Impact of prescription length supply policy on patient medication adherence in Thailand.

BACKGROUND: Phramongkutklao Hospital is one of the largest military hospitals in Thailand. Beginning in 2016, an institutional policy was implemented in which medication prescription length was increased from 30 to 90 days. However, there have been no formal investigations into how this policy has impacted medication adherence among patients in hospitals. As such, this study evaluated how prescription length impacted medication adherence among dyslipidemia and type-2 diabetes patients who were treated at Phramongkutklao Hospital. METHODS: This pre-post implementation study compared patients who received prescription lengths of 30 and 90 days based on information recorded in the hospital database between 2014 and 2017. Therein, we used the medication possession ratio (MPR) to estimate patient adherence. Focusing on patients with universal coverage insurance, we employed the difference-in-difference method to examine changes in adherence from before and after policy implementation, then conducted a logistic regression to test for associations between the predictors and adherence. RESULTS: We analyzed data from a total of 2,046 patients, with equal amounts of 1,023 placed into the control group (no change to 90-day prescription length) and intervention group (change from 30 to 90-day prescription length). First, we found that increased prescription length was associated with 4% and 5% higher MPRs among dyslipidemia and diabetes patients in the intervention group, respectively. Second, we found that medication adherence was correlated with sex, comorbidities, history of hospitalization, and the number of prescribed medications. CONCLUSION: Increasing the prescription length from 30 to 90 days improved medication adherence in both the dyslipidemia and type-2 diabetes patients. This shows that the policy change was successful for patients in the hospital considered for this study.

Switching, Persistence and Adherence to Statin Therapy: a Retrospective Cohort Study Using the Australian National Pharmacy Data.

BACKGROUND: Statins are widely prescribed for the primary and secondary prevention of cardiovascular disease (CVD), but their effectiveness is dependent on the level of adherence and persistence. OBJECTIVES: This study aimed to explore the patterns of switching, adherence and persistence among the Australian general population with newly dispensed statins. METHODS: A retrospective cohort study was conducted using a random sample of data from the Australian national prescription claims data. Switching, adherence to and persistence with statins were assessed for people starting statins from 1 January 2015 to 31 December 2019. Switching was defined as either switching to another intensity of statin, to another statin or to a non-statin agent. Non-persistence to treatment was defined as discontinuation (i.e. ≥90 days with no statin) of coverage. Adherence was measured using proportion of days covered (PDC), and patients with PDC < 0.80 were considered non-adherent. Cox proportional hazard models were used to compare discontinuation, switching and reinitiation between different statins. RESULTS: A cohort of 141,062 people dispensed statins and followed over a median duration of 2.5 years were included. Of the cohort, 29.3% switched statin intensity, 28.4% switched statin type, 3.7% switched to ezetimibe and in 2.7%, ezetimibe was added as combination therapy during the study period. Overall, 58.8% discontinued statins based on the 90-day gap criteria, of whom 55.2% restarted. The proportion of people non-adherent was 24.0% at 6 months to 49.0% at 5 years. People on low and moderate intensity statins were more likely to discontinue compared to those on high-intensity statins (hazard ratio [HR] 1.20, 95% confidence interval [CI] 1.09-1.31), (HR 1.28, 95%CI 1.14-1.42), respectively. Compared to maintaining same statin type and intensity, switching statins, which includes up-titration (HR 0.77, 95%CI 0.70 to 0.86) was associated with less likelihood of discontinuation after reinitiation. CONCLUSIONS: Long-term persistence and adherence to statins remains generally poor among Australians, which limits the effectiveness of these medicines and the consequent health impact they may provide for individuals (and by extension, the population impact when poor persistence and adherence is considered in the statin-taking population). Switching between statins is prevalent in one third of statin users, although any clinical benefit of the observed switching trend is unknown. This, combined with the high volume of statin prescriptions, highlights the need for better strategies to address poor persistence and adherence.

Does adherence to lipid-lowering medications improve cancer survival? A nationwide study of breast and colorectal cancer, and melanoma.

