Statin Therapy In High-risk Patients Research Articles

Guideline adherence to statin therapy and association with major adverse cardiac events in high-risk patients following major noncardiac surgery

Abstract Introduction Statins are widely used for the prevention of coronary artery disease (CAD) and associated secondary cardiovascular complications. Despite established evidence in acute and chronic cardiovascular disease, the optimal perioperative use of statins remains uncertain. We aimed to evaluate adherence to current guideline recommendations regarding statin therapy in high-risk patients undergoing major noncardiac surgery and its association with major adverse cardiac event (MACE). Methods Class I indications for statin therapy according to current ESC clinical practice guidelines were assessed among consecutive high-risk patients undergoing major noncardiac surgery enrolled in a prospective multicentre cohort study. The primary endpoint MACE, a composite of cardiovascular death and spontaneous acute myocardial infarction, was recorded during 120-day follow up and centrally adjudicated by cardiologists blinded to statin therapy. As a co-primary endpoint, perioperative myocardial infarction/injury (PMI) due to a type 1 MI (T1MI) or likely type 2 MI (lT2MI) within the first three postoperative days was used. After multivariable adjustment with inverse probability of treatment weighting (IPTW) to account for differences between statin and non-statin users, we performed a Cox proportional hazard model with MACE and a logistic regression model with PMI due to T1MI or lT2MI as endpoints. Results Between October 2014 and February 2018, we included 8116 high-risk patients undergoing major noncardiac surgery. 4227 of 8116 patients (52.1%) had at least one class I indication for statin therapy. The most common indication for statin use was CAD in 2235 patients (52.9%) followed by diabetes with comorbidities in 1676 patients (39.6%) and peripheral artery disease in 1514 patients (35.8%). From all patients with a class I indication for statin use, only 2440 (57.7%) were on statins preoperatively. Usage was highest in patients with prior myocardial infarction (828/1110 [74.6%]) and lowest in patients with chronic kidney disease stage 3-5 (494/996 [49.6%]). During the follow up of 120 days, 192 MACE occurred (4.6%) including 116 cardiovascular deaths. After multivariable adjustment, preoperative use of statins was associated with a reduced risk of MACE (weighted hazard ratio 0.59, 95% confidence interval [CI] 0.41-0.86; p = 0.006). PMI due to T1MI or lT2MI occurred in 508 of 4170 (12.2%) patients. After IPTW, the weighted odds ratio for PMI in patients receiving preoperative statin therapy was 1.15 (95%CI 1.01-1.31; p = 0.036). Conclusion Current adherence to guideline-recommended statin therapy in the noncardiac surgery population is suboptimal. The use of statins was associated with reduced rates of adverse cardiac events within 120 days, but not with cardiac PMI.Percentage of patients receiving statinsMACE within 120 days

Benefit of Combination Ezetimibe/Simvastatin Among High-Risk Populations: Lessons from the IMPROVE-IT Trial.

The Improved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT) demonstrated the clinical benefit of the combination of ezetimibe-simvastatin compared to placebo-simvastatin following acute coronary syndrome (ACS). This review highlights key findings from this study with particular attention to the practice-changing impact on guidelines for low-density lipoprotein cholesterol (LDL-C) reduction after ACS, especially among high-risk populations. Consistent reductions in LDL-C have been reported with newer lipid-lowering therapies (proprotein convertase subtilisin/kexin type 9 inhibitors, cholesterol ester transfer proteins, bempedoic acid) in combination with statin in high-risk subgroups. Since high-risk subgroups remain a focus of guidelines, exploration of high-risk subgroups can help define the optimal use of new therapies. Ezetimibe reduced the LDL-C by 16.7mg/dL compared to placebo at 1year, resulting in a significant reduction in the primary composite endpoint (absolute risk difference 2.0%; relative risk difference 6.4%, hazard ratio, 0.936; 95% confidence interval, 0.89 to 0.99; P = 0.016). The benefits achieved with ezetimibein both LDL-C reduction and the primary clinical composite across 10 pre-specified high-risk subgroups, including the elderly; women; patients with diabetes, prior coronary artery bypass graft, history of stroke, polyvascular disease, low baseline LDL-C, renal dysfunction, prior heart failure, and an elevated TIMI risk score for secondary prevention, were similar or greater than in the corresponding non-high-risk subgroups. Safety events were similar between ezetimibe and placebo across the high-risk subgroups. These data support the addition of ezetimibe to statin therapy in high-risk patients who require additional therapy to lower the LDL-C post-ACS.

