what should we expect from New Dyslipidemia Management Guidelines ( ATP IV)?

The pace of new research findings in patients with dyslipidemia is rapid, and evidence-based guidelines for the management of dyslipidemia quickly become out of date. The ATP III guidelines were published in 2001 and updated in 2004.

An updated guideline for secondary prevention and risk reduction in patients with CHD and other atherosclerotic vascular disease from AHA and the American College of Cardiology (ACC) was released in November 2011. A 2012 version of the American Diabetes Association (ADA) standards of medical care in diabetes that addresses dyslipidemia in this patient population also is available.The release of new NCEPguidelines (ATP IV) has been delayed several times since 2009 and is now expected sometime this year.

Question: What are likely to be some of the main differences between the recommendations in ATP IV and those in ATPIII, and what evidence is the basis for these changes?

The primary target in treating dyslipidemia has been and will likely continue to be LDL cholesterol because it is the most atherogenic lipoprotein and it correlates more closely than other lipids with CHD.Statin therapy will likely continue to be emphasized because statins are the most effective lipid- lowering agents for reducing LDL cholesterol concentrations, and their efficacy for lowering the risk for cardiovascular events has been proven.

The goal LDL cholesterol levels in ATP III (Table 1) depend on the presence of atherosclerotic vascular disease (e.g., CHD, ischemic stroke, peripheral arterial disease, abdominal aortic aneurysm), diabetes, and major cardiovascular risk fac-tors (age ≥45 years for men or ≥55 years for women, hypertension, smoking, family history of premature CHD, and high-density lipoprotein [HDL] cholesterol <40 mg/dL).
Table 1

a  risk equivalents include clinical manifestations of non-coronary forms of atherosclerotic vascular disease (peripheral arterial disease, abdominal aortic aneurysm, and carotid artery disease [transient ischemic attacks or stroke of carotid origin or >50% obstruction of a carotid artery]), diabetes, and ≥2 risk factors with 10-year risk for hard CHD >20%.
b  Risk factors include cigarette smoking, hypertension (blood pressure ≥140/90 mm Hg or on antihypertensive medication), low HDL cholesterol, (<40 mg/dL), family history of premature CHD (CHD in male first-degree relative <55 years of age or female first-degree relative <65 years of age), and age (men ≥45 years; women ≥55 years).

In ATP III, an optional LDL cholesterol goal of less than 70 mg/ dL applies only to individuals who are at very high risk for cardiovascular events.Very high risk is defined as the presence of established CVD plus multiple major risk factors (especially diabetes), severe and poorly controlled risk factors (especially continued cigarette smoking), multiple metabolic syndromerisk factors (especially triglycerides ≥200 mg/dL plus non-HDL-cholesterol ≥130 mg/dL with HDL cholesterol <40 mg/dL), or acute coronary syndrome (ACS).

The ATP IV recommendations should reflect the results of recent clinical trials evaluating the impact of aggressive LDL cholesterol reduction on cardiovascular events. The benefit of intensive LDL cholesterol reduction using atorvastatin 80 mg/day instead of atorvastatin 10 mg/

day (the control group) for 5 years was demonstrated in a subgroup analysis of 1501 patients with CHD and diabetes participating in the randomized, double-blind Treating to New Targets trial.

A significant 25% lower incidence of major cardiovascular events was observed in the intensive therapy group compared with the control group. The mean LDL cholesterol at the end of the study was 77 mg/dL with intensive therapy and 99 mg/dL with less intensive therapy.

The benefit of intensive LDL cholesterol reduction using statins in patients with CHD, dyslipidemia, and relatively low baseline LDL cholesterol levels (<77 mg/dL) was demonstrated in the Cholesterol Treatment Trialists’ Collaboration.

In this meta-analysis of five randomized, controlled clinical trials involving 39,612 study participants with CHD and a median follow-up time of 5.1 years, the use of more intensive regimens instead of less intensive ones was associated with a weighted mean further reduction in LDL cholesterol concentration after 1 year of approximately 19 mg/dL. Significant further reductions in major vascular events by 15%, coronary death or non-fatal MI by 13%, coronary revascularization by 19%, and ischemic stroke by 16% were realized from the use of more intensive regimens instead of less intensive ones. The cardiovascular event reductions were proportionate to LDL cholesterol concentration reductions, even when the baseline LDL cholesterol concentration was low. Thus, the ATP IV guidelines are likely to recommend an LDL cholesterol goal less than 70 mg/dL for all patients with CHD, regardless of the presence of other comorbidities.

Question: What LDL cholesterol goals and treatment strategies are likely to be recommended in ATP IV for patients with diabetes?

The ATP IV recommendations for patients with diabetes and dyslipidemia probably will reflect the results of several noteworthy clinical trials. The effectiveness of aggressive LDL cholesterol reduction using atorvastatin 10 mg/day for primary prevention of major cardiovascular events in patients with type 2 diabetes without high baseline concentrations of LDL cholesterol was demonstrated in a randomized, double-blind, placebo-controlled study. 

Although 70 mg/dL or lower is considered an optional LDL cholesterol goal that applies only to patients at very high risk for cardiovascular events in current ATP III guidelines, new ATP IV guidelines are likely to recommend this goal for all patients with coronary heart disease, regardless of the presence of other comorbidities.

The most recent (2012) ADA standards of medical care in diabetes call for the addition of statin therapy to lifestyle therapy, regardless of baseline lipid levels, for patients with overt CVD.

This therapeutic approach also is recommended by ADA for patients without CVD if they are more than 40 years of age and have at least one other CVD risk factor. The goal LDL cholesterol is less than 70 mg/dL for patients with overt CVD and less than 100 mg/dL in patients without overt CVD, according to ADA.

The new ATP IV guidelines are likely to recommend statin-based therapy for all patients with diabetes who are more than 40 years of age, regardless of their baseline LDL cholesterol value. These patients stand to benefit based on the results of the Heart Protection Study.

The new ATP IV guidelines probably also will recommend a goal LDL cholesterol
less than 70 mg/dL for patients with CVD (regardless of the presence of diabetes) and a goal less than 100 mg/dL for patients without CVD but with multiple major risk factors (including diabetes). These goals are optional in ATP III but evidence supports their usein patients who meet these criteria, so there is an evidence-based argument to make the formerly optional goals standard goals in ATP IV.

Question: What recommendations do you expect to see in ATP IV for the use of fibrates or nicotinic acid in combination with statins?

According to ATP III, combining a fibrate or nicotinic acid with LDL-lowering therapy should be considered for patients with high triglycerides or low HDL cholesterol values once LDL cholesterol is addressed. However, the results of recent studies have raised concerns about the usefulness of this treatment approach. 

Because of the disappointing results from studies of the impact of adding a fibrate or nicotinic acid to statin-based LDL-lowering drug therapy on cardiovascular events, recommendations for the use of such combination therapies in ATP IV probably will be tempered. Reserving the use of fibrates and nicotinic acid primarily for patients with severe hypertriglyceridemia (triglycerides ≥500 mg/dL), an undisputed role for these agents in the management of dyslipidemia, may be suggested in ATP IV. 


About Dr.Nabil Paktin

Cardiologist , M.D.,F.A.C.C.

Posted on December 12, 2012, in Uncategorized. Bookmark the permalink. 1 Comment.

  1. thanks for beutiful information

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