AIMS: Inconclusive findings of lipid-lowering medications (LLMs) on cancer survival benefit require more evidence. We tested the hypothesis that adherence to this drug is associated with reduced cancer-specific mortality in a homogeneous population who had used this drug before cancer diagnosis. METHODS: The Australian Cancer Database was linked to the Pharmaceutical Benefits Scheme database, and to the National Death Index (up to 2015). Medication adherence was calculated by proportion of days covered. Cox regression models with time-varying covariates were used to derive multivariable-adjusted cause-specific hazard ratio (HR) and 95% confidence interval (CI) for the associations between adherence to LLMs, statins, lipophilic, and hydrophilic statins and cancer-specific mortality. RESULTS: From 2003 to 2013, 3 separate cohorts of 20 046, 11 719 and 6430 female patients with newly diagnosed breast, colorectal cancer, and melanoma respectively were identified. The 1-year adherence was similar at 1-year prediagnosis in the 3 cohorts, on average 82%. Each 10% increase in 1-year adherence to LLMs was inversely associated with cancer-specific mortality among women with breast cancer (fully adjusted HR = 0.92, 95% CI 0.91-0.93), colorectal cancer (fully adjusted HR = 0.92, 95% CI 0.91-0.93), or melanoma (fully adjusted HR = 0.97, 95% CI 0.94-1.00). The reductions in cancer-specific mortality were more pronounced for women who adhered to lipophilic than hydrophilic statins in all 3 cancers albeit not statistically significant for melanoma. CONCLUSION: Among LLM users, adherence to this drug is associated with a decrease in cancer-specific mortality. If confirmed, LLMs could be considered as an adjuvant cancer therapy to improve prognosis in cancer survivors.

Prescription of lipid-lowering medications for patients with type 2 diabetes mellitus and risk-associated LDL cholesterol: a nationwide study of guideline adherence from the Swedish National Diabetes Register.

BACKGROUND: Management of type 2 diabetes mellitus (T2DM) encompasses intensive glycaemic control, along with treatment of comorbidities and complications to handle the increased risk of cardiovascular disease (CVD). Improved control of LDL-cholesterol (LDL-C) with lipid-lowering medications is associated with reduced CVD risk in T2DM patients. Thus, treatment guidelines recommend lipid-lowering medications for T2DM patients with LDL-C above risk-associated thresholds. This study aimed to assess healthcare provider adherence to guidelines regarding lipid-lowering medication prescription among T2DM patients and to analyse factors associated with lipid-lowering medication prescription. METHODS: Observations in 2007 - 2014 for T2DM patients age ≥ 18 were collected from the Swedish National Diabetes Register. Observations were excluded if they lacked information about LDL-C, lipid-lowering medication prescription or CVD. Observations with established CVD were attributed to secondary prevention; remaining observations were attributed to primary prevention. The analyses included primary and secondary prevention observations with LDL-C above risk-associated thresholds (LDL-C ≥ 2.5 mmol/l and LDL-C ≥ 1.8 mmol/l respectively). Guideline adherence was analysed as the probability of prescribing lipid-lowering medications using mixed-effect model regression adjusted for potential confounders. Factors associated with prescribing lipid-lowering medications were analysed for patient and healthcare provider characteristics using mixed-effect model regression and odds ratio. RESULTS: A total of 1,204,376 observations from 322,046 patients reported by 1352 healthcare providers were included. Primary prevention accounted for 63%; 52% were men, mean age was 64 and mean LDL-C was 3.4 mmol/l. For secondary prevention, 60% were men, mean age was 72 and mean LDL-C was 2.7 mmol/l. During 2007-2014, guideline adherence ranged from 36 to 47% for primary prevention and 59 to 69% for secondary prevention. In general, concomitant prescription of diabetes medications, antiplatelets and antihypertensives along with smoking and specialised care were associated with higher prescription of lipid-lowering medications. Patients age ≥ 80 were associated with lower prescription of lipid-lowering medications. Higher prescription was associated with longer diabetes duration in primary prevention and men in secondary prevention. CONCLUSIONS: Adherence to treatment guidelines levelled off after an initial increase in both prevention groups. Lipid-lowering medication prescription was based on individualised CVD risk.

