{"product_id":"paul-d-thompson-statin-rule-of-six-17","title":"The statin \"Rule of six\" 17","description":"\u003ch1\u003eLow-Dose Statin Treatment: Diminishing Returns, Intermittent Dosing, and Ezetimibe\u003c\/h1\u003e\n\u003ch3\u003eJump To Section\u003c\/h3\u003e\n\u003cul\u003e\n  \u003cli\u003e\u003ca href=\"#low-dose-statins\"\u003eLDL reduction per milligram at low doses\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#statin-rule-of-six\"\u003eThe statin rule of six\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#intermittent-rosuvastatin\"\u003eRosuvastatin taken a few days a week\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#adding-ezetimibe\"\u003eAdding ezetimibe instead of doubling the dose\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#guidelines\"\u003eWhy these approaches are not in guidelines\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#experiment-of-one\"\u003eEach patient as an experiment of one\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#full-transcript\"\u003eFull Transcript\u003c\/a\u003e\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003ch2 id=\"low-dose-statins\"\u003eLDL reduction per milligram at low doses\u003c\/h2\u003e\n\u003cp\u003eLow-dose statin treatment is one of the favorite topics of cardiologist Dr. Paul D. Thompson, MD. Dr. Anton Titov, MD, asks how a patient can lower cholesterol with the smallest statin dose and when ezetimibe makes more sense than a higher statin dose. Dr. Thompson's starting point is that the most LDL cholesterol reduction per milligram of medication comes at very low doses, and that doubling the dose does not add much.\u003c\/p\u003e\n\u003ch2 id=\"statin-rule-of-six\"\u003eThe statin rule of six\u003c\/h2\u003e\n\u003cp\u003eThe statin rule of six is his name for this pattern. Dr. Thompson illustrates it with an example: with an LDL level of 200, pravastatin 20 milligrams should give about a 25% reduction, to about 150. Doubling to pravastatin 40 does not bring another 50-point fall. It adds only 6% of the baseline, or 12 points, taking LDL from 150 to 138 on average.\u003c\/p\u003e\n\u003cp\u003eHe adds that the returns are even smaller at the top of the dose range. In his account, going from 40 to 80 milligrams of atorvastatin, the highest dose, gives only about a 4% further reduction, and going from 20 to 40 milligrams of rosuvastatin, its highest dose, only about 3%.\u003c\/p\u003e\n\u003ch2 id=\"intermittent-rosuvastatin\"\u003eRosuvastatin taken a few days a week\u003c\/h2\u003e\n\u003cp\u003eIntermittent dosing of longer-acting statins is something his group has studied. Dr. Thompson describes giving 5 milligrams of rosuvastatin on Monday and on Thursday. After seven doses, measured on Thursday morning before the eighth dose, patients had a 27 percent reduction in LDL cholesterol, which he calls a big reduction.\u003c\/p\u003e\n\u003cp\u003eHe also mentions studies showing that 5 milligrams of rosuvastatin once a week produced roughly a 15% LDL reduction. His conclusion is that there is room to adjust these schedules.\u003c\/p\u003e\n\u003ch2 id=\"adding-ezetimibe\"\u003eAdding ezetimibe instead of doubling the dose\u003c\/h2\u003e\n\u003cp\u003eEzetimibe is what Dr. Thompson often adds instead of doubling the statin dose. He explains that statins block cholesterol production in the liver by acting on the rate-limiting enzyme, hydroxymethylglutaryl CoA reductase. When production falls, the body responds by absorbing more cholesterol from the gut. Ezetimibe blocks that absorption.\u003c\/p\u003e\n\u003cp\u003eIn his figures, ezetimibe alone gives about a 20% average LDL reduction, and ezetimibe added to a statin about 24%. Because ezetimibe has a long half-life, he says he will often give it on Monday, Wednesday, and Friday.