What medications should be held prior to major surgery?

Medications to Hold Prior to Major Surgery

For major elective surgery, discontinue P2Y12 inhibitors (clopidogrel, ticagrelor) at least 5 days preoperatively and prasugrel at least 7 days preoperatively, while continuing aspirin in most cases unless bleeding risk in closed spaces exceeds thrombotic risk. 1, 2

Antiplatelet Agents

P2Y12 Inhibitors (Thienopyridines)

• Clopidogrel and ticagrelor: Stop ≥5 days before elective surgery 1, 2
• Prasugrel: Stop ≥7 days before elective surgery 1
• Urgent surgery: May discontinue clopidogrel/ticagrelor ≥24 hours before procedure to reduce major bleeding, though this increases thrombotic risk 1
• Critical caveat: In patients with recent coronary stents (bare-metal <30 days, drug-eluting <6-12 months), delay elective surgery if possible rather than stopping dual antiplatelet therapy, as premature discontinuation dramatically increases stent thrombosis risk 3

Aspirin

• Continue aspirin perioperatively in most major surgeries, as benefits outweigh modest bleeding risk 1, 3
• Discontinue 5-7 days preoperatively only for: intracranial surgery, spinal canal surgery, posterior chamber eye surgery, or other closed-space procedures where even minor bleeding is catastrophic 1, 4
• Primary prevention only: May stop 7-10 days preoperatively if bleeding risk exceeds cardiac risk 3

GP IIb/IIIa Inhibitors

• Eptifibatide and tirofiban: Stop ≥2-4 hours before surgery 1
• Abciximab: Stop ≥12 hours before surgery 1

Anticoagulants

Novel Oral Anticoagulants (NOACs)

• Dabigatran: Stop 5 days before major surgery or neuraxial blockade (3 days for minor procedures in patients with normal renal function) 1
• Rivaroxaban and apixaban: Stop 3 days before major surgery or neuraxial blockade (24-48 hours for minor procedures) 1
• Bridging NOT required except in patients with recent (<3 months) venous thromboembolism 1

Warfarin

• Stop ≥5 days preoperatively 1
• Bridging with heparin only for selected high-risk patients (mechanical heart valves, recent VTE, high-risk atrial fibrillation) 1
• Vitamin K: Use subcutaneously only for urgent/emergency surgery 5

Herbal Supplements and Dietary Products

Bleeding Risk Supplements

• Hold for 2 weeks preoperatively: garlic, ginkgo, ginseng (all types), ginger, feverfew, turmeric, vitamin E, saw palmetto, dong quai, danshen, devil's claw, arnica, boldo, bromelain, cat's claw, horse chestnut, policosanol, resveratrol, vanadium, guarana, fenugreek, evodia, and aloe 1
• Hold for 48 hours: chondroitin and glucosamine 1
• Continue: fish oil/omega-3 fatty acids (prior bleeding concerns not supported by prospective studies) 1

CNS Depression Risk Supplements

• Hold for 2 weeks preoperatively: kava, lemon balm, skullcap 1

Hypoglycemia Risk Supplements

• Monitor closely but may continue with increased perioperative glucose surveillance 1

Cardiovascular Medications

Continue Perioperatively

• Beta-blockers: Continue to avoid rebound angina, MI, and arrhythmias 3
• Statins: Continue without interruption; discontinuation is potentially harmful 3
• Clonidine: Continue to avoid rebound hypertension 3

Consider Holding

• ACE inhibitors and ARBs: May hold due to intraoperative hypotension risk requiring vasopressor support; restart postoperatively when clinically feasible 3

Diabetes Medications

• SGLT-2 inhibitors (empagliflozin, dapagliflozin): Omit the day before and day of surgery due to euglycemic ketoacidosis risk 3
• GLP-1 receptor agonists (semaglutide, liraglutide): Continue with aspiration precautions 3
• Basal insulin: Continue at reduced dose 3

Psychiatric Medications

• Antidepressants (SSRIs, SNRIs, TCAs): Continue perioperatively to avoid withdrawal; monitor for serotonin syndrome if multiple serotonergic agents used 3
• Benzodiazepines: Avoid restarting postoperatively due to delirium, falls, and cognitive impairment risk, especially in patients >50 years 6

Antirheumatic Medications

• Conventional DMARDs (methotrexate, hydroxychloroquine): Continue 3
• Mycophenolate, azathioprine, cyclosporine, tacrolimus: Hold 1 week before surgery in non-severe SLE 3
• JAK inhibitors (tofacitinib, baricitinib, upadacitinib): Hold ≥3 days before surgery 3

NSAIDs

• Stop 1 day preoperatively: diclofenac, ibuprofen, ketorolac 7
• Stop 2 days preoperatively: etodolac, indomethacin 7
• Stop 4 days preoperatively: meloxicam, naproxen, nabumetone 7
• Stop 6 days preoperatively: oxaprozin 7
• Stop 10 days preoperatively: piroxicam 7

Critical Pitfalls to Avoid

• Never substitute heparin or LMWH for antiplatelet therapy in patients with coronary stents—this does not protect against stent thrombosis 4
• Defer elective surgery if BP ≥180/110 mmHg 3
• Resume anticoagulants and antiplatelets as soon as hemostasis achieved postoperatively to minimize thrombotic complications 2
• 50-70% of patients fail to disclose herbal supplement use—specifically ask about these during preoperative evaluation 8