A retrospective study on the preventive effect of statin after carotid artery stenting.

ABSTRACT: This retrospective study appraised the preventive effect of statin after carotid artery stenting (CAS).Records were extracted for 100 patients with CAS surgery indicator, aged between 20 and 75 years old, and treated for statin. The cohort study included treatment group (statin and routine treatment) and control group (routine treatment), each group 50 patients. Outcomes consisted of degree of nerve defect (as measured by National Institute of Health Stroke Scale), lipid profiles (mg/dL), and CAS complications within 30 days after surgery.After treatment, there were no significant differences in National Institute of Health Stroke Scale, lipid profiles, and mortality rate between 2 groups. However, significant differences in total cholesterol (mg/dL, P = .03), low-density lipoprotein (mg/dL, P = .01), transient ischemic attack (P = .03), ischemic stroke (P = .04), and cardiac complications (P = .03) were identified within 30 days after CAS between 2 groups.The results of this study showed that prior statin treatment may be effective for the prevention of CAS complications.

Method development for quantitative determination of seven statins including four active metabolites by means of high-resolution tandem mass spectrometry applicable for adherence testing and therapeutic drug monitoring.

Background Statins are used to treat and prevent cardiovascular diseases (CVDs) by reducing the total serum cholesterol concentration. Unfortunately, dose-related side effects and sub-optimal response, attributed to non-adherence amongst others, were described. Therefore, a fast and sensitive liquid chromatography-high-resolution tandem mass spectrometry (LC-HRMS/MS) method for adherence testing and therapeutic drug monitoring of all currently marketed statins and their active metabolites in human blood plasma should be developed, validated and tested for applicability. Methods Atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, and simvastatin, as well as ortho- and para-hydroxy-atorvastatin, lovastatin hydroxy acid and simvastatin hydroxy acid were included and several internal standards (IS) tested. Validation was performed according to the guideline of the European Medicines Agency including selectivity, carry-over, accuracy, precision, matrix effects, dilution integrity and analyte stability. Finally, applicability was tested using 14 patient samples submitted for regular toxicological analysis. Results Due to an analytical interference of atorvastatin-d5, diazepam-d5 and pentobarbital-d5 were chosen as IS for positive and negative ionization mode, respectively. All statins and metabolites fulfilled the validation acceptance criteria except for fluvastatin, which could not be quantified reliably and reproducibly, most probably due to instability. Analyses of human plasma samples revealed concentrations of statins and metabolites below the reference plasma concentrations in the case of eight patients. However, nothing was known concerning patients' adherence and time between intake and sampling. Conclusions An LC-HRMS/MS method for identification and quantification of atorvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, simvastatin and four active metabolites was successfully developed and applicability demonstrated.

Statin Use in the U.S. for Secondary Prevention of Cardiovascular Disease Remains Suboptimal.

BACKGROUND: Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of mortality in the United States. The purpose of this study is to examine the rates of statin use for secondary prevention of ASCVD events in the United States over the last decade and determine whether disparities in the treatment of ASCVD still persist among women and racial/ethnic minorities. METHODS: We conducted a trend analysis using data from 2008 through 2016 to describe age-adjusted trends in the use of statins for secondary prevention using the Medical Expenditure Panel Survey. We also conducted a multivariable logistic regression analysis to determine whether sociodemographic characteristics are associated with statin use during the 3 years that followed the publication of the 2013 American College of Cardiology/American Heart Association (ACC/AHA) guideline (2014 through 2016). RESULTS: The prevalence of statin use among those with a history of ASCVD remained unchanged from 2008 through 2016. In 2014 to 2016, more than 40% of those aged 40 years and older with a history of ASCVD did not use statins, corresponding to approximately 9.5 million Americans. Increasing age and having been diagnosed with high cholesterol (odds ratio [OR], 6.22; P < .001) were associated with higher odds of statin use while being female (OR, 0.65; P < .001) or Hispanic (OR, 0.69; P = .011) were associated with lower odds of statin use. CONCLUSIONS: Our study found there was no increase in the national rates of statin use following the ACC/AHA 2013 secondary prevention guideline and the availability of generic statins. Significant gender and ethnic disparities in ASCVD treatment remained in the United States.

Combining Multiple Treatment Comparisons with Personalized Patient Preferences: A Randomized Trial of an Interactive Platform for Statin Treatment Selection.

