Statins are the most prescribed drugs in the world for lowering cholesterol. If your ApoB or LDL-C is high and diet and training haven't fixed it, this is the default next step.
Within a few weeks your LDL and ApoB drop 30-55% depending on dose. Atorvastatin (Lipitor) and rosuvastatin (Crestor) are the two most potent options and the ones covered here.
Statins competitively inhibit HMG-CoA reductase which is responsible for the rate at which the liver produces its cholesterol, and you end up pulling more cholesterol out of circulation the blood as a counterforce. In turn lowering LDL-C
Deep-dive
Statins competitively inhibit HMG-CoA reductase, the rate-limiting enzyme in cholesterol biosynthesis in the liver. They bind the enzyme's active site with roughly 10,000 times the affinity of its natural substrate, shutting down the conversion of HMG-CoA to mevalonate. With less cholesterol being made internally, hepatocytes upregulate LDL receptors on their surface to pull more cholesterol out of circulation. That's why LDL in your blood drops, not because the statin is stripping cholesterol out of your arteries, but because your liver has become a more aggressive LDL vacuum.
Depending on the specific statin and dose, LDL-C drops 18-55%, HDL-C rises 5-10%, and triglycerides fall 7-30%, as summarised in this therapeutic class review. Rosuvastatin is the most potent on a milligram basis. In the STELLAR trial, rosuvastatin 10-80mg reduced LDL-C an average of 8.2% more than equivalent doses of atorvastatin, 12-18% more than simvastatin, and 26% more than pravastatin. In head-to-head comparisons for secondary prevention after acute coronary syndromes, rosuvastatin 40mg beat atorvastatin 80mg on LDL reduction (POLARIS: 56% vs 52%; LUNAR: 46.8% vs 42.7%).
Atorvastatin is lipophilic and primarily metabolised by CYP3A4, which creates more interaction potential with drugs like clarithromycin, certain antifungals, and grapefruit juice. Rosuvastatin is hydrophilic, more hepato-selective, and not meaningfully metabolised by CYP enzymes — it's excreted mostly unchanged. That selectivity is partly why rosuvastatin tends to have slightly fewer muscle complaints in practice despite being more potent on paper.
Pleiotropic effects. Beyond LDL lowering, statins inhibit isoprenoid intermediates (farnesyl-PP and geranylgeranyl-PP) downstream of mevalonate, which in turn blunts activation of small GTPases like Rho and Rac. The downstream consequences, covered in this Circulation Research review, include upregulation of endothelial nitric oxide synthase (eNOS), reduced oxidative stress, improved endothelial function, suppression of NF-κB and pro-inflammatory cytokines, platelet inhibition, and enhanced plaque stability. Whether these "pleiotropic" effects add meaningfully to outcomes beyond what LDL lowering alone explains is still debated, because it's genuinely hard to separate the two in humans. But they're real mechanisms, and they likely explain why statin benefits appear earlier than pure lipid kinetics would predict.
Primary vs secondary prevention. In secondary prevention (already had an MI, stroke, or known CAD), the evidence is overwhelming, statins reduce cardiovascular events, cardiovascular mortality, and all-cause mortality. In primary prevention, benefits are smaller in absolute terms but still present. The USPSTF evidence review found statins reduced all-cause mortality (RR 0.92), stroke (RR 0.78), and cardiovascular events across 22 trials and 90,000 participants. The higher your baseline cardiovascular risk, the more you benefit in absolute terms.
Women get equal benefit. Full stop. For years there was a narrative that statins don't work as well in women. The largest individual-patient meta-analysis ever done, covering 46,675 women and over 127,000 men, killed that idea. Per 1 mmol/L of LDL reduction, major vascular events fell 16% in women and 22% in men, a difference that's not statistically significant. All-cause mortality dropped in both sexes (RR 0.91 in women, 0.90 in men). The earlier confusion came from women being underrepresented in early trials, not from a real biological difference. Women should be treated based on their cardiovascular risk, not their sex. Practically, women tend to present with cardiovascular disease about ten years later than men on average, which means the conversation about statins tends to come up later, not never.