\u003c\/p\u003e\n\u003ch2 id=\"guidelines\"\u003eWhy these approaches are not in guidelines\u003c\/h2\u003e\n\u003cp\u003eClinical guidelines do not include these approaches, and Dr. Thompson explains why. Guidelines have to be based on science and on completed studies. In his view, no pharmaceutical company wants patients to take its daily medication twice a week, so nobody studies it. Studies like his show a reduction in LDL cholesterol, but there are no big outcome studies showing a reduction in heart attacks, so this kind of approach does not get into the guidelines.\u003c\/p\u003e\n\u003ch2 id=\"experiment-of-one\"\u003eEach patient as an experiment of one\u003c\/h2\u003e\n\u003cp\u003eIndividual response is the theme of his closing remarks. Dr. Thompson tells every patient that they are an experiment of one: he never knows exactly what will happen until treatment starts and both doctor and patient pay attention. He says patients can help their doctor a lot by observing along with them, while asking them, with some humor, not to drive their doctor nuts with their observations.\u003c\/p\u003e\n\u003ch2 id=\"full-transcript\"\u003eFull Transcript\u003c\/h2\u003e\n\u003cp\u003e\u003cstrong\u003eDr. Anton Titov, MD:\u003c\/strong\u003e Low-dose statin treatment, the statin rule of six. On your blog you wrote that doubling a statin dose lowers cholesterol only a little more. You were senior author of an article on rosuvastatin taken twice a week by statin-intolerant patients. Cholesterol fell, and most patients tolerated the schedule. Professor Thompson, how can a patient lower cholesterol with the smallest statin dose? When does ezetimibe make more sense than a higher statin dose?\u003c\/p\u003e\n\u003cp\u003e\u003cstrong\u003eDr. Paul D. Thompson, MD:\u003c\/strong\u003e This whole thing about low-dose statins is one of my favorite topics. Believe it or not, you get the most reduction in LDL cholesterol per milligram of drug. Did you hear that?\u003c\/p\u003e\n\u003cp\u003e\u003cstrong\u003eDr. Paul D. Thompson, MD:\u003c\/strong\u003e Per milligram of drug at very low drug levels. You do not get that much more by doubling the dose. So let me give you an example.\u003c\/p\u003e\n\u003cp\u003e\u003cstrong\u003eDr. Paul D. Thompson, MD:\u003c\/strong\u003e Suppose my LDL, my ugly cholesterol, is 200 milligrams, and you decide to put me on pravastatin 20 milligrams. Now, that should give me about a 25% reduction. So I was 200, I got a 25% reduction, and I come down to about 150.\u003c\/p\u003e\n\u003cp\u003e\u003cstrong\u003eDr. Paul D. Thompson, MD:\u003c\/strong\u003e You say that is not good enough. I am going to double your statin. We are going to go from pravastatin 20 to pravastatin 40.\u003c\/p\u003e\n\u003cp\u003e\u003cstrong\u003eDr. Paul D. Thompson, MD:\u003c\/strong\u003e I am not going to get another 50-point reduction. I am only going to get 6% of the baseline, so 6% of 200. I am not going to get another 50-point reduction; I am only going to get a 12-point reduction.\u003c\/p\u003e\n\u003cp\u003e\u003cstrong\u003eDr. Paul D. Thompson, MD:\u003c\/strong\u003e So I went from 200 to 150 with 20 milligrams. I go from 150 to 138, on average, with 40 milligrams. That is called the statin rule of six.\u003c\/p\u003e\n\u003cp\u003e\u003cstrong\u003eDr. Paul D. Thompson, MD:\u003c\/strong\u003e Doubling the dose of the statin only gives you an additional 6% LDL reduction. And it actually is worse than that, because when you go from the highest dose of atorvastatin, 40 to 80, you only get about a 4% reduction. When you go from 20 milligrams of rosuvastatin to the highest dose, 40, you only get about a 3% reduction, so it is diminishing returns.\u003c\/p\u003e\n\u003cp\u003e\u003cstrong\u003eDr. Paul D. Thompson, MD:\u003c\/strong\u003e We have studied giving the longer-acting statins, like rosuvastatin, Monday and Thursday, 5 milligrams. The daily dose should be five milligrams daily. We did five milligrams Monday. We did five milligrams Thursday.