Initiation Of Statin Therapy Research Articles

An assessment by the Statin Diabetes Safety Task Force: 2014 update.

Statin therapy reduces the risk of myocardial infarction, stroke, and cardiovascular death by 25% to 30% in primary as well as secondary prevention patients. Thus, statins are the pharmacologic therapy of choice for the management of high blood cholesterol levels. Prompted by examination of clinical trial data suggesting a modest, but statistically significant, increase in the incidence of new-onset type 2 diabetes mellitus with statin use, the US Food and Drug Administration in 2012 added a statement to the labels of statin medications indicating that increases in glycated hemoglobin (HbA1C) and fasting glucose levels have been reported with statin use. This labeling change has raised questions among clinicians regarding the relative benefits and risks of statin use, both among patients with diabetes mellitus and among those with diabetes risk factors. This 2014 report from the Diabetes Subpanel of the National Lipid Association Expert Panel on Statin Safety reviews the published evidence relating statin use to the hazard for diabetes mellitus or worsening glycemia, examines potential mechanisms that may mediate the relationship between statin use and diabetes mellitus risk, and suggests future research efforts. Given the well-established benefits of statin therapy in the primary and secondary prevention of cardiovascular events among those with indications for treatment, no changes to clinical practice are recommended other than the measurement of HbA1C or fasting glucose in those deemed to also be at elevated diabetes risk after initiating statin therapy, and potentially before initiation in selected patients considered to be at elevated risk of developing diabetes. The panel advocates following recommendations from the American Diabetes Association, or other relevant guidelines if outside the United States, for screening and diagnosis as well as lifestyle modification for prevention or delay of diabetes mellitus in those with prediabetes or other risk factors.

An assessment by the Statin Liver Safety Task Force: 2014update.

In the 2006 Report of the National Lipid Association's Statin Safety Task Force, a panel of experts in hepatology published their findings on specific questions related to the liver blood testing during statin therapy. Among their recommendations was that regulatory agencies reconsider the statin-labeling recommendation at that time, which required post-statin liver enzyme testing. Since then, the Food and Drug Administration altered statin labeling such that unless clinically indicated for other reasons, after a pre-statin therapy baseline evaluation, follow-up liver enzyme testing was not uniformly required after statin initiation. This 2014 report provides an update on interim issues relevant to statins and liver safety. Some of the points discussed include the value of baseline liver enzymes before initiating statin therapy, safety of statin use in patients with nonalcoholic fatty liver disease, potential drug interactions between statins and drugs used to treat hepatitis, the use of statins in liver transplant recipients, and the use of statins in patients with autoimmune liver disease. Finally, this panel provides diagnostic and algorithmic approaches when evaluating statin-treated patients who experience elevations in liver enzymes.

Low Vitamin D as a Risk Factor for the Development of Myalgia in Patients Taking High-Dose Simvastatin: A Retrospective Review

BackgroundStatins are the treatment of choice for dyslipidemia, primarily lowering elevated LDL-C levels and reducing the occurrence of major cardiovascular events. In June 2011, the Food and Drug Administration issued a warning regarding the use of high-dose simvastatin 80 mg and its risk of myopathy. ObjectiveThe incidence of myalgia, myopathy, and rhabdomyolysis was analyzed in a veteran population prescribed simvastatin 80 mg. Risk factors for myalgia were examined and compared with the results of recently published studies. MethodsThis was a retrospective medical record review of 450 patients who were prescribed simvastatin 80 mg at the Veterans Affairs Western New York Healthcare System between August 1, 2006, and July 31, 2011. Records were examined for evidence of myalgia, myopathy (incipient or definite), and rhabdomyolysis. Variables that may have contributed to the development of myalgia were also collected and analyzed. ResultsMyalgia was reported by 50 patients (11.1%), whereas rhabdomyolysis developed in 1 patient (0.22%). No patient fit the criteria for myopathy (incipient or definite). Myalgia was statistically more likely to occur in younger patients, patients with a history of myalgia, and patients with low vitamin D levels. The mean (SD) vitamin D level in patients experiencing myalgia was 26.2 (12.9) versus 36.3 (11.8) ng/mL. The 25-hydroxyvitamin D level in those who reported myalgia was approximately 10 ng/mL lower compared with those who tolerated simvastatin 80 mg (P = 0.0003). There was no statistically significant association between length of therapy and development of myalgia. ConclusionA lower incidence of adverse muscle events with high-dose simvastatin 80 mg was found in patients with higher vitamin D levels, suggesting that correction of 25-hydroxyvitamin D levels before statin therapy initiation may mitigate one risk factor in the development of statin-related myalgia. Vitamin D insufficiency appears to be a risk factor for the development of myalgia.

