Reduction In Atherosclerotic Cardiovascular Disease Events Research Articles

Does Elevated High-Density Lipoprotein Cholesterol Protect Against Cardiovascular Disease?

High-density lipoprotein (HDL) contributes to reverse cholesterol transport, which is 1 of the main explanations for the described inverse association between HDL-cholesterol (HDL-C) and atherosclerotic cardiovascular disease (ASCVD) risk. However, efforts to therapeutically raise HDL-C levels with niacin, fibrates, or cholesteryl ester transfer protein inhibitors have not demonstrated a reduction in ASCVD events when compared with placebo among individuals treated with statins. Furthermore, mendelian randomization studies suggest that HDL-C is unlikely to be a direct biologic variable impacting ASCVD risk. More recently, observations from well-conducted epidemiologic studies have indicated a nonlinear U-shaped relationship between HDL-C and subclinical atherosclerosis, and that very high HDL-C (≥80 mg/dL in men, ≥100 mg/dL in women) is paradoxically associated with higher all-cause and ASCVD-related mortality. These observations suggest that HDL-C is not a universal protective factor for atherosclerosis. Thus, there are several opportunities for reframing the contribution of HDL-C to ASCVD risk and related clinical calculators. Here, we examine our growing understanding of HDL-C and its role in ASCVD risk assessment, treatment, and prevention. We discuss the biological functions of HDL-C and its normative values in relation to demographics and lifestyle markers. We then summarize original studies that observed a protective association between HDL-C and ASCVD risk and more recent evidence indicating an elevated ASCVD risk at very high HDL-C levels. Through this process, we advance the discussion regarding the future role of HDL-C in ASCVD risk assessment and identify knowledge gaps pertaining to the precise role of HDL-C in atherosclerosis and clinical ASCVD.

Omega-3 Fatty Acids in Cardiovascular Disease and Diabetes: a Review of Recent Evidence.

Omega-3 fatty acids (n-3 FA) lower triglycerides, have anti-inflammatory properties, and improve metabolism. Clinical evidence of cardiovascular benefit with omega-3 fatty acids is mixed. We discuss mechanisms providing biological plausibility of benefit of omega-3 fatty acids in cardiovascular risk reduction and review clinical trials investigating the benefits of prescription omega-3 fatty acids in dyslipidemia, atherosclerotic cardiovascular disease (ASCVD), and diabetes. Although early trials showed no benefit of omega-3 fatty acids in ASCVD, the REDUCE-IT trial noted significant risk reduction in ASCVD events with highly purifiedEPA (icosapent ethyl) use which has changed the landscape for currently available therapeutic options. However, other large trials like STRENGTH and VITAL, which used different formulations of prescription omega-3 fatty acids, did not note significant cardiovascular risk reduction. Thus the effectiveness of omega-3 fatty acids for cardiovascular disease prevention is an ongoing topic of debate. A relative paucity of studies examining benefits for glycemic outcomes in persons with diabetes exists; however, fewstudies have suggested lack of benefit to date. Significant residual cardiovascular risk exists for individuals with hypertriglyceridemia. Prescription omega-3 fatty acids are more commonly used for CV risk reduction in these patients. Clinical guideline statements now recommend icosapent ethyl use for selected individuals with hypertriglyceridemia to reduce cardiovascular eventsgiven recent evidence from theREDUCE-IT trial. Nonetheless, data from other large scale trials has been mixed, and future research is needed to better understand how different preparations of omega-3 may differ in their cardiovascular and metabolic effects, and the mechanisms for their benefit.

Recurrent atherosclerotic cardiovascular disease events preventable with guideline recommended lipid-lowering treatment following myocardial infarction

