duration. Research focus trended toward study interventions other than anti-thrombotic or lipid-modifying agents.

Statin, Ezetimibe, or Fibrate Initiation and Subsequent Use for the Primary and Secondary Prevention of Cardiovascular Diseases among Japanese Patients Aged ≥55 Years: A Nationwide Cohort Study.

The use of lipid-modifying agents (LMAs) other than statins has rarely been reported in real clinical settings. We aimed to compare the initiation and subsequent use of LMA classes for prevention of cardiovascular diseases. Using the national claims database, this retrospective cohort study was conducted on patients aged ≥55 years who initiated to use statins, ezetimibe, or fibrates between Fiscal Years (FYs) 2014 and 2017 as the first pharmacotherapy for dyslipidemia in Japan. A permissible gap for defining persistence was set as the median days of supply of a class to an individual. Kaplan-Meier estimates were calculated for rates. Cohorts for primary prevention without/with risk and secondary prevention comprised 1307438, 908378, and 503059 initiators for statins; 44116, 34206, and 11373 for ezetimibe; and 124511, 96380, and 27751 for fibrates. The persistence rates declined shortly after the therapy initiation regardless of the classes, which was approximately 50% at 1 year for any class for primary prevention without risk. A notable sex difference in terms of persistence rates was observed only for statins of secondary prevention. The restarting rates were similar between prevention settings: approximately 50-60% for statins and 30-40% for ezetimibe and fibrates 1 year after first discontinuation. For ezetimibe and fibrates, approximately 10% of initiators were added or switched to statins within 1 year of initiation. Collectively, any class tended to be discontinued early and some restarted; however, there were some unique classes. The findings are useful for improvement of dyslipidemia therapy.

Medication profiling in women with type 1 diabetes highlights the importance of adequate, guideline-based treatment in low-risk groups

Effective treatment may prevent kidney complications, but women might be underprescribed. Novel, data-driven insights into prescriptions and their relationship with kidney health in women with type 1 diabetes may help to optimize treatment. We identified six medication profiles in 1164 women from the FinnDiane Study with normal albumin excretion rate based on clusters of their baseline prescription data using a self-organizing map. Future rapid kidney function decline was defined as an annual estimated glomerular filtration rate (eGFR) loss > 3 ml/min/1.73 m2 after baseline. Two profiles were associated with future decline: Profile ARB with the highest proportion of angiotensin receptor blockers (odds ratio [OR] 2.75, P = 0.02) and highly medicated women in profile HighMed (OR 2.55, P = 0.03). Compared with profile LowMed (low purchases of all), profile HighMed had worse clinical characteristics, whereas in profile ARB only systolic blood pressure was elevated. Importantly, the younger women in profile ARB with fewer kidney protective treatments developed a rapid decline despite otherwise similar baseline characteristics to profile ACE & Lipids (the highest proportions of ACE inhibitors and lipid-modifying agents) without a future rapid decline. In conclusion, medication profiles identified different future eGFR trajectories in women with type 1 diabetes revealing potential treatment gaps for younger women.

Antibiotics and Lipid-Modifying Agents: Potential Drug-Drug Interactions and Their Clinical Implications.

Evidence-based prescribing requires taking into consideration the many aspects of optimal drug administration (e.g., dosage, comorbidities, co-administered drugs, etc.). A key issue is the administration of drugs for acute disorders that may potentially interfere with previously prescribed long-term medications. Initiating an antibiotic for an acute bacterial infection constitutes a common example. Hence, appropriate knowledge and awareness of the potential DDIs of antibiotics would lead to proper adjustments, thus preventing over- or under-treatment. For example, some statins, which are the most prescribed lipid-modifying agent (LMA), can lead to clinically important drug-drug interactions (DDIs) with the concurrent administration of antibiotics, e.g., macrolides. This review discusses the clinically significant DDIs of antibiotics associated with co-administrated lipid-lowering therapy and highlights common cases where regimen modifications may or may not be necessary.