\u003c\/p\u003e\n\u003cp\u003e\u003cstrong\u003eDr. Paul D. Thompson, MD:\u003c\/strong\u003e What we showed, after seven doses of the drug, on Thursday morning before the eighth dose, was that the patients had a 27 percent reduction in LDL cholesterol. A big reduction. So what do I do instead of doubling the dose?\u003c\/p\u003e\n\u003cp\u003e\u003cstrong\u003eDr. Paul D. Thompson, MD:\u003c\/strong\u003e I often add a drug called ezetimibe. Now, what ezetimibe does is it blocks the absorption of cholesterol in your gut. Statins block the production of cholesterol in your liver by affecting the rate-limiting enzyme hydroxymethylglutaryl CoA reductase.\u003c\/p\u003e\n\u003cp\u003e\u003cstrong\u003eDr. Paul D. Thompson, MD:\u003c\/strong\u003e So you block the production in the liver and the cholesterol falls down, but your body is not stupid. What the body starts to do is it starts to absorb more cholesterol from the gut. If you are not taking a statin and you take this drug ezetimibe, which blocks cholesterol absorption in the gut, you get about a 20% LDL reduction on average.\u003c\/p\u003e\n\u003cp\u003e\u003cstrong\u003eDr. Paul D. Thompson, MD:\u003c\/strong\u003e If you are taking a statin and you take ezetimibe, you get about a 24% LDL reduction. So what I often do is, rather than doubling the statin, I often add ezetimibe. And also, because ezetimibe has a long half-life, oftentimes I will give it Monday, Wednesday, Friday rather than the highest dose.\u003c\/p\u003e\n\u003cp\u003e\u003cstrong\u003eDr. Paul D. Thompson, MD:\u003c\/strong\u003e Now, why are these recommendations not in the guidelines? Why is that not the sort of thing that everybody does? The guidelines that we publish and put out have to be based on science.\u003c\/p\u003e\n\u003cp\u003e\u003cstrong\u003eDr. Paul D. Thompson, MD:\u003c\/strong\u003e They have to be based on completed studies, and none of the pharmaceutical companies want you to take their daily drug twice a week, so nobody studies it. So there are not big studies with outcomes. You have studies like mine that show a reduction, a reduction in LDL cholesterol, but there are not studies that show a reduction in heart attacks.\u003c\/p\u003e\n\u003cp\u003e\u003cstrong\u003eDr. Paul D. Thompson, MD:\u003c\/strong\u003e So that sort of an approach does not get into the guidelines. Believe it or not, there are actually studies that show that taking five milligrams of rosuvastatin once a week produced like a 15% reduction in LDL cholesterol. So you can play around with these things.\u003c\/p\u003e\n\u003cp\u003e\u003cstrong\u003eDr. Paul D. Thompson, MD:\u003c\/strong\u003e I tell every patient that they are an experiment of one. They are a single-person experiment. I never know exactly what is going to happen with a patient until we treat them and we pay attention.\u003c\/p\u003e\n\u003cp\u003e\u003cstrong\u003eDr. Paul D. Thompson, MD:\u003c\/strong\u003e And you actually help your doctor a lot if you pay attention along with them. So do not be a pain in the butt, driving them nuts with your observations and stuff. But you can be very helpful by seeing what goes on.\u003c\/p\u003e\n","brand":"Diagnostic Detectives Network","offers":[{"title":"Default Title","offer_id":48388659478684,"sku":null,"price":0.0,"currency_code":"USD","in_stock":true}],"thumbnail_url":"\/\/cdn.shopify.com\/s\/files\/1\/0599\/5449\/5644\/files\/2225156378-0cf282289b7c9a48554366a019bc1fd21a7700b23449f37cd66afcc4a9e8821d-d_1920x1080_ace4b69e-2863-45ac-aab7-20f994044f1d.jpg?v=1794435431","url":"https:\/\/diagnosticdetectives.com\/sv\/products\/paul-d-thompson-statin-rule-of-six-17","provider":"DiagnosticDetectives.Com","version":"1.0","type":"link"}