Abstract Background The 2018 American Heart Association/American College of Cardiology (AHA/ACC) cholesterol guideline provides recommendations for lipid-lowering therapy (LLT) including statins, ezetimibe and proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i) to prevent recurrent atherosclerotic cardiovascular disease (ASCVD) events in adults with established ASCVD. Many adults with ASCVD who are recommended to take statins, ezetimibe and/or PCSK9i do not receive these medications. Purpose To estimate the number of recurrent ASCVD events potentially prevented by population-wide use of guideline recommended LLT following a myocardial infarction (MI). Methods We simulated the population-wide impact of receipt of 2018 AHA/ACC cholesterol guideline recommended LLT over 3 and 5 years among US adults with government health insurance through Medicare or commercial health insurance following hospital discharge for MI. We used data from patients with an MI hospitalization in 2018–2019 to estimate the percentage receiving guideline recommended LLT defined by having the medications available to take in the 30 days after their discharge date. We used data from patients with an MI hospitalization in 2013–2016 to estimate the 3 and 5-year cumulative incidence of recurrent ASCVD events (i.e., MI, coronary revascularization or ischemic stroke). The reduction in ASCVD events associated with guideline recommended LLT was estimated from a meta-analysis by the Cholesterol-Lowering Treatment Trialists Collaboration. We conducted a sensitivity analysis estimating the number and percentage of ASCVD events prevented if LLT recommendations from the 2019 European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) cholesterol guideline were followed. We repeated all analyses with recurrent coronary heart disease (i.e., MI or coronary revascularization) and ischemic stroke events as separate outcomes. Results Among 279,395 adults with an MI hospitalization in 2018–2019 (mean age 75 years, 54% men, mean low-density lipoprotein cholesterol 92 mg/dL), 27% were receiving guideline recommended LLT. With current lipid-lowering medication use, we estimated that 70,698 (95% CI: 70,311–71,077) and 89,255 (95% CI: 88,841–89,730) ASCVD events would occur in 3 and 5 years, respectively, after MI hospital discharge (Table, top panel). If all patients were to receive 2018 AHA/ACC guideline recommended LLT, the number of ASCVD events was estimated to be reduced by 21.6%, representing 15,264 (95% CI: 14,451–16,679) events prevented over 3 years and 19,271 (95% CI: 18,245–21,055) events prevented over 5 years. A higher number of recurrent ASCVD events were estimated to be averted following the LLT recommendations of the 2019 ESC/EAS cholesterol guideline (Table, bottom panel). Conclusions Population-wide implementation of guideline recommended LLT in adults with an MI hospitalization could prevent a substantial number of recurrent ASCVD events. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Amgen Inc.

Bempedoic acid and PCSK9 inhibitor eligibility in a contemporary population with atherosclerotic cardiovascular disease

Abstract Funding Acknowledgements Type of funding sources: None. Background and Purpose The reduction of low-density lipoprotein cholesterol (LDL-C) in patients with established coronary heart disease (CHD) reduces the risk of atherosclerotic cardiovascular disease (ASCVD) events.(1) Many CHD patients fail to achieve guideline-recommended LDL-C targets without prohibitively expensive proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9 inhibitors).(2, 3, 4) This study aims to assess the impact that bempedoic acid may have on PCSK9 inhibitor eligibility in a population with CHD and ascertain whether its universal adoption would lead to overall cost-savings and a cost-effective reduction in ASCVD events. Methods and Results This retrospective analysis included 635 participants from the iASPIRE study, which recently assessed secondary prevention in an Irish cohort of CHD patients. We applied the 2019 ESC/EAS dyslipidaemia guideline LDL-C target of <1.4mmol/L and simulated the average treatment effect of improved lipid-lowering therapy with statins, ezetimibe and bempedoic acid. 86.3% of iASPIRE participants did not have LDL-C control and qualified for treatment intensification. Optimisation of statin therapy would allow 24.4% of patients to achieve their LDL-C goal, while the addition of ezetimibe would improve this to 55.7% leaving 44.3% eligible for a PCSK9 inhibitor. Utilising bempedoic acid would further reduce the proportion eligible to 18.7%. Based on current market prices and the universal application of ESC/EAS recommendations,(1, 5) the adoption of bempedoic acid would reduce the annual treatment costs associated with PCSK9 inhibitor use by almost 50% and result in cost savings per prevented CVD event. Conclusions The vast majority of CHD patients currently fail to achieve the recommended LDL-C target in everyday clinical practice. Ezetimibe and optimised statin therapy would enable most patients to meet their LDL-C goal. Employing bempedoic acid in patients with poor LDL-C control would significantly reduce the requirement for PCSK9 inhibitors and lead to cost savings per prevented CVD event.

The Yin and Yang of High-density Lipoprotein and Atherosclerotic Cardiovascular Disease: Focusing on Functionality and Cholesterol Efflux to Reframe the HDL Hypothesis.

