Statin Therapy For Secondary Prevention Research Articles

Statin Therapy for Secondary Prevention in Ischemic Stroke Patients With Cerebral Microbleeds.

The association between statin use and the risk of intracranial hemorrhage (ICrH) following ischemic stroke (IS) or transient ischemic attack (TIA) in patients with cerebral microbleeds (CMBs) remains uncertain. This study investigated the risk of recurrent IS and ICrH in patients receiving statins based on the presence of CMBs. We conducted a pooled analysis of individual patient data from the Microbleeds International Collaborative Network, comprising 32 hospital-based prospective studies fulfilling the following criteria: adult patients with IS or TIA, availability of appropriate baseline MRI for CMB quantification and distribution, registration of statin use after the index stroke, and collection of stroke event data during a follow-up period of ≥3 months. The primary endpoint was the occurrence of recurrent symptomatic stroke (IS or ICrH), while secondary endpoints included IS alone or ICrH alone. We calculated incidence rates and performed Cox regression analyses adjusting for age, sex, hypertension, atrial fibrillation, previous stroke, and use of antiplatelet or anticoagulant drugs to explore the association between statin use and stroke events during follow-up in patients with CMBs. In total, 16,373 patients were included (mean age 70.5 ± 12.8 years; 42.5% female). Among them, 10,812 received statins at discharge, and 4,668 had 1 or more CMBs. The median follow-up duration was 1.34 years (interquartile range: 0.32-2.44). In patients with CMBs, statin users were compared with nonusers. Compared with nonusers, statin therapy was associated with a reduced risk of any stroke (incidence rate [IR] 53 vs 79 per 1,000 patient-years, adjusted hazard ratio [aHR] 0.68 [95% CI 0.56-0.84]), a reduced risk of IS (IR 39 vs 65 per 1,000 patient-years, aHR 0.65 [95% CI 0.51-0.82]), and no association with the risk of ICrH (IR 11 vs 16 per 1,000 patient-years, aHR 0.73 [95% CI 0.46-1.15]). The results in aHR remained consistent when considering anatomical distribution and high burden (≥5) of CMBs. These observational data suggest that secondary stroke prevention with statins in patients with IS or TIA and CMBs is associated with a lower risk of any stroke or IS without an increased risk of ICrH. This study provides Class III evidence that for patients with IS or TIA and CMBs, statins lower the risk of any stroke or IS without increasing the risk of ICrH.

Trends and Gaps in Statin Use for Cardiovascular Disease Prevention in Type 2 Diabetes: A Real-World Study in Shanghai, China

BackgroundCardiovascular disease (CVD) is the major cause of death among persons with diabetes. As the preventative use of statin has been proved to reduce CVD risks, understanding the current status and the trend in statin use is crucial to improve clinical treatment strategies. ObjectiveOur study aimed to answer the question of what were the status and trend of statin use in Shanghai, China. MethodsOur study estimated statin use and trends from 2015 to 2021 among 702 727 patients with type 2 diabetes mellitus (T2DM) based on electronic health records from the Shanghai Hospital Link Database. Patients were grouped according to the presence of CVDs, tested separately for statin primary and secondary prevention use, and stratified by age and sex. ResultsIn the study population, 221 127 patients (31.5%) received statin therapy, and among patients with CVD, 157 622 patients (51.62%) received statin therapy for secondary prevention, but only 15% of patients received statins for primary prevention. The trend in the use of statins was still on the rise from 28.3% in 2015. Statin use increased with age (18-39 years, 14.0%; 40-59 years, 26.8%; 60-74 years, 33.35%; and 75 and over, 36.1%), and women (29.7%, n = 93 977) were less likely to receive statin therapy compared to men (32.9%, n = 127 150). ConclusionDespite the rise in statin use in T2DM in recent decades, a large proportion of subjects with T2DM did not receive statin therapy.

Thrombotic Risk Stratification and Intensive Statin Therapy for Secondary Prevention of Coronary Artery Disease - Insights From the REAL-CAD Study.