Using the Practical Robust Implementation and Sustainability Model (PRISM) to Identify and Address Provider-Perceived Barriers to Optimal Statin Prescribing and Use in Community Health Centers.

Statins are an important but underutilized therapy to prevent cardiovascular events, particularly in high-risk patients. To increase use of statin therapy in high-risk patients, the Centers for Disease Control and Prevention funded a project led by the National Association of Community Health Centers to discover reasons for statin underuse in health centers and identify possible leverage points, particularly among vulnerable and underserved patients. The project further sought to develop training and educational materials to improve statin prescribing for and acceptance in eligible high-risk patients. As a first step, investigators implemented a questionnaire to clinical providers (n = 45) at health centers participating in the project to obtain their perspective on barriers to optimal statin use. We used the practical robust implementation and sustainability model (PRISM) domains to frame the overall project and guide the development of our questionnaire. This paper summarizes top perceived barriers to patient and health system/provider statin initiation and sustainment, as well as facilitators to prescribing, using PRISM as an organizing framework. Our questionnaire yielded important suggestions related to public awareness, education materials, health information technology (HIT)/data solutions, and clinical guidelines as key factors in optimizing statin use. It also informed the design of patient education resources and provider training tools. Future directions include using the full application of the PRISM implementation science model to assess how well our educational and training resources help overcome barriers to statin use in high-risk patients, including evaluating how key contextual factors influence successful implementation.

Abstract 11627: Effectiveness of Statin Therapy in an Urban Metropolitan Patient Population

Introduction: Severely elevated serum LDL (>190 mg/dL) is an independent risk factor in the development of ASCVD complications. Despite current guidelines recommending the immediate initiation of high dose statin therapy in high-risk patients, limitations in care continue to exist, especially amongst different genders, races and populations with a higher burden of health disparities. Hypothesis: We assessed the hypothesis of whether or not race and gender affected the timeliness and appropriateness of initiating statin therapy in a patient population that has a higher burden of health disparities. Methods: We performed a single centered, retrospective observational study where 499 patients with an initial LDL level greater than 190 mg/dL were identified. These patients were then stratified according to race and gender and evaluated for intensity and timing of statin therapy for 12 months after their initial lipid profile. Institutional survey data was acquired to quantify health disparities of our patient population in comparison to US census and Chicago Public Health data. Results: All 499 patients were included in the study. The mean LDL was 224.72 mg/dL and the SEM was 1.775 mg/dL. When compared to state and national averages, respectively, patients from our geographic region were found to have a higher percentage of unemployment (11% vs 7% vs 7%), uninsured status (13% vs 9% vs 10%) and inadequate access to transportation (25% vs 11% vs 9%). There was no significant difference between race or gender regarding the timing of statin initiation or degree of statin intensity. Of all patients, 38.2% were not started on any statin while 29.8% were immediately started on statin therapy (p=0.04). Of those patients started on statin therapy, only 11.4% were started on a high intensity statin (p=0.039). Conclusions: In conclusion, we found that, regarding race or gender, there was no significant difference in initiation of statin or strength of statin started. However, the overall percentage of patients that were started on a timely and appropriate dosage was significantly lower, especially in comparison to national averages. This may be due to the high degree of health disparities that are prevalent amongst our patient population.

Clinical outcome of statin plus ezetimibe versus high-intensity statin therapy in patients with acute myocardial infarction propensity-score matching analysis