Characterization of diabetes risk factors in patients prescribed chronic statin therapy.

Determine the incidence of major diabetes risk factors over time in patients prescribed chronic statin therapy. Retrospective observational chart review of adult patients without diabetes in primary care who initiated statin therapy between 2005 and 2010. Presence of diabetes risk factors were determined 1 year prior to statin initiation and continued up to a maximum of 7 years. Diabetes risk factors included impaired fasting glucose, body mass index (BMI) ≥30 kg/m(2), hemoglobin A1c >6% and metabolic syndrome. Descriptive statistics were used to describe the incidence of diabetes risk factors over time. A total of 98 patients met study criteria; mean age was 57 ± 13 years, 43% were men and 71% self-identified as Caucasian/white. Mean baseline values were A1c of 5.97%, fasting glucose of 104 mg/dl and BMI of 28 kg/m(2). There were zero diabetes risk factors over time in 54% ± 7% of patients. The incidence over time of 1 risk factor was 25 ± 9%, 2 risk factors was 17 ± 5% and 3 risk factors was 3 ± 2%. A total of 12 patients were diagnosed with type 2 diabetes during the course of the study period. The incidence of diabetes risk factors did not change over time in an ambulatory adult population prescribed chronic statin therapy. Larger population studies assessing the incidence of and change in diabetes risk factors in patients on chronic statin therapy may help assess the association between statin therapy and presence of such risk factors.

EARLY INITIATION OF HIGH-DOSE SIMVASTATIN DURING ST-ELEVATION MYOCARDIAL INFARCTION DECREASES THE INCIDENCE OF CARDIOVASCULAR EVENTS, EVEN IN PATIENTS WITH LOW ADMISSION LDL CHOLESTEROL LEVELS

Early initiation of statin therapy during acute phase of ST-elevation myocardial infarction (STEMI) has been considered controversial particularly in patients with low plasma levels of low-density lipoprotein cholesterol (LDL-C). In this context we aimed to evaluate the impact of early use of statin

EFFICACY AND SAFETY OF ROSUVASTATIN THERAPY FOR CHILDREN AND ADOLESCENTS WITH FAMILIAL HYPERCHOLESTEROLEMIA: RESULTS FROM THE CHARON STUDY

Familial hypercholesterolemia (FH) is a common inherited disorder leading to premature atherosclerosis. Current guidelines recommend initiating statin therapy in children with FH. Previous studies evaluated rosuvastatin in children aged ≥10 years (yrs), but its use in younger children has not yet

Comparison of Cost-Effectiveness, Safety, and Efficacy of Rosuvastatin Versus Atorvastatin, Pravastatin, and Simvastatin in Dyslipidemic Diabetic Patients With or Without Metabolic Syndrome

The aim of the current study was to determine the efficacy of the 4 most commonly prescribed statins (rosuvastatin, atorvastatin, pravastatin, and simvastatin) for managing dyslipidemia among diabetic patients with and without metabolic syndrome (MetS). This was a cohort observational population-based study conducted at Hamad Medical Hospital and Primary Health Care Centre. The participants were 1542 consecutive diabetes patients who were diagnosed with dyslipidemia and were prescribed any of the indicated statins. Sociodemographic and clinical characteristics were taken from medical records, and lipid profile at baseline and 2 years after the initiation of statin therapy were retrieved from electronic medical records database (EMR-viewer). Reduction in different lipid profile after 2 years of therapy was compared among different types of statins between patients with and without MetS. Out of total 1542 subjects, 562(36.4%) were diagnosed with MetS using the criteria of International Diabetes Federation. Among those with MetS, 125 were prescribed with atorvastatin, 162 pravastatin, 177 rosuvastatin, and 98 simvastatin. Among those without MetS, 365 used atorvastatin, 172 pravastatin, 345 rosuvastatin, and 98 simvastatin therapies. Among patients with MetS, rosuvastatin therapy resulted in significantly higher low-density lipoprotein cholesterol and total cholesterol reduction (23%, P = .006; and 20.3%, P = .015, respectively) as compared with other statins. Similarly, significantly higher percentage of patients receiving rosuvastatin therapy were successful in achieving the target of total cholesterol <4 mmol/L and triglycerides <1.7 mmol/L after 2 years (38.4%, P = .012; and 67.2%, P = .010, respectively) as compared with other therapies. In contrast, among patients without MetS, rosuvastatin therapy resulted in highest percentage drop in total cholesterol (20.1%; P = .016) than other statin therapies. The present study confirmed that rosuvastatin therapy in commonly prescribed doses is the most effective statin for low-density lipoprotein cholesterol goal achievement and for improving the lipid profile in hypercholesterolemic diabetic patients with and without MetS.

