The recommendations that follow are those from the guideline's executive summary; detailed recommendations can be found in the original guideline document. Each recommendation is rated based on the level of the evidence and the classes of the recommendation. Definitions of the levels of the evidence (A, B, C, and Good Practice Point [GPP]) and classes of the recommendations (Level I through Level IV) are presented at the end of the "Major Recommendations" field.
Note from the National Guidelines Clearinghouse (NGC): These guidelines were updated by the developer in February 2006. Following are major changes or additions that have been made to the November 2001 version of the guidelines, followed by a summary of the guidelines. Please refer to the original guideline document for further details.
The following is a list of major changes or additions to the guidelines:
- The ranking of evidence and recommendations has been changed from a format from the American College of Cardiology/American Heart Association to the format based on the Scottish Intercollegiate Guidelines Network that has been adopted in all Ministry of Health Clinical Practice Guidelines.
- In Section 2 of the original guideline document, the epidemiology of lipids in Singapore has been updated based on data obtained from the 2004 National Health Survey.
- In Section 5 of the original guideline document, the classification of dyslipidaemia has been simplified.
- Section 8 of the original guideline document on risk assessment has been revised. Three risk categories, i.e., High Risk, Intermediate Risk and Low Risk groups, have been identified. The table of major risk factors for Coronary Heart Disease (CHD) has been updated. For individuals with >2 risk factors, estimation of the 10-year CHD risk is recommended using new risk score tables which have been recently developed.
- In Section 9 of the original guideline document on goal lipid levels, the Table on the goal levels of low density lipoprotein cholesterol (LDL-C), triglyceride (TG), and high density lipoprotein cholesterol (HDL-C) in the 3 risk category groups have been amended. Also in this section, an "optional goal" of LDL-C <2.1 mmol/L (80 mg/dL) in very high risk patients has been added.
- Annex 2A and 2B have been deleted.
- In Section 11 of the original guideline document on drug therapy, cost effectiveness issues of lipid therapy have been updated. Newly introduced drugs (e.g., rosuvastatin, ezetimibe and niaspan) have been added.
Laboratory Lipid Measurements
A lipid profile consisting of total cholesterol (TC), LDL-C, HDL-C, and TG should be obtained in the following individuals:
A - Patients with CHD, cerebrovascular or peripheral artery disease. (Heart Protection Study Collaborative Group, 2002) (Grade A, Level Ib)
A - Patients with diabetes mellitus (Colhoun et al, 2004) (Grade A, Level Ib)
A - Individuals with a family history or clinical evidence of familial hyperlipidaemia. (Civeira, 2004) (Grade A, Level Ib)
A - Individuals with other risk factors for CHD (Sever et al., 2003) (Grade A, Level Ib)
Goal Lipid Levels
For the prevention of coronary heart disease, the first priority is the optimization of LDL-C level.