BACKGROUND: Patients and clinicians are often required to make tradeoffs between the relative benefits and harms of multiple treatment options. Combining network meta-analysis results with user preferences can be useful when choosing among several treatment alternatives. OBJECTIVE: Using cholesterol-lowering statin drugs as a case study, we aimed to determine whether an interactive web-based platform that combines network meta-analysis findings with patient preferences had an effect on the decision-making process in a general population sample. METHOD: This was a pilot parallel randomized controlled trial. We used Amazon's Mechanical Turk to recruit adults residing in the United States. A total of 349 participants were randomly allocated to view either the interactive tool (intervention) or a series of bar charts (control). The primary endpoint was decisional conflict, and secondary endpoints included decision self-efficacy, preparation for decision making, and the overall ranking of statins. RESULTS: A total of 258 participants completed the trial and were included in the analysis. On the primary outcome, participants randomized to the interactive tool had significantly lower levels of decisional conflict than those in the control group (difference, -8.53; 95% confidence interval [CI], -12.96 to -4.11 on a 100-point scale; P = 0.001). They also appeared to have higher levels of preparation for decision making (difference, 4.19; 95% CI, -0.24 to 8.63 on a 100-point scale; P = 0.031). No difference was found for decision self-efficacy, although groups were statistically significantly different in how they ranked different statins. CONCLUSION: The findings of our proof-of-concept evaluation suggest that an interactive web-based tool combining published clinical evidence with individual preferences can reduce decisional conflict and better prepare individuals for decision making.

Underutilization of antiplatelet and statin therapy after postoperative myocardial infarction following vascular surgery.

OBJECTIVE: The objective of this study was to investigate adherence to practice guidelines for antiplatelet and statin use after postoperative myocardial infarction (POMI) and its effect on late mortality following vascular surgery in a multicenter registry. METHODS: Antiplatelet and statin use was examined in 1749 vascular surgery procedures with POMI within the Vascular Quality Initiative (VQI) from 2005 to 2015. Our primary aim was to assess cardiac medication (CM) use at discharge, defined as (1) single antiplatelet therapy (SAPT; aspirin or P2Y12 inhibitor) or dual antiplatelet therapy (DAPT; aspirin and P2Y12 inhibitor) and (2) statin therapy. Long-term mortality in patients with POMI was analyzed on the basis of discharge CM. A proportional hazards model was developed to control for factors associated with mortality. Regional differences in CM use at discharge after POMI were compared. RESULTS: Overall discharge CM use after POMI included aspirin (81%), P2Y12 inhibitor (38%), statin therapy (76%), and combined antiplatelet and statin (74%). At discharge, 26% of patients were not receiving combined antiplatelet and statin therapy. SAPT (50%) was more common than DAPT (35%; P < .001). Patients with POMI undergoing carotid endarterectomy were more likely to be discharged on CM (80%) compared with patients undergoing infrainguinal bypass (78%), suprainguinal bypass (72%), endovascular aneurysm repair (71%), and open abdominal aortic aneurysm repair (59%; P < .001). Patients receiving SAPT or DAPT plus statin therapy had improved survival (79%) compared with those receiving noncombination or no therapy (69%) with mean follow-up of 5.5 years and 4.9 years, respectively (log-rank, P = .001). After adjustment for covariates including preoperative medications, treatment with SAPT or DAPT plus statin at discharge was associated with lower late mortality compared with noncombination or no therapy (hazard ratio, 0.72; 95% confidence interval, 0.56-0.93; P = .01). Regional variation in CM at discharge following POMI was also observed with a range of 33% to 100% (P = .05). CONCLUSIONS: Within the VQI, regional and procedure-specific variation exists in CM regimen after POMI following vascular surgery. Absence of combined antiplatelet and statin therapy at discharge after POMI was associated with higher late mortality and represents an area for quality improvement in the care of these patients.

Utilization and adherence to guideline-recommended lipid-lowering therapy at an academic medical center.