Trends in statin therapy initiation during the period 2000–2010 in Israel

The aim of this population-based study is to describe trends in the characteristics and treatment patterns of statin initiators over the first decade of the 21st century. New statin use was studied retrospectively using the database of Maccabi Healthcare Services (MHS), a large Israeli health maintenance organization. Statin initiators were defined as MHS members aged ≥ 30 years who first purchased statins between 2000 and 2010. The starting dose was calculated in simvastatin equivalents based on the World Health Organization's daily defined dose index. Persistence was calculated as the percentage of days covered (PDC) with statins during the first year of therapy. Statin initiation peaked in 2005 and decreased from 38.6 to 18.6 per 1,000 in the period 2005-2010. The average age at therapy initiation decreased from 58.9 (± 12.0) to 54.5 (± 11.7) years, and the average (SD) baseline low-density lipoprotein cholesterol (LDL-C) decreased from 4.2 (± 1.1) to 4.0 (± 0.9) mmol/l during the study period. Women were on average 3 years older than men at treatment initiation, with a higher baseline LDL-C. Among statin initiators, the prevalence of ischemic heart disease (IHD) decreased from 17.8 to 6.7 %, and diabetes prevalence increased from 8.6 to 15.7 %, peaking in 2008 (18.0 %). The PDC with statins ranged between 52.9 and 57.7 %. Simvastatin use at initiation increased from 27.5 % in 2000 to >90 % since 2002. Starting dose increased from 18.5 (± 8.9) to 24.3 (± 13.7) mg simvastatin equivalent. Among the study population, statin initiators were increasingly characterized by a lower cardiovascular risk-namely, younger individuals without IHD and with a lower baseline LDL-C. These trends underscore the important shift towards statin initiation for primary prevention, as well as the need to balance between benefits and the potential side effect of statins.

Cardiovascular prevention: lifestyle and statins--competitors or companions?

Favourable lifestyles promote cardiovascular protection. Exercise can induce beneficial changes in the genome that decrease low-density lipoprotein cholesterol (LDL-C) and increase anti-inflammatory markers. The Mediterranean dietary pattern, fortified by nuts, while not reducing weight, reduces mortality. Lifestyle changes combined with statin therapy provide potent protection against coronary heart disease, especially when used for secondary prevention after cardiovascular events. Decisions regarding the initiation of statin therapy for primary prevention are more difficult, requiring consideration of both the LDL-C level and the degree of cardiovascular risk for dyslipidaemic patients. Combining intensive exercise and statin therapy substantially reduces the mortality risk, and thus is potentially the ideal risk-reducing combination.

Preemptive Genotyping for Personalized Medicine: Design of the Right Drug, Right Dose, Right Time—Using Genomic Data to Individualize Treatment Protocol

