Statin Initiation Research Articles

Abstract P128: Statin Prescribing, Switching, and Low-density Lipoprotein Cholesterol Goal Attainment Across Racial/Ethnic Groups With Atherosclerotic Cardiovascular Disease

Introduction: Statins are effective in reducing low-density lipoprotein cholesterol (LDL-C) and preventing cardiovascular (CV) events in patients with a history of atherosclerotic CV disease (ASCVD), irrespective of race/ethnicity (R/E). Differences in statin utilization, including prescribing and switching, in relationship to LDL-C goal attainment by R/E has not been well studied. Hypothesis: We expect differences in attaining LDL-C <70 mg/dL (goal) by R/E and that differences in goal attainment are associated with patterns in statin utilization. Methods: We selected patients ≥40 years of age in the Sutter Health electronic health records (EHR) with ASCVD based on International Classification of Diseases 9/10 diagnoses (2006-2016), with a new statin prescription (defined as no evidence of a statin in the year prior) and LDL-C values. Patient demographics and clinical characteristics at statin initiation (index) were extracted. We examined differences in LDL-C goal attainment after 1-year follow-up (mean ~16 months) from index date by R/E and initial statin intensity (low/moderate [L/MIS] vs. high [HIS]) using logistic regression. Differences in rates of statin intensity increases or decreases were estimated during follow-up by R/E using negative binominal regression. Incident rate ratios (IRR) were calculated. All models were adjusted for demographic and clinical characteristics. Results: From a database of 3.1 million patients, 241,912 had ASCVD and 11,499 met inclusion criteria (66% non-Hispanic white [NHW], 9% Asian, 3% black, 8% Hispanic, 14% other/unknown). About 18% of patients initiated treatment on HIS and 82% on L/MIS statin, with no significant differences by R/E. LDL-C goal was attained by 33% of patients, overall, and 42% and 30% on HIS and L/MIS, respectively. Of those on HIS, Asians were more likely to have statin intensity decreases than NHWs (IRR:1.89) but were also more likely to attain LDL-C goal than NHWs (58% vs. 39%). Among those on L/MIS, intensity increases were not different by R/E, yet Asians were still more likely to attain goal than NHWs (38% vs. 30%), whereas black patients were less likely (24%). Hispanics on L/MIS were more likely to have intensity decreases (IRR: 1.44), yet similarly met goal (33%) as compared with NHWs. When included in statistical models, statin intensity increases and decreases were independent predictors of higher and lower odds of goal attainment, respectively, but did not alter relationships between R/E and goal attainment. Conclusions: In this ASCVD cohort receiving statins, LDL-C goal attainment differed by R/E, and was highest among Asians and lowest among black patients, however this difference in goal attainment does not appear to be related to differences in statin utilization. Other modifiable factors, such as adherence or access to care, need to be investigated further to improve goal attainment across all R/E groups.

Abstract P1-17-03: Statin use, site of recurrence, and survival among post-menopausal women taking bisphosphonates as adjuvant therapy for breast cancer (SWOG S0307)

