Initiation Of Statin Therapy Research Articles

Beyond exchangeability: The other conditions for causal inference in medical research

The assumption of exchangeability of the treated and the untreated – or, in general, of those subjects receiving different levels of the exposure – often gets most of the attention in discussions about causal inference. A key argument to prefer randomised experiments over observational studies is precisely that exchangeability is expected by design in the former. In contrast, investigators conducting observational studies need to use their expert knowledge to identify and measure many potential confounders. Their hope is to collect sufficient data to achieve exchangeability conditional on the measured covariates. Unfortunately, these investigators can never be certain that they have succeeded, even if they have actually succeeded. Exchangeability cannot be empirically tested in observational studies. Lack of exchangeability arises when the distributions of prognostic factors for the outcome differ between the treated and the untreated. There are two main reasons why these differences may occur. First, exchangeability will not generally hold if there are common causes of the treatment and the outcome. For example, having a high level of LDL-cholesterol increases the probability of initiating statin therapy and, independently, the probability of having a myocardial infarction.We then say that the association between statin therapy and myocardial infarction risk is confounded, or that there is confounding bias for the effect of statin therapy on myocardial infarction risk. This terminology explains that the assumption of conditional exchangeability given the measured variables is often referred to as the assumption of no unmeasured confounding. In randomised experiments confounding for the effect of assigned treatment is not expected because a random assignment of treatment results in balanced distributions of prognostic factors between the treated and the untreated. Second, exchangeability will not generally hold if the analysis is restricted to selected individuals and the selection process was affected by both the treatment and the outcome, or by causes of the treatment and the outcome. For example, suppose a third of the subjects were lost to follow-up during a study on statins and myocardial infarction, and the risk of being lost to follow-up was affected by both the presence of treatment’s side effects and of symptoms of coronary heart disease (i.e. angina). In this setting the analysis needs to be restricted to the selected two thirds who stayed in the study until their outcome was ascertained. We say that the association between statin therapy and myocardial infarction is biased in this selected group, or that there is selection bias for the effect of statin therapy on myocardial infarction risk. Confounding is a common source of lack of exchangeability in observational studies, but not in randomised experiments – as long as one sticks to an intention-to-treat analysis. On the other hand, selection bias due to loss to follow-up can happen in both observational studies and randomised experiments. Selection bias can be due to many forms of selection process besides loss to follow-up (e.g. self-selection, missing data, healthy worker). It may also arise when conventional methods for

Dyslipidemia Management

: Numerous studies have been conducted in the past decade evaluating the use of statins and other lipid therapies for reducing vascular events. These studies have impacted the area of stroke prevention. : For patients with established coronary artery disease, statins reduce the rate of stroke. High-dose statin treatment has also been found to reduce the rate of stroke in patients with recent cerebrovascular events and no evidence of heart disease. As a result, initiation of statin therapy for patients with stroke or TIA is now recommended in clinical guidelines. Whether agents that modulate high-density lipoprotein cholesterol are effective in reducing stroke is still the subject of clinical study. : Most patients with stroke or TIA should be treated with statins. The era of multimodal medical therapy for stroke prevention is now well established.

Initiation of Statin Therapy: Are There Age Limits?

Cardiovascular disease (CVD) is the leading cause of death, with a higher prevalence in older adults who form an increasing proportion of the population of the United States. Statin treatment reduces cardiovascular morbidity and mortality in middle-aged adults. However, few studies have included older individuals, particularly ages 80years or older. We review recent publications regarding primary and secondary prevention of CVD with statin therapy in older adults. Risk scores and their limitations in this population are discussed. The association of adverse effects with intensive doses of statin and their interactions with other drugs may be more problematic in older adults. Statin therapy appears cost-effective for individuals with higher CVD risk but this is dependent on the assumptions used. Evidence remains limited regarding the overall benefit of starting statin therapy in adults ages 80years and older; thus, clinical judgment remains necessary in making this decision.

