Statin Discontinuation Research Articles

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.

Abstract 16715: Rare or Disregarded; A Case of Autoimmune Myopathy

Introduction: Statin-induced myopathy can present with symptoms ranging from mild myalgia to significant muscle weakness. This case report highlights how statin-induced autoimmune myopathy often goes undiagnosed. Case Presentation: We present a 69 year old male with a past medical history of coronary artery disease who presented with myalgia and progressive proximal muscle weakness for 2 months. On admission, creatinine kinase (CK) level was noted to be elevated at 8323 u/L. Atorvastatin was held on admission and the patient received intravenous (IV) fluid as treatment for presumed rhabdomyolysis. Although CK was trending down, the patient did not show any significant improvement in muscle weakness or myalgia. At this point, myositis was suspected, so a myositis panel including anti-HMG Co-A Reductase antibody was ordered and the patient was started on IV steroids. Anti-HMG Co-A Reductase antibody was positive and the rest of myopathy workup was negative; meanwhile, the patient's muscle weakness significantly improved. The patient was discharged on a methylprednisolone with close outpatient rheumatology follow-up. Discussion: Drug-induced rhabdomyolysis is one of many causes of myalgia. It is crucial to review a patient’s medication list and discontinue any possible medications that are possible offenders. Statin-induced myopathy should also be suspected when typical treatment for rhabdomyolysis is failing. Statin induced autoimmune myopathy is associated with muscle weakness, elevated CK and a positive anti-HMG Co-A Reductase antibody, which requires discontinuation of Statin and initiation of immunosuppressive therapy. Conclusions: This case report highlights the importance of early identification and management of statin-induced autoimmune myopathy as a possible differential diagnosis in patients with muscle weakness, elevated CK levels while on statin therapy who do not respond to IV fluid alone.

Prescribing statin therapy in physically (in)active individuals vs prescribing physical activity in statin-treated patients: A four-scenario practical approach

Statins are among the most commonly prescribed medications worldwide. Statin-associated muscle symptoms (SAMS) represent a frequent statin-related adverse effect associated with statin discontinuation and increased cardiovascular disease (CVD) events. Emerging evidence indicate that the majority of SAMS might not be actually caused by statins, and the nocebo/drucebo effect (i.e. adverse effects caused by negative expectations) might also explain SAMS. Physical activity (PA) is a cornerstone in the management of CVD risk. However, evidence of increased creatine-kinase levels in statin-treated athletes exposed to a marathon has been generalized, at least to some extent, to the general population and other types of PA. This generalization is likely inappropriate and might induce fear around PA in statin users. In addition, the guidelines for lipid management focus on aerobic PA while the potential of reducing sedentary behavior and undertaking resistance training have been overlooked. The aim of this report is to provide a novel proposal for the concurrent prescription of statin therapy and PA addressing the most common and clinically relevant scenarios by simultaneously considering the different stages of statin therapy and the history of PA. These scenarios include i) statin therapy initiation in physically inactive patients, ii) PA/exercise initiation in statin-treated patients, iii) statin therapy initiation in physically active patients, and iv) statin therapy in athletes and very active individuals performing SAMS-risky activities.

Statin Discontinuation After Coronary Revascularization

There is a scarcity of studies evaluating statin discontinuation in patients with coronary artery disease in real-world practice. In 11,144 patients who underwent first coronary revascularization and taking statins in the CREDO-Kyoto Registry Cohort-3, we evaluated the incidence of statin discontinuation, defined as stopping statins for at least 2months. The reasons for statin discontinuation included nonadherence, side effects, worsening co-morbidities, surgery, prescription error, and direction by physicians for other reasons. During a median 6years of follow-up, the cumulative incidence of statin discontinuation was 6.1% at 1year, 12.4% at 3years, 17.4% at 5years, and 21.4% at 7years. The major components of the reasons for statin discontinuation were nonadherence, side effects, and worsening co-morbidities. Compared with patients with statin discontinuation because of other reasons, patients with statin discontinuation because of nonadherence more often had younger age, men, acute coronary syndrome, and current smoking; patients with statin discontinuation because of side effects more often had liver cirrhosis; and patients with statin discontinuation because of worsening co-morbidities more often had advanced age and co-morbidities such as malignancy. Statin discontinuation was strongly associated with subsequent mortality (hazard ratio [HR] 3.54; 95% confidence interval [CI] 3.18 to 3.94, p <0.001), which was consistent, regardless of the reasons, except for the small group of patients with prescription error (nonadherence: HR 2.35, 95% CI 1.69 to 3.27, p <0.001; side effects: HR 2.48, 95% CI 1.84 to 3.34, p <0.001; worsening co-morbidities: HR 22.08, 95% CI 18.55 to 26.29, p <0.001). In conclusion, in real-world practice, approximately 1 in 5 patients discontinued statins after coronary revascularization during a median of 6years of follow-up. Statin discontinuation was associated with subsequent mortality.