Abstract Purpose: Statins may mediate suppression of molecular pathways conferring benefit in cancer. Statins have shown anti-tumor effects in preclinical studies and have been associated with decreased recurrence and improved disease-specific survival. While designed to target cholesterol biosynthesis, statins can also have liver, bone and brain effects. We collected data on statin use in the S0307 adjuvant bisphosphonate trial to test the hypothesis that statin use may decrease risk of recurrence to liver, bone and brain as well as second primary (contralateral) breast cancers, and may act synergistically with bisphosphonates to decrease the risk of recurrence to bone. Patients and Methods: In S0307, 6097 patients diagnosed with Stage I-III breast cancer who had undergone surgery and were receiving adjuvant systemic therapy were randomized to receive zoledronic acid, clodronate, or ibandronate for 3 years. No significant difference was found in disease-free survival (DFS) among the 3 groups, including a sub-analysis of patients > age 55. Statin use was infrequent in younger women in S0307, consequently we analyzed statin use in those > age 55. Cox proportional hazard models were used to determine which variables were independently associated with DFS and to estimate hazard ratios (HR) and 95% confidence intervals (CI). Results: Among women aged ≥ 55 years, 684 (27%) reported taking a statin at baseline and 1,848 did not. Both groups were similar in terms of hormone receptor and HER2 status (p = 0.82). Median age in the statin group was 64.3 versus 61.0 years in the no statin group, mean BMI 31.2 v. 29.5, mean tumor size 2.1cm v. 2.3cm, negative lymph nodes 60% v. 54%, Stage I disease 47% v. 36%, and receipt of chemotherapy 62% v. 71% (all p < 0.01). In the statin group, 122 (17.8%) experienced a DFS event compared to 313 (16.9%) in the no statin group (HR 1.18, CI 0.95-1.46). No difference was observed by statin use in overall recurrence (p=0.28), distant recurrence (p=0.64), or recurrences to the bone (p=0.64), liver (p=0.38) or brain (p=0.65) at initial recurrence. There was no synergy between statin use and specific bisphosphonates. Recurrence and statin useOutcomeGroup 1: On stan at baseline n=684Group 2: No statin at baseline n=1848DFS events122 (17.8%)313 (16.9%)Died without recurrence51 7.5%)97 (5.2%)Recurrence71 (10.4%)216 (11.7%)Contralateral breast cancer9 (1.3%)17 (0.9%)Distant recurrence48 (7%)157 (8.5%)Bone as 1st site of distant recurrence (% distant recurrence)31 (65%)76 (48%)Liver as 1st site of distant recurrence (% distant recurrence)6 (13%)24 (16%)Brain/CNS as 1st site of distant recurrence (% distant recurrence)5 (10%)17 (11%) Conclusions: We found no evidence that statins reduce risk of second primary breast cancers or distant metastases among post-menopausal women with early-stage breast cancer. Despite promising preclinical data, they did not appear to act in synergy with a specific bisphosphonate. Though women in the statin group had less advanced disease at study entry, statin use was not associated with improved DFS. Results are limited by lack of information about type of statin used, adherence, or initiation of statin in control group. Citation Format: Kizub D, Miao J, Stopeck A, Thompson P, Paterson AH, Clemons M, Dees EC, Ingle JN, Falkson CI, Barlow W, Hortobagyi GN, Gralow JR. Statin use, site of recurrence, and survival among post-menopausal women taking bisphosphonates as adjuvant therapy for breast cancer (SWOG S0307) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-17-03.

Statins, myalgia, and rhabdomyolysis.

Statin-associated muscle symptoms (SAMSs) vary considerably in frequency and severity, with a spectrum extending from myalgia with normal creatine kinase (CK) levels or asymptomatic hyperCKemia to potentially life-threatening rhabdomyolysis and necrotizing autoimmune myopathy. Myalgia with CK elevation is the most common presentation. Onset is usually within 1 month after statin initiation or dosage intensification, and the symptoms can be expected to resolve within a few weeks after treatment discontinuation. The mechanism of muscle injury combines statin accumulation within muscles, which varies with the type and dosage of the drug; muscle fragility; abnormalities in statin transport or liver metabolism; drug-drug interactions; and genetic susceptibility. HMG-CoA reductase inhibition in muscles by statins exerts pleiotropic effects that can affect energy metabolism, induce mitochondrial dysfunction, modify lipid oxidation, promote apoptosis and cell membrane lysis, alter muscle protein synthesis, or trigger an autoimmune process. Statins are used to treat several chronic conditions and comorbidities, including inflammatory rheumatic diseases, which are associated with an increased cardiovascular risk. When the cardiovascular risk is high or very high, statin therapy is indispensable and has a very favorable risk/benefit ratio. Otherwise, the risks should be weighed against the benefits before reinitiating statin therapy, and a different statin or lower dosage should be used. If statin therapy cannot be successfully reintroduced, other classes of lipid-lowering drugs should be considered. Severe SAMSs with major weakness and marked CK elevation should suggest the rare eventuality of necrotizing autoimmune myopathy and prompt an anti-HMGCR antibody assay and muscle biopsy to ensure that immunosuppressant therapy is started rapidly if needed.

Statins and Risk of Intracerebral Haemorrhage in a Stroke-Free Population: A Nationwide Danish Propensity Score Matched Cohort Study

BackgroundStatins may increase the risk of intracerebral haemorrhage (ICH) in individuals with previous stroke. It remains unclear whether this applies to individuals with no history of stroke. This study is the first to explore the statin-associated risk of ICH in stroke-free individuals while considering the timing of statin initiation. MethodsWe conducted a population-based, propensity score matched cohort study using information from five Danish national registers. We included all stroke-free individuals initiating statins in 2004–2013 and a propensity score matched group of non-users. Adjusted hazard ratios (aHRs) for ICH risk among statin users compared to non-users were calculated as a function of time since statin initiation. Findings519,894 stroke-free individuals initiating statins and their 1:5 matched stroke-free reference subjects were included and followed for up to ten years. During this period, 1409 ICHs occurred in statin users. Statin users had an overall aHR of 0.85 (95% confidence interval: 0.80–0.90) compared to non-users, but this risk was modified by time since statin initiation. Statin users and non-users had similar ICH risk during the first six months after statin initiation. Hereafter, statin users had a 22–35% lower risk throughout the study period. InterpretationStatin users had lower ICH risk than non-users from six months after statin initiation. This finding could not be explained by healthy initiator bias or differences between users and non-users in terms of sociodemographic characteristics, comorbidity, or parallel treatment regimens. Our study suggests that statin use in stroke-free populations is associated with reduced ICH risk. FundingThe Novo Nordisk Foundation.