To report the design and implementation of the Right Drug, Right Dose, Right Time-Using Genomic Data to Individualize Treatment protocol that was developed to test the concept that prescribers can deliver genome-guided therapy at the point of care by using preemptive pharmacogenomics (PGx) data and clinical decision support (CDS) integrated into the electronic medical record (EMR). We used a multivariate prediction model to identify patients with a high risk of initiating statin therapy within 3 years. The model was used to target a study cohort most likely to benefit from preemptive PGx testing among the Mayo Clinic Biobank participants, with a recruitment goal of 1000 patients. We used a Cox proportional hazards model with variables selected through the Lasso shrinkage method. An operational CDS model was adapted to implement PGx rules within the EMR. The prediction model included age, sex, race, and 6 chronic diseases categorized by the Clinical Classifications Software for International Classification of Diseases, Ninth Revision codes (dyslipidemia, diabetes, peripheral atherosclerosis, disease of the blood-forming organs, coronary atherosclerosis and other heart diseases, and hypertension). Of the 2000 Biobank participants invited, 1013 (51%) provided blood samples, 256 (13%) declined participation, 555 (28%) did not respond, and 176 (9%) consented but did not provide a blood sample within the recruitment window (October 4, 2012, through March 20, 2013). Preemptive PGx testing included CYP2D6 genotyping and targeted sequencing of 84 PGx genes. Synchronous real-time CDS was integrated into the EMR and flagged potential patient-specific drug-gene interactions and provided therapeutic guidance. This translational project provides an opportunity to begin to evaluate the impact of preemptive sequencing and EMR-driven genome-guided therapy. These interventions will improve understanding and implementation of genomic data in clinical practice.

Comparative effectiveness of rosuvastatin versus simvastatin in primary prevention among new users: a cohort study in the French national health insurance database

PurposeUsing the French claims database (Système National d'Information Inter-Régimes de l'Assurance Maladie) linked to the hospital discharge database (Programme de Médicalisation des Systèmes d'Information), this observational study compared the effectiveness of rosuvastatin and simvastatin prescribed at doses with close LDL-cholesterol-lowering potency on all-cause mortality and cardiovascular and cerebrovascular diseases (CCDs) in primary prevention.MethodsThis historical cohort included patients with no prior CCD, aged 40–79 years, who initiated statin therapy with rosuvastatin 5 mg or simvastatin 20 mg in 2008–2009 in general practice. Follow-up started after a 1-year period used to select patients who regularly received the initial treatment.In an intention-to-treat analysis, patients were followed up to December 2011. In a per-protocol analysis, they were censored prematurely when they discontinued their initial treatment. Adjustment for baseline covariates (age, deprivation index, comedications, comorbidities, prior hospital admissions) was carried out by a Cox proportional hazards model. In the per-protocol analysis, estimation was done by “inverse probability of censoring weighting” using additional time-dependent covariates. Analyses were gender-specific.ResultsA total of 106 941 patients initiated statin therapy with rosuvastatin 5 mg and 56 860 with simvastatin 20 mg. Mean follow-up was 35.8 months. For both genders and both types of analyses, the difference in incidence rates of mortality and/or CCD between rosuvastatin 5 mg and simvastatin 20 mg users was not statistically significant after adjustment (e.g., for CCD and/or mortality in men, in intention-to-treat analysis HR = 0.94 [95% CI = 0.85–1.04], in per-protocol analysis HR = 0.98 [0.87–1.10]).ConclusionsThe results of this real-life study based on medico-administrative databases do not support preferential prescription of rosuvastatin compared to simvastatin for primary prevention of CCD.

Continuation of statin therapy and a decreased risk of atrial fibrillation/flutter in patients with and without chronic kidney disease

BackgroundTo contain cost, Taiwan's previous National Health Insurance Reimbursement Policy requested that physicians discontinue their patients' statin therapy once the serum cholesterol had reached appropriate levels. This allowed us to evaluate the association between statin continuation and the occurrence of atrial fibrillation/flutter and whether it was modified by chronic kidney disease (CKD) status. MethodsPatients who initiated statin therapy between January 1, 2001 and December 31, 2009 were identified from a random sample of one million subjects in the Taiwan National Health Insurance Research Database. The outcome was atrial fibrillation/flutter. A proportional hazard regression model with time-varying statin use was applied to estimate the hazard ratios (HR) and 95% confidence intervals (CIs) for atrial fibrillation/flutter according to current statin use versus treatment discontinuation, adjusted for baseline disease risk scores and time-varying covariates. ResultsA total of 6767 CKD and 63,678 non-CKD patients initiating statin therapy were included and followed for an average of 4.0 years. A total of 1118 participants experienced new-onset atrial fibrillation/flutter. The incidence of atrial fibrillation/flutter was approximately 2 fold higher in the CKD patients. Continuation of statin therapy was associated with a 22% (adjusted hazard ratio 0.78; 95% CI: 0.65–0.93) and 57% (adjusted HR 0.43; 95% CI: 0.27–0.68) decrease in atrial fibrillation/flutter hazard as compared with discontinuation in non-CKD and CKD patients, respectively. ConclusionsContinuation of statin therapy was associated with a decreased risk of atrial fibrillation/flutter among CKD and non-CKD patients. However, further randomized studies are still needed to assess the association.