It is unknown whether beneficial effects of higher-dose statins on cardiovascular events are different according to the thrombotic risk in patients with chronic coronary syndrome (CCS). The Randomized Evaluation of Aggressive or Moderate Lipid-Lowering Therapy with Pitavastatin in Coronary Artery Disease (REAL-CAD) study is a randomized trial comparing 4 mg and 1 mg pitavastatin in patients with CCS. This study categorized 12,413 patients into 3 strata according to the CREDO-Kyoto thrombotic risk score: low-risk (N=9,434; 4 mg: N=4,742, and 1 mg: N=4,692), intermediate-risk (N=2,415; 4 mg: N=1,188, and 1 mg: N=1,227); and high-risk (N=564; 4 mg: N=269, and 1 mg: N=295). The primary endpoint was a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal ischemic stroke, or unstable angina. Cumulative 4-year incidence of the primary endpoint was significantly higher in the high-risk stratum than in the intermediate- and low-risk strata (11.0%, 6.3%, and 4.5%, P<0.0001). In the low-risk stratum, the cumulative 4-year incidence of the primary endpoint was significantly lower in the 4 mg than in the 1 mg group (4.0% and 4.9%, P=0.02), whereas in the intermediate- and high-risk strata, it was numerically lower in the 4 mg than in the 1 mg group. There was no significant treatment-by-subgroup interaction for the primary endpoint (P-interaction=0.77). High-dose pitavastatin therapy compared with low-dose pitavastatin therapy was associated with a trend toward lowering the risk for cardiovascular events irrespective of the thrombotic risk in patients with CCS.

LDL-C control according to risk: Is there a gender paradox?

Background and Aims : Background Low density lipoprotein cholesterol (LDL-C) treatment goals used for cardiovascular disease (CVD) prevention. Sex differences in CVD have been reported and women are less likely to receive statin therapy for secondary prevention. Nevertheless, little is known about gender according to risk categories Aims

Effect of Omega-3 Fatty Acids on Coronary Plaque Morphology - A Serial Computed Tomography Angiography Study.

Omega-3 fatty acids have been proposed to be useful in the prevention of cardiac events. High-risk plaque (HRP) and plaque progression on serial coronary computed tomography angiography (CTA) have been suggested to be the predecessor of acute coronary syndrome (ACS). The purpose of this study was to investigate whether addition of omega-3 fatty acids to statin therapy for secondary prevention would lead to change in plaque characteristics detected by using serial CTA. This study enrolled 210 patients with ACS: no eicosapentaenoic acid (EPA)/ docosahexaenoic acid (DHA; EPA/DHA), low-dose EPA+DHA, high-dose EPA+DHA, and high-dose EPA alone. HRP was significantly more frequent in patients with plaque progression (P=0.0001). There was a significant interaction between plaque progression and EPA dose regardless of the DHA dose; 20.3% in EPA-none (no EPA/DHA), 15.7% in EPA-low (low-dose EPA+DHA), and 5.6% in EPA-high (high-dose EPA+DHA and high-dose EPA alone). On multivariate logistic regression analysis, HRP (OR 6.44, P<0.0001), EPA-high (OR 0.13, P=0.0004), and Rosvastatin (OR 0.24, P=0.0079) were the independent predictors for plaque progression. In quantitative analyses (n=563 plaques), the interval change of low attenuation plaque (LAP) volume was significantly different based on EPA dose; LAP was significantly increased in the EPA-none group and significantly decreased in the EPA-high group. In patients with ACS, addition of high-dose EPA (EPA-high) to statin therapy, compared to statin therapy without EPA, was associated with a lower rate of plaque progression.