Association of Primary Care Providers' Beliefs of Statins for Primary Prevention and Statin Prescription.

BackgroundThe 2013 American College of Cardiology/American Heart Association Cholesterol Treatment Guideline increased the number of primary prevention patients eligible for statin therapy, yet uptake of these guidelines has been modest. Little is known of how primary care provider (PCP) beliefs influence statin prescription.Methods and ResultsWe surveyed 164 PCPs from a community‐based North Carolina network in 2017 about statin therapy. We evaluated statin initiation among the PCPs’ statin‐eligible patients between 2014 and 2015 without a previous prescription. Seventy‐two PCPs (43.9%) completed the survey. The median estimate of the relative risk reduction for high‐intensity statins was 45% (interquartile range, 25%–50%). A minority of providers (27.8%) believed statins caused diabetes mellitus, and only 16.7% reported always/very often discussing this with patients. Most PCPs (97.2%) believed that statins cause myopathy, and 72.3% reported always/very often discussing this with patients. Most (77.7%) reported always/very often using the 10‐year atherosclerotic cardiovascular disease risk calculator, although many reported that in most cases other risk factors or patient preferences influenced prescribing (59.8% and 43.1%, respectively). Of 6172 statin‐eligible patients, 22.3% received a prescription for a moderate‐ or high‐intensity statin at follow‐up. Providers reporting greater reliance on risk factors beyond atherosclerotic cardiovascular disease risk were less likely to prescribe statins.ConclusionsAlthough beliefs and approaches to statin discussions vary among community PCPs, new prescription rates are low and minimally associated with those beliefs. These results highlight the complexity of increasing statin prescriptions for primary prevention and suggest that strategies to facilitate standardized discussions and to address external influences on patient beliefs warrant future study.

Benefit of Early Statin Initiation within 48 Hours after Admission in Statin-Naïve Patients with Acute Myocardial Infarction Undergoing Percutaneous Coronary Intervention.

Background and ObjectivesAlthough current guidelines recommend early initiation of statin in patients with acute myocardial infarction (AMI), there is no consensus for optimal timing of statin initiation.MethodsA total of 3,921 statin-naïve patients undergoing percutaneous coronary intervention were analyzed, and divided into 3 groups according to statin initiation time: group 1 (statin initiation <24 hours after admission), group 2 (24–48 hours) and group 3 (≥48 hours). We also made 3 stratified models to reduce bias: model 1 (<24 hours vs. ≥24 hours), model 2 (<48 hours vs. ≥48 hours) and model 3 (<24 hours vs. 24–48 hours). The endpoint was major adverse cardiac events (MACE; composite of cardiac death, myocardial infarction and target-vessel revascularization) during median 3.8 years.ResultsDuring follow-up, incidence of MACE was lower in early statin group in both model 1 (14.3% vs. 18.4%, hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.66–0.91; p=0.002) and model 2 (14.6% vs. 19.7%, HR, 0.81; 95% CI, 0.67–0.97; p=0.022). After propensity-score matching, results remained unaltered. Statin initiation <24 hours reduced MACE compared to statin initiation ≥24 hours in model 1. Statin initiation <48 hours also reduced MACE compared to statin initiation later in model 2. However, there was no difference in incidence of MACE between statin initiation <24 hours and 24–48 hours) in model 3.ConclusionsEarly statin therapy within 48 hours after admission in statin-naïve patients with AMI reduced long-term clinical outcomes compared with statin initiation later.Trial RegistrationClinicalTrials.gov Identifier: NCT02385682

Causes and prevention of postoperative myocardial injury.