Impact of statin use on cancer recurrence and mortality in breast cancer: A systematic review and meta-analysis.

Statins have shown antineoplastic properties in preclinical studies with breast cancer cells. They inhibit the enzyme "HMG CoA reductase" and the expression of this enzyme in cancer cells has been implicated as a favorable prognostic factor in patients with breast cancer. After a search of MEDLINE and Embase from inception through November 2015, 817 abstracts were reviewed to identify studies that described an association between statin use and outcomes in breast cancer. A total of 14 studies which included 75,684 women were identified. In a meta-analysis of 10 studies, statin use was associated with improved recurrence-free survival (RFS; HR 0.64; 95% CI 0.53-0.79, I(2) = 44%). Furthermore, this RFS benefit appeared to be confined to use of lipophilic statins (HR 0.72; 95% CI 0.59-0.89) as hydrophilic statin use was not associated with improvement in RFS (HR 0.80; 95% CI 0.44-1.46). Statin users similarly showed improved overall survival in a meta-analysis with substantial heterogeneity (8 studies, HR 0.66; 95% CI 0.44-0.99, I(2) = 89%). Statin users also had improved cancer-specific survival, although this relationship was measured with less precision (six studies, HR 0.70; 95% CI 0.46-1.06, I(2) = 86%). In conclusion, breast cancer patients who use statins, or specifically, lipophilic statins show improved recurrence-free survival. Statin users also had improved overall survival and cancer-specific survival. These findings should be assessed in a prospective randomized cohort and the choice of statin, dose and biomarkers that may predict the efficacy of these drugs should be identified.

Effect of lipid-lowering therapy on carotid plaque burden in older adults.

BACKGROUND: Little is known about the benefits of lipid-lowering medications in those age ≥ 75 years. We assessed the effect of lipid-lowering medications on progression to severe atherosclerosis in patients age > 75. METHODS: Data was retrospectively obtained from the Stroke Prevention & Atherosclerosis Research Centre, Canada. Atherosclerosis burden was measured as carotid total plaque area (TPA), a powerful predictor of cardiovascular risk. Survival time free of severe atherosclerosis (SFSA) was defined as the period when TPA remained <1.19 cm2. Kaplan-Meier, multiple Cox proportional hazard and hierarchical mixed-effect models were used to determine the effects of lipid-lowering medications on progression to severe atherosclerosis. RESULTS: In total 1404 cases (mean age 81 ± 4 years; women 52%) were included. Those taking lipid-lowering medications were more likely to have a history of diabetes and a higher burden of atherosclerosis at baseline. In Kaplan-Meier analysis, the SFSA was significantly longer in those receiving lipid-lowering therapy. In multivariable-adjusted analyses, those not receiving lipid lowering therapy (irrespective of their vascular disease at baseline) were more likely to have TPA > 1.19 cm2 (hazard ratio (HR) = 1.37, 95% confidence interval (CI): 1.09,0.71). Similar findings were observed in mixed effects models when plaque progression was defined as any change >0.05 cm2 per year (odds ratio (OR):2.17, 95% CI:1.38,3.57). CONCLUSION: Lipid-lowering therapy is effective in controlling the burden of atherosclerosis among older adults with and without vascular disease. The measurement of plaque burden can guide selection and follow-up of those who may benefit from treatment.

Analyzing the causal relationship between lipid-lowering drug target genes and epilepsy: a Mendelian randomization study.