Lipid Goal Levels in the Three Risk Group Categories
| |
High Risk Group
| Intermediate Risk Group |
Low Risk Group |
| LDL Cholesterol mmol/L (mg/dL) |
<2.6 (100) |
<3.4 (130) |
<4.1 (160) |
| Triglyceride mmol/L (mg/dL) |
<2.3 (200) |
<2.3 (200) |
<2.3 (200) |
| HDL Cholesterol mmol/L (mg/dL) |
>1.0 (40) |
>1.0 (40) |
>1.0 (40) |
A - The recommended LDL-C goal level for the High Risk Group is <2.6 mmol/L (100 mg/dL) (Heart Protection Study Collaborative Group, 2002; Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults, 2001). (Grade A, Level Ib)
C - The recommended LDL-C goal level for the Intermediate Risk Group is <3.4 mmol/L (130 mg/dL), with an LDL-C level of <2.6 mmol/L (100 mg/dL) being an option (Sever et al, 2003; Genest et al., 2003; Mosca et al., 2004). (Grade C, Level IV)
C - The recommended LDL-C goal level for the Low Risk Group is <4.1mmol/L (160 mg/dL), with an LDL-C level of <3.4 mmol/L (130 mg/dL) being an option (Genest et al., 2003; Mosca et al., 2004). (Grade C, Level IV)
C - In very high risk patients (e.g., patients with established CHD and diabetes mellitus or multiple other risk factors) an "optional goal" of LDL-C <2.1 mmol/L (80 mg/dL) may be considered by the physician, who, however, must balance the benefits against the cost and potential side effects of high doses of medication or combination therapy which are often required to achieve very low LDL-C levels (Grundy et al., 2004). (Grade C, Level IV)
GPP - The goal TG level for all three risk groups is <2.3 mmol/L (200 mg/dL). (GPP)
C - Individuals with very high levels of TG, e.g., >4.5 mmol/L (400 mg/dL) or especially >10 mmol/L (900 mg/dL), have an increased risk of acute pancreatitis and should be treated for this reason. In these patients, the first priority is to reduce the TG level to prevent acute pancreatitis (Haffner, 2004). (Grade C, Level IV)
C - The goal HDL-C level for all three risk groups is greater than or equal to 1.0 mmol/L (40 mg/dL) (National Heart Foundation of Australia & Cardiac Society of Australia and New Zealand, 2001; Mosca et al., 2004). (Grade C, Level IV)
Lifestyle Changes
| Nutrient |
Recommended Intake |
| Total fat |
20 to 30% of total calories |
| Saturated fat* |
<7% of total calories |
| Polyunsaturated fat* |
6 to 10% of total calories |
| Trans-fatty acid |
<1% of total calories |
| Carbohydrate |
50 to 60% of total calories (mainly from complex carbohydrates) |
| Dietary fibre |
20 to 30 g per day |
| Protein |
About 15% of total calories |
| Cholesterol |
<200 mg/day |
| Food Group |
Recommended Intake |
| Fruit and vegetables |
2 + 2 servings(> 400 g) per day |
| Total calories |
Enough to achieve and maintain a body mass index (BMI) of 18.5 to 23 kg/m2 |
*Monounsaturated fat: Difference of Total fat minus Saturated and Polyunsaturated fat, i.e. Total fat – (Saturated fat + Polyunsaturated fat)
A -Lifestyle changes are an integral part of overall management. They are the mainstay in population based primary prevention strategies. In addition, it is very important to continue these lifestyle changes in patients who have been started on drug therapy. (Grade A, Level Ib)
A - Patients who smoke should be advised to stop smoking immediately (Singapore Ministry of Health, 2002; Doll et al., 2004; De Backer et al., 2003). (Grade A, Level Ib)
A - Weight reduction is achieved mainly by dietary therapy and exercise. (Grade A, Level Ib)
C - It is recommended that individuals engage in at least 30 minutes of moderate intensity physical activity most days of the week (Pate et al., 1995; World Health Organization (WHO), 2004). For individuals who have difficulty exercising, they should be encouraged to engage in less strenuous physical activity. (Grade C, Level IV)
A - The appropriate drug must be chosen for the particular type of dyslipidaemia, e.g., statins for lowering high LDL-C levels ("Randomised trial of cholesterol lowering," 2002; LaRosa et al., 2005) and fibrates for lowering TG levels or for elevating low HDL-C levels (Rubins et al., 1999; "Secondary prevention," 2000). (Grade A, Level Ib)
C - The cost of therapy should be considered in the choice of a particular lipid medication (Hass et al., 2005). (Grade C, Level IV)
C - Generic formulations cost less than non-generic drugs and can be considered if they meet prescribed standards (Hass et al., 2005; Mihaylorva et al, 2005; "Countering delays," 2002). (Grade C, Level IV)
Recommended Drug Therapy in the Different Dyslipidaemias
| Dyslipidaemia |
Drugs of Choice |
| Hypercholesterolaemia |
Statin with or without Ezetimibe |
| Mixed Dyslipidaemia |
- Statin with or without Fibrate*
- Fibrate* with or without Statin
|
| Hypertriglyceridaemia |
Fibrate* |
| Severe Hypertriglyceridaemia |
Fibrate* + Omega 3 Fish Oil |
| Isolated low HDL-C |
Fibrate* |
*In all individuals in whom a fibrate is recommended, nicotinic acid can also be considered.