Cognitive and dementia effects. Early scare stories about statins and memory loss were mostly based on case reports and self-report. Large cohort and meta-analysis data points the other direction. A 2022 meta-analysis of 36 observational studies found statin use was associated with a 20% lower risk of dementia and a 32% lower risk of Alzheimer's disease, with no evidence of cognitive harm. A meta-analysis of 25 randomised trials covering 46,836 patients found no effect of statins on any cognitive domain in initially cognitively normal subjects. If you or someone you know experienced memory issues on a statin, it's worth rechallenging, because the population-level signal is either neutral or protective.
Plaque regression. In the PARADIGM CT imaging study, patients on statins had a slower rate of plaque volume progression, more plaque calcification (a sign of stabilisation), and fewer high-risk plaque features compared with statin-naïve patients. This is why cardiologists don't panic when a patient's coronary artery calcium score goes up on a statin, the calcification is the scar tissue of a stabilising plaque, not new disease.
Dosing:
- Atorvastatin: 10-20mg daily is moderate intensity (lowers LDL 30-49%), 40-80mg daily is high intensity (>50% LDL reduction). Start at 20mg for most people, titrate up at 6-8 week intervals based on ApoB/LDL response
- Rosuvastatin: 5-10mg daily is moderate intensity, 20-40mg daily is high intensity. Start at 10mg for most people. Women of East Asian descent should start at 5mg due to higher plasma concentrations at the same dose
- Timing: Both atorvastatin and rosuvastatin have long half-lives (14-20 hours), so they can be taken any time of day, with or without food. Consistency matters more than timing. Shorter half-life statins like simvastatin need to be dosed at night, but not these two
- Choosing between the two: Rosuvastatin is slightly more potent per mg, raises HDL a bit more, doesn't go through CYP3A4 (fewer drug interactions), and is usually the default for anyone on other medications or compounds. Atorvastatin has the longest safety track record, is cheaper, and is better studied in acute coronary syndrome settings. Either is a reasonable first choice
- Women: no female-specific dose adjustment needed outside the East Asian rosuvastatin note above. Do not take either statin during pregnancy or while breastfeeding. If you're trying to conceive, discontinue before attempting
- If muscle symptoms develop: don't stop outright. Options include dropping to alternate-day dosing (rosuvastatin's long half-life makes this viable and it still provides ~70% of the LDL benefit), switching statins (atorvastatin ↔ rosuvastatin), or trying pravastatin or fluvastatin which have less muscle signal. The National Lipid Association recommends multiple strategies before labeling someone "statin intolerant"
- With food interactions: avoid grapefruit juice with atorvastatin (it inhibits CYP3A4 and raises blood levels). Rosuvastatin is unaffected by grapefruit. Avoid taking rosuvastatin within 2 hours of aluminum/magnesium antacids
Here's what you can expect:
LDL-C and ApoB start dropping within the first 1-2 weeks and reach their new steady state by 4-6 weeks. Most people see 30-55% LDL reductions depending on dose and drug, with ApoB falling slightly less proportionally (roughly 40-45% reduction when LDL drops 50%). If your numbers aren't where you want them after 8 weeks, it's either a dose issue, an adherence issue, or you need add-on therapy like ezetimibe.
You won't feel anything. Statins don't produce noticeable subjective effects, there's no energy change, no mood change, no libido change in the vast majority of people. If you feel dramatically different within days of starting, that's almost certainly expectation effect rather than the drug, which is supported by the SAMSON trial data below.
Side effects & risks:
- Muscle aches are the most common reason people quit statins, but most of it isn’t actually the drug. When patients who’d previously stopped statins for side effects were given alternating months of the drug, a placebo, and nothing at all, symptoms were nearly identical on the statin and the placebo, and both were worse than taking nothing. Roughly 90% of what people feel is the act of taking a tablet, not the statin inside it. True pharmacologic muscle pain caused by the drug sits around 0.5% of users. Rhabdomyolysis (the dangerous version) is vanishingly rare.
If you get muscle aches on a statin, don’t quit. Drop the dose, switch to the other statin, or try alternate-day dosing before deciding you can’t tolerate it. Most people who “can’t take statins” actually can.