BACKGROUND: Clinical guidelines for managing blood cholesterol were updated in November 2013. OBJECTIVE: To evaluate the adherence to the 2013 American College of Cardiology/American Heart Association (ACC/AHA) guideline recommendations for statin therapy in the treatment of elevated blood cholesterol in high-risk patients. DESIGN: A single-center, retrospective, observational study. SETTING: A tertiary care academic medical center in Riyadh, Saudi Arabia. PATIENTS: Consecutive adult patients discharged with a prescription for any of the statin medications group between 1 June 2015 and 31 December 2015. MAIN OUTCOME MEASURE(S): Adherence to the 2013 ACC/AHA guidelines for management of cholesterol by statin therapy in high-risk patients. RESULTS: Of 1094 patients, 753 (68.8%) met the inclusion criteria of the study. Of these 753 patients, 53.5% had atherosclerotic cardiovascular diseases; 29.2% had diabetes; 0.9% had an LDL-C level > 190 mg/dL; 10.8% had an estimated 10-year risk > 7.5%; and 4.9% had no risk. Two hundred and eight (27.6%) patients received statin therapy at an inappropriate intensity according to their risk group based on the guideline; 126 (16.7%) received less than the ideal intensity. CONCLUSION: Approximately one-third of patients received statin therapy at an inappropriate intensity according to the guideline recommendation. Wide application of the 2013 ACC/AHA cholesterol guidelines in our practice would optimize the utilization of statin therapy at the ideal intensity in high-risk patients. LIMITATION: Drug-drug interactions and intolerance to statin therapy were not considered when we evaluated adherence among high-risk patients.

Are recent statin recommendations to employ fixed doses and abandon targets effective for treatment of hypercholesterolaemia? Investigation based on number needed to treat.

BACKGROUND: Assessed by number needed to treat (NNT) to prevent one event, it was previously shown that for those at similar atherosclerotic cardiovascular disease (CVD) risk, the benefit accruing from treating people with higher cholesterol levels with statins is greater than for those with lower levels. METHOD: By estimating NNT from both the absolute atherosclerotic cardiovascular risk and the pre-treatment low density lipoprotein cholesterol (LDL-C) concentration, recent recommendations for fixed dose high and moderate intensity statin treatment in the primary and secondary prevention of CVD were compared with cholesterol-lowering therapy aimed at a target LDL-C. RESULTS: We report that the USA and UK recommendations to employ a fixed dose of atorvastatin 20 mg daily for primary prevention will produce good results in people with low cholesterol levels, but are a disadvantage for those with higher levels who benefit more from a therapeutic target and statin dose titration and, where necessary, adjunctive cholesterol-lowering therapy to achieve this target. The higher dose of atorvastatin 80 mg daily with no target recommended for secondary prevention is generally more effective than aiming for a LDL-C goal except in people with particularly high cholesterol. CONCLUSION: For optimum clinical effectiveness, initial LDL-C concentration must be considered in deciding whether a target will allow a greater decrease in LDL-C and thus a lower NNT than a fixed dose regimen. Individual variation in the LDL-C response to statins also makes post-treatment cholesterol measurement essential.

PHARMACEUTICAL QUALITY OF GENERIC ATORVASTATIN PRODUCTS COMPARED WITH THE INNOVATOR PRODUCT: A NEED FOR REVISING PRICING POLICY IN PALESTINE.

Atorvastatin reduces morbidity and mortality due to cardiovascular events. This study was conducted to assess the prices and pharmaceutical quality of innovator atorvastatin 20 mg with its locally available generics in Palestine and to assess the suitability of their interchangeability. The prices of innovator and generic atorvastatin 20 mg were determined and compared. Innovator atorvastatin and four generic products were tested for their pharmaceutical quality. Tablets were tested for their drug contents, weight uniformity, hardness, disintegration and dissolution. Three out of four generics were less expensive than the innovator. Pharmaceutical quality assessments were satisfactory and within limits for all atorvastatin tested products. The average weight ranged from 206.6 ± 8.40 to 330 ± 3.92 mg and the %RSDs were within the permitted limits as per USP. Tablet hardness ranged from 102 ± 1.41 to 197.4 ± 6.88 kg and drug contents ranged from 92.2% to 105.3%. All products disintegrated within permitted time limits and showed very rapid dissolution. Products released more than 85% of their drug contents in less than 15 min. Our results showed that all tested innovator and generic atorvastatin products were of good pharmaceutical quality. Despite the lack of in vivo evaluation, our results indicate that these products are equivalent in vitro. Considering the in vitro release characteristics, these products might be used interchangeably. However, regulatory authorities permit the use of in vitro data in establishing similarity between immediate release oral dosage forms containing biopharmaceutical classification system class I and III drugs only.

Reporting on the Strategies Needed to Implement Proven Interventions: An Example From a "Real-World" Cross-Setting Implementation Study.