PCV127 Time to Initiation of Oral Antihyperglycaemic and Statin Therapy in Patients with Newly Diagnosed Type 2 Diabetes Mellitus

PCV127 Time to Initiation of Oral Antihyperglycaemic and Statin Therapy in Patients with Newly Diagnosed Type 2 Diabetes Mellitus

Statins and Intracerebral Hemorrhage

A recent post hoc analysis of a large randomized trial in patients with cerebrovascular disease suggested that statins may increase the risk of intracerebral hemorrhage (ICH). To examine the association between statins and ICH in patients with recent ischemic stroke in a population-based setting. Retrospective propensity-matched cohort study with accrual from July 1, 1994, to March 31, 2008. Ontario, Canada. A total of 17872 patients aged 66 years and older who initiated statin therapy following acute ischemic stroke and were followed for a median of 4.2 years (interquartile range, 2.4-5.0 years). To enhance causal inference, we conducted several tests of specificity to exclude healthy user bias in this sample. Main Outcome Measure Hospitalization or emergency department visit for ICH defined using validated diagnosis coding. Overall, 213 episodes of ICH occurred. In the primary analysis comparing statin users with nonusers, we found no association between statins and ICH (hazard ratio=0.87; 95% confidence interval, 0.65-1.17). Subgroup and dose-response analyses yielded similar results. In tests of specificity, statin therapy was not associated with bone mineral density testing, vitamin D or B(12) screening, gastrointestinal endoscopy, or elective knee arthroplasty, suggesting that results were not due to healthy user bias or differences in quality of care. Statin exposure following ischemic stroke was not associated with ICH.

Primary Prevention of Coronary Heart Disease With Statins

In the current issue of Circulation , Lazar et al report the results of their modeling of the cost-effectiveness of alternative statin treatment strategies for primary prevention using low-cost, lower-potency generic statins.1 Lazar's study informs clinical decisions and practice guidelines about the potential use of statin therapy in people at low to moderate risk for coronary heart disease. It also provides an opportunity to consider the appropriate use and potential misuse of decision models to inform and guide clinical practice, and it highlights research opportunities, challenges, and potential limitations of comparative effectiveness, as well. Patients and providers commonly express the desire to make medical decisions solely on the basis of anticipated clinical benefits, harms, and patient preferences and values, without considering the distorting effects of cost. With the widespread availability of generic forms of most US-licensed statins (as of November 2011, rosuvastatin will be the only Food and Drug Administration-approved patent-protected statin in the United States), the cost of statin therapy has dropped precipitously. All currently available generic statins, with the exception of simvastatin 80 mg, can be purchased for as little $0.11 to $0.13 a pill at 1 or more major national pharmacy chains. Article see p 146 At these acquisition costs, Lazar et al find that low/moderate potency statin therapy is cost saving for those without a prior cardiovascular event at a moderately high risk of experiencing a coronary heart disease (CHD) event (10% to 20% over 10 years; 2 Framingham Heart Study [FHS] risk factors and a low-density lipoprotein-cholesterol [LDL-C] >100 mg/dL), and those with 2 risk factors but a 130 mg/dL, as well. They further identify a cost-effective maximum impact strategy that comprises all people with 2 Framingham risk factors, regardless of 10-year FHS risk or LDL-C level, those …

Practice variation in a longitudinal perspective: a multilevel analysis of the prescription of simvastatin in general practices between 2003 and 2009

The Dutch national guideline for Cardiovascular Risk Management advised in 2006 initiation of statin therapy in new patients with simvastatin. After the introduction of this guideline several measures were taken to increase the prescription of simvastatin in general practice. The aim of this paper is to describe the trend and interpractice variation in the relative share of simvastatin in statin prescription over a 7-year period (2003-2009) in Dutch general practices. Data were used from the National Registration Network of General Practice (LINH) in the Netherlands. We used multilevel logistic regression analysis with individuals nested within practices. We evaluated the variance at different time points by the intra-class correlation (ICC). The share of simvastatin prescriptions of all statin prescriptions increased from 40% in 2003 to 82% in 2009. While the ICC was above 20% during the periods 2005 to 2007, it decreased rapidly from 25% in 2007 to only 9% in 2009. Our results indicate that a combination of several intervention measures seems to have been successful. While it seems like the implementation of the guidelines alone had some effect, there was an additional effect when reimbursement measures were implemented. Furthermore, the practice seemed to have affected the adoption of the national CVRM guideline as the variation initially increased after the guideline implementation. By including information on both the proportion of simvastatin prescribed and interpractice variation, we achieved a more complete evaluation of how simvastatin prescription developed over time and how it was related to the different measures taken.