Use of statins for the prevention of cardiovascular disease in 41 low-income and middle-income countries: a cross-sectional study of nationally representative, individual-level data

SummaryBackgroundIn the prevention of cardiovascular disease, a WHO target is that at least 50% of eligible people use statins. Robust evidence is needed to monitor progress towards this target in low-income and middle-income countries (LMICs), where most cardiovascular disease deaths occur. The objectives of this study were to benchmark statin use in LMICs and to investigate country-level and individual-level characteristics associated with statin use.MethodsWe did a cross-sectional analysis of pooled, individual-level data from nationally representative health surveys done in 41 LMICs between 2013 and 2019. Our sample consisted of non-pregnant adults aged 40–69 years. We prioritised WHO Stepwise Approach to Surveillance (STEPS) surveys because these are WHO’s recommended method for population monitoring of non-communicable disease targets. For countries in which no STEPS survey was available, a systematic search was done to identify other surveys. We included surveys that were done in an LMIC as classified by the World Bank in the survey year; were done in 2013 or later; were nationally representative; had individual-level data available; and asked questions on statin use and previous history of cardiovascular disease. Primary outcomes were the proportion of eligible individuals self-reporting use of statins for the primary and secondary prevention of cardiovascular disease. Eligibility for statin therapy for primary prevention was defined among individuals with a history of diagnosed diabetes or a 10-year cardiovascular disease risk of at least 20%. Eligibility for statin therapy for secondary prevention was defined among individuals with a history of self-reported cardiovascular disease. At the country level, we estimated statin use by per-capita health spending, per-capita income, burden of cardiovascular diseases, and commitment to non-communicable disease policy. At the individual level, we used modified Poisson regression models to assess statin use alongside individual-level characteristics of age, sex, education, and rural versus urban residence. Countries were weighted in proportion to their population size in pooled analyses.FindingsThe final pooled sample included 116 449 non-pregnant individuals. 9229 individuals reported a previous history of cardiovascular disease (7.9% [95% CI 7.4–8.3] of the population-weighted sample). Among those without a previous history of cardiovascular disease, 8453 were eligible for a statin for primary prevention of cardiovascular disease (9.7% [95% CI 9.3–10.1] of the population-weighted sample). For primary prevention of cardiovascular disease, statin use was 8.0% (95% CI 6.9–9.3) and for secondary prevention statin use was 21.9% (20.0–24.0). The WHO target that at least 50% of eligible individuals receive statin therapy to prevent cardiovascular disease was achieved by no region or income group. Statin use was less common in countries with lower health spending. At the individual level, there was generally higher statin use among women (primary prevention only, risk ratio [RR] 1.83 [95% CI 1.22–2.76), and individuals who were older (primary prevention, 60–69 years, RR 1.86 [1.04–3.33]; secondary prevention, 50–59 years RR 1.71 [1.35–2.18]; and 60–69 years RR 2.09 [1.65–2.65]), more educated (primary prevention, RR 1.61 [1.09–2.37]; secondary prevention, RR 1.28 [0.97–1.69]), and lived in urban areas (secondary prevention only, RR 0.82 [0.66–1.00]).InterpretationIn a diverse sample of LMICs, statins are used by about one in ten eligible people for the primary prevention of cardiovascular diseases and one in five eligible people for secondary prevention. There is an urgent need to scale up statin use in LMICs to achieve WHO targets. Policies and programmes that facilitate implementation of statins into primary health systems in these settings should be investigated for the future.FundingNational Clinician Scholars Program at the University of Michigan Institute for Healthcare Policy and Innovation, and National Institute of Diabetes and Digestive and Kidney Diseases.

Statin Treatment in Specific Patient Groups: Role for Improved Cardiovascular Risk Markers.

Ample evidence supports the use of statin therapy for secondary prevention in patients with a history of atherosclerotic cardiovascular disease (ASCVD), but evidence is wanting in the case of primary prevention, low-risk individuals, and elderly adults 65+. Statins are effective in lowering low-density lipoprotein (LDL), which has long been a target for treatment decisions. We discuss the weakening dependence between cholesterol levels and mortality as a function of age and highlight recent findings on lipoprotein subfractions and other superior markers of ASCVD risk. The efficacy of statins is compared for distinct subsets of patients based on age, diabetes, ASCVD, and coronary artery calcium (CAC) status. Most cardiovascular risk calculators heavily weight age and overestimate one’s absolute risk of ASCVD, particularly in very old adults. Improvements in risk assessment enable the identification of specific patient populations that benefit most from statin treatment. Derisking is particularly important for adults over 75, in whom treatment benefits are reduced and adverse musculoskeletal effects are amplified. The CAC score stratifies the benefit effect size obtainable with statins, and forms of coenzyme Q are discussed for improving patient outcomes. Robust risk estimator tools and personalized, evidence-based approaches are needed to optimally reduce cardiovascular events and mortality rates through administration of cholesterol-lowering medications.

