Statins


 

Atorvastatin, Fluvastatin, Pravastatin, Rosuvastatin, Simvastatin


  Issues for Surgery


Increased risk of myocardial infarction if omitted (see Further Information).

Risk of myopathy and rhabdomyolysis if continued (see Further Information).


  Advice in the Perioperative period


Elective Surgery

Continue1 – including combination products containing fibrates or ezetimibe (see Ezetimibe monograph).

Vascular Surgery
Most patients with peripheral artery disease (PAD) should receive statins. For those patients who undergo open vascular or endovascular intervention, statins should be continued post-operatively. In patients not previously treated, statins should ideally be initiated at least 2 weeks before intervention for maximal plaque-stabilising effects1.

Emergency Surgery

Continue1 – including combination products containing fibrates or ezetimibe (see Ezetimibe monograph).

Post-operative Advice

A potential limitation of perioperative statin use is the lack of parenteral formulation; statins with a long half-life (e.g. atorvastatin) may be favoured to bridge therapy in the period immediately after surgery when oral intake is not feasible1.

Monitor LFTs and renal function (see Further Information).


  Interaction(s) with Common Anaesthetic Agents


Midazolam

Atorvastatin is noted to reduce clearance of intravenous midazolam by 33% and increases area under curve (AUC) by 40% – monitor for midazolam adverse effects (e.g. prolonged sedation and respiratory depression)2, 3.

Suxamethonium

Concurrent use of statins and suxamethonium has resulted in an increase in myoglobin concentrations, but this is not considered clinically relevant2, 4.


  Interaction(s) with other Common Medicines used in the Perioperative Period


Antimicrobials (see also under Hepatotoxicity)

Macrolide antimicrobials (e.g. clarithromycin) markedly increase the exposure to simvastatin. They have a moderate effect on atorvastatin and pravastatin exposure and little effect on fluvastatin and rosuvastatin exposure2.

Whilst single surgical prophylactic doses should not pose a problem, continued post-operative treatment may require adjustment of statin therapy as follows2, 5, 6, 7, 8, 9, 10:-

  • atorvastatin – withhold doses > 20mg until macrolide course complete, doses < 20mg continue and monitor for symptoms of myopathy (e.g. muscle pain or weakness)
  • fluvastatin – continue
  • pravastatin – caution with concomitant use, warn patients to report immediately any symptoms of myopathy (e.g. muscle pain or weakness)
  • rosuvastatin – continue*
  • simvastatin – withhold until macrolide course complete

*Erythromycin reduces the area under the curve (AUC) of rosuvastatin by 20%. This is thought to be due to the increase in gut motility caused by erythromycin9.

Hepatotoxicity

Concomitant use of statins and the following medications may increase the risk of hepatotoxicity5: -

  • clavulanic acid (found in co-amoxiclav)
  • doxycycline
  • flucloxacillin
  • tigecycline
  • paracetamol


  Further Information


Pleiotropic Effects

Statins induce coronary plaque stabilisation through pleiotropic effects, which may prevent plaque rupture and subsequent myocardial infarction in the perioperative period1.

Skeletal Muscle Effects

A concern with perioperative statin therapy is the risk of statin-induced myopathy and rhabdomyolysis. Perioperatively, factors increasing the risk of statin-induced myopathy include impairment of renal function after major surgery, and multiple drug use during anaesthesia1 (particularly with co-administration of medicines that act as CYP3A4 inhibitors). Monitor the patient for signs and symptoms of skeletal muscle effects such as muscle pain, cramps or weakness, especially if accompanied by malaise or fever. If symptoms occur, measure creatinine kinase (CK) level – if found to be > 5 times the upper limit of normal (ULN), the statin should be stopped6, 7, 8, 9, 10.

Liver Effects

Patients who develop increased serum transaminase levels (alanine aminotransferase, ALT and aspartate aminotransferase, AST) should be monitored until the abnormality(ies) resolve. If serum transaminases of > 3 times ULN persist, reduction of dose or withdrawal of the statin is recommended6, 7, 8, 9, 10.


  References


  1. The Joint Task Force on non-cardiac surgery: cardiovascular assessment and management of the European Society of Cardiology (ESC) and the European Society of Anaesthesiology (ESA). 2014 ESC/ESA Guidelines on non-cardiac surgery: cardiovascular assessment and management. European Heart Journal, 2014); 35:2383-2431
  2. Baxter K, Preston CL (eds), Stockley’s Drug Interactions (online) London: Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 10th October 2019] 
  3. McDonnell CG, Harte S, O’Driscoll J et al. The effects of concurrent atorvastatin therapy on the pharmacokinetics of intravenous midazolam. Anaesthesia. 2003; 58:899–904
  4. Turan A, Mendoza ML, Gupta S et al. Consequences of succinylcholine administration to patients using statins. Anesthesiology. 2011; 115:28–35
  5. British National Formulary (online) London: BMJ Group and Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 12th April 2019]
  6. Summary of Product Characteristics – Atorvastatin 40mg Film Coated Tablets. Pfizer Limited. Accessed via www.medicines.org.uk 12/10/2019 [date of revision of the text September 2019]
  7. Summary of Product Characteristics – Fluvastatin 20mg Capsules. Sandoz Limited. Accessed via www.medicines.org.uk 12/10/2019 [date of revision of the text September 2019]
  8. Summary of Product Characteristics – Pravastatin Sodium 40mg Tablets. Accord Healthcare Limited. Accessed via www.medicines.org.uk 12/10/2019 [date of revision of the text May 2019]
  9. Summary of Product Characteristics – Crestor® (rosuvastatin) 10mg film-coated tablets. AstraZeneca UK Limited. Accessed via www.medicines.org.uk 13/04/2019 [date of revision of the text January 2019]
  10. Summary of Product Characteristics – Simvastatin 40mg Tablets. Accord Healthcare Limited. Accessed via www.medicines.org.uk 12/10/2019 [date of revision of the text July 2018]