The inverse relationship between low plasma high-density lipoprotein cholesterol (HDL-C) concentrations and increased risk of Atherosclerotic Cardiovascular Disease (ASCVD) is well-known. However, plasma HDL-C concentrations are highly variable in subjects with ASCVD. In clinical outcome trials, pharmacotherapies that increase HDL-C concentrations are not associated with a reduction in ASCVD events. A causal relationship between HDL-C and ASCVD has also been questioned by Mendelian randomization studies and genome-wide association studies of genetic variants associated with plasma HDL-C concentrations. The U-shaped association between plasma HDL-C concentrations and mortality observed in several epidemiological studies implicates both low and very high plasma HDL-C concentrations in the etiology of ASCVD and non- ASCVD mortality. These data do not collectively support a causal association between HDL-C and ASCVD risk. Therefore, the hypothesis concerning the association between HDL and ASCVD has shifted from focus on plasma concentrations to the concept of functionality, in particular cellular cholesterol efflux and HDL holoparticle transport. In this review, we focus on these new concepts and provide a new framework for understanding and testing the role of HDL in ASCVD.

Profound reductions in first and total cardiovascular events with icosapent ethyl in the REDUCE-IT trial: why these results usher in a new era in dyslipidaemia therapeutics.

The aims of this clinical review are to: (i) highlight the importance of elevated baseline triglycerides (TG) in the setting of well-controlled low-density lipoprotein cholesterol (LDL-C) on statins as a major contributor to residual atherosclerotic cardiovascular disease (ASCVD) risk, particularly among patients with type 2 diabetes mellitus, metabolic syndrome, and obesity whose distinctive lipid phenotype cannot be optimally treated with LDL-C reduction therapy alone; (ii) describe the findings and clinical implications of the landmark REDUCE-IT trial in which ethyl eicosapentaenoic acid significantly improved ASCVD outcomes. While many genetic studies have shown that elevated TG are an independent causal factor for ASCVD, prior placebo-controlled trials using niacin, fibrates, omega-3 fatty acids, and dietary supplement fish oil preparations have failed to demonstrate significant CV event reduction when added to statin therapy. In contrast, the REDUCE-IT trial in 8179 participants showed convincingly that the administration of 4 g daily of icosapent ethyl (an ethyl ester of eicosapentaenoic acid) in patients at high risk for ASCVD with increased levels of baseline TG [median value, 2.44 mmol/L (216.0 mg/dL)] but well-controlled LDL-C [median value, 1.94 mmol/L (75.0 mg/dL)] reduced significantly incident events across both the trial primary endpoint and multiple prespecified secondary endpoints, including cardiovascular death, as well as both subsequent and total primary endpoint and key secondary endpoint events. Icosapent ethyl unequivocally contributed to ASCVD event reduction over and above statin therapy. The REDUCE-IT trial results should alter our approach to managing a growing population of hypertriglyceridaemic patients whose lipid phenotype requires more intensive treatment beyond LDL-C lowering alone.

Lowering Targeted Atherogenic Lipoprotein Cholesterol Goals for Patients at "Extreme" ASCVD Risk.