BackgroundIt is unclear whether simvastatin–ezetimibe could be an alternative therapy to high-intensity statin therapy in high-risk patients. The aim of this study was to compare the clinical outcomes of simvastatin–ezetimibe and high-intensity statin therapy in patients with acute myocardial infarction (AMI), and especially in those with high-risk factor. MethodsA total of 3520 AMI patients in the KAMIR (Korea Acute Myocardial Infarction Registry) were classified into simvastatin–ezetimibe group (n=1249) and high-intensity statin group (n=2271). Multivariate analysis and propensity-score matching analysis were performed. The primary endpoint was major adverse cardiac events (MACE) at 12-months follow-up. ResultsIn overall AMI patients, MACE occurred in 116 patients (9.3%) in simvastatin–ezetimibe group and 116 patients (5.1%) in high-intensity statin group. The difference in MACE between groups was driven by repeat revascularization (5.9% vs. 2.2%). After propensity matching analysis, simvastatin–ezetimibe was associated with a higher incidence of MACE than high-intensity statin therapy (adjusted hazard ratio: 3.090, 95% confidence interval: 1.715 to 5.566, p<0.001). However, in patients with high-risk factors, such as diabetes, old age, or heart failure, simvastatin-ezetimibe had similar incidence of MACE compared with high-intensity statin therapy in further adjusted analysis. ConclusionsIn overall AMI patients, high-intensity statin therapy had better clinical outcomes than simvastatin–ezetimibe. However, in patients with high-risk factor, simvastatin–ezetimibe had comparable clinical outcomes to high-intensity statin therapy. Therefore, simvastatin–ezetimibe could be used as an alternative to high-intensity statin therapy in such patients.

Incremental Benefit and Cost-Effectiveness of High-Dose Statin Therapy in High-Risk Patients With Coronary Artery Disease

Incremental Benefit and Cost-Effectiveness of High-Dose Statin Therapy in High-Risk Patients With Coronary Artery Disease

High-dose statins are cost-effective compared with conventional-dose statins in patients with acute coronary syndromes

Source Citation Chan PS, Nallamothu BK, Gurm HS, Hayward RA, Vijan S. Incremental benefit and cost-effectiveness of high-dose statin therapy in high-risk patients with coronary artery disease. Circ...

Effects of Increasing Doses of Atorvastatin on the Atherogenic Lipid Subclasses Commonly Associated With Hypertriglyceridemia

The increased cardiovascular risk associated with hypertriglyceridemia is thought to be due in part to high levels of triglyceride (TG)-rich lipoproteins and small dense low-density lipoprotein (LDL). In this post hoc analysis, effects of increasing doses of atorvastatin (10, 20, 40, and 80 mg) on atherogenic lipid subclasses commonly associated with hypertriglyceridemia were evaluated in 191 men and women who were candidates for lipid-lowering therapy and had baseline TG levels >200 mg/dl (2.3 mmol/L). After 8 weeks of treatment, in addition to significantly decreasing LDL cholesterol and TG levels, atorvastatin significantly increased LDL peak particle diameter (p <0.01) and significantly decreased the concentration of small LDL subclasses IIIa and IIIb (p <0.0001) from baseline at all doses. These effects were more pronounced with higher compared with lower doses of atorvastatin. Each dose of atorvastatin also significantly lowered levels of very LDL, intermediate-density lipoprotein (p <0.0001), and small very LDL subclass 3 (p <0.0001). Greater decreases were achieved by those patients receiving higher doses of atorvastatin (20, 40, and 80 mg). The increase in LDL size correlated with the decrease in TG levels, but not with the decrease in LDL cholesterol levels. However, the decrease in small dense LDL cholesterol concentrations correlated significantly with TG and LDL cholesterol decreases. In conclusion, atorvastatin significantly lowered levels of TG-rich remnant lipoproteins and favorably changed LDL particle size in patients with hypertriglyceridemia. These effects may explain the benefits of statin therapy in high-risk patients with hypertriglyceridemia even when levels of LDL cholesterol are at goal.

Incremental Benefit and Cost-Effectiveness of High-Dose Statin Therapy in High-Risk Patients With Coronary Artery Disease

