Discontinuation Of Statin Therapy Research Articles

Potential Benefits and Risks Associated with the Use of Statins.

HMG-CoA reductase inhibitors, commonly known as statins, are the primary treatment choice for cardiovascular diseases, which stand as the leading global cause of mortality. Statins also offer various pleiotropic effects, including improved endothelial function, anti-inflammatory properties, reduced oxidative stress, anti-thrombotic effects, and the stabilization of atherosclerotic plaques. However, the usage of statins can be accompanied by a range of adverse effects, such as the development of type 2 diabetes mellitus, muscular symptoms, liver toxicity, kidney diseases, cataracts, hemorrhagic strokes, and psychiatric complications. These issues are referred to as statin-associated symptoms (SAS) and are relatively infrequent in clinical trials, making it challenging to attribute them to statin use definitively. Therefore, these symptoms can lead to significant problems, necessitating dose adjustments or discontinuation of statin therapy. This review aims to provide a comprehensive overview of the mechanism of action, potential advantages, and associated risks of statin utilization in clinical settings.

Effect of statin treatment on metabolites, lipids and prostanoids in patients with Statin Associated Muscle Symptoms (SAMS).

Between 5-10% of patients discontinue statin therapy due to statin-associated adverse reactions, primarily statin associated muscle symptoms (SAMS). The absence of a clear clinical phenotype or of biomarkers poses a challenge for diagnosis and management of SAMS. Similarly, our incomplete understanding of the pathogenesis of SAMS hinders the identification of treatments for SAMS. Metabolomics, the profiling of metabolites in biofluids, cells and tissues is an important tool for biomarker discovery and provides important insight into the origins of symptomatology. In order to better understand the pathophysiology of this common disorder and to identify biomarkers, we undertook comprehensive metabolomic and lipidomic profiling of plasma samples from patients with SAMS who were undergoing statin rechallenge as part of their clinical care. We report our findings in 67 patients, 28 with SAMS (cases) and 39 statin-tolerant controls. SAMS patients were studied during statin rechallenge and statin tolerant controls were studied while on statin. Plasma samples were analyzed using untargeted LC-MS metabolomics and lipidomics to detect differences between cases and controls. Differences in lipid species in plasma were observed between cases and controls. These included higher levels of linoleic acid containing phospholipids and lower ether lipids and sphingolipids. Reduced levels of acylcarnitines and altered amino acid profile (tryptophan, tyrosine, proline, arginine, and taurine) were observed in cases relative to controls. Pathway analysis identified significant increase of urea cycle metabolites and arginine and proline metabolites among cases along with downregulation of pathways mediating oxidation of branched chain fatty acids, carnitine synthesis, and transfer of acetyl groups into mitochondria. The plasma metabolome of patients with SAMS exhibited reduced content of long chain fatty acids and increased levels of linoleic acid (18:2) in phospholipids, altered energy production pathways (β-oxidation, citric acid cycle and urea cycles) as well as reduced levels of carnitine, an essential mediator of mitochondrial energy production. Our findings support the hypothesis that alterations in pro-inflammatory lipids (arachidonic acid pathway) and impaired mitochondrial energy metabolism underlie the muscle symptoms of patients with statin associated muscle symptoms (SAMS).

LDL cholesterol target attainment in a representative German cohort of high- and very-high-CV risk patients with statin intolerance: a simulation study