Recommended Drugs for Hypercholesterolaemia
A - Hydroxy-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) are the preferred drugs for hypercholesterolaemia ("Randomised trial of cholesterol lowering," 1994; Heart Protection Study Collaborative Group, 2002; LaRosa et al., 2005). (Grade A, Level Ia)
Ezetimibe when added to a statin will produce a further 18% lowering of the LDL-C.
C - Check serum transaminases before and 8 to 12 weeks after starting statin therapy. If they are normal, consider repeating this test at least once annually (especially when the dosages of the drugs are increased or when combination therapy is initiated) (Fletcher et al., 2005; Pasternak et al., 2002; Anfossi et al., 2004; Gotto & Pownall, 2003). (Grade C, Level IV)
C - Monitoring of serum creatine kinase is also advisable in patients with renal disease, when high dosages of statins are used or when statins are combined with fibrates or nicotinic acid. Patients should be advised to report promptly to their doctors if they have muscle pain, tenderness or weakness (Pasternak et al., 2002; Gotto & Pownall, 2003). (Grade C, Level IV)
C - Elevation in the levels of serum transaminases above 3 times the upper limit of the normal range is an indication to stop statins. The drugs can be reintroduced at a lower dose when the liver function has returned to normal (Fletcher et al., 2005). (Grade C, Level IV)
C - Elevation of serum creatine kinase greater than 5 to 10 times the upper limit of the normal range, associated with muscle pain, is an indication to stop statins. Patients who are troubled by muscle pain, even in the absence of a raised serum creatine kinase, may benefit from either: (i) stopping the statin therapy or (ii) reducing the dosage (Borja, 2005). (Grade C, Level IV)
Recommended Drugs for Hypertriglyceridaemia
In all individuals in whom a fibrate is recommended, nicotinic acid can also be considered.
A - Fibrates are the drugs of choice in the treatment of hypertriglyceridaemia ("Secondary prevention," 2000). (Grade A, Level Ib)
A - In severe hypertriglyceridaemia (e.g., TG >10 mmol/L [900 mg/dL]), where fibrates alone may not adequately lower the markedly elevated TG levels, omega 3 fish oils should be added in dosages of 3 to 12 g per day (Harris et al., 1997). (Grade A, Level Ib)
Recommended Drugs for Mixed Dyslipidaemia
A - A statin is recommended if the predominant lipid abnormality is an elevated LDL-C. If the TG remains unacceptably high or if the HDL-C remains low despite the statin, consider adding a fibrate (Koh et al., 2005; Grundy et al., 2005). (Grade A, Level Ib)
C - A fibrate is recommended if the TG is >4.5 mmol/L (400 mg/dL) (Haffner, 2004). If the LDL-C remains elevated despite the fibrate, consider adding a statin. (Grade C, Level IV)
C - The decision to combine a statin and a fibrate must be individualized and should be initiated only when it is strongly indicated (Barter, 1998; Davidson, 2002). (Grade C, Level IV)
B - When a fibrate is combined with a statin, fenofibrate is recommended. Gemfibrozil should not be given because it significantly increases the level of most statins and this may increase the risk of complications (Prueksaritanont et al., 2002; Jones & Davidson, 2005). (Grade B, Level III)
C - In combination therapy: (i) start the second drug at a low dosage and increase the dose gradually until the goal level is achieved. High dosages of statins should be avoided, (ii) monitor serum transaminases and creatine kinase before and 6 to 8 weeks after initiation of the combination therapy. Thereafter, these 2 tests should be repeated at least once annually or whenever the dosages of the drugs are increased, (iii) patients should be advised to promptly report to their doctors if they have muscle pain, tenderness or weakness, (iv) consider doing serum creatine kinase in patients who complain of muscle pain (Gotto & Pownall, 2003; Knopp, 1999).