Assessment of Trends in Statin Therapy for Secondary Prevention of Atherosclerotic Cardiovascular Disease in US Adults From 2007 to 2016

Atherosclerotic cardiovascular disease (ASCVD) is highly prevalent in the US, with studies indicating substantial rates of nonadherence to and undertreatment with statin therapy. The 2013 American College of Cardiology/American Heart Association guideline recommended high-intensity statins for all patients age 75 years and younger with documented ASCVD in whom such therapy is tolerated, but there is limited evidence documenting population trends of statin use, adherence, and outcomes in the periods before and after the update to the guideline. To assess trends in the use, adherence, cost, and outcomes of statin therapy for secondary prevention in patients with different types of ASCVD between 2007 and 2016. This retrospective cohort study used data from the OptumLab Data Warehouse database containing privately insured and Medicare Advantage enrollees with demographic characteristics similar to the national US population. Participants were adult patients (age ≥21 years) who had their first ASCVD event between January 1, 2007, and December 31, 2016. Data were characterized as belonging to 3 groups: (1) cardiovascular heart disease (CHD); (2) ischemic stroke or transient ischemic attack (TIA); and (3) peripheral artery disease (PAD). Data were analyzed from July 1 to August 1, 2018. Calendar year of the initial ASCVD event. Trends in the statin use (within 30 days of discharge from hospitalization), adherence (proportion of days covered ≥80% within the first year), cost, major adverse cardiac events (1-year cumulative risk), and statin intolerance (within the first year). Of the 284 954 patients with a new ASCVD event, 128 422 (45.1%) were women; the median age was 63 years (interquartile range [IQR], 54-72 years); 207 781 (72.9%) were White. The use of statins increased from 50.3% in 2007 to 59.9% in 2016, the use of high-intensity statins increased from 25.0% to 49.2%, and the adherence increased from 58.7% to 70.5% (P < .001 for all trends). Patients with CHD were more likely to receive statins and high-intensity statins and adhere to medications than patients with ischemic stroke, TIA, or PAD despite similar observed treatment benefit. In 2016, 80.9% of patients with CHD used a statin vs 65.8% of patients with ischemic stroke or TIA and 37.5% of patients with PAD. Out-of-pocket cost per 30-day decreased from a median of $20 (interquartile range, $7.6-$31.9) in 2007 to $2 (interquartile range, $1.6-$10.0) in 2016 (P < .001) with the increasing use of generic statins (42.0% in 2007 vs 94.9% in 2016; P < .001). Major adverse cardiac events decreased from 8.9% in 2007 to 6.5% in 2016 (P < .001) whereas statin intolerance increased from 4.0% to 5.1% (P < .001). There have been modest improvements in the use, adherence, and cardiovascular outcomes over the past decade for statin therapy in patients with ASCVD, but a substantial and persistent treatment gap exists between patients with and without CHD, between men and women.

Changes to aspects of ongoing randomised controlled trials with fixed designs

BackgroundDespite careful planning, changes to some aspects of an ongoing randomised clinical trial (RCT), with a fixed design, may be warranted. We sought to elucidate the distinction between legitimate versus illegitimate changes to serve as a guide for less experienced clinical trialists and other stakeholders.MethodsUsing data from a large trial of statin therapy for secondary prevention, we generated a set of simulated trial datasets under the null hypothesis (H0) and a set under an alternative hypothesis (H1). Through analysis of these simulated trials, we assessed the performance of the strategy of changing aspects of the design/analysis with knowledge of treatment allocation (illegitimate) versus the strategy of making changes without knowledge of treatment allocation (legitimate). Performance was assessed using the type 1 error, as well as measures of absolute and relative bias in the treatment effect.ResultsIllegitimate changes led to a relative bias of 61% under H1, and a type 1 error rate under H0 of 23%—well in excess of the 5% significance level targeted. Legitimate changes produced unbiased estimates under H1 and did not inflate the type 1 error rate under H0.ConclusionsChanges to pre-specified aspects of the design and analysis of an ongoing RCT may be a necessary response to unforeseen circumstances. Such changes risk introducing a bias if undertaken with knowledge of treatment allocation. Legitimate changes need to be adequately documented to provide assurance to all stakeholders of their validity.