Abstract Background The LDL cholesterol (LDL-C) treatment goals recommended by the 2019 ESC/EAS guidelines are only achieved in a minority of patients. Reasons include the inability to tolerate sufficient doses of statins. To reduce cardiovascular risk in these patients, alternative lipid-lowering therapies (LLT) are required. Purpose Simulation of LDL-C target attainment and achievable LDL-C reductions with oral LLT including ezetimibe and bempedoic acid in patients with statin intolerance (SI) using electronic health records. Methods Data were obtained from the IQVIATM Disease Analyzer database containing a representative sample of German outpatients. We selected patients with high or very-high cardiovascular risk based on ESC/EAS guidelines and diagnosed hypercholesterolaemia. Within this cohort, statin-intolerant patients were classified by applying the following literature-informed definitions pointing towards SI with high confidence (among others): patients with LLT only consisting of non-statins, long-term discontinuation of statin therapy, down-titration of statins, and documented side effects in the electronic health records. We used a Monte Carlo approach to simulate sequentially escalating oral LLT, by adding ezetimibe and bempedoic acid in patients with uncontrolled LDL-C in this population. Results Of the total study population (n=130,778 patients), 33.9% had high and 66.1% had very-high cardiovascular risk. Within this cohort, 11,286 patients (8.6%) met the criteria of SI. Compared to the total study population, in the SI group, there were higher proportions of patients who exhibited atherosclerotic manifestations and who were classified as "very-high cardiovascular risk" (73.7% vs. 66.1%). Their LDL-C levels were slightly higher (105.6 vs. 103.6 mg/dL). 46.5% received a low-intensity statin monotherapy. Ezetimibe, both as monotherapy or in combination, was more frequently prescribed. 12.3% did not receive any LLT (Table). Patients classified as statin-intolerant entered into the simulation model. At baseline, 7.7% were at LDL-C target. In patients without ezetimibe, consecutive treatment with ezetimibe and bempedoic acid increased the calculated proportion of patients at goal to 22.6% and 52.0%. A higher proportion of patients classified as high risk achieved the target compared to those at very-high risk (58.1% vs. 49.9%). The median LDL-C (IQR) after simulation of ezetimibe and bempedoic acid treatment was 62 (48–84) mg/dL (Figure). Conclusions Patients meeting the definition of SI based on their electronic health records represented 8.6% of the total cohort of the patients with high or very-high cardiovascular risk. In this population, oral combination LLT with ezetimibe and bempedoic acid has the potential to substantially increase the proportion of patients achieving clinically relevant LDL-C reductions.

Abstract 17536: Real World Analysis from the "Fast STEMI" Registry on Adherence and Discontinuation of Statin Therapy Within 6 Months After ST-Elevation Myocardial Infarction on First Year Follow-Up: Prognostic Impact and Predictors of Adherence

Background: The impact of statin therapy on cardiovascular outcomes after ST-elevation acute myocardial infarction (STEMI) in real-world patients is understudied. Objectives: to identify predictors of low adherence and discontinuation to statin therapy within 6 months after STEMI and to estimate their impact on cardiovascular outcomes at one year follow-up. Methods: We evaluated real-world adherence to statin therapy by comparing the number of bought tablets to the expected ones at 1 year follow-up through pharmacy registries. A total of 6043 STEMI patients admitted from 2012 to 2017 were enrolled in the FAST STEMI registry and followed up for 4,7±1,6 years; 299 patients with intraprocedural and intrahospital deaths were excluded. The main outcomes evaluated were all-cause death, cardiovascular death, myocardial infarction, major and minor bleeding events, and ischemic stroke. The compliance cut-off chosen was 80% as mainly reported in literature. Results: From a total of 5744 patients, 418 (7,2%) patients interrupted statin therapy within 6 months after STEMI. After univariate and multivariate analysis age over 75 years old, known ischemic cardiopathy and female gender resulted as predictors of therapy discontinuation. Statin discontinuation within 6 months showed an increase of both cardiovascular (5% vs 1.7%; HR 2.23; 95%CI 1.37-3.65; p=0,001) and all-cause mortality (14.8% vs 5.1%, HR 2.32; 95%CI 1.73-3.11; p<0,001) at 1 year follow-up. Regarding cardiovascular outcomes, statin optimal adherence (>80%) reduced ischemic stroke incidence (1% vs 2.5%, p=0.001) and both cardiovascular and all-cause death (0.1% vs 4.6%; 0.3% vs 13.4%; p<0.001) at 1 year follow-up. Age over 75 years old, chronic renal failure, previous atrial fibrillation, vasculopathy, known ischemic cardiopathy were found to be predictors of low statin adherence. Conclusions: In our real-world registry low statin adherence and discontinuation therapy within 6 months after STEMI were independently associated to an increase of cardiovascular and all-cause mortality at 1 year follow-up. Low statin adherence led to higher rates of ischemic stroke. This analysis confirmed the predictive factors of adherence and discontinuation therapy already described in literature.

The Effects of Statins, Ezetimibe, PCSK9-Inhibitors, Inclisiran, and Icosapent Ethyl on Platelet Function.

