Cardiovascular Events In High-risk Patients Research Articles

Antihyperglycemic Therapies With Expansions of US Food and Drug Administration Indications to Reduce Cardiovascular Events: Prescribing Patterns Within an Academic Medical Center.

Sodium-glucose cotransport protein-2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been shown to reduce cardiovascular events in high-risk patients with type 2 diabetes mellitus (T2DM). We examined real-world use of these agents at a US academic medical center in the state of Mississippi. Prescriptions, provider specialty, and insurance status of users of SGLT2is and GLP-1RAs in patients with T2DM, and T2DM and cardiovascular disease (CVD) seen from 1st January 2013 to 30th June 2019 were obtained by electronic health records review. We identified 21,173 patients with T2DM and CVD. Overall, 306 (1.4%) and 349 (1.6%) patients received a SGLT2i and GLP-1RA, respectively. After the US Food and Drug Administration (FDA) expanded empagliflozin and liraglutide indications, a mean difference of 19.2 and 12.7 greater quarterly new prescriptions was noted, respectively, whereas no such rise in canagliflozin was observed. Primary care physicians accounted for 53.4% SGLT2i prescriptions, endocrinology for 30.3%, and cardiology for 6.0%. Primary care physicians accounted for 45.1% GLP-1RA prescriptions, endocrinology for 45.0%, and cardiology for 1.4%. Prescription patterns did not largely differ by patient insurance status. In conclusion, prescription of evidence-based therapies to improve CVD outcomes in high-risk patients with T2DM remains very low after several years of evidence generation. Low uptake was evident across insurance types. Modest increases in use were observed after regulatory expansions in labeling; however, cardiologists rarely engaged in prescription, underscoring the need for widespread implementation strategies across health care systems.

2-OR: Impact of N Terminal Pro B-Type Natriuretic Peptide and High Sensitivity Cardiac Troponin on the Prediction of Death and Cardiovascular Events in High-Risk Patients with Type 2 Diabetes

We assessed the relative contributions of N-terminal pro-B-type natriuretic peptide (NTBNP) and high sensitivity cardiac troponin (hsTnT) to the prediction of death and cardiovascular (CV) events in 5597 (with complete data) of 8561 patients with type 2 diabetes (T2DM) and CV disease (CVD) and/or chronic kidney disease (CKD) enrolled in the Aliskiren Trial in Type 2 Diabetes Using Cardiorenal Endpoints (ALTITUDE). We analysed Harrell’s C-statistics (Cs) to estimate Cox model performance to predict death (n= 473) and a CV composite outcome (CVCO: CV death, resuscitated cardiac arrest, nonfatal myocardial infarction, stroke or heart failure hospitalization, n= 1129) after a median follow-up of 2.6 years, using a base model (BM) of 19 clinical baseline variables. The Cs for predicting death in the BM (0.724) was augmented by adding hsTnT (0.744, p= 0.002) which was further improved by NTBNP (0.779, p <0.001). Similarly, the BM for predicting CVCO Cs (0.716) was improved by hsTnT (0.732, p= 0.001) and enhanced further by including NTBNP in the model (0.763, p <0.001). Notably, NTBNP by itself was as predictive as BM plus hsTNT for predicting death (both 0.744, p= 1.0) and the CVCO (0.732 vs. 0.721, p= 0.27). In patients with T2DM and CVD or/and CKD, NTBNP was the major prognostic factor and should be considered for risk stratification. Disclosure M.V.B. Malachias: Speaker’s Bureau; Self; Biolab Sanus Farmaceutica, Libbs Farmaceutica. P. Jhund: Advisory Panel; Self; Cytokinetics Inc. Research Support; Self; Boehringer Ingelheim International GmbH. Speaker’s Bureau; Self; Novartis AG. Other Relationship; Self; AstraZeneca. B. Claggett: None. M.O. Wijkman: None. R. Bentley-Lewis: Consultant; Self; Novo Nordisk Inc. Research Support; Self; Janssen Pharmaceuticals, Inc. P.C. Brunel: Consultant; Self; Novartis AG. N. Chaturvedi: Consultant; Self; AstraZeneca. A.S. Desai: Consultant; Self; Abbott, Alnylam Pharmaceuticals, AstraZeneca, Biofourmis, Boehringer Ingelheim Pharmaceuticals, Inc., Boston Scientific, DalCor Pharmaceuticals, Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Regeneron Pharmaceuticals, Relypsa, Inc. Research Support; Self; Alnylam Pharmaceuticals, AstraZeneca, Novartis Pharmaceuticals Corporation. S.M. Haffner: None. H.D. Parving: None. M.F. Prescott: Employee; Self; Novartis Pharmaceuticals Corporation. S. Solomon: Consultant; Self; AstraZeneca, Theracos, Inc. Research Support; Self; AstraZeneca, Theracos, Inc. D. de Zeeuw: Advisory Panel; Self; AbbVie Inc., Bayer AG, Boehringer Ingelheim International GmbH, Fresenius Medical Care, Janssen Pharmaceuticals, Inc., Mitsubishi Tanabe Pharma Corporation. J.J. McMurray: Other Relationship; Self; AbbVie Inc., Alnylam Pharmaceuticals, Amgen, AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Bristol-Myers Squibb, Cardurion, GlaxoSmithKline plc., Novartis Pharmaceuticals Corporation, Theracos, Inc. M.A. Pfeffer: Consultant; Self; AstraZeneca, CinCor, Correvio, Corvidia, DalCor Pharmaceuticals, GlaxoSmithKline plc., Innovative Science, Jazz Pharmaceuticals, MyoKardia, Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., PharmaScience, Sanofi US, Servier, Takeda Development Center Americas, Inc. Research Support; Self; Novartis Pharmaceuticals Corporation. Funding Novartis Pharmaceuticals (NCT00549757)