The impact of manufacturer coupon use in the statin market.

Pharmaceutical manufacturer coupons are a rapidly growing promotional activity intended to encourage initiation and continuing use of brand-name medications, but little is known about impacts on medication adherence and expenditures. To understand which patients use manufacturer coupons and the impact of coupons on brand-name statin (atorvastatin and rosuvastatin) use and expenditures 1 year after initiation of statin therapy. Using commercially available claims data spanning 3 years and representing 340,350 patients, we compared demographics, statin use, and expenditures of patients initiating generic statins, brand-name statins without manufacturer coupons, and brand-name statins with manufacturer coupons. Differences in user groups were tested using chi-squared statistics and Wilcoxon-Mann-Whitney tests. Main outcome measures included statin fills, adherence, and expenditures, including patient out-of-pocket, payer, and total costs. With the exception of population density, there were no significant demographic differences between new to therapy brand-name statin users filling prescriptions with and without coupons. New to therapy patients using generics were younger and lived in less populated areas compared with new to therapy brand-name statin noncoupon users. The number of statin fills in the 12 months following initiation was highest for coupon users, slightly lower for patients initiating generic statins, and lowest for noncoupon users (7.1 vs. 6.3 vs. 5.8; P < 0.001), with corresponding medication adherence rates (61.1% vs. 60.1% vs. 53.8%; P < 0.001). Coupon users had higher total statin prescription costs than generic initiators and noncoupon users ($798 vs. $92 vs. $678; P < 0.001), and higher precoupon out-of-pocket costs ($339 vs. $53 vs. $169; P < 0.001). Health plan costs for statins excluding rebates were lower for coupon users than noncoupon users ($460 vs. $508; P < 0.001) but were much higher compared with generic statin initiators ($460 vs. $39; P < 0.001). Brand-name statin initiators using coupons have higher adherence than patients initiating generic statins or brand-name statins without coupons. While the differences in adherence were statistically significant, they may not be clinically significant. Higher adherence among coupon users appears to occur at the expense of higher out-of-pocket and total statin expenditures.

Initiation of statin therapy after acute myocardial infarction is not associated with worsening depressive symptoms: Insights from the Prospective Registry Evaluating Outcomes After Myocardial Infarctions: Events and Recovery (PREMIER) and Translational Research Investigating Underlying Disparities in Acute Myocardial Infarction Patients' Health Status (TRIUMPH) registries

Whereas statins are considered the cornerstone of prevention after acute myocardial infarction (AMI), concerns about worsening depression in association with their use have been raised. Using data from 2 prospective AMI registries (PREMIER and TRIUMPH), we examined the change in depressive symptoms from baseline and at 1, 6 and 12 months among statin-naïve patients who were and were not discharged on a statin. Depressive symptoms were assessed with the 8-item Patient Health Questionnaire (PHQ-8). Within-group change in PHQ-8 scores from baseline to each follow-up period was assessed using paired t tests. A repeated-measures propensity-matched analysis examined whether changes in PHQ-8 scores from baseline were different between statin-treated and statin-untreated patients. Of 3,675 patients not previously treated with statins, 3,050 (83%) were discharged on a statin and 625 (17%) were not. Scores of PHQ-8 in the statin group decreased from baseline by a mean (± SD) of 0.9 (± 5.1), 1.2 (± 5), and 1.1 (± 5.1) at 1, 6, and 12 months, respectively. Corresponding changes in the nonstatin group were 0.9 (± 5.2), 1.3 (± 5.1), and 1.5 (± 5.8), respectively (P < .0001 for all comparisons). After propensity matching, 451 patients not discharged on statins with 1,240 patients discharged on statins, the mean change in PHQ-8 scores between baseline and the 3 follow-up time points was not significantly different between groups (mean between-group difference at 1 month: -0.13, 95% CI [-0.69 to 0.43], P = .65; at 6 months: -0.07, 95% CI [-0.66 to 0.52], P = .82; and at 12 months: -0.05, 95% CI [-0.67 to 0.58], P = .88). Initiation of statins after AMI was not associated with worsening depression.

