Intensive Statin Therapy Research Articles

8-OR: Use of Guideline-Recommended Risk-Reduction Strategies among Patients with Type 2 Diabetes and Established ASCVD: Insights from Getting to an Improved Understanding of Low-Density Lipoprotein Cholesterol and Dyslipidemia Management (GOULD)

Background: Among people with ASCVD, those with T2D have excess CVD risk and derive greater absolute benefit from CVD risk reduction therapies. We describe the use of evidence-based therapies for secondary prevention in participants (pts) with T2D. Methods: We report a registry to longitudinally describe LDL-C treatment patterns among U.S. pts with ASCVD and LDL-C ≥70mg/dL taking lipid-lowering therapy. Pts (n=5006) were enrolled in 1 of 3 cohorts: taking PCSK9i (11%); LDL-C 70-99mg/dL (53%); and LDL-C ≥100mg/dL (36%). Results: Overall, 1655 (33%) had diabetes (96% with T2D): 146 in the PCSK9i cohort, 874 in the LDL-C 70-99mg/dL cohort, and 635 in the LDL-C ≥100mg/dL cohort. Mean age among pts with diabetes was 68 y, 60% were male, 81% had CAD (including 33% with prior MI), 17% with PAD, and 17% had HF. Mean LDL-C was 100mg/dL. Although overall statin use was at 87%, high-intensity statins were used in only 45% and ezetimibe in only 9.5% of pts. Aspirin and ACE-I/ARB were each used in 72% and beta blockers in 71% of pts. The most commonly used glucose-lowering medications among patients with T2D were metformin (56%), insulin (34%), and sulfonylurea (22%). Only 10% and 8% of pts with T2D were treated with SGLT2i or GLP-1RA, respectively. The proportion of pts with T2D that were receiving all guideline-recommended therapies for optimal risk reduction (high-intensity statins, aspirin, ACE-I/ARB, and either SGLT2i or GLP-1RA) was just 3%. Conclusion: In GOULD, among pts with T2D, ASCVD, and LDL-C ≥70mg/dL, most are not receiving high intensity statin therapy at baseline and few receive ezetimibe. Furthermore, less than 20% are treated with glucose-lowering therapies that have a proven CVD benefit, and a strikingly low proportion receive all guideline-recommended risk reduction strategies. These results highlight an opportunity to improve care and outcomes. Disclosure M.N. Kosiborod: Consultant; Self; Amgen Inc., AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Eisai Co., Ltd., GlaxoSmithKline plc., Glytec, LLC, Intarcia Therapeutics, Inc., Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novartis AG, Novo Nordisk A/S, Sanofi. Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc. J. De Lemos: Other Relationship; Self; Amgen Inc., Novo Nordisk A/S, Regeneron Pharmaceuticals. R.S. Rosenson: Consultant; Self; CVS/Caremark, Regeneron Pharmaceuticals. Research Support; Self; Akcea Therapeutics, Amgen Inc., Medicines Company, Regeneron Pharmaceuticals. Other Relationship; Self; Amgen Inc., Kowa Pharmaceutical Europe Co. Ltd. C.M. Ballantyne: Consultant; Self; Abbott, Akcea Therapeutics, Amarin Corporation, Amgen Inc., AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Esperion, Gilead Sciences, Inc., Matinas BioPharma, Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Regeneron Pharmaceuticals, Roche Diagnostic USA, Sanofi. Research Support; Self; Abbott, Akcea Therapeutics, Amarin Corporation, Amgen Inc., Esperion, Novartis Pharmaceuticals Corporation, Regeneron Pharmaceuticals, Roche Diagnostic USA, Sanofi. Other Relationship; Self; Roche Diagnostic USA. K. Philip: Employee; Self; Amgen Inc. Stock/Shareholder; Self; Amgen Inc. Y. Liu: None. K.E. Mues: Employee; Self; Amgen Inc. Stock/Shareholder; Self; Amgen Inc. S. Alam: Employee; Self; Amgen Inc. Stock/Shareholder; Self; Amgen Inc. M. Elliott: Employee; Self; Amgen Inc. Stock/Shareholder; Self; Amgen Inc. D.L. Bhatt: Research Support; Self; Abbott, Amarin Corporation, Amgen Inc., AstraZeneca, Bayer Vital GmbH, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb Company, Chiesi USA, Inc., Eisai Inc., Eli Lilly and Company, Ethicon, Inc., FlowCo, Forest Laboratories, Inc., Idorsia, Ironwood Pharmaceuticals, Inc., Ischemix, Medicines Company, Medtronic, Merck & Co., Inc., Novo Nordisk Inc., Pfizer Inc., PhaseBio Pharmaceuticals, Inc., PLx Pharma, Regeneron Pharmaceuticals, Roche Pharma, Sanofi, Synaptic, Takeda Pharmaceutical Company Limited. C.P. Cannon: Consultant; Self; Alnylam, Amarin Corporation, Amgen Inc., Corvia Medical, Inc., Eisai Inc., Kowa Pharmaceutical Europe Co. Ltd., Pfizer Inc., Regeneron Pharmaceuticals, Sanofi. Research Support; Self; Daiichi Sankyo Company, Limited. Other Relationship; Self; Amgen Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Bristol-Myers Squibb Company, Janssen Pharmaceuticals, Inc., Merck & Co., Inc. Funding Amgen Inc.

