The Timing of Cholesterol Medications & Measurements

One of our cardiologists asked my advice on starting a statin on one of his patients. After I gave my opinion, he said he would start the statin and repeat the lipid measurements in 2 months. I asked, “Why wait so long?”. He said, “To see the full effect of the drug”. Hmmm.

The effect of most cholesterol medications such as statins and ezetimibe is quite prompt and is maximized by about 2 weeks. I usually wait 3 weeks to be sure but never more than a month. I want the patient to see how effective these drugs are on lipids levels, and I believe that such prompt positive feedback enhances adherence. Even my least scientific patients can figure out that a 50% reduction in LDL cholesterol in 3 weeks is probably due to the new drug.

I do wait 2 months for folks doing “diet first”. The effect of diet is also quite prompt and near maximum in about 2 weeks. Waiting 2 months with diet is not testing the effect of the diet but testing adherence to the diet. Almost anyone can follow a strict diet for 2 weeks, but 2 months is a different story. Unfortunately, most people fail getting adequate lipid reductions via diet alone at 2 months and recognize that they need a statin.

I measure the effect of PCSK9 inhibitors at 6 weeks and just before the next injection. Here again the effect is usually quite prompt, but I wait 6 weeks because the companies suggest re-measurement at 4 to 8 weeks after starting the drug. I always measure the effect of a PCSK9 inhibitors just before the next dose, say 1–2 days before the next dose. Again, the effect of the drug is prompt but some patients rebound almost to their pretreatment LDL levels just before the next injection. We reported one such example (Thompson PD. Interindividual and Intraindividual Responses to PCSK9 Inhibition. JAMA Cardiol. 2019 Jun 1;4(6):600). I want to see the minimal effect of the drug to decide if the patient needs more than just a PCSK9 inhibitor.

Timing is also important as to when you give the drugs.

Short acting statins such as lovastatin and pravastatin are most effective at night or at bedtime. That is because you make most of your lipid particles at night. Overnight is the only time that most Americans fast. Fasting decreases insulin levels. Since insulin pushes free fatty acids into the fat cell, having lower insulin levels allows free fatty acids to exit the fat cell and go to the liver where they are made into cholesterol and triglycerides. So, with short acting statins you get about a 5% additional reduction if you administer the drug at bedtime.

In contrast, long-acting statins like atorvastatin, rosuvastatin and pitavastatin can be given anytime during the day. There is slightly more LDL reduction with these drugs at night, but not enough to require nighttime dosing. The same is true for ezetimibe. In fact the long half-life of these statins and ezetimibe allows every other day and even twice a week dosing (Gadarla M, Kearns AK, Thompson PD. Efficacy of rosuvastatin (5 mg and 10 mg) twice a week in patients intolerant to daily statins. Am J Cardiol. 2008 Jun 15;101(12):1747–8).

Niacin, which we rarely use anymore, is much more effective when given at night. Niacin reduces triglycerides by inhibiting fat lipolysis, and (as noted above) fat lipolysis occurs during fasting and periods of low insulin levels. Small doses of bedtime niacin are often more effective than larger doses administered during the day.

I hope this information is useful.