Circulation : Clinical Summaries

<i>Circulation</i> : Clinical Summaries

Levels and Changes of HDL Cholesterol and Apolipoprotein A-I in Relation to Risk of Cardiovascular Events Among Statin-Treated Patients

Background— It is unclear whether levels of high-density lipoprotein cholesterol (HDL-C) or apolipoprotein A-I (apoA-I) remain inversely associated with cardiovascular risk among patients who achieve very low levels of low-density lipoprotein cholesterol on statin therapy. It is also unknown whether a rise in HDL-C or apoA-I after initiation of statin therapy is associated with a reduced cardiovascular risk. Methods and Results— We performed a meta-analysis of 8 statin trials in which lipids and apolipoproteins were determined in all study participants at baseline and at 1-year follow-up. Individual patient data were obtained for 38 153 trial participants allocated to statin therapy, of whom 5387 suffered a major cardiovascular event. HDL-C levels were associated with a reduced risk of major cardiovascular events (adjusted hazard ratio [HR], 0.83; 95% confidence interval [CI], 0.81–0.86 per 1 standard deviation increment), as were apoA-I levels (HR, 0.79; 95% CI, 0.72–0.82). This association was also observed among patients achieving on-statin low-density lipoprotein cholesterol levels &lt;50 mg/dL. An increase of HDL-C was not associated with reduced cardiovascular risk (HR, 0.98; 95% CI, 0.94–1.01 per 1 standard deviation increment), whereas a rise in apoA-I was (HR, 0.93; 95% CI, 0.90–0.97). Conclusions— Among patients treated with statin therapy, HDL-C and apoA-I levels were strongly associated with a reduced cardiovascular risk, even among those achieving very low low-density lipoprotein cholesterol. An apoA-I increase was associated with a reduced risk of major cardiovascular events, whereas for HDL-C this was not the case. These findings suggest that therapies that increase apoA-I concentration require further exploration with regard to cardiovascular risk reduction.

Therapeutic practice patterns related to statin potency and ezetimibe/simvastatin combination therapies in lowering LDL-C in patients with high-risk cardiovascular disease

Statin combination therapy and statin uptitration have been shown to be efficacious in low-density lipoprotein cholesterol (LDL-C) lowering and are recommended for patients with high-risk coronary heart disease (CHD) who do not reach guideline-endorsed LDL-C goals on statin monotherapy. This analysis evaluated treatment practice patterns and LDL-C lowering for patients with CHD/CHD risk equivalent on statin monotherapy in a real-world practice setting in the United States. In this retrospective, observational study, patients with CHD/CHD risk equivalent on statin therapy were identified during 2004 to 2008 in a US managed care database. Prescribing patterns and effect of switching from statin monotherapy to combination ezetimibe/simvastatin therapy vs uptitration to higher statin dose/potency level and no change from initial statin potency on LDL-C lowering were assessed. Percentage of change from baseline in LDL-C levels and odds ratios for LDL-C goal attainment were estimated with analyses of covariance and logistic regression. Of 27,919 eligible patients on statin therapy, 2671 (9.6%) switched to ezetimibe/simvastatin therapy, 11,035 (39.5%) uptitrated statins, and 14,213 (50.9%) remained on the same statin monotherapy. LDL-C reduction from baseline and attainment of LDL-C <100 and <70 mg/dL were substantially greater for patients who switched to ezetimibe/simvastatin therapy (-24.0%, 81.2%, and 35.2%, respectively) than for patients who titrated (-9.6%, 68.0%, and 18.4%, respectively) or remained on initial statin therapy (4.9%, 72.2%, and 23.7%, respectively). The odds ratios for attainment of LDL-C <100 and <70 mg/dL were also higher for patients who switched than for patients who uptitrated and had no therapy change than for patients who titrated vs no therapy change. Similarly, among a subgroup of patients not at LDL-C <100 mg/dL on baseline therapy, attainment of LDL-C <100 and <70 mg/dL was greater for patients who switched than for statin uptitration vs no change, as well as for patients who uptritrated statins vs no therapy change. In this study, LDL-C lowering and goal attainment rates improved substantially for patients with high-risk CHD on statin monotherapy who switched to combination ezetimibe/statin or uptitrated their statin therapies; however, approximately one-third of these patients still did not attain the optional recommended LDL-C goal of <70 mg/dL. Moreover, these higher efficacy lipid-lowering therapies were infrequently prescribed, indicating the need for further assessment of barriers to LDL-C goal attainment in actual practice settings.