This review aims to examine the complex interaction between dyslipidemia, platelet function, and related drug treatments. In particular, the manuscript provides an overview of the effects of major hypolipidemic drugs on platelet function. Indeed, growing evidence supports the view that statins, ezetimibe, PCSK9 inhibitors, inclisiran, and icosapent ethyl also act as antithrombotics. It is known that platelets play a key role not only in the acute phase of coronary syndromes but also in the early phase of atherosclerotic plaque formation. The goal of cholesterol-lowering therapy is to reduce cardiovascular events. The direct effects of cholesterol-lowering drugs are widely described in the literature. Lowering LDL-c (low-density lipoprotein cholesterol) by 1 mmol/L results in a 22-23% reduction in cardiovascular risk. Numerous studies have examined the direct antithrombotic effects of these drugs on platelets, endothelium, monocytes, and smooth muscle cells, and thus, potentially independent of blood LDL-cholesterol reduction. We reviewed in vitro and in vivo studies evaluating the complex interaction between hypercholesterolemia, hypertriglyceridemia, platelet function, and related drug treatments. First, we discussed the role of statins in modulating platelet activation. Discontinuation of statin therapy was associated with increased cardiovascular events with increased ox-LDL, P-selectin, and platelet aggregation. The effect of PCSK9-I (inhibitors of proprotein convertase subtilisin/kexin type 9, PCSK9 involved in the degradation of LDL receptors in the liver) was associated with a statistically significant reduction in platelet reactivity, calculated in P2Y12 reaction units (PRU), in the first 14 days and no difference at 30 days compared to placebo. Finally, in patients with hypertriglyceridemia, the REDUCE-IT study showed that icosapent ethyl (an ethyl ester of eicosapentaenoic acid that reduces triglyceride synthesis and improves triglyceride clearance) resulted in a 25% reduction in ischemic events and cardiovascular death. However, to date, there is not yet clear clinical evidence that the direct antithrombotic effects of the drugs may have a beneficial impact on outcomes independently from the reduction in LDL-C or triglycerides.

Association of lipid composition and unsaturated fatty acids of VLDL with atrial remodeling in metabolic syndrome

Subjects with metabolic syndrome (MetS) commonly have atrial remodeling, which indicates a risk for atrial fibrillation. This study determined MetS-related changes in lipid components in very-low-density lipoprotein (VLDL), which has been shown to cause atrial remodeling, the effect of statins on these changes, and the correlation between atrial remodeling and VLDL lipid compositions. Blood samples were collected from 12 non-MetS and 27 sex- and age-matched MetS subjects. Fourteen patients with MetS (MetS-off statin) discontinued statin therapy 14 days before the study, while the remaining 13 remained on it (MetS-on statin). The VLDLs were isolated and processed for mass-based lipid profiling. Lipidomic analyses were performed and associated with atrial remodeling markers measured using standard echocardiography and electrocardiography. Compared with the VLDL components of the non-MetS group, glucosyl/galactosyl ceramide, lyso-phosphatidylcholine, lyso-phosphatidylethanolamine, and triglycerides were enriched in the MetS-off statin group. Statin therapy attenuated all abnormally abundant lipid classes in MetS, except for triglycerides. In addition, lyso-phosphatidylcholine, lyso-phosphatidylethanolamine, and triglycerides were significantly correlated with atrial dilatation, and the latter two were also correlated with the PR interval. Enrichment of double bonds, which indicate unsaturated fatty acids, was also significantly correlated with atrial remodeling and P-wave duration. This study suggests that the pathological lipid payload of MetS-VLDL may contribute to atrial remodeling in patients.