Optimizing Dyslipidemia Management for the Prevention of Cardiovascular Disease: a Focus on Risk Assessment and Therapeutic Options

Primary prevention of incident atherosclerotic cardiovascular disease (ASCVD) as well as decreasing the risk of future events in those with established atherosclerosis is critical from a public health perspective. Management of dyslipidemias constitutes a key target in decreasing the risk of developing ASCVD events. While there have been great strides in the treatment of dyslipidemia over the last three decades, there are important recent developments and ongoing research that will expand the available therapeutic options and enable further cardiovascular risk reduction. PURPOSE OF REVIEW: The purpose of this paper is to review new developments relating to the primary prevention and management of ASCVD with a specific focus on optimizing the treatment of dyslipidemias. RECENT FINDINGS: In the realm of ASCVD risk prediction, mounting evidence over the last decade has demonstrated that coronary artery calcium testing is superior to any serum biomarker in the prediction of future ASCVD events and in discriminating future cardiovascular risk. As such, it has been incorporated into the most recent ACC/AHA primary prevention guideline to help guide management decisions in select patients. In terms of the management of dyslipidemias, PCSK9 inhibitors lower LDL-C by 50-70% and provide an additional 15% reduction in key cardiovascular events in high-risk patients with known ASCVD, as demonstrated in the ODYSSEY and FOURIER trials. Cholesteryl ester transfer protein (CETP) inhibitors, which significantly increase HDL-C levels, demonstrated mixed results in large clinical trials and have helped reframe HDL-C as a risk marker rather than a modifiable risk factor. In regard to the management of triglycerides, the REDUCE-IT trial demonstrated a nearly 5% absolute reduction in key cardiovascular events with a highly purified fish-oil derivative named icosapent ethyl in high-risk patients already on statin therapy. Finally, in regard to lipoprotein(a)-which is a strong risk factor for ASCVD-there are exciting developments in the therapeutic pipeline which reduce circulating lipoprotein(a) levels by nearly 90%. The management of dyslipidemias continues to be an exciting field with several ongoing cardiovascular outcomes trials, improvement in risk prediction models, and new therapeutic agents in the pipeline that will further mitigate residual cardiovascular risk in both primary and secondary prevention patients.

Insulin Resistance and Atherosclerosis: Implications for Insulin-Sensitizing Agents.

Patients with type 2 diabetes mellitus (T2DM) are at high risk for macrovascular complications, which represent the major cause of mortality. Despite effective treatment of established cardiovascular (CV) risk factors (dyslipidemia, hypertension, procoagulant state), there remains a significant amount of unexplained CV risk. Insulin resistance is associated with a cluster of cardiometabolic risk factors known collectively as the insulin resistance (metabolic) syndrome (IRS). Considerable evidence, reviewed herein, suggests that insulin resistance and the IRS contribute to this unexplained CV risk in patients with T2DM. Accordingly, CV outcome trials with pioglitazone have demonstrated that this insulin-sensitizing thiazolidinedione reduces CV events in high-risk patients with T2DM. In this review the roles of insulin resistance and the IRS in the development of atherosclerotic CV disease and the impact of the insulin-sensitizing agents and of other antihyperglycemic medications on CV outcomes are discussed.