To review randomized interventional clinical and imaging trials that support lower targeted atherogenic lipoprotein cholesterol goals in "extreme" and "very high" atherosclerotic cardiovascular disease (ASCVD) risk settings. Major atherosclerotic cardiovascular event (MACE) prevention among the highest risk patients with ASCVD requires aggressive management of global risks, including lowering of the fundamental atherogenic apolipoprotein B-associated lipoprotein cholesterol particles [i.e., triglyceride-rich lipoprotein remnant cholesterol, low-density lipoprotein cholesterol (LDL-C), and lipoprotein(a)]. LDL-C has been the long-time focus of imaging studies and randomized clinical trials (RCTs). The 2004 adult treatment panel (ATP-III) update recognized that the long-standing targeted LDL-C goal of < 100mg/dL potentially fostered substantial undertreatment of the very highest coronary heart disease (CHD) risk individuals and was lowered to < 70mg/dL as an "optional" goal for "very high" 10-year CHD [CHD death + myocardial infarction (MI)] risk exceeding 20%. This evidence-based guideline change was supported by the observed benefits demonstrated in the high-risk primary and secondary prevention populations in the Heart Protection Study (HPS), the acute coronary syndrome (ACS) population in the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 trial (PROVE-IT), and the secondary prevention population in the Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) intravascular ultrasound (IVUS) study. Subsequent national and international guidelines maintained a targeted LDL-C goal < 70mg/dL, or a threshold for management of > 70mg/dL for patients with CHD, CHD risk equivalency, or ASCVD. Subgroup or meta-analyses of several RCTs, IVUS imaging studies, and the ACS population in IMProved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT) supported the evidence-based 2017 American Association Clinical Endocrinologist (AACE) guideline change establishing a targeted LDL-C goal < 55mg/dL, non-HDL-C < 80mg/dl, and apolipoprotein B (apo B) < 70mg/dL for patients at "Extreme" ASCVD risk, i.e., 10-year 3-point-MACE-composite (CV death, non-fatal MI, or ischemic stroke) risk exceeding 30%. Moreover, with no recognized lower-limit-associated intolerance or safety issues, even more intensive lowering of atherogenic cholesterol levels is supported by the following evidence base: (1) analysis of eight high-intensity statin-based prospective secondary prevention IVUS atheroma volume regression trials; (2) a distribution analysis of on-treatment, ezetimibe and background-statin, of the very low LDL-C levels reached and CVD event risk in the IMPROVE-IT ACS population; (3) the secondary prevention Global Assessment of Pl\aque Regression With a PCSK9 Antibody as Measured by Intravascular Ultrasound (GLAGOV) on background-statin; and (4) the secondary prevention population of Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk (FOURIER). By example, in FOURIER, the population on background-statin at a baseline median 92mg/dL achieved median LDL-C level of 30mg/dL and non-HDL-C to < 65mg/dl, and apo B to < 50mg/dL, and subgroup and post hoc analyses all demonstrated additional ASCVD event reduction benefits as LDL-C was further reduced. The level of ASCVD risk determines the degree, urgency, and persistence in global risk management, including fundamental atherogenic lipoprotein cholesterol particle lowering. "Extreme" risk patients may require extremely low targeted LDL-C, non-HDL-C and apo B goals; such efforts, implied by more recent interventional trials and analyses, are aimed at maximal atheroma plaque regression, stabilization, and MACE event reduction with the aspiration of improved quality lifespan.

Management of diabetic dyslipidemia: An update.

Diabetic dyslipidemia is a cluster of lipoprotein abnormalities characterized by increased triglyceride level, decreased high-density lipoprotein-cholesterol levels and increase in small dense low-density lipoprotein (LDL) particles. It is extremely common in type 2 diabetes (T2DM) affecting around 70 % of patients. Diabetic is a significant risk factor for atherosclerotic cardiovascular disease (ASCVD) which is the most common cause of death in the United States and LDL-cholesterol is the number 1 predictor of ASCVD events in T2DM. The purpose of this review is to discuss the pathophysiology and treatment of diabetic dyslipidemia. In this review, we have discussed both non-pharmacological and pharmacological treatment modalities including major treatment trials which have impacted the cardiovascular outcomes in patients with diabetes. Statin therapy is the mainstay of treatment to reduce ASCVD by decreasing LDL-C by 30%-49% or at least 50% depending on risk level. Attractive adjunctive therapies include Ezetimibe which is more cost effective and PCSK9 inhibitors which display potent LDL-cholesterol lowering and ASCVD event reduction. For severe hypertriglyceridemia, to avert the risk of pancreatitis, both fish oil and fenofibrate in concert with diet is the best strategy.

Pharmacoeconomics of PCSK9 inhibitors in 103 hypercholesterolemic patients referred for diagnosis and treatment to a cholesterol treatment center.