Lipids, lipid-modifying drug target genes and migraine: a Mendelian randomization study

IntroductionMigraine, a prevalent headache disorder with unclear mechanisms and limited treatments, may be influenced by dyslipidemia and genetic factors. Statins and emerging lipid-modifying agents show potential but lack evidence for migraine management. Mendelian Randomization analysis offers insights into causal relationships and therapeutic targets. This study aims to explore genetically predicted lipid traits, drug targets, and their association with migraine risk.MethodWe conducted Mendelian randomization (MR) analyses utilizing genetic variants associated with lipid traits and variants in genes encoding the protein targets of various classes of lipid-lowering drugs. The specific drug classes investigated included HMGCR, PCSK9, NPC1L1, ABCG5/ABCG8, LDLR, LPL, ANGPTL3, APOB, CETP, and APOC3. To determine the effects on migraine risk, we meta-analyzed MR estimates for regional variants using data from two large sample sets. The genetic variants were weighted based on their associations with specific lipid traits, such as low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), Apolipoprotein A1, and Apolipoprotein B. To obtain association weights, we utilized data from lipid genetics consortia. For lipid-modifying drug targets that exhibited suggestive significance, we further employed expression quantitative trait locus (eQTL) data. Additionally, we performed colocalization analysis to assess genetic confounding.ResultThe use of genetic proxies for HMGCR inhibition demonstrated a significant association with a decreased risk of migraine in the FinnGen dataset (OR = 0.64, 95% CI: 0.46–0.88, p = 0.0006) and a nearly significant association in the Choquet dataset (OR = 0.78, 95% CI: 0.60–1.01, p = 0.06). When pooling the estimates, the overall effect size showed a reduced risk of migraine (OR = 0.73, 95% CI: 0.60–0.89, p = 0.0016). Similarly, genetic mimicry of LPL enhancement was associated with a lower risk of migraine in the FinnGen dataset (OR = 0.82, 95% CI: 0.69–0.96, p = 0.01) and the Choquet dataset (OR = 0.91, 95% CI: 0.83–0.99, p = 0.03). Pooling the estimates showed a consistent effect size (OR = 0.89, 95% CI: 0.83–0.96, p = 0.002). Sensitivity analyses yielded no statistically significant evidence of bias arising from pleiotropy or genetic confounding.ConclusionIn the study, it was observed that among the 10 lipid-lowering drug targets investigated, LPL and HMGCR showed significant associations with migraine risk. These findings indicate that LPL and HMGCR have the potential to serve as candidate drug targets for the treatment or prevention of migraines.

Risks associated with use of statins and other lipid-modifying agents across pregnancy – A nationwide drug safety study in Norway in 2005-2018

Risks associated with use of statins and other lipid-modifying agents across pregnancy – A nationwide drug safety study in Norway in 2005-2018

Guideline-Directed Low-Density Lipoprotein Cholesterol Management After Acute Ischemic Stroke: Findings from a National Health Care Service

Patients with ischemic stroke are at high risk for future cardiovascular events and should be treated intensively with lipid-modifying agents. Combination lipid-lowering therapies are often needed to achieve updated guideline-directed treatment goals. However, real-world data on intensification of lipid-lowering therapies and attainment of low-density lipoprotein cholesterol (LDL-C) targets early after ischemic stroke are limited. We extracted data from the largest healthcare provider in Israel on patients hospitalized with acute ischemic stroke between January 2020 and February 2022. Included were 3,027 patients surviving ≥1 year after stroke, with documented LDL-C levels and lipid-lowering medications at 2 time periods (0 to 3months and 6 to 12months after discharge). Participants were classified according to preexisting stroke and/or coronary artery disease. The use of combination lipid-lowering therapy (ezetimibe and/or proprotein convertase subtilisin/kexin type 9 [monoclonal antibodies] inhibitor plus statin) in the study population increased between the 2 timepoints from 3.6% to 5.1%, reaching 10.5% in those with previous coronary artery disease and stroke. LDL-C levels <70 and <55mg/100ml were attained by 42.3% and 22.9% of patients early after hospitalization, and in 49.5% and 27.1% during 6 to 12months after hospitalization, respectively. Attainment of guideline-recommended LDL-C goals was higher in patients treated with combination lipid-lowering therapies and in those with preexisting cardiovascular disease. In conclusion, despite the advances in drug development and the availability of several mechanisms to lower cholesterol levels, the attainment of guideline-recommended LDL-C targets after acute ischemic stroke is suboptimal. Intensification of treatment with combination lipid-lowering therapies after hospitalization is uncommonly performed in clinical practice, even in those with preexisting cardiovascular disease.

Current Management and Future Perspectives in the Treatment of Lp(a) with a Focus on the Prevention of Cardiovascular Diseases.