Background: Previous research has yielded conflicting results on the link between epilepsy risk and lipid-lowering medications. The aim of this study is to determine whether the risk of epilepsy outcomes is causally related to lipid-lowering medications predicted by genetics. Methods: We used genetic instruments as proxies to the exposure of lipid-lowering drugs, employing variants within or near genes targeted by these drugs and associated with low-density lipoprotein cholesterol (LDL cholesterol) from a genome-wide association study. These variants served as controlling factors. Through drug target Mendelian randomization, we systematically assessed the impact of lipid-lowering medications, including HMG-CoA reductase (HMGCR) inhibitors, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, and Niemann-Pick C1-like 1 (NPC1L1) inhibitors, on epilepsy. Results: The analysis demonstrated that a higher expression of HMGCR was associated with an elevated risk of various types of epilepsy, including all types (OR = 1.17, 95% CI:1.03 to 1.32, p = 0.01), focal epilepsy (OR = 1.24, 95% CI:1.08 to 1.43, p = 0.003), and focal epilepsy documented with lesions other than hippocampal sclerosis (OR = 1.05, 95% CI: 1.01 to 1.10, p = 0.02). The risk of juvenile absence epilepsy (JAE) was also associated with higher expression of PCSK9 (OR = 1.06, 95% CI: 1.02 to 1.09, p = 0.002). For other relationships, there was no reliable supporting data available. Conclusion: The drug target MR investigation suggests a possible link between reduced epilepsy vulnerability and HMGCR and PCSK9 inhibition.

Lipid-lowering medications and risk of malignant melanoma: a Mendelian randomization study.

Background: The relationship between blood lipids, lipid-modifying medications, and cancer risk has been under investigation for some time. Recent studies suggest that lipid-lowering medications might influence melanoma outcomes, though findings remain controversial. Our study aims to clarify the potential causal relationship between lipid-lowering drugs commonly used and melanoma incidence through a comprehensive Mendelian randomization (MR) analysis. Methods: Genetic variations within an LDL-related drug target gene (LDL-cholesterol from a genome-wide association study) served as proxies for exposure to lipid-lowering drugs. We conducted a two-sample Mendelian randomization analysis using inverse variance weighting (IVW), MR-Egger, and weighted median approaches. The MR-PRESSO test and pleiotropy_test were utilized to identify and adjust for horizontal pleiotropy. Stability and reliability of the Mendelian randomization findings were assessed using the leave-one-out method, Cochran's Q test, and funnel plot analysis. Odds ratios (OR) were employed to evaluate the causal relationship between genetic proxies of lipid-lowering drugs and melanoma risk. Results: IVW analysis revealed that HMGCR gene expression is linked to a decreased risk of melanoma [OR: 0.624(0.439-0.888); p = 0.008]. Conversely, PCSK9 gene expression is tied to an elevated risk of melanoma [OR: 1.233(1.026-1.484); p = 0.025]. No significant association was observed between NPC1L1 and melanoma. Conclusions: HMGCR inhibitors (statins) may increase melanoma risk, while PCSK9 inhibitors (evolocumab, alirocumab) could potentially decrease melanoma risk.

Lipid-Lowering Medications for Managing Dyslipidemia: A Narrative Review.

Dyslipidemia refers to the change in the normal levels of one or more lipid components in the bloodstream, which include triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C). Dyslipidemia represents a substantial source of danger for cardiovascular disease (CVD). Effectively managing dyslipidemia involves a thorough strategy that includes changing one's lifestyle and using medications that are specifically designed to target the complex processes involved in lipid metabolism. Lipid-lowering treatments play a crucial role in this approach, providing a wide range of medications that are developed to specifically target different components of dyslipidemia. Statins are the main drug among these medications. Other drugs that are used with statin or as monotherapy include fibrates, omega-3 fatty acids (OM3FAs), ezetimibe, bile acid sequestrants, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, and bempedoic acid. Using the PubMed database, we reviewed the literature about dyslipidemia, drugs used for treating dyslipidemia, their efficacy parameters, and common adverse events. We also reviewed the international guidelines for treating dyslipidemia and discussed the future of lipid-lowering medications. More trials and experiments are still required to verify the effectiveness of many lipid-lowering drugs and to know their common adverse events to be able to manage them properly.

Longitudinal associations between use of antihypertensive, antidiabetic, and lipid-lowering medications and biological aging.