542-P: One-Year eGFR Decline Rate Predicts Renal Outcome in High-Risk Japanese Patients with Hypercholesterolemia and Diabetic Retinopathy

Objective: The slope of eGFR decline is collecting attentions for earlier recognition of eGFR decliner. We analyzed the predictive value of maximum 1-year eGFR decline rate for the renal endpoint in prospective cohort. Research Design and Methods: We analyzed the data from EMPATHY trial which was the multicenter randomized control trial to assess the benefits of intensive statin therapy for patients with hypercholesterolemia and diabetic retinopathy. We calculated 1-year eGFR decline rate in every 6 months and analyzed its relation to the renal endpoint defined as initiation of chronic dialysis or increase in serum creatinine level by at least twofold. Results: The renal endpoint developed in 101 subjects out of 5,042 patients in mean follow-up 37 ± 13 months. The AUC of maximum 1-year eGFR decline rate by ROC was 0.960, that of albuminuria at baseline was 0.913, and that of eGFR at baseline was 0.809. When we defined the cut-off value of maximum 1-year eGFR decline rate as 20%, its sensitivity was 97.8% and its specificity was 80.2%. Time until the renal endpoint from the first demonstration of 1-year eGFR decline rate more than 20% was 353.1 ± 31.9 days. Conclusions: One-year eGFR decline more than 20% was highly associated with the renal endpoint. The renal endpoint was predominantly observed in the subjects with albuminuria. Disclosure S. Meguro: Research Support; Self; Novartis Pharmaceuticals Corporation. Speaker's Bureau; Self; Abbott, Astellas Pharma Inc., AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Eli Lilly and Company, Kyowa Hakko Kirin Co., Ltd., Merck & Co., Inc., Mitsubishi Tanabe Pharma Corporation, Mochida Pharmaceutical Co., Ltd., NIPRO Medical Corporation, Novo Nordisk A/S, Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited, Terumo Medical Corporation. Y. Sato: None. H. Itoh: None.

Effects of alirocumab on types of myocardial infarction: insights from the ODYSSEY OUTCOMES trial.

Aims The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin–kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (≥1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI.Methods and results Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77–0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77–0.99; P = 0.032) and Type 2 (0.77, 0.61–0.97; P = 0.025), but not Type 4 MI.Conclusion After ACS, alirocumab added to intensive statin therapy favourably impacted on Type 1 and 2 MIs. The data indicate for the first time that a lipid-lowering therapy can attenuate the risk of Type 2 MI. Low-density lipoprotein cholesterol reduction below levels achievable with statins is an effective preventive strategy for both MI types.

Reader response: Association of statin use with spontaneous intracerebral hemorrhage: A cohort study.

The article by Saliba et al.1 further informs the debate on the important topic of statin use and spontaneous intracerebral hemorrhage. In our original Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial report (atorvastatin 80 mg/d vs placebo for secondary stroke prevention),2 we indicated that our analysis of the type of outcome stroke (ischemic, hemorrhagic, or unclassified) was unplanned and that the small numbers of participants with a baseline brain hemorrhage precluded meaningful conclusions in this population. A meta-analysis (17,000 participants; 26 randomized trials) found that more vs less intensive statin therapy reduced first ischemic strokes (risk ratio [RR] 0.84, 99% confidence interval [CI] 0.71–0.99; p = 0.005) and nonsignificantly increased hemorrhagic strokes (RR 1.21, 99% CI 0.76–1.91; p = 0.3).3 The meta-analysis did not address the risks of high-intensity statins for secondary stroke prevention. In the current analysis,1 statin dose was categorized as an average atorvastatin equivalent daily dose (AAEDD) of 20 mg/d. Although no interaction between AAEDD and previous stroke/TIA was found, given that the limited initial and subsequent exploratory SPARCL analyses prompted much of the debate regarding statin risk for secondary stroke prevention,2,4,5 it would be helpful to provide an analysis for participants with prior stroke who received an AEDD of 80 mg/d.