Lipoprotein(a) [Lp(a)] is a lipid molecule with atherogenic, inflammatory, thrombotic, and antifibrinolytic effects, whose concentrations are predominantly genetically determined. The association between Lp(a) and cardiovascular diseases (CVDs) has been well-established in numerous studies, and the ability to measure Lp(a) levels is widely available in the community. As such, there has been increasing interest in Lp(a) as a therapeutic target for the prevention of CVD. The impact of the currently available lipid-modifying agents on Lp(a) is modest and heterogeneous, except for the monoclonal antibody proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i), which demonstrated a significant reduction in Lp(a) levels. However, the absolute reduction in Lp(a) to significantly decrease CVD outcomes has not been definitely established, and the magnitude of the effect of PCSK9i seems insufficient to directly reduce the Lp(a)-related CVD risk. Therefore, emerging therapies are being developed that specifically aim to lower Lp(a) levels and the risk of CVD, including RNA interference (RNAi) agents, which have the capacity for temporary and reversible downregulation of gene expression. This review article aims to summarize the effects of Lp(a) on CVD and to evaluate the available evidence on established and emerging therapies targeting Lp(a) levels, focusing on the potential reduction of CVD risk attributable to Lp(a) concentrations.

Treatment of High Blood Pressure is associated with a Reduced Incidence of Parkinson’s disease (S42.007)

<h3>Objective:</h3> We performed an agnostic drug-wide association study (DWAS) in Norway estimating the association between all drugs prescribed in Norway and the subsequent incidence of Parkinson’s disease (PD). <h3>Background:</h3> Several drugs including treatments for cardiovascular diseases have been associated with a reduced incidence of PD. <h3>Design/Methods:</h3> We employed data on drug use in the entire Norwegian population from 2004 to 2019 (4.6 million) registered in the Norwegian Prescription Registry, including more than 600 million individual prescriptions. Drug classes were screened according to ATC codes at level 2, corresponding to therapeutic subgroups. Individuals who developed PD during the 15 years of follow-up (n=15,849) were identified using an algorithm based on drugs prescribed to treat the disease. Cox regression models with exposure as time-dependent variable were specified, and all p-values were corrected for multiple testing using the false discovery rate. <h3>Results:</h3> We found several novel associations between drug classes and the incidence of PD including a <i>decreased</i> incidence of PD among users of drugs acting on the renin-angiotensin system (0.86, 95%CI: 0.83–0.89). We also found an inverse association between calcium channel blockers and PD incidence, but we could not confirm the previously reported association between lipid-modifying agents and PD. Further, beta blocking agents and drugs for cardiac therapy were associated with an <i>increased</i> PD incidence. We also found increased PD incidence for drugs used in the treatment of prodromal symptoms of PD, including urologicals, drugs for constipation, anti-psychotics, and antidepressants. <h3>Conclusions:</h3> We observed two large drug classes of anti-hypertensives being associated with a subsequent reduced incidence of PD. The finding of two other cardiovascular drug classes being associated with an <i>increased</i> PD incidence calls for more detailed epidemiological studies and experimental studies to elucidate possible mechanisms. <b>Disclosure:</b> Trond Riise has nothing to disclose. Mr. Solheim has nothing to disclose. The institution of Dr. Bjornevik has received research support from Michael J. Fox Foundation. The institution of Dr. Bjornevik has received research support from National Multiple Sclerosis Society. The institution of Dr. Bjornevik has received research support from Department of Defense. Dr. Igland has nothing to disclose. Miss Tuominen has nothing to disclose. Dr. Abolpour Mofrad has nothing to disclose. Dr. Cortese has received personal compensation in the range of $500-$4,999 for serving as a speaker at educational event with Roche. Dr. Scherzer has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sanofi. The institution of Dr. Scherzer has received research support from NIH. The institution of Dr. Scherzer has received research support from Michael J. Fox Foundation. The institution of Dr. Scherzer has received research support from American Parkinson’s Disease Association. Dr. Scherzer has received intellectual property interests from a discovery or technology relating to health care. Mrs. Romanowska has nothing to disclose.

Patients' Perceived Importance of Medication and Adherence in Polypharmacy, a Quantitative, Cross-Sectional Study Using a Questionnaire Administered in Three Doctors' Private Practices in France.