Personalized statin treatment plan using counterfactual approach with multi-objective optimization over benefits and risks

BackgroundStatins are a class of drugs that lower cholesterol levels in the blood by inhibiting an enzyme called 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase. High cholesterol levels can lead to plaque buildup in the arteries, which can cause Atherosclerotic Cardiovascular Disease(ASCVD). Statins can reduce the risk of ASCVD events by about 25–35% but they might be associated with symptoms such as muscle pain, liver damage, or diabetes. As a result, this leads to a strong reason to discontinue statin therapy, which increases the risk of cardiovascular events and mortality and becomes a public-health problem.To solve this problem, in the previous work, we proposed a framework to produce a proactive strategy, called a personalized statin treatment plan (PSTP) to minimize the risks of statin-associated symptoms and therapy discontinuation when prescribing statin. In our previous PSTP framework, three limitations remain, and they can influence PSTP usability: (1) Not taking the counterfactual predictions and confounding bias into account. (2) The balance between multiple drug-prescribing objectives (especially trade-off objectives), such as tradeoff between benefits and risks. (3) Evaluating PSTP in retrospective data. ObjectivesThis manuscript aimed to provide solutions for the three abovementioned problems to improve PSTP robustness to produce a proactive strategy for statin prescription that can maximize the benefits (low-density lipoprotein cholesterol (LDL-C) reduction) and minimize risks (statin-associated symptoms and therapy discontinuation) at the same time. MethodsWe applied overlapping weighting counterfactual survival risk prediction (CP), multiple objective optimization (MOO), and clinical trial simulation (CTS) which consists of Random Arms, Clinical Guideline arms, PSTP Arms, and Practical Arms to improve the PSTP framework and usability. ResultsIn addition to highly balanced covariates, in the CTS, the revised PSTP showed improvements in lowering the SAS risks overall compared to other arms across all time points by at most 7.5% to at least 1.0% (Fig. 8(a)). It also has the better flexibility of identifying the optimal Statin across all time points within one year. ConclusionWe demonstrated feasibility of robust and trustworthy counterfactual survival risk prediction model. In CTS, we also demonstrated the PSTP with Pareto optimization can personalize optimal balance between Statin benefits and risks.

Patient-Reported Reasons for Switching or Discontinuing Statin Therapy: A Mixed Methods Study Using Social Media.

IntroductionStatin discontinuation can have major negative health consequences. Studying the reasons for discontinuation can be challenging as traditional data collection methods have limitations. We propose an alternative approach using social media.MethodsWe used natural language processing and machine learning to extract mentions of discontinuation of statin therapy from an online health forum, WebMD (http://www.webmd.com). We then extracted data according to themes and identified key attributes of the people posting for themselves.ResultsWe identified 2121 statin reviews that contained information on discontinuing at least one named statin. Sixty percent of people posting declared themselves as female and the most common age category was 55–64 years. Over half the people taking statins did so for < 6 months. By far the most common reason given (90%) was patient experience of adverse events, the most common of which were musculoskeletal and connective tissue disorders. The rank order of adverse events reported in WebMD was largely consistent with those reported to regulatory agencies in the US and UK. Data were available on age, sex, duration of statin use, and, in some instances, adverse event resolution and rechallenge. In some instances, details were presented on resolution of the adverse event and rechallenge.ConclusionSocial media may provide data on the reasons for switching or discontinuation of a medication, as well as unique patient perspectives that may influence continuation of a medication. This information source may provide unique data for novel interventions to reduce medication discontinuation.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40264-022-01212-0.

Factors Associated with Discontinuation of Statin Therapy in Patients with Lymphoma Aged 80 Years and Older: A Retrospective Single-Institute Study.

BackgroundThere is little evidence to support or negate the benefits of statin therapy for primary prevention of cardiovascular disease (CVD) in lymphoma patients aged 80 years or older.ObjectiveWe evaluated comprehensive geriatric assessment (CGA) scores and previously reported risk factors for failure of statin therapy discontinuation in lymphoma patients aged 80 years and older with the aim of identifying those in whom discontinuation of statins for primary CVD prevention is indicated.Patients and methodsOur study cohort comprised 50 patients aged 80 years and older treated with chemotherapy for lymphoma at our institute from January 2011 to July 2020. We retrospectively analyzed the associations between CGA, including Geriatric 8, instrumental activities of daily living, and Charlson comorbidity index, and previously reported factors associated with failure of statin therapy discontinuation, defined as reintroduction of statins after their discontinuation, in this patient cohort.ResultsTwenty years or less of statin therapy was an independent predictor of failure of statin therapy discontinuation (hazard ratio 8.240, 95% confidence interval 1.380–49.10). There were significant differences in the rate of failure of statin discontinuation between patients receiving statins for ≥ 20 years versus < 20 years (p = 0.010). Multivariate analysis of CGA-related scores identified no significant risk factors for failure of statin discontinuation.ConclusionsDiscontinuation of statin therapy may be indicated in lymphoma patients aged 80 years and older who have used statins for 20 years or more.