Over the past few years non-cardiac surgery has been recognised as a serious circulatory stress test which may trigger cardiovascular events such as myocardial infarction, in particular in patients at high risk. Detection of these postoperative cardiovascular events is difficult as clinical symptoms often go unnoticed. To improve detection, guidelines advise to perform routine postoperative assessment of cardiac troponin. Troponin elevation – or postoperative myocardial injury – can be caused by myocardial infarction. However, also non-coronary causes, such as cardiac arrhythmias, sepsis and pulmonary embolism, may play a role in a considerable number of patients with postoperative myocardial injury. It is crucial to acquire more knowledge about the underlying mechanisms of postoperative myocardial injury because effective prevention and treatment options are lacking. Preoperative administration of beta-blockers, aspirin, statins, clonidine, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, and preoperative revascularisation have all been investigated as preventive options. Of these, only statins should be considered as the initiation or reload of statins may reduce the risk of postoperative myocardial injury. There is also not enough evidence for intraoperative measures such blood pressure optimisation or intensified medical therapy once patients have developed postoperative myocardial injury. Given the impact, better preoperative identification of patients at risk of postoperative myocardial injury, for example using preoperatively measured biomarkers, would be helpful to improve cardiac optimisation.

Differences in statin utilization and lipid lowering by race, ethnicity, and HIV status in a real-world cohort of persons with human immunodeficiency virus and uninfected persons

Risks for cardiovascular diseases, including myocardial infarction and stroke, are elevated in people with HIV infection (PWH). However, no trials of statin utilization with clinical cardiovascular disease (CVD) end points have been completed in PWH, and there are sparse real-world data regarding statin use and lipid-lowering effectiveness. We therefore used a unique cohort of PWH and uninfected controls to evaluate (1) differences in statin types used for PWH versus uninfected persons; (2) lipid lowering achieved by statin use for PWH versus uninfected persons; and (3) racial and ethnic disparities in appropriate statin use among PWH and uninfected persons. We analyzed a cohort of 5,039 PWH and 10,011 uninfected demographically matched controls who received care at a large urban medical center between January 1, 2000, and May 17, 2017. Medication administration records, prescription data, and validated natural language processing algorithms were used to determine statin utilization. Statins were categorized by generic active ingredient name and intensity (high, moderate, or low). Lipid values collected in routine clinical care were available for analysis. The first set of analyses was restricted to PWH and uninfected matched controls taking statins and compared (1) differences in statin type and (2) difference in cholesterol levels after versus before statin initiation by HIV status. For the second set of analyses, we first used prevalent CVD risk factors to determine participants with statin indications and then determined how many of these participants were taking statins. We then compared statin utilization among persons with indications for statins by race/ethnic group for PWH and uninfected matched controls using multivariable-adjusted logistic regression. Among people prescribed statins, PWH were more likely than controls to have ever taken pravastatin (34.8% vs 12.3%, P < .001) or atorvastatin (72.2% vs 65.6%, P = .002) and less likely to have ever taken simvastatin (14.2% vs 39.5%, P < .001). Among PWH with indications for statin utilization, 55.7% of whites, 39.4% of blacks, and 45.8% of Hispanics were prescribed statins (P < .001). These differences in statin prescription by race/ethnicity remained significant after adjustment for demographics (including insurance status), cardiovascular risk factors, antiretroviral therapy use, HIV viremia, and CD4 count. These racial/ethnic disparities in statin utilization were less pronounced among uninfected persons. Among PWH with statin indication(s), blacks and Hispanics were less likely than whites to have been prescribed a statin. These racial/ethnic disparities were less pronounced among uninfected persons. There were significant differences in type of statin used for PWH compared to uninfected matched controls. Future efforts addressing disparities in CVD prevention among PWH are warranted.

Changing predictors of statin initiation in US women over two decades.

To describe changing roles of predictors of statin initiation before and after incident coronary heart disease, and before and after publication of National Cholesterol Education Program Adult Treatment Panel-III (ATP-III) guidelines in a cohort of US women. We identified 34382 women enrolled into the Women's Health Study from 1993 to 1995 and followed up until 2012. Proportions of previous nonusers initiating statins were described over time. We used multivariable linear regression models to estimate adjusted initiation proportion differences (IPDs) for initiation overall, separately before and after incident coronary heart disease, and separately for ATP-II and ATP-III time periods. Key predictors of initiation overall were self-reported total cholesterol, and previous incident coronary heart disease, cerebrovascular disease, and diabetes. Adjusted IPDs (percentage) for total cholesterol>240 vs <200mg/dL were 7.5 (95% confidence interval [CI], 7.0-8.0) and 9.3 (95% CI, 8.7-9.9) during ATP-II and ATP-III time periods, respectively. Adjusted IPDs in women with diabetes were 7.0 (95% CI, 6.3-7.8) and 11.9 (95% CI, 6.7-17.0) for primary and secondary prevention, respectively, and 3.1 (95% CI, 2.1-4.0) and 9.2 (95% CI 8.2-10.2) for before and after ATP-III, respectively. Secular trends reflected evolution toward risk factor-based treatment indications for statin initiation with increased initiation among diabetics and women with normal and borderline cholesterol. The role of serum cholesterol changed over time, though the character was scale (multiplicative vs additive) dependent. In pharmacoepidemiologic studies of statins, strength of confounding by important variables sometimes unmeasured in claims data, such as cholesterol level, may be calendar time dependent.