UNLABELLED: The objective of this study was to empirically demonstrate the use of a new framework for describing the strategies used to implement quality improvement interventions and provide an example that others may follow. Implementation strategies are the specific approaches, methods, structures, and resources used to introduce and encourage uptake of a given intervention's components. Such strategies have not been regularly reported in descriptions of interventions' effectiveness, or in assessments of how proven interventions are implemented in new settings. This lack of reporting may hinder efforts to successfully translate effective interventions into "real-world" practice. A recently published framework was designed to standardize reporting on implementation strategies in the implementation science literature. We applied this framework to describe the strategies used to implement a single intervention in its original commercial care setting, and when implemented in community health centers from September 2010 through May 2015. Per this framework, the target (clinic staff) and outcome (prescribing rates) remained the same across settings; the actor, action, temporality, and dose were adapted to fit local context. The framework proved helpful in articulating which of the implementation strategies were kept constant and which were tailored to fit diverse settings, and simplified our reporting of their effects. Researchers should consider consistently reporting this information, which could be crucial to the success or failure of implementing proven interventions effectively across diverse care settings. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT02299791.

Adherence to the 2013 Blood Cholesterol Guidelines in Patients With Diabetes at a PCMH: Comparison of Physician Only and Combination Physician/Pharmacist Visits.

PURPOSE: The purpose of this study is to assess adherence to the 2013 blood cholesterol guideline in a population with diabetes based on the atherosclerotic cardiovascular (ASCVD) risk. METHODS: Patients with diabetes were assessed to see whether they received the appropriate intensity statin therapy via chart review. Patients seen by a physician or pharmacist at CommUnityCare, a PCMH, from December 2013 to October 2014 were included in this retrospective study. The ASCVD risks were calculated to determine if the patients received appropriate intensity statin. RESULTS: A total of 583 patients met the inclusion criteria; there were 475 in the physician only group and 108 with additional pharmacist visits. Statin therapy was prescribed in 71% of patients in the physician group and 88% of patients in the pharmacist/physician group. The appropriate intensity statin was prescribed in 32% of patients in the physician group and 35% of patients in the pharmacist/physician group. The appropriate intensity statin in statin naïve patients was prescribed in 45% of the physician group and 50% of patients in the pharmacist/physician group. CONCLUSION: The proportion of patients prescribed an appropriate intensity statin did not differ between patients managed by physicians alone compared to those managed by pharmacists and physicians. Overall adherence to the 2013 blood cholesterol guidelines was 33%, and this measure can be used as a baseline assessment of current adherence with the guidelines.

Implications of lower risk thresholds for statin treatment in primary prevention: analysis of CPRD and simulation modelling of annual cholesterol monitoring.

OBJECTIVE: To estimate numbers affected by a recent change in UK guidelines for statin use in primary prevention of cardiovascular disease. METHOD: We modelled cholesterol ratio over time using a sample of 45,151 men (≥40years) and 36,168 women (≥55years) in 2006, without statin treatment or previous cardiovascular disease, from the Clinical Practice Research Datalink. Using simulation methods, we estimated numbers indicated for new statin treatment, if cholesterol was measured annually and used in the QRISK2 CVD risk calculator, using the previous 20% and newly recommended 10% thresholds. RESULTS: We estimate that 58% of men and 55% of women would be indicated for treatment by five years and 71% of men and 73% of women by ten years using the 20% threshold. Using the proposed threshold of 10%, 84% of men and 90% of women would be indicated for treatment by 5years and 92% of men and 98% of women by ten years. CONCLUSION: The proposed change of risk threshold from 20% to 10% would result in the substantial majority of those recommended for cholesterol testing being indicated for statin treatment. Implications depend on the value of statins in those at low to medium risk, and whether there are harms.

A simple and sensitive HPLC-UV method for quantitation of lovastatin in human plasma: application to a bioequivalence study.

An available, simple, sensitive, and rapid method has been developed for determination of the 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase inhibitor, lovastatin in human plasma. The analytical procedure involves a one-step liquid-liquid extraction method using atorvastatin as internal standard. Chromatographic separation was carried out on a reversed phase C(18) column using a mixture of 0.05 M phosphate buffer (pH 7) and acetonitrile (44.5 : 55.5, v/v) as mobile phase with UV detection set at 238 nm. The total run time of analysis was 6 min with the retention time of lovastatin being 4.3 min. A complete set of analytical method validation tests were carried out on the method. Accordingly, the method was linear in the wide range of 1-100 ng/ml. The limit of detection (LOD) and limit of quantification (LOQ) for lovastatin were 0.5 and 1 ng/ml, respectively. The method was shown to be precise with average within-run and between-run variations of 10.45+/-6.88 and 8.68+/-5.13%, respectively. The average within-run and between-run accuracy of the method throughout its linear range was 113.33+/-3.98 and 105.72+/-5.07%, respectively. The mean relative recovery of lovastatin from human plasma by the developed method was 88.61+/-7.00%. The applicability of the method in real pharmacokinetic situations was evaluated successfully during a bioequivalence study in 14 fasting healthy male volunteers.