Standard and intensive lipid-lowering therapy with statins for the primary prevention of vascular diseases: a population-based study

To describe the clinical profile of the patients that initiate statin therapy for the primary prevention of vascular diseases and to investigate the extent to which clinicians use intensive vs. standard regimens. A cross-sectional analysis of nationwide individual data regarding individuals ≥ 11 years with a first prescription of statin, recorded between 1 January 2007 and 31 December 2011. Subjects were defined as intensive therapy initiators if a statin dose superior to simvastatin 40 mg (or equivalent dose if different statin) was first prescribed. Multivariable logistic regression models were built for dependent summary variables to evaluate the strength of the association between them and the use of intensive therapy. Overall, 69,737 patients receiving a first prescription of statin for the primary prevention of vascular diseases were identified. Predictors for intensive therapy initiation were male gender (adjusted OR: 1.28; 95%CI: 1.10-1.48), history of hypothyroidism (1.47; 1.17-1.85), current treatment of diabetes (1.18; 1.00-1.41), proteinuria (1.87; 1.12-3.12), age, and year of statin prescription. Modifiable risk factors associated with intensive therapy were elevated tryglicerides (1.63; 1.39-1.91), elevated LDL-C (1.96; 1.69-2.28), obesity (1.25; 1.07-1.47), smoking (1.32; 1.14-1.55), comedication with ezetimibe (3.76; 1.87-7.55), fibrates (1.96; 1.43-2.70) and calcium antagonists in women (1.42; 1.02-1.98). The use of intensive therapy with statins in primary prevention was not very high in absolute terms, but is increasing considerably. The association between intensive therapy and previous hypothyroidism or its combination with fibrates may raise additional safety and tolerability concerns.

Discontinuation of statin therapy associates with Parkinson disease

To evaluate the effect of discontinuing statin therapy on incidence of Parkinson disease (PD) in statin users. Participants who were free of PD and initiated statin therapy were recruited between 2001 and 2008. We examined the association between discontinuing use of statins with different lipophilicity and the incidence of PD using the Cox regression model with time-varying statin use. Among the 43,810 statin initiators, the incidence rate for PD was 1.68 and 3.52 per 1,000,000 person-days for lipophilic and hydrophilic statins, respectively. Continuation of lipophilic statins was associated with a decreased risk of PD (hazard ratio [HR] 0.42 [95% confidence interval 0.27-0.64]) as compared with statin discontinuation, which was not modified by comorbidities or medications. There was no association between hydrophilic statins and occurrence of PD. Among lipophilic statins, a significant association was observed for simvastatin (HR 0.23 [0.07-0.73]) and atorvastatin (HR 0.33 [0.17-0.65]), especially in female users (HR 0.11 [0.02-0.80] for simvastatin; HR 0.24 [0.09-0.64] for atorvastatin). As for atorvastatin users, the beneficial effect was seen in the elderly subgroup (HR 0.42 [0.21-0.87]). However, long-term use of statins, either lipophilic or hydrophilic, was not significantly associated with PD in a dose/duration-response relation. Continuation of lipophilic statin therapy was associated with a decreased incidence of PD as compared to discontinuation in statin users, especially in subgroups of women and elderly. Long-term follow-up study is needed to clarify the potential beneficial role of lipophilic statins in PD.

PCV14 - Impact of initiating statin therapy at a high dose – A retrospective observational study populations in the United Kingdom

PCV14 - Impact of initiating statin therapy at a high dose – A retrospective observational study populations in the United Kingdom