Abstract 174: Healthcare Provider Compliance with the 2013 ACC/AHA Blood Cholesterol Guidelines for Statin Therapy for Diabetic Patients of Ages 40 to 75

Introduction: On the basis of documented outcome benefit in randomized clinical trials, 2013 ACC/AHA blood cholesterol guidelines advocate use of moderate to high intensity statin therapy in all diabetic patients ages 40 -75. Recent published observations suggest variable provider compliance with this recommendation. This study investigates provider adherence to this recommendation and the predictors of such decision-making at a single academic tertiary care center. Methods: We retrospectively reviewed all diabetic patients, ages of 40-75, who were evaluated at our institution in the outpatient setting in 2015. Patient characteristics including demographics, cardiovascular co-morbidities and statin use were obtained from the electronic medical records. Statin prescribing frequency was analyzed by age group, gender and indication, whether primary or secondary prevention. Correlation and regression analyses were done to determine the effect of patient characteristics on statin prescription and the predictors of prescribing statins, respectively. Results: Of the 18,389 patients with diabetes, 10,338 (56.2%) were on statin therapy of any dose. Of those treated, 94.9% were on appropriate statin intensity. In the multivariate model, independent predictors of failure to prescribe statins were: Absence of diagnosis of hyperlipidemia (OR 3.60, 95% CI 3.31-3.92, p<0.0005), absence of hypertension (OR 1.42, 95% CI 1.30-1.56, p<0.0005), absence of atherosclerotic cardiovascular disease (coronary, cerebral or peripheral arterial disease) (OR1.41, 95% CI 1.16-1.70, p=0.001), age less than 60 (OR 1.35, 95% CI 1.24-1.46, p<0.0005), and female gender (OR 1.27, 95% CI 1.17-1.38, p=0.037). Absence of coronary artery disease (46.7% vs 29.9%, p<0.0005), absence of stroke history (44.0% vs 36.9%, p=0.003), BMI less than 30 (45.3% vs 43.3%, p=0.027) and lack of a cardiologist provider (44.3% vs 41.9%, p=0.009) were associated with failure to prescribe statins, but were not independent predictors. Conclusions: Only 56.2% of patients in an outpatient setting in our study who have an indication for statin use on the basis of diabetes received a prescription for statin therapy. Independent predictors of failure to prescribe statins were: absence of hyperlipidemia, absence of hypertension, absence of ischemic vascular disease, age less than 60, and female gender. Future educational interventions should focus on these predictors in order to improve provider compliance with initiation of statin therapy in eligible diabetic patients.

Lipid-Lowering Agents in Older Individuals: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

The efficacy of lipid-lowering agents on patient-important outcomes in older individuals is unclear. We included randomized trials that enrolled individuals aged 65 years or older and that included at least 1 year of follow-up.Pairs of reviewers selected and appraised the trials. We included 23 trials that enrolled 60,194 elderly patients. For primary prevention, statins reduced the risk of coronary artery disease [CAD; relative risk (RR): 0.79, 95% CI: 0.68 to 0.91] and myocardial infarction (MI; RR: 0.45, 95% CI: 0.31 to 0.66) but not all-cause or cardiovascular mortality or stroke. These effects were imprecise in patients with diabetes, but there was no significant interaction between diabetes status and the intervention effect. For secondary prevention, statins reduced all-cause mortality (RR: 0.80, 95% CI: 0.73 to 0.89), cardiovascular mortality (RR: 0.68, 95% CI: 0.58 to 0.79), CAD (RR: 0.68, 95% CI: 0.61 to 0.77), MI (RR: 0.68, 95% CI: 0.59 to 0.79), and revascularization (RR: 0.68, 95% CI: 0.61 to 0.77). Intensive (vs less-intensive) statin therapy reduced the risk of CAD and heart failure. Niacin did not reduce the risk of revascularization, and fibrates did not reduce the risk of stroke, cardiovascular mortality, or CAD. High-certainty evidence supports statin use for secondary prevention in older individuals. Evidence for primary prevention is less certain. Data in older individuals with diabetes are limited; however, no empirical evidence has shown a significant difference based on diabetes status.

