EVIDENCE-BASED ANSWER
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.
CLINICAL COMMENTARY
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.