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Table 2 Risk-stratified treatment recommendations of the included guidelines.
| Guideline title | NCEP | NICE1 | AHA1 | AHA2 |
|---|---|---|---|---|
| Risk assessment tools | ||||
| Risk prediction model | Framingham Risk Score | 10-year risk of developing CVD, not referring to a specific risk model | Framingham Risk Score | Framingham Risk Score |
| Outcome of interest and its timeframe | CHD (10 years) | CVD (CHD and stroke, 10 years) | CHD (10 years) | CHD (10 years) |
| Information on validation of the model provided in the guideline | Yes | Unclear | Yes | Yes |
| Evidence of treatment effects | ||||
| Treatment considered | LDL-lowering therapy, therapeutic lifestyle change and LDL goals | Statin | Diet, weight management, physical activity, drug therapy and LDL-C goals | Lifestyle management, pharmacotherapy and LDL-C target levels |
| Target population | Adults | Adults at risk of CVD | Adult patients at increased risk of stroke | Adult women 20 years and older |
| Type of studies considered in the evidence of treatment benefits | Single or several RCTs Meta-analyses | Single or several RCTs Meta-analyses | Single or several RCTs Meta-analyses | Single or several RCTs Meta-analyses |
| Type of studies considered in the evidence of treatment harms | Observational studies Single or several RCTs | Single or several RCTs Meta-analyses | Treatment harms not reported | Treatment harms not reported |
| Heterogeneity of treatment effects assessed in the guideline | Yes | Yes | No | No |
| Application of treatment evidence to baseline risks | ||||
| Methods to apply treatment evidence to baseline risks | Used evidence of relative risk reduction from RCT/meta-analysis and applied it to different absolute risks | Unclear, presumably used evidence of relative risk reduction from RCT/meta-analysis and applied it to different absolute risks | Not reported | Not reported |
| Assumptions specified when applying treatment evidence | 'For every 30-mg/dL change in LDL-C, the relative risk for CHD is changed in proportion by about 30%, and the relative risk is set at 1.0 for LDL-C = 40 mg/dL.' 'For every 1% reduction in LDL-C levels, relative risk for major CHD events is reduced by approximately 1%.' | 'Statins do not differ in their relative effectiveness in a number of subgroups: in women compared with men at a similar level of cardiovascular risk; in people with diabetes compared with people without diabetes; or in people aged over 65 years compared with people aged under 65 years.' | Not reported | Not reported |
| Development of treatment thresholds | ||||
| Risk stratification in which different treatments were recommended | •10-year CHD risk > 20% •10-year CHD risk 10 to 20% •10-year CHD risk < 10% | •10-year CVD risk ≥20% | •0 to 1 CHD risk factor •≥2 CHD risk factors and 10-year CHD risk < 20% •≥2 CHD risk factors and 10-year CHD risk 10% to 20% •CHD or CHD risk equivalent (10-year risk > 20%) | •10-year CHD absolute risk > 20% •10-year CHD absolute risk 10% to 20% •10-year CHD absolute risk < 10% |
| Methods to develop treatment thresholds | Unclear | Expert consensus | Referring to NCEP ATP-III guideline | Not reported |
| Explicitly planned benefit and harm assessment as the basis for making recommendations | No | No | No | No |
| Patient preferences considered when developing recommendations | No | No | No | No |
| Guideline title | MSC1 | NICE2 | ACCP | MSC2 |
| Risk assessment tools | ||||
| Risk prediction model | Framingham Risk Score (for patients without diabetes) and UKPDS Risk Engine (for patients with diabetes) | Framingham Risk Score | Framingham Risk Score | Framingham Risk Score or UKPDS Risk Engine for patients with diabetes |
| Outcome of interest and its timeframe | CHD (10 years) | CVD (CHD and stroke, 10 years) | CHD (10 years) | CHD (10 years) |
| Information on validation of the model provided in the guideline | No | Yes | No | No |
| Evidence of treatment effects | ||||