Alirocumab in Patients With Polyvascular Disease and Recent Acute Coronary Syndrome: ODYSSEY OUTCOMES Trial

BackgroundPatients with acute coronary syndrome (ACS) and concomitant noncoronary atherosclerosis have a high risk of major adverse cardiovascular events (MACEs) and death. The impact of lipid lowering by proprotein convertase subtilisin–kexin type 9 inhibition in such patients is undetermined. ObjectivesThis pre-specified analysis from ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) determined whether polyvascular disease influenced risks of MACEs and death and their modification by alirocumab in patients with recent ACS and dyslipidemia despite intensive statin therapy. MethodsPatients were randomized to alirocumab or placebo 1 to 12 months after ACS. The primary MACEs endpoint was the composite of coronary heart disease death, nonfatal myocardial infarction, fatal or nonfatal ischemic stroke, or unstable angina requiring hospitalization. All-cause death was a secondary endpoint. ResultsMedian follow-up was 2.8 years. Of 18,924 patients, 17,370 had monovascular (coronary) disease, 1,405 had polyvascular disease in 2 beds (coronary and peripheral artery or cerebrovascular), and 149 had polyvascular disease in 3 beds (coronary, peripheral artery, cerebrovascular). With placebo, the incidence of MACEs by respective vascular categories was 10.0%, 22.2%, and 39.7%. With alirocumab, the corresponding absolute risk reduction was 1.4% (95% confidence interval [CI]: 0.6% to 2.3%), 1.9% (95% CI: −2.4% to 6.2%), and 13.0% (95% CI: −2.0% to 28.0%). With placebo, the incidence of death by respective vascular categories was 3.5%, 10.0%, and 21.8%; the absolute risk reduction with alirocumab was 0.4% (95% CI: −0.1% to 1.0%), 1.3% (95% CI: −1.8% to 4.3%), and 16.2% (95% CI: 5.5% to 26.8%). ConclusionsIn patients with recent ACS and dyslipidemia despite intensive statin therapy, polyvascular disease is associated with high risks of MACEs and death. The large absolute reductions in those risks with alirocumab are a potential benefit for these patients. (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab [ODYSSEY OUTCOMES]: NCT01663402)

Intensity of Statin Therapy Affects Progression of Coronary Artery Vasculopathy

Purpose Statin therapy offers long-term morbidity and mortality benefits after orthotopic heart transplant (OHT), regardless of lipid levels. Multiple statins have been specifically studied in post-OHT patients, showing decrease in dyslipidemia and development of cardiac allograft vasculopathy (CAV). CAV is an accelerated form of coronary artery disease characterized by concentric fibrous intimal hyperplasia along the length of coronary vessels. CAV is detectable by angiography in 43% of survivors in the first 8 years after OHT. Treatment with statins significantly reduces the incidence of transplant CAV and shows mortality benefit at ten years. This retrospective study examines the relationship between certain variables and the risk of developing CAV in a cohort of OHT patients at a single center. Methods Retrospective data points from 212 OHT patients at a single center were collected from the electronic medical record. For all patients, statin dosage was recorded as low, moderate, and high intensity based on the 2013 ACC/ AHA guidelines. Patient's yearly catheterization reports were reviewed for diagnosis of CAV. Time from OHT to CAV diagnosis was calculated from the date of the diagnosing catheterization. If a patient was diagnosed with CAV, data points including degree of CAV, systolic blood pressure, lipid levels, and HbA1c at the time of CAV diagnosis were recorded. Results Statin intensity was the only significant variable in the Cox Proportional Hazards model (p= 0.0025; HR = 1.49 (95% CI: 1.15-1.93). Similar models to predict rejection were considered, and no variables were found to be significant. A binary logistic regression model was run to predict the presence of any malignancy, and no variables were found to be significant at the 0.05 level. Elevated systolic blood pressure and HbA1c were also significant findings in the CAV group as compared to the non-CAV group of OHT patients (p=0.003 and p=0.035 respectively). Conclusion The intensity of statin therapy significantly affects the progression of CAV. OHT programs should be vigilant in prescribing their OHT patients statins and encouraging compliance due to the risk of life threatening complications. As well, as prescribing statins, patients should be monitored closely for hypertension and diabetes as these disease processes are more often found in patients with CAV, than those would do not have a CAV diagnosis.

Higher Intensity Statin Therapy Reduces Clinical Endpoints after Heart Transplantation Independent of Lipid Levels

Higher Intensity Statin Therapy Reduces Clinical Endpoints after Heart Transplantation Independent of Lipid Levels

Prehospital statin use and low-density lipoprotein cholesterol levels at admission in acute coronary syndrome patients with history of myocardial infarction or revascularization: Findings from the Improving Care for Cardiovascular Disease in China (CCC) project