Among the determinants of nonadherence, polypharmacy (common in people with multiple pathologies and especially in elderly patients), plays a major role. In patients who are subject to polypharmacy involving different classes of medications, the first aim is to assess the impact of medication importance given by patients on (i) medication adherence and (ii) the respective effect of intentionality and habit in medication importance and medication adherence. The second objective is to compare the importance given to medication and adherence in the different therapeutic classes. Patients taking 5-10 different medications for at least 1 month were included in a cross-sectional survey in three private practices in one region in France. This study included 130 patients (59.2 % female) with 851 medications in total. The mean ± standard deviation (SD) age was 70.5 ± 12.2 years. The mean ± SD of medications taken was 6.9 ± 1.7. Treatment adherence had a strong positive correlation with the patient-perceived medication importance (p < 0.001). Counter-intuitively, taking a large number of medications (≥7) was associated with being fully adherent (p = 0.02). A high intentional nonadherence score was negatively associated with high medication importance (p = 0.003). Furthermore, patient-perceived medication importance was positively associated with taking treatment by habit (p = 0.03). Overall nonadherence more strongly correlated with unintentional nonadherence (p < 0.001) than with intentional nonadherence (p = 0.02). Compared to the antihypertensive class, a decrease in adherence by medication was observed in psychoanaleptics (p < 0.0001) and drugs used in diabetes class (p = 0.002), and a decrease in importance in lipid-modifying agents class (p = 0.001) and psychoanaleptics (p < 0.0001). The perception of the importance of a medicine is associated with the place of intentionality and habit in patient adherence. Therefore, explaining the importance of a medicine should become an important part of patient education.

Associations of genetically determined lipid traits and lipid-modifying agents with the risk of diabetic retinopathy: A Mendelian randomization study

Background and aimsThe evidence that dyslipidemia is associated with hyperglycemia calls for an investigation of whether dyslipidemia, as well as lipid-modifying agents, could affect the subsequent development of diabetic retinopathy (DR). Therefore, we aimed to address these unanswered questions by utilizing Mendelian randomization (MR) analysis. MethodsGenetic variants were selected from the UK Biobank as instruments to serve as proxies for lipid traits [high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), apolipoprotein A-I (APOA-I) and apolipoprotein B (APOB)]. Univariable and multivariable MR analyses were performed to examine the associations of these lipid traits with DR and different levels of severity of DR. Based on the evidence for the effects of lipids on outcomes, we estimated the causal relevance of cholesteryl ester transfer protein (CETP) inhibitors in severe nonproliferative and proliferative DR using protein quantitative trait loci (pQTLs) and expression quantitative trait loci (eQTLs) as instruments. ResultsGenetically determined HDL-C levels were inversely associated with the risk of severe nonproliferative DR (OR = 0.70, 95% CI = 0.52–0.94) and proliferative DR (OR = 0.90, 95% CI = 0.83–0.97) in the main analyses utilizing the inverse variance-weighted (IVW) MR method and a couple of sensitivity analyses. No association was noted between genetically proxied CETP inhibitors and DR. ConclusionsThis MR study suggests the casual protective roles of HDL-C in severe nonproliferative DR and proliferative DR, which calls for further studies to confirm these findings. Current lipid-modifying agents acting on HDL-C may not reduce the risk of DR and new treatments are required in the future.

Drug binding and drug-drug interaction considerations in individuals with obesity before and after bariatric surgery: A retrospective cross-sectional study

Obesity impacts pharmacokinetic and pharmacodynamic parameters, changing the drug-binding state via plasma proteins, which is critical for drug effectiveness and toxicity. Albumin and α1-acid glycoprotein (AAG) are the two main proteins accountable for drug binding in humans. Previous studies have shown higher values of AAG in individuals with obesity, but the interference of AAG in the pharmacokinetics of drugs remains unclear. We, therefore, aimed to analyze the pharmacotherapeutic profile and interfering factors in patients undergoing bariatric surgery in the pre-operative period and after 12 months. A retrospective cross-sectional study design was conducted and serum AAG was determined, and potential drug-drug interactions were monitored in patients with severe obesity who underwent bariatric surgery. The drug classes most used were antidepressants, cardiovascular agents, and lipid-modifying agents, with a decrease in use after 12 months of surgery. Before surgery, it was found that more than half of the patients had at least one drug interaction in their therapeutic regimen. Of these, most were classified as moderate. After surgery, a decrease in drug interaction was observed. Serum AAG showed a significant reduction after 12 months, which can influence the free fraction of drugs with a high-affinity rate and how they impact therapeutic efficacy.

Atherogenic Dyslipidemias: Unmet Needs and the Therapeutic Potential of Emerging and Novel Approaches and Drugs.

Innovative lipid-modifying agents are valuable resources to improve the control of atherogenic dyslipidemias and reduce the lipid-related residual cardiovascular risk of patients with intolerance or who are not fully responsive to a consolidated standard of care (statins plus ezetimibe). Moreover, some of the upcoming compounds potently affect lipid targets that are thus far considered "unmodifiable". The present paper is a viewpoint aimed at presenting the incremental metabolic and cardiovascular benefits of the emerging lipid-modulating agents and real-life barriers, hindering their prescription by physicians and their assumption by patients, which need to be worked out for a more diffuse and appropriate drug utilization.