| Treatment considered | Lifestyle management, pharmacologic treatment and desirable lipid results | Lifestyle advice and statin | Aspirin and vitamin K antagonists | Lifestyle management and antihypertensive drugs |
| Target population | Men aged > 40 years and women aged > 50 years | Adults aged 18 and older and who have established CVD or who are at high risk of developing CVD | Patients at risk for coronary artery disease | Non-pregnant adults (age 19 years and older) with hypertension |
| Type of studies considered in the evidence of treatment benefits | Other guidelines | Meta-analyses | Meta-analyses | Meta-analyses |
| Type of studies considered in the evidence of treatment harms | Treatment harms not reported | Meta-analyses | Single or several RCTs Meta-analyses | Treatment harms not reported |
| Heterogeneity of treatment effects assessed in the guideline | No | Yes | Yes | No |
| Application of treatment evidence to baseline risks | ||||
| Methods to apply treatment evidence to baseline risks | Not reported | Not reported | Unclear, presumably used evidence of relative risk reduction from RCT/meta-analysis and applied it to different absolute risks | Used evidence of relative risk reduction from RCT/meta-analysis and applied it to different absolute risks |
| Assumptions specified when applying treatment evidence | Not reported | Not reported | Not reported | 'This assumes 20% risk reduction of CHD based on average outcomes for appropriately used blood pressure lowering medications and statin medications.' |
| Development of treatment thresholds | ||||
| Risk stratification in which different treatments were recommended | •Framingham CHD risk ≥20% without CHD •Framingham CHD risk 10% to 19% •Framingham CHD risk < 10% | •CVD risk < 20% •CVD risk ≥20% | Moderate risk for a coronary event (10-year risk of a cardiac event > 10%) | Diagnosis of hypertension confirmed and CHD risk ≥20% over 10 years |
| Method to develop treatment thresholds | Referring to 2005 British Columbia guideline Diabetes Care | Referring to the NICE technology appraisal Statins for the Prevention of Cardiovascular Events | Unclear, presumably putting benefits and harms on the same scale and find a balance between them | Unclear |
| Explicitly planned benefit and harm assessment as the basis for making recommendations | No | Unclear | No | Unclear |
| Patient preferences considered when developing recommendations | No | No | No | No |
| Guideline title | USPSTF | UMHS1 | ISCI | MQIC |
| Risk assessment tools | ||||
| Risk prediction model | Framingham Risk Score | Framingham Risk Score | Framingham Risk Score | Framingham Risk Score |
| Outcome of interest and its timeframe | CHD (10 years) in men and stroke (10 years) in women | Hard CHD (myocardial infarction and coronary death, 10 years) | CHD (10 years) | CHD (10 years) |
| Information on validation of the model provided in the guideline | No | No | No | No |
| Evidence of treatment effects | ||||
| Treatment considered | Aspirin | Lifestyle changes, drug therapy and LDL-C goals | Drug therapy and LDL goals | Drug therapy and goal for LDL-C |
| Target population | Men aged 45 to 79 years and women aged 55 to 79 years | Adults 20 to 75 years of age without familial or severe dyslipidemias | Adults 20 years and older and who are dyslipidemic | Adults ≥18 years |
| Type of studies considered in the evidence of treatment benefits | Meta-analyses | Treatment benefits reported but study type unclear | Single or several RCTs Meta-analyses | Treatment benefits not reported |
| Type of studies considered in the evidence of treatment harms | Observational studies | Treatment harms reported but study type unclear | Single or several RCTs Meta-analyses | Treatment harms not reported |
| Heterogeneity of treatment effects assessed in the guideline | Yes | Yes | No | No |
| Application of treatment evidence to baseline risks | ||||