Lowering low-density lipoprotein cholesterol (LDL-C) by statins is a key strategy for secondary prevention of acute coronary syndrome (ACS). However, few studies have examined prehospital statin use and admission LDL-C levels in ACS patients with history of myocardial infarction (MI) or revascularization. This study aimed to assess use of prehospital statins and LDL-C levels at admission in ACS patients with history of MI or revascularization. Improving Care for Cardiovascular Disease in China project was a nationwide registry, with 192 participating hospitals reporting details of clinical information of ACS patients from November 2014. By May 2018, 80,282 patients with ACS were included. LDL-C levels were obtained from the initial admission lipid testing. Of the 80,282 ACS patients, 6,523 with a history of MI or revascularization were enrolled. Among them, 50.8% were receiving lipid-lowering therapy before hospitalization (statin monotherapy in 98.4%, combination in 1.2%). A total of 30.1% of patients had LDL-C < 70 mg/dL at admission. In patients receiving prehospital statins, 36.1% had LDL-C < 70 mg/dL compared to 24.0% without prehospital statins (P < .001). At discharge, 91.8% of patients were treated with statin monotherapy, 90.7% at moderate doses irrespective of prehospital statin use and LDL-C levels at admission. Among ACS patients with history of MI or revascularization, half were not being treated with statin therapy prior to admission, and most had not attained LDL-C < 70 mg/dL despite prehospital statin use. There is an important opportunity to provide intensive statin or combination lipid-lowering therapy to these very high risk patients.

IMPACT OF EARLY STATIN TITRATION ON SUBSEQUENT CARDIOVASCULAR EVENTS: ESTIMATES FROM SWEDISH POPULATION-BASED REGISTRY DATA

Clinical studies have demonstrated efficacy of intensive statin therapy in lowering low-density lipoprotein cholesterol and cardiovascular (CV) events. The study objective was to examine the association between statin titration patterns and subsequent CV events in very high CV risk patients using

Time-dependent prognostic effect of high sensitivity C-reactive protein with statin therapy in acute myocardial infarction

BackgroundElevated high sensitivity C-reactive protein (hs-CRP) in acute myocardial infarction (AMI) patients undergoing percutaneous coronary intervention (PCI) has prognostic value for future cardiovascular events. This study aimed to ascertain a valid prognostic time-period for predicting cardiovascular outcome based on baseline hs-CRP in AMI patients undergoing successful PCI on statin therapy. MethodsOverall, 4410 AMI patients were enrolled from the Korea Acute Myocardial Infarction-National Institutes of Health (KAMIR-NIH) registry. Participants were divided into groups according to cut-off values of baseline hs-CRP (1.0, 3.0, and 10.0mg/L) and statin therapy intensity. The primary outcome was 36-month major adverse cardiovascular events (MACE), a composite of all-cause mortality, any myocardial infarction, and repeat revascularization. The secondary outcome was MACE developed 0–6, 6–12, and 12–36 months after AMI. ResultsThe overall incidence of 36-month MACE was significantly higher as baseline hs-CRP increased (by groups: 8.8% vs. 8.6% vs. 10.7% vs. 15.4%, log-rank p<0.001). The prognostic effect of baseline hs-CRP was mostly confined to the first 6 months after AMI (0–6 months MACE by groups: 1.6% vs. 2.3% vs. 4.3% vs. 6.1%, log-rank p<0.001) and attenuated in high-intensity statin users. Six months after AMI, this prognostic effect of baseline hs-CRP was remarkably reduced (6–12 month MACE by groups: 2.4% vs. 2.1% vs. 2.8% vs. 4.0%, log-rank p=0.111, 12–36 month MACE by groups: 4.7% vs. 4.1% vs. 4.0% vs. 6.2%, log-rank p=0.218); however, high-intensity statin treatment showed a consistent improvement in outcome. The observed time-dependent prognostic effects remained consistent following multivariate analysis. ConclusionsThe prognostic impact of elevated hs-CRP at baseline was most evident during the first 6 months after AMI; however, the use of high-intensity statin persistently improved the clinical outcome even after the resolution of inflammatory reactions.

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.

Efficacy and safety of statin therapy in older people: a meta-analysis of individual participant data from 28 randomised controlled trials