Bulletin: New findings show Vascepa significantly reduces cardiovascular events in high-risk patients; Pediatric telemedicine visits yield more antibiotic prescriptions; National data trends show long-term opioid prescriptions increased over time; FDA takes major step to lower insulin prices

Bulletin: New findings show Vascepa significantly reduces cardiovascular events in high-risk patients; Pediatric telemedicine visits yield more antibiotic prescriptions; National data trends show long-term opioid prescriptions increased over time; FDA takes major step to lower insulin prices

Ankle Brachial Pressure Index: An update for the vascular specialist and general practitioner.

Objectives Ankle brachial pressure index (ABPI) is an invaluable tool for assessing the severity of peripheral arterial disease. In addition, it can be used as an independent marker of cardiovascular risk, with a predictive ability similar to the Framingham criteria. Identification of an abnormal ABPI should therefore trigger aggressive cardiac risk factor modulation for a patient. Unfortunately, the significance of abnormal ABPIs is poorly understood within the general medical community. This is compounded by the influence of various comorbidities on accurate measurement of ABPI, potentially leading to a wide variability in readings that need to be considered before interpretation in these patient populations. We aim to address these issues by revealing several common misunderstandings and pitfalls in ABPI measurement, describing accurate methodology, and highlighting patient cohorts in whom additional or alternative approaches may be required. Methods We present a narrative review of the role of ABPI in both the community and hospital setting. We have performed a literature review, exploring the validity and reproducibility of methodology for obtaining ABPI, alongside the utility of ABPI in different clinical scenarios. Results The measurement of ABPI is often performed incorrectly. Common pitfalls include inadequate patient preparation, failure to obtain the blood pressure from the correct lower limb artery in patients with tibial disease, failure to account for differences in brachial blood pressure between the arms, inappropriately chosen equipment and patient factors such as highly calcified arteries. Standardisation of methodology greatly improves reliability of the test. Exercise ABPI can identify significant peripheral arterial disease in patients with normal resting ABPI. In addition to its role in peripheral arterial disease, ABPI measurement has a role in assessing venous ulcers, entrapment syndromes and injured extremities; conversely, it has a more limited utility in the diabetic population. Conclusions A thorough understanding of the correct technique and associated limitations of ABPI measurement is essential in accurately generating and interpreting the data it provides. With this knowledge, the ABPI is an invaluable tool to help manage patients with peripheral arterial disease. Perhaps more importantly, ABPI can be used to identify and risk stratify patients with asymptomatic peripheral arterial disease, itself a major indicator of significant underlying cardiovascular disease. With the emergence of best medical therapy, targeted pharmacotherapy and lifestyle changes can reduce the risk of major cardiovascular events in high-risk patients by approximately 30%, particularly in diabetic patients. Therefore, the utility of ABPI transgresses vascular surgery, with an essential role in general practice and public health.

Icosapent ethyl for dyslipidaemia in patients with diabetes and coronary artery disease: Act now to reduce it.

The risk of atherosclerotic cardiovascular disease (ASCVD) can be significantly reduced in patients with diabetes who are undergoing low-density lipoprotein cholesterol-reducing therapies. However, the elevated triglyceride levels seen in diabetic dyslipidaemia can contribute to residual ASCVD risk. Icosapent ethyl (IPE) has recently been shown to substantially reduce major cardiovascular events in high-risk patients with hypertriglyceridaemia who are undergoing statin therapy. In a real-world study of patients with diabetes and acute coronary syndrome (ACS), 17.1% were found to be eligible for treatment with IPE based on Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial (REDUCE-IT) criteria. A significant proportion of patients with diabetes and ACS merit receiving IPE therapy, with important implications for evolving clinical practice guidelines and best standard of care.