| Methods to apply treatment evidence to baseline risks | Used evidence of relative risk reduction from RCT/meta-analysis and applied it to different absolute risks | Used evidence of relative risk reduction from RCT/meta-analysis and applied it to different absolute risks | Used evidence of relative risk reduction from RCT/meta-analysis and applied it to different absolute risks | Not reported |
| Assumptions specified when applying treatment evidence | There is 'a 32% risk reduction of MIs with regular aspirin use' (in men) and 'a 17% risk reduction of strokes with regular aspirin use' (in women). 'The risk for gastrointestinal bleeding increases with age.' | Not reported | Not reported | Not reported |
| Development of treatment thresholds | ||||
| Risk stratification in which different treatments were recommended | •Men aged 45 to 59 years and 10-year CHD risk ≥4%; men aged 60 to 69 years and 10-year CHD risk ≥9%; men aged 70 to 79 years and 10-year CHD risk ≥12% •Women aged 55 to 59 years and 10-year stroke risk ≥3%; women aged 60 to 69 years and 10-year stroke risk ≥8%; women aged 70 to 79 years and 10-year stroke risk ≥11% | •0 to 1 risk factors •2+ risk factors and 10-year CHD risk < 10% •2+ risk factors and 10-year CHD risk 10% to 20% | •0 to 1 risk factor and 10-year CHD risk < 10% •2+ risk factors and 10-year CHD risk < 10% •2+ risk factors and 10-year CHD risk 10% to 20% •CHD or CHD equivalent and/or 10-year risk > 20% | •CHD or CHD risk equivalents 10-year risk > 20% •2+ risk factors 10-year CHD risk ≤20% •0 to 1 risk factor |
| Method to develop treatment thresholds | Putting benefits and harms on the same scale (events saved/in excess per 1,000 people) and find a balance between them | Expert consensus and referring to NCEP ATP-III guideline | Referring to NCEP ATP-III guideline | Referring to ICSI Lipid Management in Adults guideline |
| Explicitly planned benefit and harm assessment as the basis for making recommendations | Yes | No | No | No |
| Patient preferences considered for the development of recommendations | Yes | No | No | No |
| Guideline title | ES | NICE3 | MSC3 | ADA |
| Risk assessment tools | ||||
| Risk prediction model | Framingham Risk Score, PROCAM and SCORE | UKPDS Risk Engine | UKPDS Risk Engine | Not specified, presumably Framingham Risk Score |
| Outcome of interest and its timeframe | 10-year CHD risk (Framingham and PROCAM) and 10-year total cardiovascular mortality (SCORE) | CHD (10 years) in patients with diabetes | CHD (10 years) in patients with diabetes | CVD (CHD and stroke, 10 years) |
| Information on validation of the model provided in the guideline | Yes | Yes | No | No |
| Evidence of treatment effects | ||||
| Treatment considered | Aspirin, LDL-C goals and non-HDL-C goals | Simvastatin and statin | Statin and lipid targets | Aspirin |
| Target population | Patients at high metabolic risk for CVD | People with type 2 diabetes | Non-pregnant adults with type 2 diabetes | Patients with type 1 or type 2 diabetes mellitus |
| Type of studies considered in the evidence of treatment benefits | Single or several RCTs Meta-analyses | Single or several RCTs Meta-analyses | Single or several RCTs | Meta-analyses |
| Type of studies considered in the evidence of treatment harms | Treatment harms reported but study type unclear | Single or several RCTs | Treatment harms not reported | Treatment harms reported but study type unclear |
| Heterogeneity of treatment effects assessed in the guideline | No | No | No | Yes |
| Application of treatment evidence to baseline risks | ||||
| Methods to apply treatment evidence to baseline risks | Not reported | Not reported | Not reported | Unclear, presumably used evidence of relative risk reduction from RCT/meta-analysis and applied it to different absolute risks |
| Assumptions specified when applying treatment evidence | Not reported | Not reported | Not reported | Not reported |
| Development of treatment thresholds | ||||