BackgroundPCSK9 inhibitor therapy has been approved by the FDA as an adjunct to diet-maximal tolerated cholesterol lowering drug therapy for adults with heterozygous familial hypercholesterolemia (HeFH) or clinical atherosclerotic cardiovascular disease (ASCVD) with suboptimal LDL cholesterol (LDLC) lowering despite maximal diet-drug therapy. With an estimated ~24million of US hypercholesterolemic patients potentially eligible for PCSK9 inhibitors, costing ~ $14,300/patient/year, it is important to assess health-care savings arising from PCSK9 inhibitors vs ASCVD cost.MethodsIn 103 patients with HeFH, and/or ASCVD and/or suboptimal LDLC lowering despite maximally tolerated diet-drug therapy, we assessed pharmacoeconomics of PCSK9 inhibitor therapy with lowering of LDLC. For HeFH diagnosis, we applied Simon Broome’s or WHO Dutch Lipid Criteria (score >8). Estimates of direct and indirect costs for ASCVD events were calculated using American Heart Association (AHA), U.S. DHHS, Healthcare Bluebook, and BMC Health Services Research databases. We used the ACC/AHA 10-year ASCVD risk calculator to estimate 10-year ASCVD risk and estimated corresponding direct and indirect costs. Assuming a 50 % reduction in ASCVD events on PCSK9 inhibitors, we calculated direct and indirect health-care savings.ResultsWe started 103 patients (58 [56 %] women and 45 [44 %] men), on either alirocumab (62 %) or evolocumab (38 %), median age 63, BMI 29.0, and LDLC 149 mg/dl. Of the 103 patients, 28 had both HeFH and ASCVD, 33 with only ASCVD, 33 with only HeFH, and 9 had neither. Of the 103 patients, 61 had a first ASCVD event at median age 55 and on best tolerated cholesterol-lowering therapy median LDLC was 137 mg/dl. In these 61 patients, total direct costs attributable to ASCVD were $8,904,361 ($4,328,623 direct, $4,575,738 indirect), the median 10-year risk of a new CVD event was calculated to be 13.1 % with total cost $1,654,758. Assuming a 50 % reduction in ASCVD events on PCSK9 inhibitors in our 61 patients, $4,452,180 would have been saved in the past; and future 10-year savings would be $1,123,345.ConclusionIn the 61 CVD patients, net costs/patient/year were estimated to be $7,000 in the past, with future 10-year intervention net costs/patient/year being $12,459, both below the $50,000/year quality adjusted life-year gained by PCSK9 inhibitor therapy.

Lipids, Lipoproteins, and Cardiovascular Disease: Clinical Pharmacology Now and in the Future.

While substantial benefit has accrued with respect to prevention and treatment of atherosclerotic cardiovascular disease (ASCVD) since the advent of statin therapy, much remains unknown and there is considerable need to address residual risk beyond statins. Moreover, many individuals are unable to tolerate statins. As a result of several recent clinical trials and publications describing early Phase 1-3 clinical trials, the authors briefly discuss the current situation regarding pharmacological management for the prevention and treatment of individuals with disorders of lipid and lipoprotein metabolism, outline some of the unanswered questions, and speculate on where we might expect to be in 5-10 years. Fortunately, recent developments in drug therapy hold considerable promise of additional benefits. In addition, new drugs in the pipeline, ongoing clinical trials, and new approaches to treatment hold promise for further improvements in therapy in the foreseeable future. During the next 5-10 years, we expect to know whether the PCSK9 inhibitors indeed live up to their promise and result in the hoped-for reduction in ASCVD events, whether triglyceride lowering indeed adds additional benefit, how best to approach HDL, and the importance of lipoprotein (a). Advances in the use of molecular biological approaches such as anti-sense oligonucleotides and RNA silencing, and the use of biological agents such as PSCK9 antibodies, is likely to play an important role in these advances. The advent of PCSK9 inhibitors is likely to provide a major breakthrough in the management of individuals with heterozygous familial hypercholesterolemia, patients with established ASCVD who are unable to reach targets with other therapies, and high-risk individuals with statin intolerance. The next 5-10 years should also clarify uncertainties concerning the pharmacological management of individuals with low levels of HDL-cholesterol, hypertriglyceridemia, and elevated lipoprotein (a).

Preventing Cardiovascular Disease in Patients with Diabetes: Use of Aspirin for Primary Prevention

Diabetics are at high risk for atherosclerotic cardiovascular disease (ASCVD) and are considered a coronary heart disease risk equivalent. The utility of aspirin in primary prevention of ASCVD in diabetic patients has been widely studied and is still debated. Overall, the current evidence suggests a modest benefit for reduction in ASCVD events with the greatest benefit among those with higher baseline risk, but at the cost of increased risk of gastrointestinal bleeding. Diabetic patients at higher risk (with 10-year ASCVD risk >10%) are generally recommended for aspirin therapy if bleeding risk is felt to be low. A patient-provider discussion is recommended before prescribing aspirin therapy. Novel markers such as coronary artery calcium scores and high-sensitivity C-reactive protein may help refine ASCVD risk prediction and guide utility for aspirin therapy. This article will review the literature for the most up-to-date studies evaluating aspirin therapy for primary prevention of ASCVD in patients with diabetes.