Trends in statin prescription prevalence, initiation, and dosing: Hong Kong, 2004–2015

Background and aimsClinical practice guidelines recommend specific statin doses for the primary and secondary prevention of cardiovascular disease. Little is known about how statin utilization and dosing have evolved over time in Hong Kong. The aim of this study was to describe trends in statin prevalence, initiation, and dosing from 2004 to 2015. MethodsPatients receiving public health services, who were prescribed a statin, were included if they received a lipid test at a single center (n = 58,672). Using the territory-wide electronic health record, prescribed daily statin dose, nondaily dose frequency, and statin dose intensity were determined for statin prescriptions from 2004 to 2015. Statin prescription prevalence and initiation rates were estimated using the appropriate at-risk population in the hospital catchment area as the denominator. Prescribed daily doses were stratified by primary or secondary cardiovascular prevention status to assess changes in statin dosing over time. ResultsThe prescription prevalence of statins was higher in 2015 (8.68%; 95% CI, 8.60%–8.75%) as compared with 2004 (1.82%; 95% confidence interval [CI], 1.78%–1.86%). Initiation rates for new statin users increased from 2004 to 2013. High-intensity statins were infrequently prescribed. New users generally had higher statin initiation rates for primary prevention. There were small increases in the prescribed daily doses of statins. Nondaily statin dosing was infrequent (0.42% of all prescriptions). ConclusionsThe prevalence and initiation of statin prescriptions increased in Hong Kong, and was in part driven by low-intensity statins for the primary prevention of cardiovascular disease.

Risk of Incident Osteoarthritis of the Hand in Statin Initiators: A Sequential Cohort Study.

To investigate the association between statin therapy initiation and incident hand osteoarthritis (OA). We performed a propensity score-matched cohort study using data from the UK-based Clinical Practice Research Datalink. Statin initiators had ≥1 statin prescription between 1996 and 2015 and were matched 1:1 on their propensity score to noninitiators within 10 sequential 2-year cohort entry blocks. After a 180-day run-in period, patients were followed in an as-treated approach until a recorded diagnosis of hand OA or until censoring (change in exposure status, development of an exclusion criterion, or maximum follow-up of 5.5years). We applied Cox proportional hazard regression to calculate hazard ratios (HRs) with 95% confidence intervals (95% CIs) overall and in subgroups of sex, age, statin dose, statin agent, preexisting dyslipidemia, and treatment duration. To compare results, we ran all analyses with negative and positive control outcomes and assessed generalized OA as a secondary outcome. We further performed the overall analysis with an active comparator (topical glaucoma therapy initiators). Among 233,608 statin initiators and the same number of noninitiators, we observed an overall HR for hand OA of 0.98 (95% CI 0.88-1.09). The observed null result remained unchanged in all subgroups. Results were highly similar for generalized OA and negative control outcomes. In addition, the active comparator analysis showed a null result with an HR for hand OA of 0.85 (95% CI 0.56-1.29). Previously known associations with positive control outcomes were observed. There was no association between statin initiation and incident hand OA in this study.

Predictors of first-year nonadherence and discontinuation of statins among older adults: a retrospective cohort study.

The aim of this study was to examine the level of and predictors of statin nonadherence and discontinuation among older adults. Among 22 340 Australians aged ≥65 years who initiated statin therapy from January 2014 to December 2015, we estimated the first-year nonadherence (proportion of days covered [PDC] <0.80) and discontinuation (≥90 days without statin coverage) rates. Predictors of nonadherence and discontinuation were examined via multivariable logistic regression. Analyses were performed separately for general beneficiaries (with a higher co-payment; n=4841) and concessional beneficiaries (with a lower co-payment; n=17 499). During the one-year follow-up, 55.1% were nonadherent (concessional 52.6%; general beneficiaries 64.2%) and 44.7% discontinued statins (concessional 43.1%; general beneficiaries 50.4%). Among concessional beneficiaries, those aged 75-84 years and ≥85 years were more likely to discontinue than people aged 65-74 years (odds ratio 1.11, 95% confidence interval 1.04-1.19 and 1.38, 1.23-1.54, respectively). Diabetes was associated with an increased likelihood of nonadherence and discontinuation, while hypertension, angina and congestive heart failure were associated with a lower likelihood of nonadherence and discontinuation. Anxiety was associated with an increased likelihood of discontinuation, but polypharmacy (concurrent use of five or more drugs) was associated with a lower likelihood of nonadherence and discontinuation. Statin initiation by a general medical practitioner was associated with both increased likelihood of nonadherence and discontinuation. Similar predictors of nonadherence and discontinuation were identified for the general beneficiaries. Among older adults prescribed statins, first-year nonadherence and discontinuation are high. Specific population subgroups such as people aged ≥85 years, those with diabetes or anxiety may require additional attention to improve statin adherence.