Cost-effectiveness of statin therapy for secondary prevention among patients with coronary artery disease and baseline LDL-C 70–100 mg/dL in Taiwan

The recommended target low-density lipoprotein cholesterol (LDL-C) level for coronary artery disease (CAD) patients has been lowered from 100 to 70mg/dL in several clinical guidelines for secondary prevention. We aimed to assess whether initiating statin treatment in CAD patients with baseline LDL-C 70-100mg/dL in Taiwan could be cost-effective. A Markov model was developed to simulate a hypothetical cohort of CAD patients with a baseline LDL-C level of 90mg/dL. The incidence and recurrence of MI and stroke related to specific LDL-C levels as well as the statin effect, mortality rate, and health state utilities were obtained from the literature. The direct medical costs and rate of fatal events were derived from the national claims database. The incremental cost-effectiveness ratio (ICER) per quality-adjusted life years (QALYs) was calculated, and sensitivity analyses were performed. Moderate-intensity statin use, a treatment regimen expected to achieve LDL <70mg/dL in the base case, resulted in a net gain of 562 QALYs but with an additional expenditure of $11.4 million per 10,000 patients over ten years. The ICER was $20,288 per QALY gained. The probabilities of being cost-effective at willingness-to-pay thresholds of one and three gross domestic product per capita ($24,329 in 2017) per QALY were 51.1% and 94.2%, respectively. Annual drug cost was the most influential factor on the ICER. Lowering the target LDL-C level from 100 to 70mg/dL among treatment-naïve CAD patients could be cost-effective given the health benefits of preventing cardiovascular events and deaths.

321 Review of Statin Therapy in Frail Older Patients over 75 Years Old Residing in Long Term Care

Abstract Background Statins are frequently prescribed in older patients for prevention of cardiovascular disease and treatment of hypercholesterolemia. However, there is little evidence to indicate that statins have any benefit in older patients with life expectancy less than 10 years and of those patients in long term care whose average life expectancy is approximately 3-5 years. In addition, statins are associated with significant adverse side effects and contribute to the burden of polypharmacy in older patients. Methods Patients residing in a long term care facility were reviewed and data was collected from their medical notes and medication records in order to; (1) Quantify the proportion of patients on statin therapy (2) Review the indication for statin therapy (3) Investigate the inappropriate prescribing of statins in nursing home patients. Results 55 patients were included in the study. Of the 55 patients, 7 [12.7%] patients were on a statin. Average age of patients on a statin was 77.8 years[SD 9.4]. Of the 7 patients, 2 were on a statin for primary prevention and 5 patients were on for secondary prevention. Average cholesterol in primary prevention group was 3.3mmol/L, average LDL was 1.3 mmol/L. Of the 7 patients on statin for secondary prevention, indications included ischaemic stroke[n= 4] and ischaemic heart disease [n=3]. Average Total cholesterol in secondary prevention group was 3.8 mmol/L and average LDL was 1.91 mmol/L. The average Rockwood Clinical Frailty Scale Score of the patients on statin therapy was 7. Conclusion Firstly, this study highlights the incidence of inappropriate prescribing of statins for primary prevention in frail older patients in long term care. It also raises the question surrounding the indication of statin therapy in secondary prevention where cholesterol level are within target range highlighting the need for further studies examining the benefit of statins in frail older patients in LTC.

57-Year-Old Man With Vertigo

57-Year-Old Man With Vertigo

Underutilization of Statin Therapy for Secondary Prevention of Cardiovascular Disease Among Older Adults.