Interactions Between Statins, Exercise, and Health: A Clinical Update

Interactions Between Statins, Exercise, and Health: A Clinical Update

A comprehensive assessment of statin discontinuation among patients who concurrently initiate statins and CYP3A4-inhibitor drugs; a multistate transition model.

The aim of this study was to describe the 1-year direct and indirect transition probabilities to premature discontinuation of statin therapy after concurrently initiating statins and CYP3A4-inhibitor drugs. A retrospective new-user cohort study design was used to identify (N = 160 828) patients who concurrently initiated CYP3A4 inhibitors (diltiazem, ketoconazole, clarithromycin, others) and CYP3A4-metabolized statins (statin DDI exposed, n = 104 774) vs. other statins (unexposed to statin DDI, n = 56 054) from the MarketScan commercial claims database (2012-2017). The statin DDI exposed and unexposed groups were matched (2:1) through propensity score matching techniques. We applied a multistate transition model to compare the 1-year transition probabilities involving four distinct states (start, adverse drug events [ADEs], discontinuation of CYP3A4-inhibitor drugs, and discontinuation of statin therapy) between those exposed to statin DDIs vs. those unexposed. Statistically significant differences were assessed by comparing the 95% confidence intervals (CIs) of probabilities. After concurrently starting stains and CYP3A, patients exposed to statin DDIs, vs. unexposed, were significantly less likely to discontinue statin therapy (71.4% [95% CI: 71.1, 71.6] vs. 73.3% [95% CI: 72.9, 73.6]) but more likely to experience an ADE (3.4% [95% CI: 3.3, 3.5] vs. 3.2% [95% CI: 3.1, 3.3]) and discontinue with CYP3A4-inhibitor therapy (21.0% [95% CI: 20.8, 21.3] vs. 19.5% [95% CI: 19.2, 19.8]). ADEs did not change these associations because those exposed to statin DDIs, vs. unexposed, were still less likely to discontinue statin therapy but more likely to discontinue CYP3A4-inhibitor therapy after experiencing an ADE. We did not observe any meaningful clinical differences in the probability of premature statin discontinuation between statin users exposed to statin DDIs and those unexposed.

Lipid-Targeted Atherosclerotic Risk Reduction in Older Adults: A Review.

Aggressive lipid-lowering lifestyle modifications and pharmacologic therapies are the cornerstones of the primary and secondary prevention of atherosclerotic cardiovascular disease events. While statins are highly effective, inexpensive, and generally well-tolerated medications, many clinicians and patients express uncertainty regarding the necessity of statin treatment in older adults. Citing concerns such as polypharmacy, muscle symptoms, and even potential cognitive changes with statins, many patients and health care providers elect to de-intensify or discontinue statin therapy during the process of aging. A lack of clear representation of older individuals in many clinical trials and practice guidelines may contribute to the ambiguity. However, the recently prevailing data and practice patterns supporting the benefits, safety, and tolerability of a variety of lipid-lowering therapeutics in older adults are discussed here, with particular mention of a potential protective effect from incident dementia among a statin-treated geriatric population and an admonishment of the historical concept of “too-low” low-density lipoprotein cholesterol (LDL-C) levels.

Relative contributions of statin intensity, achieved low-density lipoprotein cholesterol level, and statin therapy duration to cardiovascular risk reduction in patients with type 2 diabetes: population based cohort study