Using Previous Medication Adherence to Predict Future Adherence.

Medication nonadherence is a major public health problem. Identification of patients who are likely to be and not be adherent can guide targeted interventions and improve the design of comparative-effectiveness studies. To evaluate multiple measures of patient previous medication adherence in light of predicting future statin adherence in a large U.S. administrative claims database. We identified a cohort of patients newly initiating statins and measured their previous adherence to other chronic preventive medications during a 365-day baseline period, using metrics such as proportion of days covered (PDC), lack of second fills, and number of dispensations. We measured adherence to statins during the year after initiation, defining high adherence as PDC ≥ 80%. We built logistic regression models from different combinations of baseline variables and previous adherence measures to predict high adherence in a random 50% sample and tested their discrimination using concordance statistics (c-statistics) in the other 50%. We also assessed the association between previous adherence and subsequent statin high adherence by fitting a modified Poisson model from all relevant covariates plus previous mean PDC categorized as < 25%, 25%-79%, and ≥ 80%. Among 89,490 statin initiators identified, a prediction model including only demographic variables had a c-statistic of 0.578 (95% CI = 0.573-0.584). A model combining information on patient comorbidities, health care services utilization, and medication use resulted in a c-statistic of 0.665 (95% CI = 0.659-0.670). Models with each of the previous medication adherence measures as the only explanatory variable yielded c-statistics ranging between 0.533 (95% CI = 0.529-0.537) for lack of second fill and 0.666 (95% CI = 0.661-0.671) for maximum PDC. Adding mean PDC to the combined model yielded a c-statistic of 0.695 (95% CI = 0.690-0.700). Given a sensitivity of 75%, the predictor improved the specificity from 47.7% to 53.6%. Patients with previous mean PDC < 25% were half as likely to show high adherence to statins compared with those with previous mean PDC ≥ 80% (risk ratio = 0.49, 95% CI = 0.46-0.50). Including measures of previous medication adherence yields better prediction of future statin adherence than usual baseline clinical measures that are typically used in claims-based studies. This study was funded by the Patient-Centered Outcomes Research Institute (ME-1309-06274). Kumamaru, Kohsaka, and Miyata are affiliated with the Department of Healthcare Quality Assessment at the University of Tokyo, which is a social collaboration department supported by National Clinical Database. The department was formerly supported by endowments from Johnson & Johnson K.K., Nipro, Teijin Pharma, Kaketsuken K.K., St. Jude Medical Japan, Novartis Pharma K.K., Taiho Pharmaceutical, W. L. Gore & Associates, Olympus Corporation, and Chugai Pharmaceutical. Gagne has received grants from Novartis Pharmaceuticals and Eli Lilly and Company to the Brigham and Women's Hospital for unrelated work. He is a consultant to Aetion, a software company, and to Optum. Choudhry has received grants from the National Heart, Lung, and Blood Institute, PhRMA Foundation, Merck, Sanofi, AstraZeneca, CVS, and MediSafe. Schneeweiss is consultant to WHISCON and Aetion, a software manufacturer of which he also owns equity. He is principal investigator of investigator-initiated grants to the Brigham and Women's Hospital from Bayer, Genentech, and Boehringer Ingelheim unrelated to the topic of this study. He does not receive personal fees from biopharmaceutical companies. No potential conflict of interest was reported by the other authors.

Statin use in cancer survivors versus the general population: cohort study using primary care data from the UK clinical practice research datalink