- New-onset diabetes. This one is real. Large meta-analyses show high-intensity statins increase new diabetes diagnoses by 10-20% in relative terms, but the absolute excess is small (about 1 extra case per 1000 person-years on moderate intensity, slightly more on high intensity). The risk is concentrated almost entirely in people already near the diabetic threshold at baseline, roughly 62% of new cases came from patients already in the top quarter of baseline glucose. The cardiovascular benefit still vastly outweighs this risk in anyone who actually needs a statin. Monitor HbA1c
- Liver enzyme elevation. ALT/AST can rise in the first few months. Clinically significant liver injury from statins is rare (around 1 in 100,000). Routine liver monitoring is no longer mandated but a baseline and a 3-month check are still sensible
- Testosterone. Statins modestly lower total testosterone. A 2022 meta-analysis found total T dropped by roughly 13-27 ng/dL on average, which is real but usually not enough to move someone from normal into clinically deficient range. It can be more noticeable if you were already borderline.
- CoQ10. Statins reduce plasma CoQ10 by 16-54% because CoQ10 shares the mevalonate pathway. Whether supplementation actually helps muscle symptoms is mixed. A 2018 meta-analysis of 12 RCTs found CoQ10 reduced statin-associated muscle pain. But a well-designed 2015 trial in patients with blinded-confirmed statin myalgia found 600mg/day ubiquinol did not reduce pain or improve muscle strength. Reasonable to try (100-200mg/day) if you have muscle complaints, don't expect miracles
- Drug interactions. Atorvastatin interacts with CYP3A4 inhibitors (clarithromycin, ketoconazole, ritonavir, cyclosporine, grapefruit juice). Rosuvastatin interacts with cyclosporine, gemfibrozil, and some HIV medications. Always cross-check with a pharmacist if you're on other prescription drugs
- Haemorrhagic stroke. A small increase in haemorrhagic stroke risk has been observed in some trials, offset by a larger reduction in ischaemic stroke
- Pregnancy. Contraindicated. Historically category X. If you're trying to conceive, discontinue
- What's not a real concern: cognitive decline (population data is neutral to protective), cancer risk (no signal across millions of patient-years), cataracts (association is inconsistent and likely confounded)
Blood markers
ApoB is the single best marker, measure baseline and at 8-12 weeks. Target <90 mg/dL for primary prevention, <80 mg/dL for intermediate risk, <65 mg/dL for established cardiovascular disease or high risk. ApoB counts the actual number of atherogenic particles and outperforms LDL-C in every discordance analysis to date. If you can only pick one lipid test on a statin, pick this one.
Full lipid panel (LDL-C, HDL, triglycerides, total cholesterol, non-HDL-C) at baseline and 8-12 weeks. Recheck every 6-12 months once stable. LDL-C is still useful but tends to underestimate residual risk in people with metabolic syndrome, diabetes, or high triglycerides, which is where ApoB-LDL discordance is most common.
Lp(a) once in your life at baseline. It's genetically set and statins don't meaningfully lower it, but it determines whether you need more aggressive overall lipid lowering. If Lp(a) is >50 mg/dL (or >125 nmol/L), your ApoB target should be lower.
ALT/AST (liver enzymes) at baseline and at 3 months. Routine ongoing monitoring isn't required unless symptomatic or elevations are found.
HbA1c and fasting glucose at baseline and annually. Particularly important if you're overweight, have metabolic syndrome, or have a family history of diabetes, since this is where the diabetes risk concentrates.
Creatine kinase (CK) only if you develop muscle symptoms. Baseline CK before starting is worth having if you're an athlete with chronically elevated CK from training, so you have a reference point.
Total testosterone (morning) at baseline and at 3 months if you're male, particularly if you were borderline to begin with.
Serum creatinine/eGFR at baseline. Rosuvastatin is partly renally cleared and high doses in advanced kidney disease need adjustment.
For most people starting a statin: ApoB, full lipid panel, Lp(a), ALT, HbA1c, and testosterone at baseline. Repeat ApoB and lipids at 8-12 weeks to confirm response, then settle into annual monitoring.
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