Secondary cardiovascular disease (CVD) clinical trials have demonstrated that higher intensity levels of statin therapy are more effective than lower levels in reducing mortality rates. Despite updated treatment guidelines, statin therapy may be underutilized, with evidence that females are treated less aggressively than males. The primary objective of this study was to determine the prevalence of statin utilization by varying therapy intensity by sex. The secondary objective was to document the benefits of statin therapy intensity levels on all-cause mortality for males and females. A 25% random sample of adults ≥65 years was utilized to identify those with established CVD. Inclusion criteria included: (1) 12-month pre period and (2) up to 30 months post period. Five categories of statin utilization were established: adherent to high-, moderate-, or low-intensity statin therapy, nonadherent, and no statins. Among eligible insureds (N = 49,530 males; N = 44,710 females), 20% of males and 12% of females were identified as high-intensity statin users. Mortality rates significantly increased similarly for males and females as statin therapy intensity decreased. Likewise, mortality hazard ratios indicated the most benefit from high-intensity statin therapy compared to all other categories. Statin therapy for secondary prevention of CVD is beneficial in reducing mortality for males and females but is underutilized, especially among females. Education programs among patients to increase heart health awareness and among physicians to promote the benefits of updated statin guidelines should be encouraged.

PCV36 - Cost-Effectiveness of Statin Therapy For Secondary Prevention Among Patients With Coronary Artery Disease With Baseline LDL-C Level Of 70–100 Mg/DL In Taiwan

PCV36 - Cost-Effectiveness of Statin Therapy For Secondary Prevention Among Patients With Coronary Artery Disease With Baseline LDL-C Level Of 70–100 Mg/DL In Taiwan

Healthcare Utilization and Statin Re-Initiation Among Medicare Beneficiaries With a History of Myocardial Infarction.

BackgroundContact with the healthcare system represents an opportunity for individuals who discontinue statins to re‐initiate treatment. To help identify opportunities for healthcare providers to emphasize the risk‐lowering benefits accrued through restarting statins, we determined the types of healthcare utilization associated with statin re‐initiation among patients with history of a myocardial infarction.Methods and ResultsMedicare beneficiaries with a statin pharmacy fill claim within 30 days of hospital discharge for a myocardial infarction in 2007 to 2012 (n=158 795) were followed for 182 days postdischarge to identify treatment discontinuation, defined as 60 continuous days without statins (n=24 461). Re‐initiation was defined as a statin fill within 365 days of the discontinuation date (n=13 136). Using a case‐crossover study design and each beneficiary as their own control, healthcare utilization during 0 to 14 days before statin re‐initiation (case period) was compared with healthcare utilization 30 to 44 days before statin re‐initiation (control period). The mean age of beneficiaries was 75.4 years; 52.8% were women and 81.9% were white. For routine healthcare utilization, the odds ratio (95% confidence interval) for statin re‐initiation associated with lipid panel testing was 2.65 (1.93–3.65), outpatient primary care was 1.31 (1.23–1.40), and outpatient cardiologist care was 1.38 (1.28–1.50). For acute healthcare utilization, the odds ratio (95% confidence interval) for statin re‐initiation associated with emergency department visits was 1.77 (1.31–2.40), coronary heart disease (CHD) hospitalizations was 3.16 (2.41–4.14) and non–coronary heart disease hospitalizations was 1.73 (1.49–2.01).ConclusionsThe weaker association of routine versus acute healthcare utilization with statin re‐initiation suggests missed opportunities to reinforce the importance of statin therapy for secondary prevention.

A randomized controlled trial of eicosapentaenoic acid in patients with coronary heart disease on statins