BackgroundCancer survivors may be at increased risk of cardiovascular diseases, but little is known about whether prescribing guidelines for the primary prevention of cardiovascular disease are adequately implemented in these patients. We compared levels of statin initiation and cessation among cancer survivors compared to the general population to determine differences in uptake of pharmaceutical cardiovascular risk prevention measures in these groups.MethodsThe study population included individuals aged ≥40 during 2005–13 within the UK Clinical Practice Research Datalink primary care database. Within this population we identified cancer survivors who were alive and under follow-up at least 1 year after diagnosis, and controls with no cancer history. Follow-up time prior to cancer diagnosis was included in the control cohort. Using logistic regression, we compared these groups with respect to uptake of statins within 1 month of a first high recorded cardiovascular risk score. Then, we used Cox modelling to compare persistence on statin therapy (time to statin cessation) between cancer survivors and controls from the main study population who had initiated on a statin.ResultsAmong 4202 cancer survivors and 113,035 controls with a record indicating a high cardiovascular risk score, 23.0% and 23.5% respectively initiated a statin within 1 month (adjusted odds ratio 0.98 [91.8–1.05], p = 0.626). Cancer survivors appeared more likely to discontinue statin treatment than controls (adjusted hazard ratio 1.07 [1.01–1.12], p = 0.02). This greater risk of discontinuing was only evident after the first year of therapy (p-interaction < 0.001).InterpretationAlthough cardiovascular risk is thought to be higher in cancer survivors compared to the general population, cancer survivors were no more likely to receive statins, and marginally more likely to cease long-term therapy, than general population controls. There may be an opportunity to mitigate the suspected higher cardiovascular risk in the growing population of cancer survivors by improving uptake of lipid-lowering treatment and persistence on therapy.

GW29-e0785 Statin in combination with β-blocker therapy reduces the risk of major adverse cardiovascular events in patients with acute coronary syndrome

Early initiation of statins or beta blockers alone have been advocated to improved event-free survival in patients with acute coronary syndrome(ACS), but the benefits of the combined treatment remains to be evaluated. Thus, we assessed the impact of statin in combination with β-blocker therapy on

T2 mapping MRI technique quantifies carotid plaque lipid, and its depletion after statin initiation, following acute myocardial infarction

Background & aimsA recently-validated, highly-sensitive T2 mapping magnetic resonance (MRI) technique accurately quantifies carotid plaque lipid. The aims of this study were to determine: (i) the extent of carotid plaque lipid in patients with acute coronary syndromes (ACS); (ii) the effects of initiation of high-intensity statin on plaque lipid content and (iii) whether plaque lipid content is related to standard or ‘functional’ blood lipid measurements. MethodsStatin naïve subjects presenting with ACS underwent carotid artery MRI at 3 T scanner to quantify plaque lipid. Patients were subsequently commenced on high dose statin as part of clinical care and underwent a second MRI after three months. Plaque composition was measured using objective semi-automated techniques. Results23 out of 24 patients had measurable lipid. Three months after statin initiation there was a significant reduction in carotid lipid percentage [from 10.3% (7.2–14.2) to 7.4% (5.4–10.0), p = 0.002] and a significant increase in fibrous percentage [from 83.3% ± 6.6–85.5% ± 4.8, p = 0.039]. None of the studied functional blood biomarkers were related to either baseline carotid plaque lipid content or its propensity to change with statin treatment. ConclusionsT2-mapping demonstrated depleted carotid plaque lipid following the initiation of high-intensity statin treatment. Standard or ‘functional’ blood biomarkers were dissociated from plaque lipid content or changes with treatment. These findings further reinforce the importance of disease characterisation over risk factor assessment. Subject to clinical trial findings, quantification of plaque lipid may provide the basis for an approach to identify patients suitable for intensive lipid reduction regimes.

The Effect of Statin Use on Mortality in Systemic Autoimmune Rheumatic Diseases.

Systemic autoimmune rheumatic diseases (SARD) are associated with an increased risk of premature cardiovascular disease (CVD) and all-cause mortality. We examined the potential survival benefit of statin use among patients with SARD in a general population setting. We conducted an incident user cohort study using a UK general population database. Our population included patients with a SARD as determined by Read code diagnoses of systemic lupus erythematosus, systemic sclerosis, Sjögren syndrome, dermatomyositis, polymyositis, mixed connective tissue disease, Behçet disease, or antineutrophil cytoplasmic antibodies-associated vasculitis between January 1, 2000, and December 31, 2014. We compared propensity score-matched cohorts of statin initiators and noninitiators within 1-year cohort accrual blocks to account for potential confounders, including disease duration, body mass index, lifestyle factors, comorbidities, and medication use. Of 2305 statin initiators, 298 died during the followup period (mean 5.1 yrs), whereas among 2305 propensity score-matched noninitiators, 338 died during the followup period (mean 4.8 yrs). This corresponded to mortality rates of 25.4/1000 and 30.3/1000 person-years, respectively. Statin initiation was associated with reduced all-cause mortality (HR 0.84, 95% CI 0.72-0.98). When we compared the unmatched cohorts, the statin initiators (n = 2863) showed increased mortality (HR 1.85, 95% CI 1.58-2.16) compared with noninitiators (n = 2863 randomly selected within 1-year cohort accrual blocks) because of confounding by indication. In this general population-based study, statin initiation was shown to reduce overall mortality in patients with SARD after adjusting for relevant determinates of CVD risk.