Statins, Risk of Dementia, and Cognitive Function: Secondary Analysis of the Ginkgo Evaluation of Memory Study

Lipid-lowering medications (LLMs) and especially statin drugs can delay cognitive decline and dementia onset in individuals with and without mild cognitive impairment (MCI) at baseline. A longitudinal, observational study was conducted of 3069 cognitively healthy elderly patients (≥75 years of age) who were enrolled in the Ginkgo Evaluation of Memory Study. The primary outcome measure was the time to adjudicated all-cause dementia and Alzheimer dementia (AD). The secondary outcome measure was the change in global cognitive function over time measured by scores from the Modified Mini-Mental State Exam (3MSE) and the cognitive subscale of the AD Assessment Scale (ADAS-Cog). Among participants without MCI at baseline, the current use of statins was consistently associated with a reduced risk of all-cause dementia (hazard ratio [HR], 0.79; 95% confidence interval [95% CI], 0.65-0.96; P = .021) and AD (HR, 0.57; 95% CI, 0.39-0.85; P = .005). In participants who initiated statin therapy, lipophilic statins tended to reduce dementia risk more than nonlipophilic agents. In contrast, there was no significant association between LLM use (including statins), dementia onset, or cognitive decline in individuals with baseline MCI. However, in individuals without MCI at baseline, there was a trend for a neuroprotective effect of statins on cognitive decline. Statins may slow the rate of cognitive decline and delay the onset of AD and all-cause dementia in cognitively healthy elderly individuals, whereas individuals with MCI may not have comparable cognitive protection from these agents. However, the results from this observational study need to be interpreted with caution and will require confirmation by randomized clinical trials stratifying treatment groups based on MCI status at baseline.

Statin intolerance

Statins are the most effective and widely used drugs for treating dyslipidemia, a major risk factor for coronary heart disease. These are one of the safest hypolipidemic drugs but many patients are bound to discontinue statins due to their side effects. Hepatotoxicity, myotoxicity and peripheral neuropathy are important out of them. Discontinuation of statins leads to dylipidemia and its grave consequences. Hence, there should be enough strategies for statin intolerant patients, so that they can be saved from these consequences. These side effects can be avoided by the awareness of certain factors viz. potential drug interactions and dose adjustment according to patho-physiology of the patient. Baseline investigations for liver function and muscle toxicity should be done before initiating statin therapy. Here, we are discussing various options for statin intolerant hyperlipidemic patients such as lower and intermittent dosing of statins, alternate hypolipidemic drugs, red yeast rice, supplementation with coenzyme Q10 and vitamin D. A number of hypolipidemic drugs are in trial phases and hold promise for statin intolerant patients.

The safety and efficacy of statin therapy in the pediatric population.

New guidelines from the American Academy of Pediatrics now recommend the consideration of statin therapy as a first-line pharmacological measure in children as young as 8 years old with marked hypercholesterolemia. Thus, it is important to review both the safety and efficacy of initiating statin therapy prior to adulthood. Statins interfere with cholesterol synthesis, thereby lowering serum cholesterol levels. However, there are special considerations that need to be made when initiating medications such as statins in the pediatric population. Cholesterol is crucial for various biologic processes including neurological development. Cholesterol also serves as a biochemical precursor to many hormones including those critical in sexual development. This article examines the current evidence for the safety and efficacy of statin use in the pediatric population and identifies areas for future research.