Effect of statin therapy patterns on readmission and mortality in patients with intracerebral hemorrhage.

There is limited and inconsistent evidence for the association of statin therapy and statin treatment patterns with the risk of recurrent intracerebral hemorrhage (ICH) in patients with prior ICH. To assess the association of statin therapy and its intensity, type, initiation time, and discontinuation with the risk of recurrent ICH and mortality in Chinese patients with ICH. Patients with newly diagnosed ICH in the Beijing Employee Medical Claims Data database from 2010 to 2017 were included. Post-ICH statin users (post-diagnosis only) and nonusers (never), statin discontinuers (pre-diagnosis only) and continuers (pre- and post-diagnosis) were matched on a 1:1 propensity score, respectively. Adjusted Cox proportional risk models were used to estimate the risk ratios for ICH readmission and mortality under various statin patterns. A total of 2668 post-ICH statin users and 2668 nonusers without a history of statin use were enrolled. Post-ICH statin users had a lower risk of ICH readmission (HR, 0.57; 95% CI 0.48, 0.69) and all-cause death (0.56: 0.49, 0.63) than nonusers. Low/moderate-intensity treatment was associated with a 63% lower risk of recurrent ICH compared with nonusers (0.37: 0.29, 0.46), whereas high-intensity treatment did not reduce the risk (0.93: 0.74, 1.16). Both low/moderate-intensity (0.42: 0.36, 0.48) and high-intensity statins (0.57: 0.48, 0.69) were associated with a lower risk of all-cause mortality. The risk of ICH readmission was 53% (0.47: 0.30, 0.74) lower with adherence to rosuvastatin than with atorvastatin. Only starting medication within 30days of the first diagnosis of ICH reduced the risk of ICH readmission (0.49: 0.40, 0.60). Among patients with a history of statin use, 1807 discontinuing and 1,807 continuing users of statins were included. The risk of ICH readmission (4.00: 3.32, 4.80) and the risk of all-cause death (4.01: 3.57, 4.50) were substantially increased in statin discontinuation compared with continued statin use. Statin therapy after ICH was associated with lower risks for ICH readmission and all-cause mortality compared with non-statin therapy, especially at low/moderate intensity and early initiation of statins after ICH. Adherence to rosuvastatin was associated with a lower risk of recurrence of ICH than atorvastatin. Among patients with a statin history prior to ICH, discontinuation of statins after ICH was associated with increased risk of ICH recurrence and death.

Association of PCSK9 Inhibitor Initiation on Statin Adherence and Discontinuation.

Background PCSK9is (proprotein convertase subtilisin/kexin type 9 inhibitors) are well tolerated, potently lower cholesterol, and decrease cardiovascular events when added to statins. However, statin adherence may decrease after PCSK9i initiation and alter clinical outcomes. We evaluate the association of PCSK9i initiation on statin discontinuation and adherence. Methods and Results In this retrospective pre-post difference-in-difference analysis, new PCSK9i claims were propensity matched with statin-alone users (April 2017-September 2019). The primary outcomes were statin adherence (proportion of days covered) and statin discontinuation (absence of statin coverage for at least 60 days) 12 months following PCSK9i initiation. Secondary outcomes included low-density lipoprotein cholesterol levels after 1 year. A total of 220 538 statin users and 700 PCSK9i users were identified, from which 178 on PCSK9i were included and matched to 712 on statins alone. At 12 months, mean statin proportion of days covered decreased from 67% to 48% in the PCSK9i group but increased from 68% to 86% in the statin-alone groups (P<0.0001). Statin discontinuation rates increased from 11% to 39% in the PCSK9i group and from 7% to 9% in the statin-alone group (P=0.0041). Patients with low-density lipoprotein cholesterol <70 mg/dL increased from 5% to 68% with PCSK9i but increased from 16% to 24% with statins alone (P<0.0001). Changes in hospitalization rates were similar between both groups during the follow-up period. Conclusions PCSK9i initiation was associated with decreased low-density lipoprotein cholesterol, higher statin discontinuation, and reduced statin adherence.