Adherence to and Persistence With Statin Therapy in a Veteran Population.

A relative cardiovascular risk reduction of 25% to 35% has been reported in patients starting a statin for elevated cholesterol; yet many patients fail to consistently take these medications as directed. To evaluate factors affecting adherence and persistence with statin therapy. This retrospective study analyzed data from a Veterans Affairs database of facilities west of the Rocky Mountains. Patient demographics, co-morbidities, and prescription information was collected for individuals newly prescribed a statin between July 1, 2007, and December 31, 2012. Adherence was determined using the medication possession ratio (MPR). Persistence was defined as the time from initiation of therapy until a refill gap of 135 days or greater occurred. Of 164 687 unique patients, overall adherence to statins a mean MPR of 0.843. Approximately 63% of patients were persistent with statin therapy 675 days after statin initiation. Patients prescribed pravastatin, atorvastatin, lovastatin, and rosuvastatin and those who took more than 1 different statin during the follow-up period had statistically significantly higher rates of adherence than those prescribed simvastatin. Older patients and those with a greater number of active prescriptions were found to be more adherent to statin medications. Patients with hypertension were more adherent to a statin, and those with diabetes mellitus and/or posttraumatic stress disorder (PTSD) were less adherent. Conclusion and Relevance: In veterans, overall statin adherence was excellent. Certain populations may benefit from interventions targeted at improving statin adherence, including younger veterans, those prescribed fewer medications, those taking simvastatin, and veterans with PTSD or diabetes mellitus.

Using marginal structural models to adjust for treatment drop-in when developing clinical prediction models.

Clinical prediction models (CPMs) can inform decision making about treatment initiation, which requires predicted risks assuming no treatment is given. However, this is challenging since CPMs are usually derived using data sets where patients received treatment, often initiated postbaseline as “treatment drop‐ins.” This study proposes the use of marginal structural models (MSMs) to adjust for treatment drop‐in. We illustrate the use of MSMs in the CPM framework through simulation studies that represent randomized controlled trials and real‐world observational data and the example of statin initiation for cardiovascular disease prevention. The simulations include a binary treatment and a covariate, each recorded at two timepoints and having a prognostic effect on a binary outcome. The bias in predicted risk was examined in a model ignoring treatment, a model fitted on treatment‐naïve patients (at baseline), a model including baseline treatment, and the MSM. In all simulation scenarios, all models except the MSM underestimated the risk of outcome given absence of treatment. These results were supported in the statin initiation example, which showed that ignoring statin initiation postbaseline resulted in models that significantly underestimated the risk of a cardiovascular disease event occurring within 10 years. Consequently, CPMs that do not acknowledge treatment drop‐in can lead to underallocation of treatment. In conclusion, when developing CPMs to predict treatment‐naïve risk, researchers should consider using MSMs to adjust for treatment drop‐in, and also seek to exploit the ability of MSMs to allow estimation of individual treatment effects.

Timing of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor initiation and allograft vasculopathy progression and outcomes in heart transplant recipients.

AimsEarly studies from the 1990s have shown that statins improve survival and attenuate cardiac allograft vasculopathy (CAV). However, little contemporary data are available on the incremental benefit of statins with the current use of new‐generation immunosuppressive agents and the use of coronary intravascular ultrasound for assessment of CAV. We sought to investigate the effect of early statin (ES) as compared with late statin (LS) initiation after heart transplantation (HT) on long‐term CAV progression and clinical outcomes in a large contemporary HT cohort.Methods and resultsWe analysed a cohort of 409 adult HT recipients. CAV progression was assessed by serial coronary intravascular ultrasound volumetric measurements of the differences between baseline and last follow‐up plaque volume (PV) and plaque index (PV/vessel volume ratio). CAV progression and clinical outcomes were compared between the ES (<2 years after HT) and the LS (>2 years after HT) groups. During a median follow‐up of 8.2 years, ES resulted in significantly lower change (Δ) of plaque index (+3.8% ± 1.7% vs. +8.2% ± 3.6%; P = 0.0008) and PV (+0.8 ± 0.3 vs. +1.9 ± 1.2; P = 0.045) compared with LS group. In a Cox proportional hazards regression model and after adjustment for baseline characteristics, ES was associated with a 52% decreased risk of CAV‐associated events (hazard ratio 0.48, 95% confidence interval: 0.27–0.91; P = 0.025) and a 42% decreased risk of the composite endpoint of all‐cause mortality and CAV‐associated events (hazard ratio 0.58, 95% confidence interval: 0.38–0.91; P = 0.019).ConclusionsEarly initiation of statin therapy after HT results in attenuated CAV progression as well as in decreased CAV‐related events and mortality.