Lipid-lowering intensification and low-density lipoprotein cholesterol achievement from hospital admission to 1-year follow-up after an acute coronary syndrome event: Results from the Medications Appl Ied a Nd Sus TAINed Over Time (MAINTAIN) registry

Current American College of Cardiology/American Heart Association guidelines recommend initiation or intensification of statin therapy to achieve low-density lipoprotein cholesterol (LDL-C) goals after an acute coronary syndrome (ACS), yet little is known about the actual practice of intensifying lipid-lowering (LL) therapy and LDL-C achievement from hospital admission to 1-year follow-up. The MAINTAIN registry enrolled ACS patients from January 2006 through September 2007, collecting data on statin formulation, dose, and lipid profiles at both baseline and 12 months. Statin intensity (estimated LDL-C lowering) was categorized by formulation and dose as either moderate (<40%) or intensive (≥40%). In-hospital LL intensification is described and LDL goal attainment is reported for patients with complete baseline and 12-month lipid panels. Of the 788 patients without contraindications to LL, 40% were on LL therapy before admission, and 89% at discharge. Among patients on LL therapy with LDL-C>100 mg/dL at admission, only 37% (n=38) had their LL therapy intensified. Among 382 patients with 12 months of data, 89% (n=341) were discharged on a statin. Of these, 89% were still on a statin at 12-month follow-up. A LDL-C goal of ≤100 mg/dL was achieved in 71% of patients, but the optional LDL-C goal≤70 mg/dL was achieved in only 31%. Most high-risk ACS patients are prescribed statin therapy at hospital discharge and remain on therapy at 12-month follow-up. Despite this, the LDL-C goal of ≤70 mg/dL is achieved in a small minority. There is substantial opportunity to intensify LL therapy after ACS to achieve guideline LDL-C goals and prevent future morbidity and mortality.

Statins in the Prevention of Prostate Cancer Recurrence: Are Certain Biases Exaggerating the Results?

witha57%riskreduction(hazardratio,0.43;95%CI,0.25to0.73)in freedom from biochemical failure and a 43% risk reduction (hazard ratio, 0.57; 95% CI, 0.39 to 0.84) in relapse-free survival. These impressive risk reductions may have been exaggerated by certain biases. First, as reported by the authors, patients who used statins had more favorable pretreatment characteristics than nonstatin users. Thus, it seems that statin users were systematically different from nonstatin users. Although the authors adjusted for some potential confounders, it is possible that residual confounding may still be present. With such large baseline differences, techniques such as propensity scores with tight matching may be more accurate. 2 Second, patients were considered continuously exposed to statins from the time they received a prescription. This simplistic definition does not consider discontinuations, which are likely to have occurred during the long follow-up of this study. Finally, for patients who received statins at some point during follow-up, the time period between cohort entry (end of radiotherapy) and first statin prescription is called immortal because no events could have occurred during this time period. Patients experiencing an event before initiating statin therapy were necessarily included in the unexposed group. This immortal person-time period should have been accounted for as unexposed until the time of statin initiation and, subsequently, as exposed, using statistical techniques for time-dependent exposures. 3 However, given

Targeting Patients for Statin Therapy for the Primary Prevention of Vascular Events: What is the Best Approach?

The optimal strategy for targeting patients for interventions for the primary prevention of cardiovascular events could be considered a central objective of personalized medicine, and the consideration of cost-effectiveness in the process of identifying the best screening strategy is a cornerstone of efficient and responsible health policy in the current era. Starting with the introduction of lovastatin in the mid 1980s, several large clinical trials have demonstrated the efficacy of statins with respect to the prevention of coronary events in patients with established vascular disease or at moderate to high risk of cardiovascular events, while also demonstrating a favorable safety profile. Indeed, statins are one of the most highly studied and prescribed medications. More recently, attention has turned to the primary prevention setting, with recognition of the fact that nearly half of all coronary events occur in patients without overt hyperlipidemia. Results from key studies, including the Heart Protection Study1 and meta analyses,2 suggest that the threshold for initiation of statin therapy should be lowered, and the optimal strategy for identifying patients for whom there is an expected net benefit with statin therapy is now actively debated. Article see p 1478 Results from the Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) trial3 brought this issue to the fore; the highly significant and large magnitude of effect of rosuvastatin on the primary end point of vascular events patients with normal low-density lipoprotein cholesterol but elevated high-sensitivity C-reactive protein (hs-CRP) suggest a potential role for hs-CRP screening in moderate- to low-risk patients who would not otherwise meet criteria for statins according to Adult Treatment Panel III (ATP-III) guidelines. Studies have shown that elevated hs-CRP is associated with an increased risk of future vascular risk, even among patients with low to normal …