The effect of discharge care plans on statin prescription rates.

Stroke discharge care bundles have been proposed to address inadequate provider statin prescription rates. Discontinuation of statins has been associated with a 37% relative risk increase in mortality in patients with a stroke diagnosis. The project site had a statin prescription rate of 86.2%. The project was initiated at a 641-bed regional community teaching medical center. Statin prescription rates upon discharge on patients with the diagnosis of transient ischemic attack or stroke were evaluated and noted to be below the benchmark of 95%. Possible interventions to improve this benchmark were discussed with key stakeholders such as the information technology team, stroke care outcomes team, and neurology service providers. The proposed intervention was incorporated into the electronic health record. Provider prescription rates were tracked monthly along with the use of the proposed intervention. A one-sided z-test was used to analyze the data collected. A stroke discharge power plan within an electronic health record was modified to increase the rate of statin prescriptions. The key modification included checking off the prescription of a statin on discharge. Reinforcement of its use was done through monthly reminders. Use of discharge care plan yielded 100% compliance. Overall compliance was 9.7%. The null hypothesis of the one-sided z-test was 89%. The p-value for all tests was <0.05. The use of a stroke discharge care plan within an electronic health record can positively affect secondary stroke prevention by increasing statin prescription rates.

A mobile health application for patients eligible for statin therapy: app development and qualitative feedback on design and usability

BackgroundCardiovascular disease is the leading cause of death in the United States (US). Despite the well-recognized efficacy of statins, statin discontinuation rates remain high. Statin intolerance is a major cause of statin discontinuation. To accurately diagnose statin intolerance, healthcare professionals must distinguish between statin-associated and non-statin-associated muscle symptoms, because many muscle symptoms can be unrelated to statin therapy. Patients’ feedback on muscle-related symptoms would help providers make decisions about statin treatment. Given the potential benefits and feasibility of existing apps for cardiovascular disease (CVD) management and the unmet need for an app specifically addressing statin intolerance management, the objectives of the study were 1) to describe the developmental process of a novel app designed for patients who are eligible for statin therapy to lower the risk of CVD; 2) to explore healthcare providers’ feedback of the app; and 3) to explore patients’ app usage experience.MethodsThe app was developed by an interdisciplinary team. Healthcare provider participants and patient participants were recruited in the study. Providers were interviewed to provide their feedback about the app based on screenshots of the app. Patients were interviewed after a 30 days of app usage.ResultsThe basic features of the app included symptom logging, vitals tracking, patient education, and push notifications. Overall, both parties provided positive feedback about the app. Areas to be improved mentioned by both parties included: the pain question asked in symptom tracking and the patient education section. Both parties agreed that it was essential to add the trend report of the logged symptoms.ConclusionsThe results indicated that providers were willing to use patient-reported data for disease management and perceived that the app had the potential to facilitate doctor-patient communication. Results also indicated that user engagement is the key to the success of app efficacy. To promote app engagement, app features should be tailored to individual patient’s needs and goals. In the future, after it is upgraded, we plan to test the app usability and feasibility among a more diverse sample.

