HMG-CoA reductase inhibitors (statins)
ATC code: C10AA05 (Atorvastatin)
Brand names
Lipitor, Atorvaliq
Reversible competitive inhibitor of HMG-CoA reductase, the rate-limiting enzyme of hepatic cholesterol synthesis. Depletes intracellular cholesterol, upregulates receptors on hepatocytes, and increases LDL clearance from plasma. Lowers LDL by 35–55 % depending on dose, triglycerides by 15–30 %, with a small rise in .
First line
In adults without established CVD, statin therapy is guided by risk stratification. 2022 recommends statins in adults 40–75 with at least one CV risk factor and a 10-year ASCVD risk of 10 % or more. 2019 uses and titrates aggressiveness by risk category.
Sources
First line
High-intensity statins (atorvastatin 40–80 mg daily) are the foundation of secondary prevention after ACS, MI, ischemic stroke, TIA, revascularization, or in established atherosclerotic vascular disease. Target per 2019 is a ≥ 50 % reduction from baseline and LDL below 1.4 mmol/L. Cholesterol Treatment Trialists meta-analyses show a 20 % reduction in major vascular events per 1 mmol/L LDL lowering.
First line
Heterozygous FH requires high-intensity statins started early (from age 8–10 per pediatric consensus). target is below 2.5 mmol/L in adults without additional risk factors and below 1.8 mmol/L with them. Ezetimibe and, if needed, PCSK9 inhibitors are added when targets are not met.
Not recommended
— Vessel cleansing: 'Vessel cleansing' is not a concept used in international clinical guidelines. Statins are prescribed based on cardiovascular risk stratification, not for 'cleansing'. The idea of mechanically 'removing plaques' with a drug contradicts pharmacokinetics. The evidence-based benefit of statins is reduced cardiovascular mortality via plaque stabilization and reduction, not 'dissolution'.
6 pairs found. Sorted from critical to minor.
Mechanism
Amiodarone inhibits CYP3A4, which partially metabolizes atorvastatin. Atorvastatin concentration rises and myopathy risk increases. The effect is less dramatic than for simvastatin or lovastatin but is clinically meaningful.
Management
Cap atorvastatin at ≤ 40 mg/day. If muscle pain appears, check CK and temporarily withhold the statin. Alternatives include pravastatin or rosuvastatin (not CYP3A4-metabolized).
Sources
Mechanism
Atorvastatin weakly inhibits CYP3A4 and CYP2C9. Clinically significant INR elevations are documented in a minority of cases, especially at 40–80 mg doses. The opposite – dose-dependent INR decrease – is also possible.
Management
Check INR 1–2 weeks after starting atorvastatin and after each dose change. Additional warfarin adjustment is usually not required but may be needed.
Sources
Mechanism
Amlodipine weakly inhibits CYP3A4 – atorvastatin concentration rises by about 18 %. Clinically significant myopathy is rare but possible in patients with additional risk factors.
Management
Routine dose adjustment is not needed. If myalgia develops, check CK. If CK is above 4× ULN, temporarily withhold atorvastatin.
Sources
Mechanism
Omeprazole weakly inhibits CYP3A4 – atorvastatin exposure rises modestly (10–20 %). Clinically meaningful additional myopathy is rare.
Management
Routine dose adjustment is not required. If muscle pain develops, check CK and reconsider the statin.
Sources
Mechanism
An early study by Lau et al. (Circulation, 2003) in 44 patients showed in vitro that atorvastatin competes with clopidogrel for CYP3A4 and blunts the aggregation response. Subsequent large-scale clinical data did not confirm the hypothesis. Analysis of more than 13,000 patients from CHARISMA (Saw et al., 2007) found no difference in cardiovascular events on DAPT between CYP3A4-metabolized statins and other statins. A systematic review by Hicks et al. (BMJ, 2010) and a meta-analysis by Mukherjee et al. (Arch Intern Med, 2008) reached the same conclusion. The , , and have issued no warnings about this pair.
Management
No statin change is needed. Per ACS 2023 and / 2018 Cholesterol Guidelines, all post-ACS patients should receive high-intensity statins (atorvastatin 40–80 mg or rosuvastatin 20–40 mg) regardless of the P2Y12 inhibitor chosen. In most DAPT patients atorvastatin remains the preferred statin.
Mechanism
Hypothyroidism by itself raises . Achieving euthyroidism with levothyroxine reduces statin requirements. Clinical significance is mainly a target-dose adjustment after TSH normalization.
Management
Repeat the lipid profile 6–8 weeks after euthyroidism is achieved and adjust atorvastatin dose if needed.
Sources
In July 2021 the FDA removed the automatic contraindication during pregnancy from labels of all statins (Drug Safety Communication, 2021-07-20). The FDA pregnancy categories (A/B/C/D/X) were retired in 2015 under the PLLR — historically atorvastatin was classified as X. The decision is now individualized: in patients without atherosclerotic CVD, statins are usually discontinued before conception and throughout pregnancy; in those with documented atherosclerosis and high event risk, continuation is possible after shared decision-making with a cardiologist. An unplanned pregnancy is a trigger for discussion, not for default discontinuation.
Systemic safety data during lactation are limited. The manufacturer and most international sources recommend avoidance. In patients with a statin indication, options include a temporary switch to formula feeding or deferring therapy until breastfeeding is complete.
atorvastatin is evaluated for the following indications with varying evidence strength: Familial hypercholesterolemia (evidence tier A), Dyslipidemia, primary CV prevention (evidence tier A), Established ASCVD, secondary prevention (evidence tier A). See the full indication matrix with dosing and citations above on this page.
Common side effects of atorvastatin (≥ 1 in 100): Myalgia without CK elevation, Headache, Dyspepsia, nausea, Arthralgia, Transient transaminase elevation (usually below 3× ULN). See the Safety section for uncommon and serious reactions.
In July 2021 the FDA removed the automatic contraindication during pregnancy from labels of all statins (Drug Safety Communication, 2021-07-20). The FDA pregnancy categories (A/B/C/D/X) were retired in 2015 under the PLLR — historically atorvastatin was classified as X. The decision is now individualized: in patients without atherosclerotic CVD, statins are usually discontinued before conception and throughout pregnancy; in those with documented atherosclerosis and high event risk, continuation is possible after shared decision-making with a cardiologist. An unplanned pregnancy is a trigger for discussion, not for default discontinuation.
Systemic safety data during lactation are limited. The manufacturer and most international sources recommend avoidance. In patients with a statin indication, options include a temporary switch to formula feeding or deferring therapy until breastfeeding is complete.
atorvastatin is contraindicated in: Active liver disease or unexplained persistent transaminase elevation; Pregnancy and planned pregnancy; Breastfeeding; Hypersensitivity to any component. Full list in the Safety section.
clinically significant transaminase elevation occurs in less than 1 % of patients and is usually transient. Routine liver enzyme monitoring in asymptomatic patients is not required.
statins are long-term (usually lifelong) therapy. Discontinuation rapidly returns LDL to baseline and raises cardiovascular risk.
a small excess risk exists (roughly 1 case of T2D per 250 patients over 4 years), but the benefit from reduced cardiovascular events clearly outweighs it in patients with an indication.