Statins and Postoperative Renal Function

Nowadays statins are a cornerstone in perioperative and long-term cardiovascular risk reduction in vascular surgery patients. As has been strongly advocated by the recent European Society of Cardiology guidelines for perioperative management statins should be prescribed to virtually all patients undergoing vascular surgery. This recommendation has subsequently been reinforced by the results of the DECREASE III trial. The results of this placebo-controlled randomized trial showed a two-fold reduction in perioperative cardiac complications in patients on statins. Though not powered for subgroup analyses there seemed to be no significant difference of effect in open or endovascular treated patients. The study by Moulakakis focusses on a different, less well understood, potential beneficial effect of statins in vascular surgery patients. In this retrospective study patients on statins experienced a significantly lower rate of renal function deterioration compared to patients not on statins when undergoing endovascular abdominal aneurysm repair requiring suprarenal fixation. Data on the potential renal protective effect of statins in patients undergoing EVAR are scarce. However in open vascular surgery large cohort studies have found similar results. Welten et al. studied 1944 patients undergoing open vascular surgery. In this population acute kidney injury, defined as >10% decrease in creatinine clearance, occurred in 664 (34%) patients within 2 days after surgery. Of the 664

Carotid Atherosclerosis Progression in Familial Hypercholesterolemia Patients

Background— Until recently, patients with heterozygous familial hypercholesterolemia (HeFH) were considered the best subjects for the assessment of changes in carotid intima-media thickness (cIMT) in randomized intervention trials. Our aims were to investigate whether contemporary statin-treated HeFH patients still show accelerated cIMT increase and to assess the impact of statin treatment, before and after random assignment, on atherosclerosis progression. Methods and Results— We retrospectively evaluated cIMT change, and prior statin treatment and postbaseline LDL-C change as predictors of cIMT change, in 1513 HeFH patients who were randomly assigned to the statin arms of the early ASAP and more recent RADIANCE 1, CAPTIVATE, and ENHANCE studies. In the 3 recent studies combined, mean cIMT increased at only 33%of the rate of the simvastatin-treated patients in the ASAP study (0.014 mm/2 years [95% confidence interval, −0.0003–0.028] versus 0.041 mm/2 years [95% confidence interval, 0.020–0.061]; P &lt;0.05). Patients whose statin therapy could be intensified, as evidenced by an LDL-C decrease after the initiation of on-trial statin therapy, showed cIMT decrease in the first 6 to 12 months and a much lower cIMT increase measured over the full 2 years. In line with this, previously statin-naive HeFH patients showed a lower overall cIMT increase. Conclusions— Over the years, intensification of statin therapy in HeFH patients has resulted in an impressive decrease in carotid atherosclerosis progression. In studies that assess other antiatherosclerotic modalities, statin therapy may still induce rapid changes in cIMT. For future cIMT studies, our analyses suggest that patient populations other than intensively pretreated HeFH patients should be selected and that the statin regimen should not be changed on study initiation.

Incidence, Predictors and Outcomes of Subacute Stent Thrombosis following Primary Stenting for ST-elevation Myocardial Infarction