Histological Study for the Effect of Squalene Supplements on Muscles Rats Treated with Simvastatin

The present study aimed to reveal the biological vitality of squalene supplements and in combination with statins. Statins are a class of drugs that are regularly administered to decrease cholesterol. The main cause of statin discontinuation is the development of statin-associated muscle symptoms. Because of the statin-related myotoxicity phenotypes that are getting worse have been proposed, the study was conducted to examine the effects of squalene supplements in combination with statin. In the experiment, thirty male rats were divided into two group, (experimental one) five rats dosage with normal saline only and other rats administrated with cholesterol 1%/BW for 28 days. Then the second group was randomly divided into four groups (experimental two). The experiment lasted about during two months, the rats were administration as the following groups, first group: six rats used as a negative control group dosage with normal saline only; second group: six rats used as a positive control group dosage with normal cholesterol 1% only; third group: six rats administrated with cholesterol 1%/BW for 28 days then treated with simvastatin 40 mg/kg dosage orally every day for 4 weeks; forth group: six rats administrated with cholesterol 1%/BW for 28 days then treated with squalene 0.2 mg orally every day for 28 day, and fifth group: six rats will have administrated with cholesterol 1%/BW for 28 days then treated with simvastatin 40 mg/kg dosage orally with squalene every day for 28 day. In conclusion: we found from the study effect of squalene supplements on rats treated with statin to avoid side effect and protecting the muscles from damage caused by statin.

Are statins making older persons weaker? A discontinuation study of muscular side effects

Thirteen percent of the Danish population are treated with a statin—half of these are in primary prevention, and most are > 65 years old. Statins have known muscular side effects (i.e., myalgia) correlated to reduced muscle performance. This study examines if years of statin treatment in older people introduce subclinical muscle discomfort and loss of muscle mass and strength. In total, 98 participants (71.1 ± 3.6 years (mean ± SD)), who were in primary prevention treatment for elevated plasma cholesterol with a statin, were included in this study. Statin treatment was discontinued for 2 months and then re-introduced for 2 months. Primary outcomes included muscle performance and myalgia. Secondary outcomes included lean mass and plasma cholesterol. Functional muscle capacity measured as a 6-min walk test increased after discontinuation (from 542 ± 88 to 555 ± 91 m, P < 0.05) and remained increased after re-introduction (557 ± 94 m). Similar significant results were found with a chair stand test (15.7 ± 4.3 to 16.3 ± 4.9 repetitions/30 s) and a quadriceps muscle test. Muscle discomfort during rest did not change significantly with discontinuation (visual analog scale from 0.9 ± 1.7 to 0.6 ± 1.4) but increased (P < 0.05) with the re-introduction (to 1.2 ± 2.0) and muscle discomfort during activity decreased (P < 0.05) with discontinuation (from 2.5 ± 2.6 to 1.9 ± 2.3). After 2 weeks of discontinuation, low-density lipoprotein cholesterol increased from 2.2 ± 0.5 to 3.9 ± 0.8 mM and remained elevated until the re-introduction of statins (P < 0.05). Significant and lasting improvements in muscle performance and myalgia were found at the discontinuation and re-introduction of statins. The results indicate a possible statin-related loss of muscle performance in older persons that needs further examination.

Restarting statins in a specialist lipid clinic setting

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Health Research Board. Background Statin therapy remains a gold standard in the primary and secondary prevention of cardiovascular disease (CVD).[1] Poor statin compliance and discontinuation due to statin intolerance (SI) remains a pervasive clinical issue.[1] Research has demonstrated that the prevalence of SI is overestimated with most SI symptoms being nocebo.[2-3] Our practice involves a patient centred intervention to restart statins with four components: 1) careful exclusion of differential diagnoses 2) an in-person discussion regarding SI based on contemporary evidence 3) an incremental introduction of statins starting at the lowest dose 4) virtual follow up to ensure implementation of the therapeutic plan. The aim of this study was to assess the effectiveness of this intervention in terms of statin reintroduction and subsequent cholesterol levels. Methods An ethically approved retrospective chart review was performed of consecutive adult patients attending a specialist lipid clinic over a six-month period in 2021. Patient data recorded included demographics, clinical characteristics, treatment received and biochemical profiles. Statistical analysis was performed using the Student T-test. Results This study included 370 patients. SI prevalence was 25% with 10% referred explicitly for SI. Patients with SI were predominantly female (71%). Statin-associated muscle symptoms were the most common SI (62%). Statin therapy was restarted in 48% of patients [Rosuvastatin: (62%), Simvastatin: (16%), Atorvastatin: (13%), Pravastatin: (9%)]. Restarting a statin demonstrated significantly improved mean reductions in both total cholesterol (TC) (P = 0.007) and low-density lipoprotein C (LDL-C) (P&amp;lt; 0.001) levels versus management with or without alternative lipid-lowering agents [primarily ezetimibe (30%)]. Statin restart: (TC mean reduction: 3.17 ± 2.27 mmol/L, LDL-C mean reduction: 2.93 ± 1.77 mmol/L). Management with or without alternative lipid-lowering agents: [TC mean reduction: 1.61 ± 1.46 mmol/L, LDL-C: 1.35 ± 0.93 mmol/L]. Conclusion This study highlights the prevalence of SI among patients attending a lipid clinic. Statins were successfully restarted in half of presenting cases and conferred significant improvement in both TC and LDL-C levels compared to management with or without alternative lipid-lowering agents. Interventions for SI are warranted given the high prevalence of nocebo effect and the undoubted benefits of statin treatment. Ideally such interventions should be replicated in a primary care setting.