BackgroundThere is a residual risk of coronary heart disease (CHD) despite intensive statin therapy for secondary prevention. The aim of this study was to investigate whether coronary plaque regression and stabilization are reinforced by the addition of eicosapentaenoic acid (EPA) to high-dose pitavastatin (PTV). MethodsWe enrolled 193 CHD patients who underwent percutaneous coronary intervention (PCI) in six hospitals. Patients were randomly allocated to the PTV group (PTV 4mg/day, n=96) or PTV/EPA group (PTV 4mg/day and EPA 1800mg/day, n=97), and prospectively followed for 6–8 months. Coronary plaque volume and composition in nonstenting lesions were analyzed by integrated backscatter intravascular ultrasound (IB-IVUS). ResultsThe PTV/EPA group showed a greater reduction in total atheroma volume compared to PTV group. IB-IVUS analyses revealed that lipid volume was significantly decreased during follow-up period in only PTV/EPA group. The efficacy of additional EPA therapy on lipid volume reduction was significantly higher in stable angina pectoris (SAP) patients compared to acute coronary syndrome patients. EPA/AA ratio was significantly improved in PTV/EPA group compared to PTV group. There was no significant difference in the incidence of major adverse cardiovascular events and side effects. ConclusionsCombination EPA/PTV therapy significantly reduced coronary plaque volume compared to PTV therapy alone. Plaque stabilization was also reinforced by EPA/PTV therapy in particular SAP patients. The addition of EPA is a promising option to reduce residual CHD risk under intensive statin therapy.

Atherothrombotic Risk Stratification and Ezetimibe for Secondary Prevention

BackgroundEzetimibe improves cardiovascular (CV) outcomes in patients stabilized after acute coronary syndrome (ACS) when added to statin therapy. After ACS, patients vary considerably in their risk for recurrent CV events. ObjectivesThis study tested the hypothesis that atherothrombotic risk stratification may be useful to identify post-ACS patients who have the greatest potential for benefit from the addition of ezetimibe to statin therapy. MethodsThe TIMI (Thrombolysis In Myocardial Infarction) Risk Score for Secondary Prevention (TRS 2°P) is a simple 9-point risk stratification tool, previously developed in a large population with atherothrombosis to predict CV death, myocardial infarction (MI), and ischemic stroke (CV death/MI/ischemic cerebrovascular accident [iCVA]). The current study applied this tool prospectively to 17,717 post-ACS patients randomized either to ezetimibe and simvastatin or to placebo and simvastatin in IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial). Treatment efficacy was assessed by baseline risk for CV death/MI/iCVA, the IMPROVE-IT composite endpoints (CE), and individual component endpoints at 7 years. ResultsAll 9 clinical variables in the TRS 2°P were independent risk indicators for CV death/MI/iCVA (p < 0.001). The integer-based scheme showed a strong graded relationship with the rate of CV death/MI/iCVA, the trial CE, and the individual components (p trend <0.0001 for each). High-risk patients (n = 4,393; 25%), defined by ≥3 risk indicators, had a 6.3% (95% confidence interval: 2.9% to 9.7%) absolute risk reduction in CV death/MI/iCVA at 7 years with ezetimibe/simvastatin, thus translating to a number-needed-to-treat of 16. Intermediate-risk patients (2 risk indicators; n = 5,292; 30%) had a 2.2% (95% confidence interval: −0.3% to 4.6%) absolute risk reduction. Low-risk patients (0 to 1 risk indicators; n = 8,032; 45%) did not appear to derive benefit from the addition of ezetimibe (p interaction = 0.010). Similar findings were observed for the IMPROVE-IT primary CE. ConclusionsAtherothrombotic risk stratification using the TRS 2°P identifies high-risk patients who derive greatest benefit from the addition of ezetimibe to statin therapy for secondary prevention after ACS. (Improved Reduction of Outcomes: Vytorin Efficacy International Trial [IMPROVE-IT]; NCT00202878)

Impact of statin therapy on long-term clinical outcomes of vasospastic angina without significant stenosis: A propensity-score matched analysis