Knowledge concerning subacute stent thrombosis (SST) following primary stenting for ST-elevation myocardial infarction (STEMI) is not widely available. We studied the incidence, predictors, and clinical outcomes of SST following STEMI. We analyzed data from 455 consecutive patients who underwent primary stenting for STEMI. Baseline clinical characteristics, coronary angiographic features, medication and outcome were compared in patients with and without SST. SST occurred in 17 patients, and the incidence was 3.7%. Univariate predictors of SST were being a current smoker (53.0%vs. 82.4%, p = 0.01), Killip class >or= II (38.4%vs. 58.8%, p = 0.05), no coronary re-flow after stenting (6.2%vs. 17.6%, p = 0.05) and lack of coprescription with a statin (39.5%vs. 5.9%, p<0.01). After multivariate analysis, being a current smoker (odds ratio = 4.76; 95% confidence interval 1.20-18.95) and using statin therapy (odds ratio = 0.09; 95% confidence interval = 0.01-0.75) were independent correlates of SST. Patients with SST were associated with higher 30-day mortality (37.5%vs. 3.1%, p<0.01) and all-cause mortality (23.5%vs. 5.3%, p = 0.01) at long-term follow-up. Although SST is rare in patients with STEMI treated by primary stenting, it imparts a significantly higher mortality at short-term and long-term follow-up. Being a current smoker and the lack of co-prescription with a statin were associated with higher incidence of SST. Our results suggest initiation of statin therapy in patients with STEMI should be considered before discharge.

292 DOES INITIATING STATIN THERAPY AFTER RADICAL PROSTATECTOMY REDUCE THE RISK FOR BIOCHEMICAL RECURRENCE? – RESULTS FROM THE SEARCH DATABASE

You have accessJournal of UrologyProstate Cancer: Localized I1 Apr 2010292 DOES INITIATING STATIN THERAPY AFTER RADICAL PROSTATECTOMY REDUCE THE RISK FOR BIOCHEMICAL RECURRENCE? – RESULTS FROM THE SEARCH DATABASE Lionel Bañez, Leah Gerber, William Aronson, Joseph Presti, Martha Terris, Christopher Amling, Christopher Kane, and Stephen Freedland Lionel BañezLionel Bañez Durham, NC More articles by this author , Leah GerberLeah Gerber Durham, NC More articles by this author , William AronsonWilliam Aronson Los Angeles, CA More articles by this author , Joseph PrestiJoseph Presti Palo Alto, CA More articles by this author , Martha TerrisMartha Terris Augusta, GA More articles by this author , Christopher AmlingChristopher Amling Portland, OR More articles by this author , Christopher KaneChristopher Kane San Diego, CA More articles by this author , and Stephen FreedlandStephen Freedland Durham, NC More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.354AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Preclinical and epidemiological evidence both suggest that statin medications may slow prostate cancer (CaP) progression though controversy remains. More recently, statin intake before surgery was found to be associated with decreased risk for adverse pathological features, tumor inflammation and PSA recurrence in men undergoing radical prostatectomy (RP). Because men at risk for cardiovascular disease are likely to be prescribed a statin regardless of CaP status, a more clinically relevant problem is determining whether men not requiring statin-related cardiovascular risk reduction should be prescribed a statin after being diagnosed with or treated for CaP. However, whether statin intake after RP influences the risk for biochemical recurrence has not been investigated. METHODS Data from 1,280 men treated with RP who were not on any statin medication prior to surgery within the Shared Equal Access Regional Cancer Hospital (SEARCH) database were used for analysis. Time to PSA recurrence was compared between statin-users and non-users using Cox proportional hazards models adjusted for demographic and clinicopathological factors including disease severity at RP. To account for differences in time interval between RP and start of statin therapy, statin use was treated as a time-varying covariate in multivariable analyses. RESULTS Among men not on a statin at the time of surgery, 350 men (27%) began statin therapy after RP. Overall, post-RP statin users had lower mean age (61.5 vs. 62.8 years; p=0.002), higher median body mass index (27.5 vs. 27.0 kg/m2; p=0.04) and lower median pre-operative PSA levels (6.5 vs. 7.8 ng/ml; p<0.001) compared to non-users. After controlling for clinical and pathological parameters, post-RP statin use was significantly associated with lower risk for biochemical recurrence (HR 0.61; 95% CI 0.40-0.93, p=0.02; see Figure). CONCLUSIONS Initiating statin therapy after RP was associated with a 39% reduction in the risk for PSA recurrence among men who underwent RP. If confirmed in larger studies, prospective randomized trials to establish whether statins have a role in preventing or delaying biochemical relapse, metastasis and CaP-specific death are warranted. © 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e115-e116 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Lionel Bañez Durham, NC More articles by this author Leah Gerber Durham, NC More articles by this author William Aronson Los Angeles, CA More articles by this author Joseph Presti Palo Alto, CA More articles by this author Martha Terris Augusta, GA More articles by this author Christopher Amling Portland, OR More articles by this author Christopher Kane San Diego, CA More articles by this author Stephen Freedland Durham, NC More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Statin treatment for patients with heart failure