| Risk stratification in which different treatments were recommended | •Individuals over age 40 and 10-year risk for CHD > 10% •10-year risk for CHD > 20% •10-year risk for CHD 10% to 20% •At least two major risk factors and 10-year risk for CHD < 10% | The cardiovascular risk exceeds 20% over 10 years | •Moderate risk (< 20% 10-year CHD risk) •High risk (≥20% 10-year CHD risk) | •Adults with type 1 or type 2 diabetes at increased cardiovascular risk (10-year CVD risk > 10%) •Adults with diabetes and 10-year CVD risk < 5% •Adults with 10-year CVD risk 5% to 10% |
| Methods to develop treatment thresholds | Unclear, presumably putting benefits and harms on the same scale and find a balance between them to recommend using aspirin; referring to NCEP ATP-III guideline on LDL-C and non-HDL-C goals | Not reported | Not reported | Unclear, presumably putting benefits and harms on the same scale and find a balance between them |
| Explicitly planned benefit and harm assessment as the basis for making recommendations | No | No | No | No |
| Patient preferences considered when developing recommendations | No | Yes | No | No |
| Guideline title | UMHS2 | NSGC | ASCO | NICE4 |
| Risk assessment tools | ||||
| Risk prediction model | NCI Breast Cancer Risk Assessment Tool | The guideline mentioned different models | NCI Breast Cancer Risk Assessment Tool | Nottingham Prognostic Index |
| Outcome of interest and its timeframe | Invasive breast cancer (5 years) | Absolute risk of developing breast cancer or the likelihood of carrying a BRCA1 or BRCA2 mutation (unclear timeframe) | Invasive breast cancer during the next 5-year period and up to age 90 (lifetime risk) | Survival (10 years) |
| Information on validation of the model provided in the guideline | No | No | Yes | No |
| Evidence of treatment effects | ||||
| Treatment considered | Tamoxifen and raloxifene | Tamoxifen; oral contraceptives; prophylactic mastectomy, prophylactic bilateral salpingo-oophorectomy | Tamoxifen and raloxifene | Aromatase inhibitors |
| Target population | Adults age 18 and older (non-pregnant) | Individuals at risk for hereditary breast and ovarian cancer | Women at increased risk of breast cancer | Women with breast cancer |
| Type of studies considered in the evidence of treatment benefits | Treatment benefits reported but study type unclear | Treatment benefits reported but study type unclear | Single or several RCTs Meta-analyses | Single or several RCTs |
| Type of studies considered in the evidence of treatment harms | Treatment harms reported but study type unclear | Treatment harms not reported | Single or several RCTs Meta-analyses | Single or several RCTs |
| Heterogeneity of treatment effects assessed in the guideline | No | No | Yes | No |
| Application of treatment evidence to baseline risks | ||||
| Methods to apply treatment evidence to baseline risks | Used evidence of relative risk reduction from the same risk profile population for which the recommendation was made | Not reported | Unclear | Unclear |
| Assumptions when applying treatment evidence | Not reported | Not reported | Not reported | Not reported |
| Development of treatment thresholds | ||||
| Risk stratification in which different treatments were recommended | Women at high risk (5-year risk of invasive cancer ≥1.7%) | The guideline made risk-stratified recommendations, but it is unclear how they defined high risk, moderate risk and low risk | Premenopausal and postmenopausal women with a 5-year projected breast cancer risk ≥1.66% or with lobular carcinoma in situ | •Postmenopausal women with estrogen-receptor-positive early invasive breast cancer not at low risk (those in the Excellent Prognosis Group or Good Prognosis Group in the Nottingham Prognostic Index) •Postmenopausal women with estrogen-receptor-positive early invasive breast cancer not at low risk and who have been treated with tamoxifen for 2 to 3 years |
| Method to develop treatment thresholds | Expert consensus | Not reported | Expert consensus | Unclear |
| Explicitly planned benefit and harm assessment as the basis for making recommendations | No | No | Yes | No |
| Patient preferences considered when developing recommendations | No | No | No | Yes |