The pleiotropic effects of statins in rheumatoid arthritis.

Rheumatoid arthritis (RA) is an inflammatory and autoimmune disease. Studies over the past two decades suggest that statins have a beneficial impact on the complications associated with RA. These complications include RA disease activity and risk for cardiovascular diseases (CVD). This review aims to discuss the efficacy of statin therapy in RA. The current evidence suggests that statins' immunomodulatory and antioxidant properties significantly reduce disease activity and inflammatory response in patients with RA. In RA patients, the risk of CVD is reduced by statin treatment, and statin discontinuation is associated with an increased cardiovascular disease risk. The combined effect of statins on improving vascular function, lowering lipid levels, and reducing inflammation in RA patients is responsible for the decreased all-cause mortality in statin users. Further clinical studies are needed to ensure the therapeutic efficacy of statins in patients with RA.

Prevalence of Statin Use and Predictors of Statin Initiation Among Patients with Alcohol-Related Cirrhosis - A Danish Nationwide Cohort Study.

Statins reportedly increase the survival of patients with cirrhosis due to alcohol-related liver disease (ALD cirrhosis), but this association might be confounded by socioeconomic status. We examined the prevalence of statin use and socioeconomic and demographic predictors of statin initiation and discontinuation among patients with ALD cirrhosis. Using Danish nationwide healthcare registries, we examined statin use among patients diagnosed with ALD cirrhosis in 1997-2018. We computed the prevalence of statin use and incidence of statin initiation and discontinuation, and we used multivariable Cox regression to identify predictors of statin initiation and discontinuation. We identified 28,260 patients with ALD cirrhosis in 1997-2018. During this period, the prevalence of statin use rose sharply, reaching 19.0% in late 2018. Among patients diagnosed with ALD cirrhosis after 2010, 16.9% were using statins when they were diagnosed with cirrhosis. Among the patients who did not use statins initially, those with lower educational attainment were more likely to begin taking them than those with higher attainment. Also, cohabiting patients were more likely to begin than patients who lived alone, and employed patients were more likely to begin compared to patients outside the labour force. Among current statin users, unemployment predicted statin discontinuation. The use of statins has become increasingly prevalent among Danish patients with ALD cirrhosis, reaching 19.0% in 2018. Employment, cohabitation, and a short education predicted statin initiation after ALD cirrhosis diagnosis, and unemployment predicted statin discontinuation. Overall, statin use was not a marker of a high socioeconomic status.

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

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

PS-C34-3: EXPERIENCES AND INFLUENCES OF ONLINE HEALTH INFORMATION-SEEKING ABOUT STATIN USE IN PATIENTS WITH HIGH CARDIOVASCULAR RISK: A QUALITATIVE STUDY.