Effects of PCSK9 inhibitors on LDL cholesterol, cardiovascular morbidity and all-cause mortality: a systematic review and meta-analysis of randomized controlled trials.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors determine a wide reduction of LDL cholesterol, greater than other lipid-lowering agents. The present meta-analysis is aimed at the assessment of PCSK9 inhibitors effect on LDL Cholesterol, cardiovascular morbidity and all-cause mortality. A Medline and Clinicaltrials.gov search for eligible studies until December 1, 2017, was performed. All randomized trials (> 12weeks) comparing PCSK-9 inhibitors with placebo or active drugs were retrieved. Primary endpoints: (a) LDL cholesterol at endpoint; (b) Major cardiovascular events (MACE); (c) All-cause mortality. Data extraction was performed independently by two of the authors, and conflicts resolved by a third investigator. A total of 38 trials fulfilling the inclusion criteria were identified, with mean duration of 36.4weeks. The reduction of LDL cholesterol at endpoint, versus placebo, ezetimibe, and high-dose statins was - 65.3 [- 69.6, - 60.9]%, - 57.7 [- 68.3;- 47.0]%, and - 34.5 [- 40.8;- 28.1]%, respectively, with alirocumab possibly showing a smaller effect than the other drugs of the class. Treatment with PCSK9 inhibitors was associated with a reduction in the incidence of MACE (Mantel-Haenszel Odds Ratio [MH-OR] 0.83 [0.78, 0.88]), with significant effects of alirocumab and evolocumab only. The number needed to treat for 2years for preventing one event was 89. All-cause mortality and cardiovascular mortality were not reduced by treatment with PCSK-9 inhibitors (MH-OR 0.94 [0.84, 1.04] and 0.97[0.86;1.09]). PCSK-9 inhibitors are effective in reducing LDL cholesterol and the incidence of major cardiovascular events in high-risk patients. Bococizumab does not show significant effects on MACE. PROSPERO-CRD42018087640.

Cholesterol-Lowering Agents.

Loss-of-function variants in PCSK9 (proprotein convertase subtilisin-kexin type 9) are associated with lower lifetime risk of atherosclerotic cardiovascular disease) events. Confirmation of these genetic observations in large, prospective clinical trials in participants with atherosclerotic cardiovascular disease has provided guidance on risk stratification and enhanced our knowledge on hitherto unresolved and contentious issues concerning the efficacy and safety of markedly lowering LDL-C (low-density lipoprotein cholesterol). PCSK9 has a broad repertoire of molecular effects. Furthermore, clinical trials with PCSK9 inhibitors demonstrate that reductions in atherosclerotic cardiovascular disease events are more effective in patients with recent myocardial infarction, multiple myocardial infarctions, multivessel coronary artery disease, and lower extremity arterial disease. The potent LDL-C lowering efficacy of PCSK9 inhibitors provides the opportunity for more aggressive LDL-lowering strategies in high-risk patients with atherosclerotic cardiovascular disease and supports the notion that there is no lower limit for LDL-C. Aggressive LDL-C lowering with fully human PCSK9 monoclonal antibodies has been associated by a safety profile superior to that of other classes of LDL-lowering agents. These clinical trials provide evidence that LDL lowering with PCSK9 inhibitors is an effective therapy for lowering cardiovascular events in high-risk patients with LDL-C levels ≥70 mg/dL on maximally tolerated oral therapies, including statins and ezetimibe.

Relation of Serum and Urine Renal Biomarkers to Cardiovascular Risk in Patients with Type 2 Diabetes Mellitus and Recent Acute Coronary Syndromes (From the EXAMINE Trial)

A deeper understanding of the interplay between the renal axis and cardiovascular (CV) disease is needed in type 2 diabetes mellitus (T2DM). We aimed to explore the prognostic value of a comprehensive panel of renal biomarkers in patients with T2DM at high CV risk. We evaluated the prognostic performance of both serum (Cystatin C) and urine renal biomarkers (neutrophil gelatinase-associated lipocalin, kidney injury molecule-1 protein, and indices of urinary protein excretion) in 5,380 patients with T2DM and recent acute coronary syndromes in the EXAMINE trial. Patients requiring dialysis within 14 days were excluded. Single- and multimarker covariate-adjusted Cox proportional hazards models were developed to predict times to events. Primary endpoint was composite nonfatal myocardial infarction, nonfatal stroke, or CV death. Median age was 61 years, 68% were men, and mean baseline estimated glomerular filtration rate (eGFR) was 74 mL/min/1.73 m2. During median follow-up of 18 months, 621 (11.5%) experienced the primary endpoint and 326 (6.1%) patients had died. All renal biomarkers were robustly associated with adverse CV events in step-wise fashion, independent of baseline eGFR. However, in the multimarker prediction model, only Cystatin C (per 1 SD) was associated with the primary endpoint (hazard ratio [HR] 1.28 [1.14 to 1.45]; p ≤ 0.001), death (HR 1.51 [1.30 to 1.74]; p ≤ 0.001), and heart failure hospitalization (HR 1.20 [0.96 to 1.49]; p = 0.11). Association between Cystatin C and the primary endpoint was similar in baseline eGFR above and below 60 mL/min/1.73 m2 (Pinteraction > 0.05). In conclusion, serum and urine renal biomarkers, when tested alone, independently predict long-term adverse CV events in high-risk patients with T2DM. In an integrative panel of renal biomarkers, only serum Cystatin C remained independently associated with subsequent CV risk. Renal biomarkers informing various aspects of kidney function may further our understanding of the complex interplay between diabetic kidney disease and CV disease.