Aging is a major risk factor for many chronic diseases. This study aimed to examine the effects of antihypertensive, lipid-lowering, and antidiabetic drugs on biological aging. We included 672 participants and 2746 repeated measurements from the Swedish Adoption/Twin Study of Aging. Self-reported medicine uses were categorized into antidiabetic, antihypertensive, and lipid-lowering drugs. A total of 12 biomarkers for biological aging (BA biomarkers) were included as outcomes. Conditional generalized estimating equations were applied conditioning on individuals to estimate the drug effect on BA biomarker level within the same person when using or not using the drug. Chronological age, body mass index, smoking status, number of multiple medication uses, blood pressure, blood glucose level, and apoB/apoA ratio were adjusted for as covariates in the model. Overall, using antihypertensive drugs was associated with a decrease in one DNA-methylation age (PCGrimAge: beta = - 0.39, 95%CI = - 0.67 to - 0.12). When looking into drug subcategories, calcium channel blockers (CCBs) were associated with a decrease in several DNA-methylation ages (PCHorvathAge beta = - 1.28, 95%CI = - 2.34 to - 0.21; PCSkin&bloodAge beta = - 1.34, 95%CI = - 2.61 to - 0.07; PCPhenoAge beta = - 1.74, 95%CI = - 2.58 to - 0.89; PCGrimAge beta = - 0.57, 95%CI = - 0.96 to - 0.17) and in functional biological ages (functional age index beta = - 2.18, 95%CI = - 3.65 to - 0.71; frailty index beta = - 1.31, 95%CI = - 2.43 to - 0.18). However, the results within other drug subcategories were inconsistent. Calcium channel blockers may decrease biological aging captured by the BA biomarkers measured at epigenetic and functional level. Future studies are warranted to confirm these effects and understand the underlying biological mechanisms.

Attainment of Low-Density Lipoprotein Cholesterol Targets and Prescribing Pattern of Lipid-Lowering Medications among Patients with Familial Hypercholesterolemia Attending Specialist Clinics.

AIMS: Patients with familial hypercholesterolemia (FH) are known to have higher exposure to coronary risk than those without FH with similar low-density lipoprotein cholesterol (LDL-C) level. Lipid-lowering medications (LLMs) are the mainstay treatments to lower the risk of premature coronary artery disease in patients with hypercholesterolemia. However, the LLM prescription pattern and its effectiveness among Malaysian patients with FH are not yet reported. The aim of this study was to report the LLM prescribing pattern and its effectiveness in lowering LDL-C level among Malaysian patients with FH treated in specialist hospitals. METHODS: Subjects were recruited from lipid and cardiac specialist hospitals. FH was clinically diagnosed using the Dutch Lipid Clinic Network Criteria. Patients' medical history was recorded using a standardized questionnaire. LLM prescription history and baseline LDL-C were acquired from the hospitals' database. Blood samples were acquired for the latest lipid profile assay. RESULTS: A total of 206 patients with FH were recruited. Almost all of them were on LLMs (97.6%). Only 2.9% and 7.8% of the patients achieved the target LDL-C of ＜1.4 and ＜1.8 mmol/L, respectively. The majority of patients who achieved the target LDL-C were prescribed with statin-ezetimibe combination medications and high-intensity or moderate-intensity statins. All patients who were prescribed with ezetimibe monotherapy did not achieve the target LDL-C. CONCLUSION: The majority of Malaysian patients with FH received LLMs, but only a small fraction achieved the therapeutic target LDL-C level. Further investigation has to be conducted to identify the cause of the suboptimal treatment target attainment, be it the factors of patients or the prescription practice.

Gene transfer and genome editing for familial hypercholesterolemia.

Familial hypercholesterolemia (FH) is an autosomal dominant inherited disease characterized by high circulating low-density lipoprotein (LDL) cholesterol. High circulating LDL cholesterol in FH is due to dysfunctional LDL receptors, and is mainly expressed by hepatocytes. Affected patients rapidly develop atherosclerosis, potentially leading to myocardial infarction and death within the third decade of life if left untreated. Here, we introduce the disease pathogenesis and available treatment options. We highlight different possible targets of therapeutic intervention. We then review different gene therapy strategies currently under development, which may become novel therapeutic options in the future, and discuss their advantages and disadvantages. Finally, we briefly outline the potential applications of some of these strategies for the more common acquired hypercholesterolemia disease.

