User login
What is the best strategy for monitoring the lipid-lowering effects of medical therapy used for the primary prevention of coronary artery disease (CAD)?
There is good evidence that treatment for primary prevention of CAD decreases risk of major first coronary events and cardiovascular mortality, though all-cause mortality has not been shown to be reduced.1-3 There is no evidence identifying the best measures for monitoring response to therapy. In the one study that titrated lovastatin, the investigators used a target fasting low-density cholesterol (LDL-C) of 110 mg/dL2. All other studies used a fixed dosage without titration. (Grade of recommendation: C.)
Evidence summary
Clinicians expecting results similar to a randomized clinical trial should use treatment regimes based on those used in the trial. The Air Force/Texas Coronary Atherosclerosis Prevention Study was the only primary prevention randomized controlled trial that titrated the dose of medication (either 20 mg or 40 mg of lovastatin daily) to reach a LDL-C of 110 mg/dL2 or lower. Titration was done after 3 months of therapy. All other studies used a fixed dose of medication without regard to the lipid levels obtained (cholestyramine 24 g/day,4 gemfibrozil 600 mg twice daily,5 clofibrate 1.6g/day,6 and pravastatin 40 mg/day1). There have been no trials that test different strategies for monitoring lipid levels.
The Munster Heart Study (PROCAM)7 demonstrated that “the ranking of continuous risk factors in terms of predicting major coronary events was LDL-C, total cholesterol (TC), high-density lipoprotein (HDL-C), triglycerides (TG)….” Grover and colleagues8 found that the TC/HDL-C and the LDL-C/HDL-C ratios both performed better than the TC in predicting heart disease mortality. The Framingham Study9 confirmed the usefulness of TC and HDL-C in assessing risk. None of the studies gave guidance on what to monitor while a patient is on treatment.
Recommendations from others
The National Cholesterol Education Program (NCEP)10 recommends that LDL-C be monitored every 6 weeks after the initiation of treatment. After the goal LDL-C is attained, measurement every 4 to 6 months is adequate.
Alex Krist, MD
Fairfax Family Practice Residency Virginia Commonwealth University program
Once lipid therapy is begun, I aim to achieve NCEP recommended LDL-C. Although these levels are not based on radomized controlled trials, drug therapy effectively lowers LDL-C. Since medications less effectively elevate HDL-C and high TG is a risk mainly with elevated LDL-C, I focus on the LDL-C response. The TC, HDL-C, and TG are necessary for calculation of LDL-C.
I check lipids 5 to 12 weeks after initiating or changing therapy, allowing time for the medication to have full effect and to detect toxicities. Once LDL-C is controlled, rechecking cholesterol every 6 months provides an opportunity to readdress diet, exercise, smoking cessation, and hypertension.
1. Shepherd J, Cobbe SM, Ford I, et al. for the West of Scotland Coronary Prevention Study Group. N Engl J Med 1995;333:1301-07.
2. Downs JR, Clearfield M, Weis S, et al. JAMA 1998;279:1615-22.
3. Larosa JC, He I, Vupputuri S. JAMA 1999;282:2340-46.
4. Lipid Research Clinics Coronary Primary Prevention Trial Results II. JAMA 1984;251:365-74.
5. Frick MH, Elo O, Haapa K, et al. N Engl J Med 1987;317:1237-45.
6. WHO cooperative trial on primary prevention of ischaemic heart disease with clofibrate to lower serum cholesterol: final mortality follow-up. Lancet 1984;2:600-04.
7. Assmann G, Cullen P, Schulte H. Eur Heart J 1998;19 (suppl):A2-11.
8. Grover SA, Coupal L, Hu SP. JAMA 1995;274:801-06.
9. Castelli WP, Garrison RJ, Wilson PWF. JAMA 1996;256:2835-38.
10. Executive summary of the third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection. Evaluation and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 2001;285:2486-2497.
There is good evidence that treatment for primary prevention of CAD decreases risk of major first coronary events and cardiovascular mortality, though all-cause mortality has not been shown to be reduced.1-3 There is no evidence identifying the best measures for monitoring response to therapy. In the one study that titrated lovastatin, the investigators used a target fasting low-density cholesterol (LDL-C) of 110 mg/dL2. All other studies used a fixed dosage without titration. (Grade of recommendation: C.)
Evidence summary
Clinicians expecting results similar to a randomized clinical trial should use treatment regimes based on those used in the trial. The Air Force/Texas Coronary Atherosclerosis Prevention Study was the only primary prevention randomized controlled trial that titrated the dose of medication (either 20 mg or 40 mg of lovastatin daily) to reach a LDL-C of 110 mg/dL2 or lower. Titration was done after 3 months of therapy. All other studies used a fixed dose of medication without regard to the lipid levels obtained (cholestyramine 24 g/day,4 gemfibrozil 600 mg twice daily,5 clofibrate 1.6g/day,6 and pravastatin 40 mg/day1). There have been no trials that test different strategies for monitoring lipid levels.
The Munster Heart Study (PROCAM)7 demonstrated that “the ranking of continuous risk factors in terms of predicting major coronary events was LDL-C, total cholesterol (TC), high-density lipoprotein (HDL-C), triglycerides (TG)….” Grover and colleagues8 found that the TC/HDL-C and the LDL-C/HDL-C ratios both performed better than the TC in predicting heart disease mortality. The Framingham Study9 confirmed the usefulness of TC and HDL-C in assessing risk. None of the studies gave guidance on what to monitor while a patient is on treatment.
Recommendations from others
The National Cholesterol Education Program (NCEP)10 recommends that LDL-C be monitored every 6 weeks after the initiation of treatment. After the goal LDL-C is attained, measurement every 4 to 6 months is adequate.