Perioperative urinary thromboxane metabolites and outcome of coronary artery bypass grafting: a nested case-control study

ObjectiveAs a marker of in vivo thromboxane generation, high-level urinary thromboxane metabolites (TXA-M) increase the occurrence of cardiovascular events in high-risk patients. To investigate whether perioperative urinary TXA-M level is...

THE A-BODY-SHAPE-INDEX AND TYPE 2 DIABETES ARE MUTUALLY INDEPENDENT PREDICTORS OF CARDIOVASCULAR EVENTS RISK IN ANGIOGRAPHIED CORONARY PATIENTS

The A-Body-Shape-Index (ABSI) is calculated based on waist circumference, height and BMI and provides a measure of visceral adiposity. In the general population, this index has been associated with premature mortality. Its power to predict cardiovascular events in high-risk patients is not known and

Patient at intermediate cardiovascular risk: statins, yes! - antihypertensive therapy, maybe.

Patient at intermediate cardiovascular risk: statins, yes! - antihypertensive therapy, maybe.

Long-Term Statin Adherence in Rural Versus Urban Patients at High Atherosclerotic Cardiovascular Disease Risk

Introduction: Australian rural populations experience a greater burden of cardiovascular disease (CVD) compared to their urban counterparts. Statins are critical in the prevention of cardiovascular events in high-risk patients; however, the difference between long-term adherence in rural and urban populations is unknown.

Residual renal and cardiovascular disease risk in conventionally-treated patients with type 2 diabetes: the potential of non-traditional biomarkers.

Diabetes is a leading cause of chronic kidney disease (CKD) in the developed world. Promoters of the progression of kidney disease include the traditional profile of cardiovascular risk factors. However, the development of CKD and vulnerability to end-stage renal disease (ESRD) is highly variable. Determinants of the susceptibility to ESRD may include non-traditional risk factors such as gene-environment interactions, socio-geographic factors and/or treatment strategies. We review the conflicting clinical relevance of studies implicating pathways related to oxidative stress. These pathways are strongly implicated in the phenotype of some groups of high-risk patients and could assume importance in clinical care. Recent clinical trial evidence has shown that newer glucose-lowering agents also have beneficial effects on reducing the incidence of renal dysfunction and cardiovascular events in high-risk patients. Research is required to identify which patients will benefit most from newer approaches to managing diabetes. Understanding the relationship of non-traditional risk factors to renal and cardiovascular disease could help clinicians targeting new therapeutic approaches in the management of type 2 diabetes.

Anacetrapib, a New CETP Inhibitor: The New Tool for the Management of Dyslipidemias?

Cholesteryl ester transfer protein (CETP) inhibitors significantly increase serum high-density lipoprotein cholesterol (HDL) cholesterol levels and decrease low-density lipoprotein cholesterol (LDL) cholesterol concentration. However, three drugs of this class failed to show a decrease of cardiovascular events in high-risk patients. A new CETP inhibitor, anacetrapib, substantially increases HDL cholesterol and apolipoprotein (Apo) AI levels with a profound increase of large HDL2 particles, but also pre-β HDL particles, decreases LDL cholesterol levels mainly due to increased catabolism of LDL particles through LDL receptors, decreases lipoprotein a (Lp(a)) levels owing to a decreased Apo (a) production and, finally, decreases modestly triglyceride (TRG) levels due to increased lipolysis and increased receptor-mediated catabolism of TRG-rich particles. Interestingly, anacetrapib may be associated with a beneficial effect on carbohydrate homeostasis. Furthermore, the Randomized EValuation of the Effects of Anacetrapib Through Lipid-modification (REVEAL) trial showed that anacetrapib administration on top of statin treatment significantly reduces cardiovascular events in patients with atherosclerotic vascular disease without any significant increase of adverse events despite its long half-life. Thus, anacetrapib could be useful for the effective management of dyslipidemias in high-risk patients that do not attain their LDL cholesterol target or are statin intolerable, while its role in patients with increased Lp(a) levels remains to be established.