Implications of the new American College of Cardiology/American Heart Association cholesterol guidelines for primary atherosclerotic cardiovascular disease event prevention in a multi ethnic cohort: Multi-Ethnic Study of Atherosclerosis (MESA)

The impact of replacing the National Cholesterol Education Program (NCEP)/Adult Treatment Program (ATP) III cholesterol guidelines with the new 2013 American College of Cardiology (ACC)/American Heart Association (AHA) guidelines for primary prevention of cardiovascular disease is unclear. We used risk factor and 10-year clinical event rate data from MESA, combined with estimates of efficacy of moderate and high-intensity statin therapy from meta-analyses of statin primary prevention trials to estimate (a) the change in number of subjects eligible for drug therapy and (2) the anticipated reduction in atherosclerotic cardiovascular disease (ASCVD) events and increment in type 2 diabetes mellitus (T2DM) associated with the change in cholesterol guidelines. Of the 6,814 MESA participants, 5,437 were not on statins at baseline and had complete data for analysis (mean age 61.4±10.3). Using the NCEP/ATP III guidelines, 1,334 (24.5%) would have been eligible for statin therapy compared with 3,015 (55.5%) under the new ACC/AHA guidelines. Among the subset of newly eligible, 127/1,742 (7.3%) had an ASCVD event during 10years of follow-up. Assuming 10years of moderate-intensity statin therapy, the estimated absolute reduction in ASCVD events for the newly eligible group was 2.06% (number needed to treat [NNT] 48.6) and the estimated absolute increase in T2DM was 0.90% (number needed to harm [NNH] 110.7). Assuming 10years of high-intensity statin therapy, the corresponding estimates for reductions in ASCVD and increases in T2DM were as follows: ASCVD 2.70% (NNT 37.5) and T2DM 2.60% (NNH 38.6). The estimated effects of moderate-intensity statins on 10-year risk for ASCVD and T2DM in participants eligible for statins under the NCEP/ATP III were as follows: 3.20% (NNT 31.5) and 1.06% (NNH 94.2), respectively. Substituting the NCEP/ATP III cholesterol guidelines with the 2013 ACC/AHA cholesterol guidelines in MESA more than doubled the number of participants eligible for statin therapy. If the new ACC/AHA cholesterol guidelines are adopted and extend the primary prevention population eligible for treatment, the risk-benefit profile is much better for moderate-intensity than high-intensity statin treatment.

The ideal management of blood cholesterol: a review of the updated 2013 ACC/AHA cholesterol guideline for reducing cardiovascular risk

질환에 의하여 사망한다[1]. 죽상경화성 심혈관질환은 건강한 Atherosclerotic cardiovascular disease (ASCVD) is the most important public health problem worldwide in terms of the size of expenditures in most healthcare budgets. In November 2013, the American College of Cardiology and American Heart Association (ACC/AHA) released a clinical practice guideline on the treatment of blood cholesterol to reduce ASCVD risk in adults. Based on the design and results of the randomized clinical trials and meta-analyses published through July 2013, four groups of individuals were identified for whom an extensive body of randomized clinical tria evidence demonstrated a clear reduction in ASCVD events from statin therapy with a good margin of safety. Together with ASCVD, in severe hypercholesterolemic (low-density lipoprotein cholesterol ≥190 mg/dL) or diabetic subjects, the guideline recommends the use of statins if the newly-developed Pooled Cohort Equations estimate a 10-year ASCVD risk of equal to or higher than 7.5%. The guideline recommendations represent a new paradigm for treating cholesterol focused on using the appropriate intensity of statin therapy for those most likely to benefit, while the guideline has eliminated low-density lipoprotein cholesterol and non–high–density lipoprotein cholesterol targets. Non-statin therapies were discouraged due to the lack of evidence for their production of acceptable ASCVD risk reduction benefits. This radical shift away from the set of previous guidelines has created controversy and confusion. This article reviews the 2013 ACC/AHA guideline for the treatment of blood cholesterol to reduce ASCVD risk in adults and the optimal strategies for using this guideline in clinical practice.