BackgroundCurrent guidelines recommend life-long use of statin for patients with type 2 diabetes (T2D), however, a number of patients discontinue statin therapy in clinical practice. We aimed to estimate the optimal statin therapy including statin therapy duration, statin intensity, and low-density lipoprotein cholesterol (LDL-C) level among patients with T2D in a real-world setting.MethodsFrom Korean National Health Insurance Service Cohort (2007–2015), 8937 patients with T2D (≥ 40 years of age) who received statin therapy for at least 90 days were included. Risk of major adverse cardiovascular event (MACE) including ischemic heart disease, ischemic stroke, and cardiovascular death was estimated according to statin intensity, achieved serum LDL-C level, and statin therapy duration, respectively. The relative contributions of these factors to MACE risk were quantified by calculating the proportion of log-likelihood explained by each factor.ResultsThe hazard ratio (HR) of MACE was lower in patients receiving moderate- or high-intensity statins than in those receiving low-intensity statins (HR, 0.72; p = 0.027). Among patients who received moderate- or high-intensity statins, lower achieved LDL-C level was associated with lower cardiovascular risk. Notably, the longer the patients received statins, the lower was the risk of MACE; the HR of MACE was significantly reduced after at least 18 months (adjusted HR, 0.70; p = 0.009) as a reference to 3–6 months of therapy. The proportion of explainable log-likelihood for MACE was greatest for statin duration (2.55), followed by achieved LDL-C level (2.18), and statin intensity (0.95).ConclusionsStatin therapy duration is as important as or more crucial than statin intensity or achieved LDL-C level for the reduction of cardiovascular risk in T2D patients. The concept of “longer is better” regarding statin therapy should be considered in clinical practice.

Statin Intolerance and Noncompliance: An Empiric Approach

Statin Intolerance and Noncompliance: An Empiric Approach

Statin therapy in hepatitis: a systematic review and meta-analysis of 9 studies with 195,602 participants

Abstract Background Conflicting data suggest that statins could cause hepatitis in certain group of patients, while improving prognosis in patients affected by some chronic liver diseases. Therefore, we aimed to quantify the potential protective role of statins on some main liver-related health outcomes in clinical studies on patients affected by hepatitis. Methods We applied fixed-effects or random-effects meta-analyses with inverse variance weighting to calculate pooled estimates and confidence intervals (95% confidence intervals [CI]). We calculated the odds ratios (OR) and 95% CI for the targets of mortality and hepatocellular carcinoma, fibrosis, and cirrhosis. Results Nine studies (N: 195,602 patients) reported data on mortality of patients affected by chronic viral hepatitis, six studies (N: 72,960) reported data on the risk to develop hepatocellular carcinoma, two studies on fibrosis progression (N: 9678) and two studies (N: 85,205) on cirrhosis development. Statins reduce the risk to develop hepatocarcinoma (OR (95% CI) = 0.47 (0.28, 0.81), p=0.005) (Figure 1), liver fibrosis (OR (95% CI) = 0.55 (0.34, 0.87), p&amp;lt;0.001), and cirrhosis (OR (95% CI) = 0.59 (0.55, 0.62), p&amp;lt;0.0001). There was also no significant link between statin therapy and alanine (Figure 2) and aspartate aminotransferases levels. Moreover, statin therapy is associated with a significant reduction in mortality but only in studies longer than 3 years (OR (95% CI) = 0.38 (0.17, 0.85), p=0.006). Conclusion Long-term treatment with statins seems to be safe in patients affected by hepatitis, while significantly improving their prognosis. Extensive education should be continued in order to avoid discontinuing statin therapy in patients with liver diseases. Funding Acknowledgement Type of funding sources: None. Figure 1Figure 2

A multistate transition model for statin-induced myopathy and statin discontinuation.

The overarching goal of this study was to simultaneously model the dynamic relationships among statin exposure, statin discontinuation, and potentially statin‐related myopathic outcomes. We extracted data from the Indiana Network of Patient Care for 134,815 patients who received statin therapy between January 4, 2004, and December 31, 2008. All individuals began statin treatment, some discontinued statin use, and some experienced myopathy and/or rhabdomyolysis while taking the drug or after discontinuation. We developed a militate model to characterize 12 transition probabilities among six different states defined by use or discontinuation of statin and its associated myopathy or rhabdomyolysis. We found that discontinuation of statin therapy was common and frequently early, with 44.4% of patients discontinuing therapy after 1 month, and discontinuation is a strong indicator for statin‐induced myopathy (risk ratio, 10.8; p < 0.05). Women more likely than men (p < 0.05) and patients aged 65 years and older had a higher risk than those aged younger than 65 years to discontinue statin use or experience myopathy. In conclusion, we introduce an innovative multistate model that allows clear depiction of the relationship between statin discontinuation and statin‐induced myopathy. For the first time, we have successfully demonstrated and quantified the relative risk of myopathy between patients who continued and discontinued statin therapy. Age and sex were two strong risk factors for both statin discontinuation and incident myopathy.