Objectives: Online health information (OHI) about statin use has created debates among healthcare professionals and the public. As a result, online misinformation about statins has led to an increase in the discontinuation of statins. OHI has been shown to influence patients’ health decisions and behaviours. This study explores the views and experiences of OHI-seeking about statins in patients with high cardiovascular risk and how OHI influences patient decision-making and statin adherence. Designs and method: This is a qualitative study with semi-structured in-depth interviews of 20 patients with high cardiovascular risk from a primary care clinic in Malaysia. We included participants who were at least 18 years old and had high cardiovascular risk where statin use is indicated as per guideline (i.e. with pre-existing cardiovascular disease (CVD), diabetes mellitus, chronic kidney disease, a 10-year risk for CVD &gt; 20% based on the Framingham General CVD risk score) and have sought OHI about statins. We used an interpretive description approach with thematic analysis. Results: The age of the participants ranged from 39–74 years, with 16 (80%) participants having hypertension. 12 (60%) participants took a statin for primary CVD prevention. The duration of statin use ranged from 2 weeks to 30 years. Six themes emerged from the interviews (Figure 1): (1) Participants sought different types of OHI throughout the disease trajectory depending on their information needs, (2) There is a changing paradigm of OHI-seeking behaviour, where passive exposure to OHI appears to have increased relative to active searching, (3) Participants sought a wide range of OHI from hypercholesterolemia, lifestyle modification and complementary alternative medicine, (4) Statin-related OHI was mainly negative and stressed the side effects of statins, (5) OHI triggered emotional reactions that may affect patients’ decision on statin adherence, (6) Doctors’ responses to participants’ OHI-seeking behaviour affected patient-doctor communication and patients’ decision in taking statins. Conclusions: This study highlights the changing information needs throughout patient journeys, suggesting the opportunity to provide needs-oriented OHI to patients with high cardiovascular risk. Passive OHI exposure appears to have an influence on patients’ adherence to statins. The quality of patient-doctor communication about OHI-seeking behaviour remains a critical factor in patient decision making. Doctors should discuss patients’ information needs and OHI-seeking behaviour throughout the disease trajectory and provide evidence-based health information to patients. Strategies are needed to address patients’ concerns about statins, acknowledge their emotional reactions toward OHI and support their need for evidence-based OHI.

Estimating prevalence and characteristics of statin intolerance among high and very high cardiovascular risk patients in Germany between 2017–2020

Abstract Background Statins remain the backbone of lipid management. Nevertheless, the degree to which statins can be used and dosed in clinical practice remains a great challenge, also due to statin intolerance (SI). The lack of widely accepted SI definition leads to poor understanding of the condition and SI patient profile Purpose To estimate the current SI prevalence and understand better the patient characteristics, using machine learning techniques Methods Retrospective cohort study, based on representative sample of electronic patient records from outpatient setting in Germany. Patients were included if they had high CV risk, atherosclerotic cardiovascular disease (ASCVD) or hypercholesterolemia (HC), between 2017 and 2020. Patients were categorized as having “absolute” (history of SI events and permanent statin discontinuation) or “partial” (history of SI events while treated with statins) SI. Machine learning techniques were utilized to calibrate the prevalence estimates and to identify patient clusters. Estimates of SI prevalence were derived based on different rules and confidence levels (high, moderate and low). The low confidence estimates contain the most uncertainty in identifying SI Results The study population consisted of 292,603 patients (57.3% aged &amp;gt;70 years; 55.6% male). Of these, ∼24% had high CV risk, ∼56% had ASCVD, and ∼20% had HC. After deploying machine learning, the SI identification improved by ∼27% in absolute SI and by ∼57% in partial SI patients, resulting in a maximum estimate of 12.5% SI with high/moderate confidence and further 11.8% with low confidence (absolute SI 15.8%, partial SI 8.5%). The low confidence group may contain patients with insufficient statin treatment due to reasons other than SI (e.g. clinical inertia). Statistically significant risk factors for SI were hypothyroidism, vitamin D deficiency, liver and chronic kidney disease. Cramps, muscle spasms, myalgia and myopathy were the most common statin associated muscle symptoms (SAMS) observed in the SI population. Atorvastatin 40mg was the most frequently down-titrated statin, while simvastatin to atorvastatin was the most predominant class switch in SI patients. Machine learning techniques applied on high confidence SI patients characteristics and the most commonly observed cluster for patients over 60 years showed predominant musculoskeletal disorders, concomitant high SAMS incidence and high use of multiple statins. In males under 60 years, depression and somatoform disorders along with musculoskeletal disorders, pain, and gastric events were common, while females under 60 years had predominant depressive episodes, along with musculoskeletal, mental, and metabolic disorders Conclusion Addressing the complexity in defining SI using advanced analytics, this study provides prevalence estimates and describes distinct patients clusters that may inform diagnosis and optimal treatment pathways for SI patients in Germany Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Daiichi Sankyo Europe GmbH