SummaryBackgroundStatin therapy has been shown to reduce major vascular events and vascular mortality in a wide range of individuals, but there is uncertainty about its efficacy and safety among older people. We undertook a meta-analysis of data from all large statin trials to compare the effects of statin therapy at different ages.MethodsIn this meta-analysis, randomised trials of statin therapy were eligible if they aimed to recruit at least 1000 participants with a scheduled treatment duration of at least 2 years. We analysed individual participant data from 22 trials (n=134 537) and detailed summary data from one trial (n=12 705) of statin therapy versus control, plus individual participant data from five trials of more intensive versus less intensive statin therapy (n=39 612). We subdivided participants into six age groups (55 years or younger, 56–60 years, 61–65 years, 66–70 years, 71–75 years, and older than 75 years). We estimated effects on major vascular events (ie, major coronary events, strokes, and coronary revascularisations), cause-specific mortality, and cancer incidence as the rate ratio (RR) per 1·0 mmol/L reduction in LDL cholesterol. We compared proportional risk reductions in different age subgroups by use of standard χ2 tests for heterogeneity when there were two groups, or trend when there were more than two groups.Findings14 483 (8%) of 186 854 participants in the 28 trials were older than 75 years at randomisation, and the median follow-up duration was 4·9 years. Overall, statin therapy or a more intensive statin regimen produced a 21% (RR 0·79, 95% CI 0·77–0·81) proportional reduction in major vascular events per 1·0 mmol/L reduction in LDL cholesterol. We observed a significant reduction in major vascular events in all age groups. Although proportional reductions in major vascular events diminished slightly with age, this trend was not statistically significant (ptrend=0·06). Overall, statin or more intensive therapy yielded a 24% (RR 0·76, 95% CI 0·73–0·79) proportional reduction in major coronary events per 1·0 mmol/L reduction in LDL cholesterol, and with increasing age, we observed a trend towards smaller proportional risk reductions in major coronary events (ptrend=0·009). We observed a 25% (RR 0·75, 95% CI 0·73–0·78) proportional reduction in the risk of coronary revascularisation procedures with statin therapy or a more intensive statin regimen per 1·0 mmol/L lower LDL cholesterol, which did not differ significantly across age groups (ptrend=0·6). Similarly, the proportional reductions in stroke of any type (RR 0·84, 95% CI 0·80–0·89) did not differ significantly across age groups (ptrend=0·7). After exclusion of four trials which enrolled only patients with heart failure or undergoing renal dialysis (among whom statin therapy has not been shown to be effective), the trend to smaller proportional risk reductions with increasing age persisted for major coronary events (ptrend=0·01), and remained non-significant for major vascular events (ptrend=0·3). The proportional reduction in major vascular events was similar, irrespective of age, among patients with pre-existing vascular disease (ptrend=0·2), but appeared smaller among older than among younger individuals not known to have vascular disease (ptrend=0·05). We found a 12% (RR 0·88, 95% CI 0·85–0·91) proportional reduction in vascular mortality per 1·0 mmol/L reduction in LDL cholesterol, with a trend towards smaller proportional reductions with older age (ptrend=0·004), but this trend did not persist after exclusion of the heart failure or dialysis trials (ptrend=0·2). Statin therapy had no effect at any age on non-vascular mortality, cancer death, or cancer incidence.InterpretationStatin therapy produces significant reductions in major vascular events irrespective of age, but there is less direct evidence of benefit among patients older than 75 years who do not already have evidence of occlusive vascular disease. This limitation is now being addressed by further trials.FundingAustralian National Health and Medical Research Council, National Institute for Health Research Oxford Biomedical Research Centre, UK Medical Research Council, and British Heart Foundation.

Assessing Changes in Statin Prescribing Patterns Surrounding the 2013 American College of Cardiology/American Heart Association Lipid Guidelines

PurposeThe American College of Cardiology (ACC) and the American Heart Association (AHA) introduced new lipid guidelines in late 2013 that were a vast departure from older guidelines. Concerns were raised regarding the likely increase in the number of adults who would be eligible for lipid-lowering therapy, namely moderate to high intensity statins. We sought to determine whether, in the first year after the ACC/AHA guideline release, more patients were prescribed statins, prescribed moderate- to high-intensity statins, and eligible for statins compared with the previous year. MethodsThis study was a retrospective, cross-sectional, observational analysis of National Ambulatory Medical Care Survey collected by the Centers for Disease Control and Prevention during the years 2013 and 2014. Survey participants who were younger than 40 years or older than 75 years, were pregnant, or had triglyceride levels ≥400 mg/dL were excluded. Descriptive analyses and χ2 tests of homogeneity (and associated odds ratios [ORs] and CIs) were constructed and reported. FindingsCompared with 2013, a higher percentage of patients in 2014 were prescribed a statin and were eligible to receive a statin. In fact, patients in 2014 were significantly more likely to be prescribed a statin (OR = 1.22; 95% CI, 1.00–1.48) and to be eligible for a statin (OR = 9.26, 95% CI 7.54–11.37) compared with 2013. Although a higher percentage of patients in 2014 were prescribed a higher-intensity statin, the difference was not statistically significant (OR = 1.17; 95% CI, 0.90–1.52). ImplicationsIn the first year after the ACC/AHA guideline introduction, more patients in the United States were prescribed a statin. However, it is unclear whether the new guidelines were strictly adhered to regarding intensity of statin therapy.