Statins and Side Effects: Homing in on the Cause

Many people discontinue statin therapy because of concerns about side effects. Investigators designed the double-blind, placebo-controlled SAMSON

The Challenge: Finding the Most Appropriate Statin and Dose for Each Patient.

• Discontinuing statin therapy results in increased cardiovascular risk. • The nocebo effect is a common reason for perceived statin intolerance. • Statin intolerance is much less commonly reported in clinical trials than in clinical practice, suggesting that patient education and other safeguards employed in clinical trials are important to include in clinical practice. • Several strategies are available that can enable continuation of statin therapy in patients who are truly statin-intolerant.

Management of LDL-cholesterol levels in patients with Diabetes Mellitus in Cardiology Practice: Real-life evidence of Under-treatment from the EPHESUS registry.

Effective treatment of high low-density lipoprotein cholesterol (LDL-C) levels has been shown to improve cardiovascular outcomes of patients with diabetes mellitus (DM). Herein, we aimed to provide insight to the real-life management of patients with DM in terms of LDL-C goal attainment and adherence to lipid management recommendations. Our objective was also to reveal the reasons of poor LDL-C goal attainment by assessing the perceptions of both physicians and patients. We compared the diabetic and non-diabetic patients from the database of a nationwide registry conducted in cardiology outpatient clinics with regard to the demographic characteristics, educational status, comorbidities, medications, laboratory parameters and LDL-C goal attainment. Also, both the patients and attending physicians were surveyed to analyse perceptions and awareness of hypercholesterolemia. Of the 1868 consecutively enrolled patients, 873 (47%) had DM. Proportion of patients on statins was significantly lower in patients with DM (67.8% vs 55.3%; P<.001). The proportion of patients who attained LDL-C targets were lower among the diabetic patients (17.8% vs 15%; P=.06). The most common causes of the discontinuation of statin therapy were negative media coverage about statins (32.1%), and recommendations of physicians to stop the lipid lowering therapy (29.6%). Analysis of the physician survey revealed that the physicians could determine the off-target patients accurately (negative predictive value 98.4%) while the positive predictive value (48.8%) was low. The reasons for not attaining the LDL-C goals in diabetic patients were not prescription of statins (38%) and inadequate (eg low-dose, non-adherent) statin (28.3%) dosages. In real-life clinical cardiology practice, diabetic patients are far below the recommended LDL-C treatment goals. High-intensity statin treatment in diabetic population is still avoided because of the concerns about polypharmacy and drug interactions. Also, the inertia of physicians and even cardiologists is probably a major cause of refraining of prescription of optimal statin dosages.

Evaluation of statin discontinuation stratified by primary versus secondary prevention following bariatric surgery: a retrospective cohort study.

Bariatric surgery leads to an improvement in hyperlipidemia and a subsequent decline in the use of hyperlipidemia-related medications, including statins. In patients with a history of atherosclerotic cardiovascular disease (ASCVD), it is recommended to continue statins; however, it is unknown whether there is a differential risk for statin discontinuation in patients with and without a history of ASCVD. To estimate the rates and factors associated with statin discontinuation following bariatric surgery. Large U.S. administrative claims database of privately insured beneficiaries, January 2005 through December2017. We identified patients aged ≥19 years who were statin users at the time of bariatric surgery. Patients were stratified into primary prevention and secondary prevention (patients with a history of ASCVD) groups. Time to statin discontinuation was defined as the first 90-day gap after exhausting the last day's supply of the last statin prescription. Factors associated with statin discontinuation were assessed using the Cox proportional hazards regression model. We identified 19,332 statin users at the time of bariatric surgery, of whom 84% (16,221) used statins for primary prevention. At 6 months, 62% and 53% of patients in the primary and the secondary prevention treatment groups, respectively, discontinued statin use. Patients in the primary prevention treatment group were 18% more likely to discontinue statin therapy compared with the patients in the secondary prevention treatment group (hazard ratio, 1.18; 95% confidence interval, 1.13-1.24) according to a multivariable analysis. Our findings suggest that the rate of discontinuation of statin therapy after bariatric surgery was more pronounced in the primary versus secondary prevention treatment group.