Statin-Associated Muscle Symptoms Among New Statin Users Randomly Assigned to Vitamin D or Placebo

Statin-associated muscle symptoms (SAMS) are common and may lead to discontinuation of indicated statin therapy. Observational studies suggest that vitamin D therapy is associated with reduced statin intolerance, but no randomized studies have been reported. To test whether vitamin D supplementation was associated with prevention of SAMS and a reduction of statin discontinuation. Men 50 years or older and women 55 years or older, free of cancer and cardiovascular disease, were enrolled in a randomized, placebo-controlled, double-blind clinical trial of vitamin D supplementation. Participants who initiated statin therapy after randomization were surveyed in early 2016. The data were analyzed in early 2022. Daily cholecalciferol (2000 international units) or placebo with assessment of statin prescriptions during follow-up. Muscle pain or discomfort lasting several days (primary outcome) and discontinuation of a statin due to SAMS (secondary outcome). Statins were initiated by 1033 vitamin D-assigned participants and 1050 placebo-assigned participants; mean (SD) age was 66.8 (6.2) years and 49% were women. Over 4.8 years of follow-up, SAMS were reported by 317 participants (31%) assigned vitamin D and 325 assigned placebo (31%). The adjusted odds ratio (OR) was 0.97 (95% CI, 0.80-1.18; P = .78). Statins were discontinued by 137 participants (13%) assigned to vitamin D and 133 assigned to placebo (13%) with an adjusted OR of 1.04 (95% CI, 0.80-1.35; P = .78). These results were consistent across pretreatment 25-hydroxy vitamin D levels (interaction P value = .83). Among participants with levels less than 20 ng/mL, SAMS were reported by 28 of 85 vitamin D-assigned participants (33%) and 33 of 95 placebo-assigned participants (35%). For those with levels less than 30 ng/ml, SAMS were reported by 88 of 330 vitamin-D assigned participants (27%) and 96 of 323 of placebo-assigned participants (30%). Vitamin D supplementation did not prevent SAMS or reduce statin discontinuation. These results were consistent across pretreatment 25-hydroxy vitamin D levels. ClinicalTrials.gov Identifier: NCT01169259.

Effects of nocebo and drusebo in determining statin-induced muscle symptoms

Statins represent an important class of cardiovascular drugs for the prevention of atherogenic complications. However, despite the effectiveness of statins, non-adherence and discontinuation of therapy with these drugs is a problem worldwide. Reasons for not using statins in patients at high CV risk include statin-associated muscle symptoms (SAMS), which are not usually associated with significant elevations of serum creatine kinase. SAMS are the most common side effects of statins: 3–5% in RCTs, 15–20% in observational studies, and 60% in patient surveys. This range is possibly due to misinterpretation of symptoms, as well as patients’ expectation of harm from statin treatment (“statin fear”). The article highlights the problem of studying the role of nocebo and drusebo effects for SAMS, presents differences in definitions and methods of detection. The concept of the drucebo effect was proposed by the International Lipid Expert Group (ILEP, 2018) as a harm to the patient, unrelated to the pharmacological action of the drug (negative effect of the drucebo). The results of studies and meta-analyses evaluating the effects of nocebo and drusebo for SAMS are presented, in which no difference was found in the frequency and severity of muscle symptoms between statin and placebo; the nocebo rate was 90% of the statin effect, and the contribution of the drusebo effect to SAMS and statin discontinuation ranged from 38 to 78%. Also presented are current international guidelines and principles of patient management aimed at preventing discontinuation of statin use in connection with SAMS.