Statins may be beneficial for the prevention and treatment of heart failure, as indicated by large observational studies, small prospective studies, and post hoc analyses of cardiovascular databases. Two large, prospective, controlled trials have, however, shown that rosuvastatin has neutral effects on the survival of patients with chronic heart failure. The benefits of statin treatment seem to mostly result from their ability to halt disease progression in heart failure, particularly in patients with coronary artery disease. Based on these results, statin treatment might only be useful for the prevention of heart failure, and possibly in patients with new-onset heart failure. This Review highlights data from observational data analyses as well as from the large prospective trials investigating the safety and efficacy of statins in patients with heart failure. The results from these studies and their implications for the timing of initiating statin therapy in this patient population are also discussed.

C-C4-01: Statin Use and Risk of Basal Cell Carcinoma

Maryam M Asgari, MD, MPH, Jean Tang, MD, PhD, Ervin Epstein, MD, Mary-Margaret Chren, MD, Margaret Warton, MPH, Charles P Quesenberry Jr, PhD, Alan S Go, MD and Gary D Friedman, MD, MS Maryam M Asgari, MD, MPH, Kaiser Permanente Northern California; Jean Tang, MD, PhD, Kaiser Permanente Northern California; Ervin Epstein, MD, Kaiser Permanente Northern California; Mary-Margaret Chren, MD, Kaiser Permanente Northern California; Margaret Warton, MPH, Kaiser Permanente Northern California; Charles P Quesenberry Jr, PhD, Kaiser Permanente Northern California; Alan S Go, MD, Kaiser Permanente Northern California; Gary D Friedman, MD, MS, Kaiser Permanente Northern California

Cost-effectiveness of single agent, uptitration and switching statin treatment strategies for lipid lowering in Sweden

Objectives:To assess which alternative treatment strategies are optimum in terms of cost-effectiveness (EUR/patient treated to target, EUR/PTT) in lowering cholesterol in high-risk patients with elevated LDL-cholesterol (LDL-C) in Sweden.Methods:A probabilistic cost-effectiveness model was developed to estimate the mean expected costs and proportion of patients reaching goal attainment (defined as LDL-C ≤2.5 mmol/L [96.5 mg/dL]) at some point in time within a 52-week period following the initiation of statin therapy. Eight different statin treatment strategies were evaluated. Key data sources used in the modeling were the scientific literature, hospital tariffs and medicine price databases.Results:Depending on baseline LDL-C and the willingness-to-pay per additional PTT, the cost-effective alternative is always found among four out of the eight assessed treatment strategies (i.e. Simva10 → Simva20 → Simva40, Rosu10, Simva20 → Rosu10 → Rosu20 → Rosu40, or Simva20 → Simva40 → Rosu20 → Rosu40). An important finding was that when LDL-C level exceed 4.0 mmol/L (154mg/dL) and when willingness to pay is less than 500 EUR per additional PTT, the optimal treatment strategy would be to initiate cholesterol-lowering treatment directly with rosuvastatin 10 mg.Conclusions:The results of this study indicate that the optimal approach to initiate lipid-lowering therapy would be to treat patients with the lower baseline LDL-C levels with the least costly treatment strategies, while initiating lipid-lowering treatment with a high-potency statin (rosuvastatin) in patients with moderately high or high baseline LDL-C levels. This recommendation can be assumed to be relevant particularly when the fact that after treatment initiation the majority of Swedish patients will not have any changes in their lipid-lowering medication or dose is taken into account. Finally, since only the short-term results are presented here, it would be valuable to conduct further studies of the long-term cost-effectiveness of different statin treatment strategies that focus on treatment persistence and LDL-C goal attainment in real practice.