BackgroundLimited data are available on the efficacy of statin therapy for secondary prevention in patients with vasospastic angina (VSA). We investigated the association of statin therapy with long-term clinical outcomes in VSA patients without significant coronary artery disease. MethodsFrom January 2003 to June 2014, we enrolled a total of 804 patients with VSA proven by an ergonovine provocation test without significant (≥70% diameter stenosis) coronary artery disease. We classified patients into a statin group (n=330) and a no-statin group (n=474) according to the use of statin. Primary outcome were major adverse cardiovascular events (MACE) defined as a composite of cardiovascular death, myocardial infarction, and any revascularization. ResultsMedian follow-up duration was 4.5years (interquartile range: 2.0 to 7.3years). MACE occurred in 14 patients (4.2%) in the statin group, and 21 patients (4.4%) in the no-statin group. There were no differences between the two groups (p=0.97). After 1:1 propensity-score matching (281 pairs), MACE (statin versus [vs.] no-statin; 3.2% vs. 4.3%, hazard ratio [HR]; 0.80, 95% confidence interval [CI]; 0.34–1.89, p=0.60) and readmission due to chest pain (17.1% vs. 17.4%, HR; 1.08, 95% CI; 0.72–1.06, p=0.72) were not statistically different between the two groups. ConclusionOur results suggest that statin therapy could not improve long-term clinical outcomes in VSA patients without significant coronary artery disease.

A novel cost-effectiveness model of prescription eicosapentaenoic acid extrapolated to secondary prevention of cardiovascular diseases in the United States

Objective: Given the substantial economic and health burden of cardiovascular disease and the residual cardiovascular risk that remains despite statin therapy, adjunctive therapies are needed. The purpose of this model was to estimate the cost-effectiveness of high-purity prescription eicosapentaenoic acid (EPA) omega-3 fatty acid intervention in secondary prevention of cardiovascular diseases in statin-treated patient populations extrapolated to the US.Methods: The deterministic model utilized inputs for cardiovascular events, costs, and utilities from published sources. Expert opinion was used when assumptions were required. The model takes the perspective of a US commercial, third-party payer with costs presented in 2014 US dollars. The model extends to 5 years and applies a 3% discount rate to costs and benefits. Sensitivity analyses were conducted to explore the influence of various input parameters on costs and outcomes.Results: Using base case parameters, EPA-plus-statin therapy compared with statin monotherapy resulted in cost savings (total 5-year costs $29,393 vs $30,587 per person, respectively) and improved utilities (average 3.627 vs 3.575, respectively). The results were not sensitive to multiple variations in model inputs and consistently identified EPA-plus-statin therapy to be the economically dominant strategy, with both lower costs and better patient utilities over the modeled 5-year period.Limitations: The model is only an approximation of reality and does not capture all complexities of a real-world scenario without further inputs from ongoing trials. The model may under-estimate the cost-effectiveness of EPA-plus-statin therapy because it allows only a single event per patient.Conclusion: This novel model suggests that combining EPA with statin therapy for secondary prevention of cardiovascular disease in the US may be a cost-saving and more compelling intervention than statin monotherapy.

Effect of Statin Therapy on Mortality in Older Adults Hospitalized with Coronary Artery Disease: A Propensity-Adjusted Analysis.

To examine the effect of statins on long-term mortality in older adults hospitalized with coronary artery disease (CAD). Retrospective analysis. University teaching hospital. Individuals aged 80 and older (mean aged 85.2, 56% female) hospitalized from January 2006 to December 2010 with acute myocardial infarction (AMI), unstable angina pectoris, or chronic CAD and discharged alive (N = 1,262). Participants were divided into those who did (n = 913) and did not (n = 349) receive a discharge prescription for a statin. All-cause mortality over a median follow-up of 3.1 years. Participants treated with statins were more likely to be male, to have a primary diagnosis of AMI, to have traditional cardiovascular risk factors, and to receive other standard cardiovascular medications in addition to statins. In unadjusted analysis, statin therapy was associated with lower mortality (hazard ratio (HR) = 0.83, 95% confidence interval (CI) = 0.71-0.96). After adjustment for baseline differences between groups and propensity for receiving statin therapy, the effect of statins on mortality was no longer significant (HR = 0.88, 95% CI = 0.74-1.05). The association between statins and mortality was similar in participants aged 80 to 84 and those aged 85 and older. In this cohort of older adults hospitalized with CAD, statin therapy had no significant effect on long-term survival after adjustment for between-group differences. These findings, although preliminary, call into question the benefit of statin therapy for secondary prevention in a real-world population of adults aged 80 and older and underscore the need for shared decision-making when prescribing statins in this age group.