I concur with Blenkinsopp that too high a dose range for rosuvastatin has been proposed by the company. The company’s recommendation for the initial dose is 10 mg, which reduces LDL-cholesterol by an average of 46–52%. This reduction far exceeds the recommendation by the National Cholesterol Education Program of a 30–40% reduction in LDL-cholesterol for high-risk patients. Indeed, the lowest dose of rosuvastatin that is marketed, 5 mg, reduces LDL-cholesterol by 45% on average, still more than initially necessary for many patients.
Not mentioned in the recent ATP3 guidelines is the fact that 2.5 mg and 1 mg of rosuvastatin reduce LDL-cholesterol by an average of 42% and 34%, respectively.
These doses therefore seem adequate to me when starting high-risk patients on rosuvastatin. However, even such low doses could be excessive for people in the moderate risk categories whose LDL-cholesterol only needs to be reduced by 20–30%. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(04)17304-2/fulltext
Since the lowest dosing of rosuvastatin is 5 mg, personally I would strongly consider taking 1/2 of 5 mg so 2.5 mg every OTHER day for potential 30-40% reduction to minimize side effects and cost would be ridiculous.
If our goal is to bring LDL-C as low as possible (which we have good indications for that we should), then taking moderate to high doses is preferred. Particularily if paired with diabetes medication such as empagliflozin.
I have read that Rosuvastatin dose prescriptions are generally much lower in Europe than in the US.
As an add-on: I am wondering if the dose of Repatha is also higher than it needs to be. I was on Repatha and it significantly lowered all lipids, including Lp(a), except slightly raised Trigs. But – it elevated glucose and insulin dropped to 2! It is known to do this in some patients – increases LDL receptors on the pancreas as well as the liver and this leads to the Beta cells putting out less insulin. I would probably be OK with a lower dose as I do not need that much lowering. I am now on a break from the Repatha since it only comes in the one-size-fits-all dose and I want to do a washout while considering what to do next. If I resume, maybe once a month rather than every two weeks. Or even every 5-6 weeks. Or wait for Pelacarsen. Or take about 1 gram of Rosuvastatin. Thanks for your post about lower dose of Rosuvastatin!
Do you have any data showing empagliflozin decreases risk of diabetes? And why wouldn’t you switch to atorvastatin if you wanted to decrease that risk?
Personally I suspect that once you drop under 70 and further benefits from going below are pretty much non-existent (it’s the bottom of the logarithmic curve) especially if you are correcting for all other risk factors. At that point pushing the statin dose will only expose you potential side effects, thus altering your risk to benefit ratio.
For example my LDL-C is 80 currently, I could take 10 mg of rosuvastatin and drop it to 40… or I can take ten times less and drop it to 50. I cannot imagine my risk of CAD will change in any meaningful way at 40 vs 50.
The average adult has an LDL-C of 130. To achieve levels below 70, they need a 50% reduction in LDL-C which is only achievable by using 10mg rosuvastatin or 5mg of rosuvastatin and 10mg of ezetimibe daily.
But that applies to most disease processes. We don’t aim for a percentage decrease in blood pressure or blood sugar?
In your example you’re technically aiming for 70, not strictly a percent.
“So if I am shooting for 70 and starting at 100, 30% gets me there.
If I start at 140 I will need 50%.”
For those who are curious here are LLM responses (Opus 4.1 Think AND Gemini 2.5 Pro):
Opus 4.1 thinking:
Top Tier (Most Optimal):
5mg every other day - Best balance for your profile
Maintains ~70-80% of daily dosing efficacy due to long half-life
Reduces potential exercise interference by 50%
Allows periodic mitochondrial recovery
Sufficient for primary prevention in low-risk individuals
2.5mg daily - Conservative continuous approach
Achieves ~35-40% LDL reduction
Minimizes side effects and exercise interference
May be insufficient if baseline ApoB >80 mg/dL
One month on (5mg), 2 months off - Interesting pulse therapy
Leverages “legacy effect” of statins
Allows full recovery of any exercise adaptations
May maintain ~60% of continuous therapy benefits
Middle Tier:
One month on, 1 month off (5mg) - Reasonable cycling
Maintains ~70% efficacy
Some recovery periods but frequent transitions
Weekly dosing (35mg once weekly) - Unconventional but studied
Similar LDL reduction to daily 5mg in small studies
Compliance advantage
Large fluctuations may be suboptimal
Daily 5mg - Standard approach
Full efficacy but no mitigation of potential exercise effects
May be excessive for primary prevention at your age/risk level
Lower Tier:
7-10. Longer off periods (3-6 months off) - Suboptimal
Insufficient time “on” for meaningful ASCVD risk reduction
Loss of pleiotropic benefits
Not supported by evidence
Gemini 2.5 Pro, Thinking:
Tier 1: Excellent Strategies (The Best Options)
5 mg every other day: This is an outstanding starting strategy. Given the 19-hour half-life, you get a significant ApoB reduction that is sustained across the 48-hour period. You achieve this with a total weekly dose of only 17.5 mg. Research on alternate-day statin dosing shows it retains ~80-90% of the efficacy of daily dosing but with a 50% reduction in total drug exposure, which is a fantastic trade-off for reducing side effect risk. Daily 2.5 mg: This is also an excellent strategy, very similar in principle to the one above. The total weekly dose is also 17.5 mg. The effect on ApoB will be very similar to 5 mg every other day, perhaps slightly more consistent. The choice between this and #3 is largely one of personal preference and adherence.
Tier 2: Good, But Likely Suboptimal Strategy Daily 5 mg: This is the standard starting dose and is highly effective. However, it delivers double the weekly drug exposure (35 mg) compared to the Tier 1 options. The dose-response for statins is logarithmic; doubling the dose from 2.5 mg to 5 mg does not double the ApoB reduction. It yields only an additional ~6% reduction (the “Rule of 6s”). You are taking 100% more drug for a small incremental benefit, while likely increasing your risk of side effects. This dose should be reserved for if the Tier 1 strategies fail to meet your ApoB target.
Tier 3: Inferior Strategy 4. 4. Weekly (e.g., 20 mg once a week): While better than nothing, this is not ideal. Due to HMG-CoA reductase upregulation, your ApoB levels will trough after the dose but then rise significantly throughout the week. This leads to inconsistent control and a higher time-averaged ApoB level compared to Tier 1 or 2 strategies. It fails to keep ApoB consistently low.
Tier 4: Biologically Flawed & Ineffective Strategies 5. 5 through 10 (One month on, X months off): These strategies are ineffective and I strongly advise against them. As explained, they misunderstand the pathophysiology of atherosclerosis. The “off” months represent periods where the disease process resumes at its full, untreated pace. The net benefit over decades will be negligible. These are the worst options on your list.
Rosuvastatin is often dosed at 2.5mg tablets in Japan. I was taking these for awhile before switching to 2mg of Pitavastatin. I believe we should think about the correct dose of a medicine from first principles rather than allowing our thinking to be anchored by the legacy medical establishment, who have zero interest in immortality. In general I think medicines are underperscribed but overdosed. I do triple therapy with 5mg of Ezetimibe and 90mg of Bempedoic acid.