National Trends in the Use of State-Reimbursed Lipid-Lowering Medications in Latvia (2012-2021).

BACKGROUND: We aimed to estimate the trends in dispensing rate and the spectrum of all state-funded lipid-lowering medications (LLMs) in Latvia over a decade. METHODS: Using data from the National Health Service of the Republic of Latvia, we retrospectively analyzed all dispensed LLM-containing drug units in a ten-year period from 2012 to 2021. RESULTS: In Latvia, 318.2 million oral and 994 subcutaneous units of LLMs were dispensed over a decade. Statins were the most dispensed LLMs (94.5%), and their use doubled from 19.7 to 43.5 million units. The proportion of high-intensity statins increased from 31.3% to 45.2%. The dispensing rate of ezetimibe increased from 184.7 thousand to 4.8 million. The share of fixed-dose statin combinations with ezetimibe grew from 0.2% to 10.0% among all statins and from 22.2% to 90.9% among all ezetimibe units. Statin use for primary and secondary prevention increased from 7.0 to 19.9 million and from 12.8 to 23.6 million units, respectively. CONCLUSION: The dispensing rate of statins doubled, and the use of ezetimibe increased more than 25 times in Latvia over a decade. The proportion of high-intensity statins increased from one third to almost half of all statins. Fixed-dose statin combinations with ezetimibe became frequently used.

Phase 2b Randomized Trial of the Oral PCSK9 Inhibitor MK-0616.

BACKGROUND: MK-0616 is an oral macrocyclic peptide inhibitor of proprotein convertase subtilisin/kexin type 9 (PCSK9) in development for the treatment of hypercholesterolemia. OBJECTIVES: This Phase 2b, randomized, double-blind, placebo-controlled, multicenter trial aimed to evaluate the efficacy and safety of MK-0616 in participants with hypercholesterolemia. METHODS: This trial was planned to include 375 adult participants with a wide range of atherosclerotic cardiovascular disease risk. Participants were assigned randomly (1:1:1:1:1 ratio) to MK-0616 (6, 12, 18, or 30 mg once daily) or matching placebo. The primary endpoints included percentage change from baseline in low-density lipoprotein cholesterol (LDL-C) at Week 8 and the proportion of participants with adverse events (AEs) and study intervention discontinuations due to AEs; participants were monitored for AEs for an additional 8 weeks after the 8-week treatment period. RESULTS: Of the 381 participants randomized, 49% were female, and the median age was 62 years. Among 380 treated participants, all doses of MK-0616 demonstrated statistically significant (P < 0.001) differences in least squares mean percentage change in LDL-C from baseline to Week 8 vs placebo: -41.2% (6 mg), -55.7% (12 mg), -59.1% (18 mg), and -60.9% (30 mg). AEs occurred in a similar proportion of participants in the MK-0616 arms (39.5% to 43.4%) as placebo (44.0%). Discontinuations due to AEs occurred in 2 or fewer participants in any treatment group. CONCLUSIONS: MK-0616 demonstrated statistically significant and robust, dose-dependent placebo-adjusted reductions in LDL-C at Week 8 of up to 60.9% from baseline and was well tolerated during 8 weeks of treatment and an additional 8 weeks of follow-up. (A Study of the Efficacy and Safety of MK-0616 [Oral PCSK9 Inhibitor] in Adults With Hypercholesterolemia [MK-0616-008]; NCT05261126).

Interactions of radiation therapy with common and innovative systemic treatments: Antidiabetic treatments, antihypertensives, lipid-lowering medications, immunosuppressive medications and other radiosensitizing methods.