Comparison of Clinical Care and In-Hospital Outcomes of Asian American and White Patients With Acute Ischemic Stroke

Although overall stroke incidence and mortality in the United States is improving, little is known about the characteristics and clinical outcomes of acute ischemic stroke in Asian American individuals. To compare the characteristics, care, and outcomes of Asian American and white patients with acute ischemic stroke. Retrospective analysis of Asian American and white patients admitted with a primary diagnosis of acute ischemic stroke to hospitals participating in the Get With The Guidelines-Stroke (GWTG-Stroke) program between April 1, 2004, and July 31, 2016. The GWTG-Stroke database is a prospectively collected stroke quality improvement registry sponsored by the American Heart Association/American Stroke Association. Multivariable logistic regression models assessed the association of Asian American race/ethnicity, clinical outcomes, and quality measures. The study population of 1 772 299 patients (mean [SD] age, 72.4 [14.2] years; 51.3% female) consisted of 64 337 Asian American patients (3.6%) and 1 707 962 white patients (96.4%) admitted to 2171 GWTG-Stroke hospitals with acute ischemic stroke. After adjustment for patient and hospital variables, Asian American patients were seen with greater stroke severity compared with white patients (National Institutes of Health Stroke Scale [NIHSS] score ≥16) (odds ratio [OR], 1.35; 95% CI, 1.30-1.40; P < .001), manifested higher in-hospital mortality (OR, 1.14; 95% CI, 1.09-1.19; P < .001), had longer length of stay (OR, 1.17; 95% CI, 1.14-1.20; P < .001), and were less likely to ambulate independently at discharge (OR, 0.84; 95% CI, 0.79-0.90; P < .001). Although Asian American patients had fewer intravenous tissue plasminogen activator (IV tPA) administrations than white patients (OR, 0.95; 95% CI, 0.91-0.98; P = .003), they had more symptomatic hemorrhage after tPA (OR, 1.36; 95% CI, 1.20-1.55; P < .001) and overall post-tPA complications (OR, 1.31; 95% CI, 1.18-1.46; P < .001). Asian American patients had better quality measure adherence overall than white patients, including rehabilitation (OR, 1.27; 95% CI, 1.18-1.36; P < .001), door to tPA within 60 minutes (OR, 1.14; 95% CI, 1.06-1.22; P < .001), and intensive statin therapy (OR, 1.14; 95% CI, 1.10-1.18; P < .001). After adjustment for stroke severity, Asian American patients had lower in-hospital mortality than white patients (OR, 0.95; 95% CI, 0.91-0.99; P = .008). Asian American patients manifested more severe ischemic strokes, were less likely to receive IV tPA, and had worse functional outcomes than white patients. These findings warrant additional research toward improving clinical outcomes for Asian American patients with acute ischemic stroke.

Intensity of Statin Treatment in Korean Patients with Acute Myocardial Infarction and Very Low LDL Cholesterol.

ObjectiveData on the intensity of statin therapy for patients with acute myocardial infarction (MI) and very low baseline low-density lipoprotein (LDL) cholesterol level are lacking. We sought to assess the impact of statin intensity in patients with acute MI and LDL cholesterol <70 mg/dL.MethodsA total of 1,086 patients with acute MI and baseline LDL cholesterol <70 mg/dL from the Korea Acute Myocardial Infarction Registry-National Institute of Health database were divided into less intensive statin (expected LDL reduction <40%, n=302) and more intensive statin (expected LDL reduction ≥40%, n=784) groups. The primary endpoint was major adverse cardiac and cerebrovascular events (MACCEs), a composite of cardiac death, MI, revascularization occurring at least 30 days after admission, and stroke, at 12 months.ResultsAfter 1:2 propensity matching, differences were not observed between less intensive (n=302) and more intensive statin (n=604) groups in incidence of cardiac death (0.3% vs. 0.3%) and hemorrhagic stroke (0.3% vs. 0.5%, p=0.727) at 12 months. Compared with the less intensive statin group, the more intensive statin group showed lower target-vessel revascularization (4.6% vs. 1.8%, p=0.027) and MACCE (11.6% vs. 7.0%, p=0.021). Major bleeding was not different between less intensive and more intensive statin groups (1.0% vs. 2.6%, p=0.118).ConclusionMore intensive statin therapy was associated with significantly lower major adverse cardiovascular events in patients with acute MI and very low LDL cholesterol compared with less intensive statin therapy.

