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Final Research Plan

Final Research Plan for Statin Use for the Primary Prevention of Cardiovascular Disease in Adults: Preventive Medication

Recommendations made by the USPSTF are independent of the U.S. government. They should not be construed as an official position of the Agency for Healthcare Research and Quality or the U.S. Department of Health and Human Services.

Preface

The final Research Plan is used to guide a systematic review of the evidence by researchers at an Evidence-based Practice Center. The resulting Evidence Report will form the basis of the USPSTF Recommendation Statement on this topic.

The draft Research Plan was available for comment from February 27 until March 26, 2014 at 5:00 p.m., ET.

Analytic Framework

Screening for Dyslipidemia to Improve Cardiovascular Outcomes

Go to Text Description below.

Text Description

Figure 1. This figure depicts the analytic framework, which outlines the evidence areas covered in the review, including the population, risk assessment, interventions, outcomes, and harms. The population includes adults ages 21 to 39 years without prior CVD events. An overarching arrow directly assesses lipid screening and its effects on CHD- and CVA-related morbidity and mortality outcomes (Key Question 1). An arrow from the population indicates screening for dyslipidemia, resulting in identification of persons with dyslipidemia, which may lead to use of lifestyle changes or medications to prevent cardiovascular events (Key Questions 4 and 5) and the assessment of associated CHD- and CVA-related morbidity and mortality outcomes. An arrow in the lipid screening area assesses different screening strategies (Key Question 3). Arrows from the lipid screening and treatment areas of the framework assess associated harms (Key Questions 2 and 6).

Use of Statins to Improve Cardiovascular Outcomes

Go to text description below.

Text Description

Figure 2. This figure depicts the analytic framework, which outlines the evidence areas covered in the review, including the population, risk assessment, interventions, outcomes, and harms. The population includes adults age 40 years and older without prior CVD events. An arrow from the population indicates CVD risk assessment, resulting in identification of specific cardiovascular risk factors or estimation of 10-year individualized CVD risk level, which may lead to use of statins to prevent cardiovascular events (Key Questions 1a-1c), and the assessment of associated CHD-related morbidity, CVA, and mortality outcomes. An arrow from the statins treatment area of the framework assesses associated harms (Key Question 2). The arrows for statin treatment also address how benefits and harms vary according to the potency of statin treatment (Key Question 3).

Abbreviations: CVD = cardiovascular disease; CHD = coronary heart disease; CVA = cerebrovascular accident; KQ = key question.

Key Questions to be Systematically Reviewed

Screening for Dyslipidemia to Improve Cardiovascular Outcomes

  1. What are the benefits of screening for dyslipidemia in asymptomatic adults ages 21 to 39 years on coronary heart disease (CHD)- or cerebrovascular accident (CVA)-related morbidity or mortality or all-cause mortality?
  2. What are the harms of screening for dyslipidemia in asymptomatic adults ages 21 to 39 years?
  3. What is the diagnostic yield of alternative screening strategies (e.g., universal vs. risk-based screening) for dyslipidemia in asymptomatic adults ages 21 to 39 years?
  4. What are the benefits of treatment (e.g., drug or lifestyle interventions) in adults ages 21 to 39 years on CHD- or CVA-related morbidity or mortality or all-cause mortality?
  5. What are the benefits of delayed versus immediate treatment in adults ages 21 to 39 years with dyslipidemia on CHD- or CVA-related morbidity or mortality or all-cause mortality?
  6. What are the harms of drug treatment for dyslipidemia in asymptomatic adults ages 21 to 39 years?

Use of Statins to Improve Cardiovascular Outcomes

  1. a. What are the benefits of treatment with statins in reducing the incidence of CHD- or CVA-related morbidity or mortality or all-cause mortality in asymptomatic adults age 40 years or older without prior cardiovascular disease (CVD) events?
    b. What are the benefits of treatment with statins that target low-density lipoprotein (LDL) cholesterol versus other treatment strategies in adults age 40 years or older without prior CVD events?
    c. Do the benefits of treatment with statins in adults age 40 years or older without prior CVD events vary by subgroups defined by demographic (e.g., age, sex, race) or clinical characteristics (e.g., specific cardiovascular risk factors, patients with familial hyperlipidemia, or 10-year or lifetime cardiovascular risk)?
  2. What are the harms of treatment with statins in adults age 40 years or older without prior CVD events?
  3. How do benefits and harms vary according to potency of statin treatment?

Contextual Questions

Contextual questions will not be systematically reviewed and are not shown in the Analytic Framework.

Screening for Dyslipidemia to Improve Cardiovascular Outcomes

  1. What are the benefits of drug treatment in adults ages 21 to 39 years on intermediate outcomes (e.g., lipid levels or atherosclerosis)?
  2. How do lipid levels change over time in adults ages 21 to 39 years?