The invention and approval of innovative anticancer therapies in the last decade have revolutionized oncology treatment. Radiotherapy is one of the three traditional pillars in oncology treatment with surgery and systemic therapies. Some standard-of-care combinations of chemoradiotherapy widened the therapeutic window of radiation, while some other chemotherapies such as gemcitabine caused unacceptable toxicities when combined with radiation in lung cancers. Fast-paced progress are specially focused on immunotherapies, targeted-therapies, anti-angiogenic treatment, DNA repair inhibitors, hormonotherapy and cell cycle inhibitors. New anticancer therapeutic arsenals provided new possibilities of combined oncological treatments. The interactions of the radiotherapy with other systemic treatments, such as non-anticancer immunomodulatory/immunosuppressive medications are sometimes overlooked even though they could offer a real therapeutic benefit. In this review, we summarize the new opportunities and the risks of historical and novel combined therapies with radiation: non-anticancer immunomodulatory/immunosuppressive drugs, systemic reoxygenation, new therapies such as nanoparticles and SMAC mimetics. Key biological mechanisms, pre-clinical and available clinical data will be provided to demonstrate the promising opportunities in the years to come.

Risk of rheumatoid arthritis diagnosis in statin users in a large nationwide US study.

OBJECTIVE: To evaluate the association between statin use and the risk of developing rheumatoid arthritis (RA) in a large, US case-control study. METHODS: Using the OptumLabs Data Warehouse, RA cases were identified as patients aged ≥18 years with ≥2 RA diagnoses between January 1, 2010 and June 30, 2019 and ≥1 prescription fills for methotrexate within 1 year of the first RA diagnosis. The first RA diagnosis was the index date. Cases were matched 1:1 to controls on age, sex, region, year of index date, and length of baseline coverage. Statin users were defined by having ≥2 statin prescription fills at least 90 days pre-index. Patients identified as statin users were further classified by statin user status (current or former), statin use duration, and intensity of statin exposure. Odds ratios for RA risk with statin use were estimated using logistic regression. RESULTS: 16,363 RA cases and 16,363 matched controls were identified. Among RA cases, 5509 (33.7%) patients were statin users compared to 5164 (31.6%) of the controls. Statin users had a slightly increased risk of RA compared to non-users (OR 1.12, 95% CI 1.06-1.18), and former statin users had an increased RA risk compared to current users (OR 1.21, 95% CI 1.13-1.28). However, risk was eliminated following adjustment for hyperlipidemia. The risk estimates for statin use duration and intensity did not reach significance. CONCLUSION: This study demonstrates no significant increase in the risk of developing RA for statin users compared to non-users after adjustment for hyperlipidemia in addition to other relevant confounders. However, more information from prospective studies would be necessary to further understand this relationship.

Lysosomal Acid Lipase Deficiency: Therapeutic Options.

Lysosomal acid lipase (LAL) deficiency is a metabolic (storage) disorder, encompassing a severe (Wolman disease) and attenuated (Cholesterol ester storage disease) subtype; both inherited as autosomal recessive traits. Cardinal clinical features include the combination of hepatic dysfunction and dyslipidemia, as a consequence of cholesteryl esters and triglyceride accumulation, predominately in the liver and vascular and reticuloendothelial system. Significant morbidity can arise, due to liver failure and/or atherosclerosis; in part related to the severity of the underlying gene defect and corresponding enzyme deficiency. Diagnosis is based on demonstration of decreased LAL enzyme activity, complemented by analysis of the cognate gene defects. Therapeutic options include dietary manipulation and the use of lipid-lowering drugs. Sebelipase alfa, a recombinant enzyme replacement therapy, has garnered regulatory approval, following demonstration of improvements in disease-relevant markers and clinical benefit in clinical trials, which included increased survival in the most severe cases.

Lipid Control Post Coronary Artery Bypass Graft: One Year Follow-Up of a Middle-Eastern Cohort.