Dyslipidemias : Diagnostics and management

For disorders of lipid metabolism the risk-adapted adjustment of low-density lipoprotein (LDL) cholesterol remains the primary treatment target, as acausal role in minimizing the progression of ACVD has been shown. Because of their efficacy in reducing cardiovascular morbidity and mortality, statins are recommended as first-line pharmacological treatment in dyslipidemias. Additionally, ezetimibe and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition have been shown to significantly reduce cardiovascular events in high-risk patients. Life style changes can improve the plasma lipid profile, particularly in the setting of hypertriglyceridemia. Evaluation of high-density lipoprotein (HDL) cholesterol and lipoprotein(a) provides further information when assessing the individual cardiovascular risk, but direct evidence that pharmacologically targeting HDL cholesterol or Lp(a) results in areduction of cardiovascular events has not yet been shown.

Atherosclerosis: PCSK9 inhibition reduces cardiovascular events in high-risk patients.

Atherosclerosis: PCSK9 inhibition reduces cardiovascular events in high-risk patients.

Diabetes and cardiovascular events in high-risk patients: Insights from a multicenter registry in a middle-income country.

The aim of this study was to determine the rate of major clinical events and its determinants in patients with previous cardiovascular event or not, and with or without diabetes from a middle-income country. REACT study is a multicenter registry conducted between July 2010 and May 2013 in Brazil. Patients were eligible if they were over 45years old and high cardiovascular risk. Patients were followed for 12months; data were collected regarding adherence to evidence-based therapies and occurrence of clinical events (all-cause mortality, non-fatal cardiac arrest, myocardial infarction, or stroke). A total of 5006 subjects was included and analyzed in four groups: No diabetes and no previous cardiovascular event, n=430; diabetes and no previous cardiovascular event, n=1138; no diabetes and previous cardiovascular event, n=1747; and diabetes and previous cardiovascular event, n=1691. Major clinical events in one-year follow-up occurred in 332 patients. A previous cardiovascular event was associated with a higher risk of having another event in the follow-up (HR 2.31 95% CI 1.74-3.05, p<0.001), as did the presence of diabetes (HR 1.28 95% CI 1.10-1.73, p=0.005). In patients with diabetes,failure to reach HbA1c targetswas related topoorer event-free survival compared to patients with good metabolic control (HR 1.70 95% CI 1.01-2.84, p=0.044). In Brazil, diabetes confers high risk for major clinical events, but this condition is not equivalent to having a previous cardiovascular event. Moreover, not so strict targets for HbA1c in patients with diabetes and previous cardiovascular events might be considered.

Treatment of Hypercholesterolemia in 2015.

Randomized, double-blind, placebo-controlled secondary prevention and primary prevention studies and observational studies have documented that statins reduce cardiovascular events in high-risk patients with hypercholesterolemia. The 2013 American College of Cardiology/American Heart Association guidelines on treatment of hypercholesterolemia support the use of statins in 4 major groups that will be discussed. The Expert Panel of these guidelines could find no data supporting the routine use of nonstatin drugs combined with statins to further reduce cardiovascular events. Since these guidelines were published, a double-blind randomized trial of 18,144 patients with an acute coronary syndrome demonstrated at a 7-year follow-up that the incidence of cardiovascular events was 34.7% in patients randomized to simvastatin plus placebo versus 32.7% in patients randomized to simvastatin plus ezetimibe (hazard ratio = 0.936; P = 0.016). Proprotein convertase subtilisin/kexin type 9 inhibitors further lower serum low-density lipoprotein cholesterol by 50%-70% in patients treated with statins and 4 phase 3 trials including more than 70,000 patients are investigating whether these monoclonal antibodies to proprotein convertase subtilisin/kexin type 9 will lower cardiovascular events.