Estimating prevalence and characteristics of statin intolerance among high and very high cardiovascular risk patients in Germany between 2017–2020

Abstract Background Statins remain the backbone of lipid management. Nevertheless, the degree to which statins can be used and dosed in clinical practice remains a great challenge, also due to statin intolerance (SI). The lack of widely accepted SI definition leads to poor understanding of the condition and SI patient profile Purpose To estimate the current SI prevalence and understand better the patient characteristics, using machine learning techniques Methods Retrospective cohort study, based on representative sample of electronic patient records from outpatient setting in Germany. Patients were included if they had high CV risk, atherosclerotic cardiovascular disease (ASCVD) or hypercholesterolemia (HC), between 2017 and 2020. Patients were categorized as having “absolute” (history of SI events and permanent statin discontinuation) or “partial” (history of SI events while treated with statins) SI. Machine learning techniques were utilized to calibrate the prevalence estimates and to identify patient clusters. Estimates of SI prevalence were derived based on different rules and confidence levels (high, moderate and low). The low confidence estimates contain the most uncertainty in identifying SI Results The study population consisted of 292,603 patients (57.3% aged &amp;gt;70 years; 55.6% male). Of these, ∼24% had high CV risk, ∼56% had ASCVD, and ∼20% had HC. After deploying machine learning, the SI identification improved by ∼27% in absolute SI and by ∼57% in partial SI patients, resulting in a maximum estimate of 12.5% SI with high/moderate confidence and further 11.8% with low confidence (absolute SI 15.8%, partial SI 8.5%). The low confidence group may contain patients with insufficient statin treatment due to reasons other than SI (e.g. clinical inertia). Statistically significant risk factors for SI were hypothyroidism, vitamin D deficiency, liver and chronic kidney disease. Cramps, muscle spasms, myalgia and myopathy were the most common statin associated muscle symptoms (SAMS) observed in the SI population. Atorvastatin 40mg was the most frequently down-titrated statin, while simvastatin to atorvastatin was the most predominant class switch in SI patients. Machine learning techniques applied on high confidence SI patients characteristics and the most commonly observed cluster for patients over 60 years showed predominant musculoskeletal disorders, concomitant high SAMS incidence and high use of multiple statins. In males under 60 years, depression and somatoform disorders along with musculoskeletal disorders, pain, and gastric events were common, while females under 60 years had predominant depressive episodes, along with musculoskeletal, mental, and metabolic disorders Conclusion Addressing the complexity in defining SI using advanced analytics, this study provides prevalence estimates and describes distinct patients clusters that may inform diagnosis and optimal treatment pathways for SI patients in Germany Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Daiichi Sankyo Europe GmbH

Assessment and management of statin-associated muscle symptoms (SAMS): A clinical perspective from the National Lipid Association

Statin-associated muscle symptoms (SAMS) are the most common form of statin intolerance and are associated with increased risk of cardiovascular events that manifest from statin underutilization and discontinuation. The reported frequencies of SAMS are divergent in the literature. The writing group estimates the prevalence of SAMS, namely all muscle symptoms temporally related to statin use but without regard to causality, to be about 10% (range 5% to 25%), and the prevalence of pharmacological SAMS, specifically muscle symptoms resulting from pharmacological properties of the statin, to be about 1-2% (range 0.5% to 4%). In clinical practice, SAMS are likely to result from a combination of pharmacological and nonpharmacological effects, however this does not make the symptoms any less clinically relevant. Regardless of the etiology, SAMS need to be addressed in accordance with patients' preferences and experiences. This clinical perspective reviews the epidemiology and underlying pathophysiology of SAMS, and the cardiovascular consequences resulting from statin discontinuation. We present patient-centered clinical and communication strategies to mitigate SAMS and improve medication adherence and outcomes among statin users. Treatment strategies include 1) optimizing lifestyle interventions, 2) modulating risk factors that may contribute to muscle symptoms, 3) optimizing statin tolerability by dose reduction, decreased dosing frequency, or use of an alternate statin with more favorable pharmacokinetic properties, and 4) use of non-statins, emphasizing those with evidence for atherosclerotic risk reduction, either in combination with or in place of statin therapy depending on the patient's circumstances. The focus of this clinical perspective is sustainable lipoprotein goal achievement, which is important for cardiovascular risk reduction.