Background: Data on patient characteristics and provider practices in the management of lipids per the new guidelines in specific secondary prevention patients in the Middle East is limited. Objective: To explore patient characteristics and lipid management practices according to the new cholesterol guidelines in secondary prevention patients, up to one year following discharge for coronary artery bypass graft surgery (CABG). Methods: A retrospective chart review of patients discharged post CABG between February 2017 and February 2018 at a quaternary care centre in the Middle East. Patients were characterized by baseline demographics, comorbidities, and use of lipid lowering medications. Results: 189 patients were included in the analysis. Most were diabetic (70.9%) and classified as very high risk per the ACC/AHA guidelines (84.1%) and as extremely high risk per the AACE guidelines (85.2%). Most patients (93.1%) were discharged on high intensity statin. About one third (28.6%) were never seen or only followed once within the first 2 weeks post discharge. Of those who continued to follow up beyond 3 months and within 1 year of discharge (44.4%), about half (51.2%) had follow-up lipid panels performed. Patients who followed up and were seen by a cardiologist were five times more likely to have lipid panels ordered than those seen solely by a CT surgeon. Of those with follow-up lipid panels beyond 3 months: 59.3% achieved LDL goal of <70 mg/dL and 29% achieved LDL <55 mg/dL based on their respective goals. Conclusions: Most patients undergoing CABG in a quaternary care centre in the Middle East are high risk ASCVD. Nonetheless, lipid goals are not commonly achieved nor routinely monitored. Providers will need to transition from the previous risk stratification and statin-only focused approach to adopt the most recent guidelines.

Despite Affordability, Low Utilization of Lipid Lowering Drugs in Iran: Trend Analysis and Benchmarking 2005-2016.

Dyslipidemia is responsible for great mortality and morbidity each year. Little data are available on the availability and affordability of Dyslipidemia medications in low and middle incomes countries. In a retrospective time-series study, we examined the utilization pattern and affordability of lipid-lowering medications in Iran as a lower middle-income country. We initially calculated the defined daily dose for 1000 inhabitants (DID) in different years and compared the results with OECD member countries in the same year. We also used 90% Drug Utilization method to rank and compare lipid lowering drugs with the WHO Essential Medicines List (EML). We measured the affordability by the minimum daily wage for one-month course of treatment. The use of lipid-lowering medications increased from 6.31 to 45.98 DID between 2005 and 2016. The utilization share of the subgroup of statins was above 80% of total utilization. Compared to OECD countries, Iran utilized 40% of the average utilization in 2015. In 2015, Atorvastatin was on 90% of DU medications. At the beginning of the study, only Lovastatin and Nicotinic acid were affordable in 2005, but at the end of the study, all lipid-lowering medications were affordable. The utilization of lipid-lowering medications, despite being affordable, was low. One of its possible reasons is the lack of proper management of patients with Dyslipidemia and low adherence of patients. Another possible cause is the high percentage of undiagnosed patients in the community. Therefore, comprehensive planning and policy-making should be taken to increase utilization and eliminate the related obstacles.

Risk of cardiovascular event and mortality in relation to refill and guideline adherence to lipid-lowering medications among patients with type 2 diabetes mellitus in Sweden.

Objective: To analyze the risk of cardiovascular (CV) events and mortality in relation to adherence to lipid-lowering medications by healthcare centers and patients with type 2 diabetes mellitus (T2DM). Research design and methods: We included 121 914 patients (12% secondary prevention) with T2DM reported by 1363 healthcare centers. Patients initiated lipid-lowering medications between July 2006 and December 2012 and were followed from cessation of the first filled supply until multidose dispensed medications, migration, CV events, death or December 2016. The study period was divided into 4-month intervals through 2014, followed by annual intervals through 2016. Adherence measures were assessed for each interval. Patients' (refill) adherence was measured using the medication possession ratio (MPR). Healthcare centers' (guideline) adherence represented the prescription prevalence of lipid-lowering medications according to guidelines. The risk of CV events and mortality was analyzed for each interval using Cox proportional hazard regression and Kaplan-Meier. Results: Compared with high-adherent patients (MPR >80%), low-adherent primary prevention patients (MPR ≤80%) showed higher risk of all outcomes: 44%-51 % for CV events, doubled for all-cause mortality and 79%-90% for CV mortality. Corresponding risks for low-adherent secondary prevention patients were 17%-19% for CV events, 88%-97% for all-cause and 66%-79% for CV mortality. Primary prevention patients treated by low-adherent healthcare centers (guideline adherence <48%) had a higher risk of CV events and CV mortality. Otherwise, no difference in the risk of CV events or mortality was observed by guideline adherence level. Conclusions: Our results demonstrate the importance of high refill adherence and thus the value of individualized care among patients with T2DM.