Computing with evidence Part II: An evidential approach to predicting metabolic drug-drug interactions.

We describe a novel experiment that we conducted with the Drug Interaction Knowledge-base (DIKB) to determine which combinations of evidence enable a rule-based theory of metabolic drug-drug interactions to make the most optimal set of predictions. The focus of the experiment was a group of 16 drugs including six members of the HMG-CoA-reductase inhibitor family (statins). The experiment helped identify evidence-use strategies that enabled the DIKB to predict significantly more interactions present in a validation set than the most rigorous strategy developed by drug experts with no loss of accuracy. The best-performing strategies included evidence types that would normally be of lesser predictive value but that are often more accessible than more rigorous types. Our experimental methods represent a new approach to leveraging the available scientific evidence within a domain where important evidence is often missing or of questionable value for supporting important assertions.

Prevention of coronary heart disease with statins in UK South Asians and Caucasians.

AIMS: To determine the prevalence of subjects eligible for primary and secondary prevention of coronary heart disease (CHD) among the British South Asian population and to compare that with British Caucasians. METHODS AND RESULTS: We used the Health Survey for England 1998 and 1999 datasets, holding data on 9950 Caucasians and 1938 South Asians. Thresholds for treatment were a total cholesterol >3.5 mmol/l and either a history of cardiovascular disease or elevated estimated CHD risk, adjusted where necessary for ethnic differences. Separate analyses were performed for primary prevention risk thresholds of >15% and >30% over 10 years. The prevalence of previous myocardial infarction, angina, or stroke was higher in South Asian men than in Caucasian but the reverse was seen in women. More than 93% [95% confidence interval (CI) 88-97] of South Asian men and nearly 68% (95% CI 66-71) of Caucasian men older than 55 years have a CHD risk greater than 15% (equivalent to cardiovascular risk of 20%) and a cholesterol above 3.5 mmol/l and would be eligible for treatment with lipid-lowering drugs. The equivalent proportions in women are 55% (95% CI 46-65) and 18% (95% CI 16-20) in South Asians and Caucasians, respectively. CONCLUSION: Treating this proportion of the population will have a societal impact, the majority of older people becoming patients, and although it may well be cost-effective for individuals, it will require substantial new resources.

Rosuvastatin is cost-effective compared with atorvastatin in reaching cholesterol goals.

BACKGROUND: Lowering low-density lipoprotein cholesterol (LDL-C) levels reduces the risk of coronary heart disease. The introduction of a highly efficacious new statin, rosuvastatin, may enable more patients to be treated to LDL-C goal within a fixed budget. OBJECTIVES: To compare the cost-effectiveness of rosuvastatin 10 mg and atorvastatin 10 mg in lowering LDL-C and achieving guideline goals after 12 weeks of treatment. The LDL-C goals were those recommended by the National Cholesterol Education Program Adult Treatment Panel (NCEP ATP) III and the Third Joint European Task Force. METHODS: The analysis was performed on pooled data from three clinical trials. Efficacy was measured as the percent reduction in LDL-C and the proportion of patients who reached guideline LDL-C goals following the first 12 weeks of treatment, prior to dose titration. Costs comprised drug acquisition costs only. The cost-effectiveness measures were cost per 1% reduction in LDL-C and cost per patient treated to their LDL-C goal. RESULTS: Treatment with rosuvastatin 10 mg costs 1.85 per 1% reduction in LDL-C, compared with 2.37 per 1% reduction with atorvastatin 10 mg. The average costs per patient treated to the European LDL-C goals were 130.18 for rosuvastatin 10 mg and 242.44 for atorvastatin 10 mg. Treating to NCEP ATP III goals costs 115 per patient treated with rosuvastatin 10 mg vs. 163 per patient treated with atorvastatin 10 mg. CONCLUSIONS: Rosuvastatin has the same acquisition costs as and is more efficacious than atorvastatin in lowering LDL-C and treating patients to target LDL-C levels.