Treatment Guideline for Dyslipidemia in Diabetes Mellitus

he Jornal of K oean D iaetes The recently published 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults published by the American Heart Association (AHA) and American College of Cardiology (ACC) changes the treatment paradigm for high cholesterol. Based on a systematic review of randomized controlled clinical trials (RCTs), the new guideline no longer targets LDL cholesterol (LDL-C) level but focuses on treating cholesterol to reduce atherosclerotic cardiovascular disease (ASCVD) risk. Only data from RCTs of cholesterol-lowering drug therapies with cardiovascular outcomes or metaanalyses of these RCTs were considered. In Type 2 diabetes in those 40~75 years of age with risk factors, the potential benefits of LDL–C reduction with a high-intensity statin are substantial. Because those with diabetes often have a lower LDL–C level than those without diabetes, goal-directed therapy often encourages use of a lower statin dose than is supported by the RCTs, and non-statin drugs may be included to address low HDL– C or high triglycerides, for which there is little RCT evidence of an ASCVD event reduction. (J Korean Diabetes 2014;15:61-64)

Treatment Targets in the Management of Dyslipidemias: Which Targets in Whom?

The public health approach to prevention of atherosclerotic cardiovascular disease (ASCVD) continues to hold great potential for prevention. This approach includes diets low in saturated fats and cholesterol, maintaining desirable body weight, regular physical activity, and absence of cigarette smoking. But drug therapy is becoming more widely used. Statins have been available for treatment of elevated serum cholesterol for a quarter of a century. They have proven efficacious for reducing risk for atherosclerotic cardiovascular disease (ASCVD). They carry little toxicity, and now that some derivatives are generic, they are inexpensive. Statins have become standard of care for patients with established ASCVD. To achieve further reduction in ASCVD events through cholesterol lowering will require new combinations with older agents and development of new drugs. The future of secondary prevention lies in testing of old and new "add-on" agents. Indications for statin use in primary prevention is less clear-cut. But clinical-trial experience with statins point to enormous potential for reducing ASCVD in the population. At the same time, there are dangers of overuse and turning society into a "drug culture". To abandon the benefits of healthy lifestyles for excessive drug intervention would be unfortunate.

Reducing Residual Risk in Secondary Prevention of Cardiovascular Disease

Prevention of cardiovascular disease (CVD) spans the human lifespan, including primordial, primary, and secondary prevention efforts. Extensive evidence from epidemiological, genetic, and animal studies confirms the central importance of elevated low-density lipoprotein (LDL) cholesterol (LDL-C) in atherosclerotic CVD events.1 The Cholesterol Treatment Trialists Collaboration provides per-person documentation from large-scale randomized clinical trials of the striking reduction in CVD events per 1 mmol (38.8 mg/dL) of LDL-C lowering with statins over a wide range of baseline LDL-C values.2,3 It is worth recalling that the major statin trials were not designed to determine the effectiveness of titration to LDL-C or even to non–high-density lipoprotein cholesterol goals by statins but were fixed-dose comparisons of various statins against placebo and then, more recently, large-dose statin therapy versus moderate-dose statin therapy. What is not so clear is whether we can intervene to reduce so-called residual risk further in secondary prevention patients optimally treated with statin therapy. A promising short list of proposed potential targets other than LDL includes efforts to promote smoking cessation and therapies to improve the prothrombotic and inflammatory state of the metabolic syndrome and to control elevated blood pressure.4 Article see p 1979 The article by Mora et al5 in this issue of Circulation is helpful in shedding light on this unresolved but important clinical problem. The investigators used data from a large-scale clinical trial of secondary prevention patients called Treating to New Targets (TNT). They evaluated risk factors for recurrent CVD events in those treated with intensive statin therapy (atorvastatin 80 mg/d) to address the challenges inherent in further risk reduction for those who had major cardiovascular events despite high-dose (atorvastatin 80 mg/d) statin therapy. The trial design of TNT included enrollment of participants with chronic coronary artery …