Recent clinical trials found that high-dose statin therapy, compared with conventional-dose statin therapy, reduces the risk of cardiovascular events in patients with acute coronary syndromes (ACS) and stable coronary artery disease (CAD). However, the actual benefit and cost-effectiveness of high-dose statin therapy are unknown. We designed a Markov model to compare daily high-dose with conventional-dose statin therapy for hypothetical 60-year-old cohorts with ACS and stable CAD over patient lifetime. Pooled estimates for major clinical end points (all-cause mortality, myocardial infarction, stroke, rehospitalization, and revascularization) from relevant clinical trials were incorporated. Incremental benefit was quantified as quality-adjusted life-years (QALYs). Threshold analyses determined at what price difference high-dose statins would yield incremental cost-effective ratios below $50,000, $100,000, and $150,000 per QALY gained. In ACS patients, a high-dose versus conventional-dose statin strategy resulted in a gain of 0.35 QALYs. In threshold analyses, a high-dose statin strategy consistently yielded incremental cost-effective ratios below $30,000 per QALY even under conservative model assumptions. In stable CAD patients, a high-dose statin strategy yielded a gain of only 0.10 QALYs and was sensitive to model assumptions about statin efficacy. The daily cost difference between a high- and conventional-dose statin would need to be <$1.70, $2.65, and $3.55 to yield incremental cost-effective ratios below $50,000, $100,000, and $150,000 per QALY. High-dose statin therapy is potentially highly effective and cost-effective in patients with ACS. In patients with stable CAD, however, the cost-effectiveness of high-dose statin therapy is highly sensitive to model assumptions about statin efficacy and cost. Use of high-dose statins can be supported on health economic grounds in patients with ACS, but the case is less clear for patients with stable CAD.

Incremental Benefit and Cost-Effectiveness of High-Dose Statin Therapy in High-Risk Patients With Coronary Artery Disease

Incremental Benefit and Cost-Effectiveness of High-Dose Statin Therapy in High-Risk Patients With Coronary Artery Disease

Mechanisms of Statin-Induced Myopathy

The advent of the HMG-CoA reductase inhibitors, or statins, in the 1980’s as highly efficacious agents for the lowering of low-density lipoprotein-cholesterol (LDL-C) revolutionized treatment of hypercholesterolemia, a long established risk factor for premature coronary heart disease. Indeed, a recent prospective meta-analysis of data from more than 90 000 participants in 14 randomized clinical trials revealed that a statin-mediated reduction of 1 mmol/L (40 mg/dL) in LDL-C that is sustained for 5 years may produce a proportional reduction in major vascular events of some 23%.1 Greater reductions in LDL-C, which may be attained with intensive statin therapy as exemplified in the recent Pravastatin or Atorvastatin Evaluation and Infection Therapy–Thrombolysis in Myocardial Infarction 22 (PROVE IT-TIMI 22), Treating to New Targets (TNT), and Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) trials involving use of atorvastatin (80 mg/d), produce larger reductions in vascular disease risk.2–4 Importantly, risk reductions are proportional to the absolute reduction in LDL-C1, and moreover clinical benefit may be apparent with intensive statin treatment as early as 30 days after initiation in acute coronary syndrome patients, with significant decrement in cardiovascular morbi-mortality.5 See page 2560 Statins not only exhibit a remarkably high benefit to risk ratio, but are equally characterized by a safety profile with excellent tolerance.6,7 Nonetheless, statins may exert toxic effects on skeletal muscle which are generally referred to as myopathy, and whose overall incidence is typically <0.1% of patients receiving statin monotherapy.6 Although myopathy can refer to any muscular disease, the recent clinical advisory on the use and safety of statins differentiated myalgia as muscle ache or weakness in the absence of elevation in creatine kinase (CK), and myositis as adverse muscular symptoms associated with increased CK levels.7 Rhabdomyolysis is a severe form of myositis involving myoglobulinuria, …

Risk for myopathy with statin therapy in high-risk patients.

Emerging data suggest that the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) offer important benefits for the large population of individuals at high risk for coronary heart disease. This population encompasses a sizable portion of individuals who are also at high risk for drug-drug interactions due to their need for multiple medications. In general, statins are associated with a very small risk for myopathy (which may progress to fatal or nonfatal rhabdomyolysis); however, the potential for drug-drug interactions is known to increase this risk in specific high-risk groups. The incidence of myopathy associated with statin therapy is dose related and is increased when statins are used in combination with agents that share common metabolic pathways. Of particular concern is the potential for interactions with other lipid-lowering agents such as fibrates and niacin (nicotinic acid), which may be used in patients with mixed lipidemia, and with immunosuppressive agents, such as cyclosporine, which are commonly used in patients after transplantation. Clinicians should be alert to the potential for drug-drug interactions to minimize the risk of myopathy during long-term statin therapy in patients at high risk for coronary heart disease.