(Grade C, Level IV)
Treatment of Isolated Low HDL-C
A - Based on the results of the recent Veterans Affairs High-Density Lipoprotein Intervention Trial (VA-HIT) Study, CHD patients whose primary lipid abnormality is a low HDL-C despite lifestyle changes can be given a fibrate to elevate the HDL-C level (Rubins et al., 1999). (Grade A, Level Ib)
Referral of Patients to Specialist
GPP - Patients who remain outside the target values despite dietary changes and maximal drug therapy should be referred to lipid specialists.GPP
Special Considerations
Children, Women, Pregnancy, Elderly
A - Statins can be used in children, but proper monitoring is required. (Grade A, Level Ib)
C - Resins can be added on to statin therapy in children if LDL-C targets are not achieved. (Grade C, Level IV)
A - In postmenopausal women as well as premenopausal women, the decision to start drug therapy should be based on the 10-Year CHD Risk Score (Cheung et al., 2004; LaRosa, He, & Vupputuri, 1999). (Grade A, Level Ib)
GPP - During pregnancy, treatment is indicated only in patients with severe hypertriglyceridaemia (e.g., TG >10 mmol/L [900 mg/dL]). The only drug recommended is omega 3 fish oils after intensive dietary therapy. GPP
C - Statins are contraindicated in women who are pregnant or who are likely to be pregnant Grade C, Level IV
A - In the elderly, the decision to start drug therapy should be based on the 10-Year CHD Risk Score, the life expectancy, as well as the quality of life of the patient. Age is not a contraindication to drug therapy if indicated (Shepherd et al., 2002). Grade A, Level Ib
Renal Disease
GPP - The starting dose of statins in chronic renal failure should be low. During therapy, serum creatine kinase and renal function should both be carefully monitored. GPP
GPP - Fibrates can be used if the renal failure is only mild or moderate but the dosages should be reduced, with appropriate monitoring for side effects, especially myopathy. When creatinine clearance is less than 10 mL/min, fibrates are contraindicated. GPP
Liver Disease
C - Screen liver function (especially transaminases) on 2 consecutive occasions in patients with chronic liver disease due to either hepatitis B or alcoholic abuse. If the level of either of these 2 transaminases is elevated but <1.5 times the upper limit of the normal range, statins can be given. If the level is >1.5 times but <3 times the upper limit of the normal range, statins can still be given but with caution. In both situations, the starting dose of the statins should be low. Statins are contraindicated in those with acute liver disease and also in those with advanced or end stage parenchymal liver disease (Anfossi et al., 2004). Grade C, Level IV
GPP - Fibrates can be given in patients whose transaminase levels are elevated <3 times the upper limit of the normal range, but again at a lower starting dosage. Careful monitoring of the serum transaminases and creatine kinase after commencement of either stain or fibrate therapy is recommended. GPP
Definitions:
Levels of Evidence
Level Ia: Evidence obtained from meta-analysis of randomised controlled trials
Level Ib: Evidence obtained from at least one randomised controlled trial
Level IIa: Evidence obtained from at least one well-designed controlled study without randomisation
Level IIb: Evidence obtained from at least one other type of well-designed quasi-experimental study
Level III: Evidence obtained from well-designed non-experimental descriptive studies, such as comparative studies, correlation studies and case studies
Level IV: Evidence obtained from expert committee reports or opinions and/or clinical experiences of respected authorities
Grades of Recommendations
Grade A (evidence levels Ia, Ib): Requires at least one randomised controlled trial as part of the body of literature of overall good quality and consistency addressing the specific recommendation.
Grade B (evidence levels IIa, IIb, III): Requires availability of well conducted clinical studies but no randomised clinical trials on the topic of recommendation.
Grade C (evidence level IV): Requires evidence obtained from expert committee reports or opinions and/or clinical experiences of respected authorities. Indicates absence of directly applicable clinical studies of good quality.
Grade GPP (good practice points): Recommended best practice based on the clinical experience of the guideline development group.