Use of Statins to Improve Cardiovascular Outcomes

  1. What is the comparative accuracy of different cardiovascular risk assessment methods?
  2. How do lipid levels change over time in adults age 40 years or older?

Research Approach

The Research Approach identifies the study characteristics and criteria that the Evidence-based Practice Center will use to search for publications and to determine whether identified studies should be included or excluded from the Evidence Report. Criteria are overarching as well specific to each of the KQs.

  Include Exclude
Screening for Dyslipidemia to Improve Cardiovascular Outcomes
Population Asymptomatic adults ages 21 to 39 years Adults with known dyslipidemia (primary or secondary) or prior CVD events
Diseases Dyslipidemia (as defined according to clinical practice guidelines, levels above the 90th percentile for lipid components positively associated with CHD risk, or other specified criteria) Lipid levels not meeting thresholds for dyslipidemia
Screening interventions Lipid panel (fasting or nonfasting lipid measurement: total or LDL cholesterol alone or in combination with HDL cholesterol, with or without measurement of other lipid markers)
  • Screening with family history only
  • Genetic screening only
Screening comparator No screening or usual care delivered in a universal or selective screening strategy Other comparators not listed as included
Treatment interventions Drug (e.g., statins) and lifestyle interventions (e.g., exercise and diet changes) Other types of treatments not listed as included
Treatment comparator No treatment or usual care Other comparators not listed
Outcomes KQs 1, 4, 5: CHD- and/or CVA-related morbidity or mortality; all-cause mortality

KQ 2: Harms associated with the screening process (e.g., false-positives, false-negatives, psychosocial consequences such as anxiety, overdiagnosis, and others as identified in the literature)

KQ 3: Diagnostic yield (true positives/number screened)

KQ 6: Harms associated with drug treatment (e.g., myopathy, rhabdomyolysis, myalgia, cognitive loss, diabetes, elevations in liver function tests or creatine phosphokinase levels, and others as identified in the literature)

KQs 1, 4, 5: Outcomes not listed as included

KQ 2: Adverse outcomes not associated with screening

KQ 3: Outcomes not listed as included

KQ 6: Other adverse outcomes not associated with drug treatment

Study design RCTs, CCTs, cohort studies, high-quality systematic reviews Other study designs
Settings
  • Publication date of 2008 to present; studies included in prior USPSTF reports
  • Conducted in countries with a Human Development Index >0.9 (as defined by the United Nations)
  • Primary care or primary care–relevant
Settings not generalizable to primary care; studies outside the stated timeframe
Use of Statins to Improve Cardiovascular Outcomes
Population Asymptomatic adults (age ≥40 years) without prior CVD events (e.g., myocardial infarction, angina, revascularization, CVA, or transient ischemic attack), including persons who are at increased risk for CVD events based on 10-year or lifetime individualized CVD risk level or presence of specific CVD risk factors Populations in other age groups or with a prior CVD-related event
Interventions Statins Other drugs or nondrug interventions (e.g., diet and exercise)
Comparators KQ 1: No treatment or usual care without statin

KQ 2: Placebo

KQ 3: Higher vs. lower-potency statin therapy

 
Outcomes KQs 1 and 3: CHD- and/or CVA-related morbidity or mortality; all-cause mortality

KQs 2 and 3: Side effects from drug interventions, such as myopathy, rhabdomyolysis, myalgia, cognitive loss, diabetes, and elevations in liver function tests or creatine phosphokinase levels

KQ 1: Intermediate outcomes (e.g., lipid levels or measures of atherosclerosis, such as intima media thickness)

KQ 2: Adverse events not related to statin use

Settings Primary care or primary care–generalizable Settings not generalizable to primary care
Study designs RCTs, CCTs, and controlled cohort studies without publication date limitations; systematic reviews published in or after 2008 Other study designs (e.g., case-control, case series)

Abbreviations: CCT = controlled clinical trial; HDL = high-density lipoprotein; RCT = randomized, controlled trial.

Response to Public Comment

The draft research plan for this topic was posted for public comment from February 27 through March 26, 2014. In response to public comments, a key question on how benefits and harms vary according to statin therapy potency was added to the framework on the use of statins. Several key questions were revised to be clearer about the included demographic factors and to indicate explicitly that lifetime cardiovascular risk will also be considered as a potential factor to determine who benefits from therapy. The inclusion and exclusion criteria for the review were revised to include more potential definitions for dyslipidemia and alternative lipid markers for screening.

 

Current as of: May 2014

Internet Citation: Final Research Plan: Statin Use for the Primary Prevention of Cardiovascular Disease in Adults: Preventive Medication. U.S. Preventive Services Task Force. October 2014.
https://www.uspreventiveservicestaskforce.org/Page/Document/final-research-plan98/statin-use-in-adults-preventive-medication1

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