COMPARISON OF METABOLIC PROFILE OF OBESE NON-DIABETIC PATIENTS WITH CORONARY ARTERY DISEASE DEPENDING ON ATORVASTATIN DOSE

Introduction:Cardiovascular diseases (CVD) are one of the most important medical-biological and social problems in Ukraine and in the world because coronary artery disease (CAD) is a major cause of death and disability. Overweight and obesity are risk factor of CVD and type 2 diabetes mellitus (T2DM). Although statins have been shown to be beneficial in secondary prevention of CVD in a number of trials, current reports of increased risk of T2DM with statin use raise concerns. The aim: To compare the metabolic profile and therapeutic targets of non-diabetic obese patients with CAD depending on the dose of atorvastatin. Materials and methods: The study included 107 patients (82 men and 25 women) with CAD and abdominal obesity. Patients were divided into two groups: those taking 20 mg and 40 mg of atorvastatin daily correspondingly. Glucose, insulin, HbA1c, HOMA-IR, lipids, hs-CRP and anthropometric parameters were measured for each subject. Results: For patients with CAD and obesity, who had taken atorvastatin in a 40-mg dose, we observed a significant increase in insulin resistance and impaired fasting glucose. Also we found a reliable correlation between the carbohydrate and lipid spectrum. These parameters reflect the mechanism of the formation of metabolic disorders as a result of intensive statin therapy. Сonclusions: Despite of the beneficial reductions in LDL and total cholesterol, atorvastatin treatment on a dose 40 mg resulted in significant increase of fasting glucose, insulin levels and insulin resistance pertaining to those patients.

Moderate-intensity versus high-intensity statin therapy in Korean patients with angina undergoing percutaneous coronary intervention with drug-eluting stents: A propensity-score matching analysis.

ObjectivesIt is unclear whether high-intensity statin therapy provides incremental clinical benefits over moderate-intensity statin therapy in Asian patients with angina. This study sought to compare the clinical outcomes of moderate- and high-intensity statin therapies in patients undergoing percutaneous coronary intervention (PCI) for angina in Korean patients.MethodsBased on the national health insurance claims data in South Korea, patients aged 18 years or older without a known history of coronary artery disease, who underwent PCI with drug-eluting stents due to angina between 2011 and 2015, were enrolled. According to the intensity of statin therapy, patients were categorized into moderate-intensity statin therapy (n = 23,863) and high-intensity statin therapy (n = 9,073) groups. The primary endpoint, defined as a composite of all-cause death and myocardial infarction, was compared between the two groups using a propensity-score matching analysis.ResultsDuring the follow-up period (median, 2.0 years; interquartile range, 1.1–3.1), 1,572 patients had 1,367 deaths and 242 myocardial infarctions. After propensity-score matching, there were 8,939 matched pairs. There was no significant difference in the incidence of the primary endpoint between the two groups (adjusted hazard ratio of high-intensity statin therapy, 1.093; 95% confidence interval: 0.950–1.259; p = 0.212).ConclusionsIn Korean patients undergoing PCI with drug-eluting stents for angina, the high-intensity statin therapy did not provide additional clinical benefits over the moderate-intensity statin therapy.

Achieving LDL cholesterol target levels

AimsTo assess the benefits of intensive statin therapy on reducing cardiovascular (CV) events in patients with type 2 diabetes complicated with hyperlipidaemia and retinopathy in a primary prevention setting in Japan. In the intension‐to‐treat population, intensive therapy [targeting LDL cholesterol <1.81 mmol/L (<70 mg/dL)] was no more effective than standard therapy [LDL cholesterol ≥2.59 to <3.10 mmol/L (≥100 to <120 mg/dL)]; however, after 3 years, the intergroup difference in LDL cholesterol was only 0.72 mmol/L (27.7 mg/dL), and targeted levels were achieved in <50% of patients. We hypothesized that the intergroup difference in CV events would have been statistically significant if more patients had been successfully treated to target.Materials and MethodsThis exploratory post hoc analysis focused on intergroup data from patients who achieved their target LDL cholesterol levels. The primary endpoint was the composite incidence of CV events. A Cox proportional hazards model was used to estimate hazard ratios (HRs) for incidence of the primary endpoint in patients who achieved target LDL cholesterol levels in each group.ResultsData were analysed from 1909 patients (intensive: 703; standard: 1206) who achieved target LDL cholesterol levels. LDL cholesterol at 36 months was 1.54 ± 0.30 mmol/L (59.7 ± 11.6 mg/dL) in the intensive group and 2.77 ± 0.46 mmol/L (107.1 ± 17.8 mg/dL) in the standard group (P < 0.05). After adjusting for baseline prognostic factors, the composite incidence of CV events or deaths associated with CV events was significantly lower in the intensive than the standard group (HR 0.48; 95% confidence interval 0.28‐0.82; P = 0.007).ConclusionsThis post hoc analysis suggests that achieving LDL cholesterol target levels <1.81 mmol/L may more effectively reduce CV events than achieving target levels ≥2.59 to <3.10 mmol/L in patients with hypercholesterolaemia and diabetic retinopathy.