Alex Krist, MD
Fairfax Family Practice Residency Virginia Commonwealth University program
Once lipid therapy is begun, I aim to achieve NCEP recommended LDL-C. Although these levels are not based on radomized controlled trials, drug therapy effectively lowers LDL-C. Since medications less effectively elevate HDL-C and high TG is a risk mainly with elevated LDL-C, I focus on the LDL-C response. The TC, HDL-C, and TG are necessary for calculation of LDL-C.
I check lipids 5 to 12 weeks after initiating or changing therapy, allowing time for the medication to have full effect and to detect toxicities. Once LDL-C is controlled, rechecking cholesterol every 6 months provides an opportunity to readdress diet, exercise, smoking cessation, and hypertension.
There is good evidence that treatment for primary prevention of CAD decreases risk of major first coronary events and cardiovascular mortality, though all-cause mortality has not been shown to be reduced.1-3 There is no evidence identifying the best measures for monitoring response to therapy. In the one study that titrated lovastatin, the investigators used a target fasting low-density cholesterol (LDL-C) of 110 mg/dL2. All other studies used a fixed dosage without titration. (Grade of recommendation: C.)
Evidence summary
Clinicians expecting results similar to a randomized clinical trial should use treatment regimes based on those used in the trial. The Air Force/Texas Coronary Atherosclerosis Prevention Study was the only primary prevention randomized controlled trial that titrated the dose of medication (either 20 mg or 40 mg of lovastatin daily) to reach a LDL-C of 110 mg/dL2 or lower. Titration was done after 3 months of therapy. All other studies used a fixed dose of medication without regard to the lipid levels obtained (cholestyramine 24 g/day,4 gemfibrozil 600 mg twice daily,5 clofibrate 1.6g/day,6 and pravastatin 40 mg/day1). There have been no trials that test different strategies for monitoring lipid levels.
The Munster Heart Study (PROCAM)7 demonstrated that “the ranking of continuous risk factors in terms of predicting major coronary events was LDL-C, total cholesterol (TC), high-density lipoprotein (HDL-C), triglycerides (TG)….” Grover and colleagues8 found that the TC/HDL-C and the LDL-C/HDL-C ratios both performed better than the TC in predicting heart disease mortality. The Framingham Study9 confirmed the usefulness of TC and HDL-C in assessing risk. None of the studies gave guidance on what to monitor while a patient is on treatment.
Recommendations from others
The National Cholesterol Education Program (NCEP)10 recommends that LDL-C be monitored every 6 weeks after the initiation of treatment. After the goal LDL-C is attained, measurement every 4 to 6 months is adequate.
Alex Krist, MD
Fairfax Family Practice Residency Virginia Commonwealth University program
Once lipid therapy is begun, I aim to achieve NCEP recommended LDL-C. Although these levels are not based on radomized controlled trials, drug therapy effectively lowers LDL-C. Since medications less effectively elevate HDL-C and high TG is a risk mainly with elevated LDL-C, I focus on the LDL-C response. The TC, HDL-C, and TG are necessary for calculation of LDL-C.
I check lipids 5 to 12 weeks after initiating or changing therapy, allowing time for the medication to have full effect and to detect toxicities. Once LDL-C is controlled, rechecking cholesterol every 6 months provides an opportunity to readdress diet, exercise, smoking cessation, and hypertension.
1. Shepherd J, Cobbe SM, Ford I, et al. for the West of Scotland Coronary Prevention Study Group. N Engl J Med 1995;333:1301-07.
2. Downs JR, Clearfield M, Weis S, et al. JAMA 1998;279:1615-22.
3. Larosa JC, He I, Vupputuri S. JAMA 1999;282:2340-46.
4. Lipid Research Clinics Coronary Primary Prevention Trial Results II. JAMA 1984;251:365-74.
5. Frick MH, Elo O, Haapa K, et al. N Engl J Med 1987;317:1237-45.
6. WHO cooperative trial on primary prevention of ischaemic heart disease with clofibrate to lower serum cholesterol: final mortality follow-up. Lancet 1984;2:600-04.
7. Assmann G, Cullen P, Schulte H. Eur Heart J 1998;19 (suppl):A2-11.
8. Grover SA, Coupal L, Hu SP. JAMA 1995;274:801-06.
9. Castelli WP, Garrison RJ, Wilson PWF. JAMA 1996;256:2835-38.
10. Executive summary of the third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection. Evaluation and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 2001;285:2486-2497.
1. Shepherd J, Cobbe SM, Ford I, et al. for the West of Scotland Coronary Prevention Study Group. N Engl J Med 1995;333:1301-07.
2. Downs JR, Clearfield M, Weis S, et al. JAMA 1998;279:1615-22.
3. Larosa JC, He I, Vupputuri S. JAMA 1999;282:2340-46.
4. Lipid Research Clinics Coronary Primary Prevention Trial Results II. JAMA 1984;251:365-74.
5. Frick MH, Elo O, Haapa K, et al. N Engl J Med 1987;317:1237-45.
6. WHO cooperative trial on primary prevention of ischaemic heart disease with clofibrate to lower serum cholesterol: final mortality follow-up. Lancet 1984;2:600-04.
7. Assmann G, Cullen P, Schulte H. Eur Heart J 1998;19 (suppl):A2-11.
8. Grover SA, Coupal L, Hu SP. JAMA 1995;274:801-06.
9. Castelli WP, Garrison RJ, Wilson PWF. JAMA 1996;256:2835-38.
10. Executive summary of the third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection. Evaluation and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 2001;285:2486-2497.
Evidence-based answers from the Family Physicians Inquiries Network