Antiplatelet agents (low dose) / NSAIDs (analgesic dose)
ATC code: B01AC06 (Acetylsalicylic acid)
Irreversible inhibitor of cyclooxygenase-1 and -2 via acetylation of the active-site serine. In platelets it blocks COX-1 → thromboxane A2 → aggregation for the platelet lifespan (7–10 days). At cardiovascular doses (75–100 mg) it inhibits platelets while relatively sparing endothelial prostacyclin. At doses ≥ 500 mg it produces antiinflammatory, analgesic, and antipyretic effects. Dose-dependently increases the risk of hemorrhagic stroke and GI bleeding.
First line
Low-dose aspirin (75–100 mg daily) is the cornerstone of secondary prevention in established ASCVD. It reduces the risk of recurrent MI, stroke, and vascular death by 20–25 %. Prescribed lifelong if no absolute contraindications exist. After ACS or stenting, dual antiplatelet therapy (aspirin plus clopidogrel, ticagrelor, or prasugrel) is given for 6–12 months.
Individual decision
Routine aspirin for primary prevention is not recommended. ASPREE, ARRIVE, and ASCEND trials showed that in moderate-risk patients, the reduction in ischemic events is offset by increased bleeding. 2022 recommends against initiating aspirin in adults 60 and older for primary prevention. In adults 40–59 with a 10-year ASCVD risk of 10 % or more, the decision is individualized.
10 pairs found. Sorted from critical to minor.
Mechanism
Additive antithrombotic effect plus platelet aggregation inhibition. Sharply increased bleeding risk including GI and intracranial.
Management
Combine only when life-indicated (e.g. post-stenting). Monitor INR and bleeding. Prefer monotherapy when possible.
Sources
Mechanism
Additive antithrombotic action: apixaban + aspirin increases major bleeding risk roughly 1.5–2-fold. For most AF patients, aspirin on top of a DOAC is not justified.
Management
If a patient has AF plus stable CAD or ACS more than 12 months ago, discontinue aspirin and keep only apixaban. Continue aspirin (75–81 mg) only with recent ACS or stenting as part of time-limited dual/triple therapy.
Sources
Mechanism
Additive antiplatelet action: aspirin inhibits COX-1 → thromboxane, clopidogrel blocks the P2Y12 receptor. Effective dual antiplatelet therapy after ACS or stenting, but GI bleeding risk doubles.
Management
DAPT (aspirin 75–100 mg + clopidogrel 75 mg) – 12 months after ACS, 6 months after elective stenting. Then switch to monotherapy (aspirin or clopidogrel). During DAPT, add a PPI (pantoprazole).
Sources
Mechanism
Aspirin's COX inhibition reduces renal prostaglandin-mediated vasodilation. In patients with already-compromised renal perfusion (HF, dehydration, CKD) combined with an ACE inhibitor, acute kidney injury and loss of antihypertensive effect can occur. The effect is clearly dose-dependent. Antiplatelet aspirin doses of 75–100 mg predominantly inhibit platelet COX-1 and barely affect renal prostaglandins. Analgesic and antipyretic doses of 500–1000 mg inhibit COX-1 and COX-2 systemically and are comparable to other nonselective NSAIDs in their effect on renal hemodynamics and BP ( Drug Safety Communication, July 2015; Scientific Statement on NSAIDs and CV risk, Circulation 2007).
Management
Antiplatelet aspirin doses of 75–100 mg are compatible with ACE inhibitors – no adjustment needed. Analgesic and antipyretic doses of 500–1000 mg, when required, should be limited to the shortest possible course (3–5 days) and ideally replaced with paracetamol. For NSAID courses longer than 5 days, check creatinine, potassium, and BP at 7–10 days. In patients with eGFR below 60 mL/min and/or aged over 75, analgesic-dose aspirin should be avoided altogether.
Mechanism
Dual mechanism. First, aspirin competes with furosemide for tubular organic-anion secretion in the proximal tubule – delivery of furosemide to the luminal side of the loop of Henle falls. The effect is pronounced at high aspirin doses. Second, inhibition of renal prostaglandin synthesis reduces preglomerular vasodilation and natriuresis. At cardiovascular aspirin doses of 75–100 mg, both mechanisms are clinically minor. At analgesic and antipyretic doses of 500–1000 mg and above, the effect becomes clinically obvious – HF and ascites patients may lose diuretic efficacy and develop worsening edema.
Management
Antiplatelet aspirin doses of 75–100 mg are compatible with furosemide. Avoid analgesic and antipyretic doses of 500–1000 mg in HF and ascites – replace with paracetamol. If an NSAID is essential, use the shortest possible course, monitor body weight daily, and check creatinine and potassium at 5–7 days. For worsening edema, temporarily increase the furosemide dose or add a thiazide (sequential nephron blockade).
Mechanism
Same as the aspirin/ACE-inhibitor pair: aspirin's NSAID effect blunts renal vasodilation, and patients with CKD or hypovolemia may develop acute kidney injury. Sartan antihypertensive effect is diminished. Antiplatelet aspirin doses of 75–100 mg barely affect renal prostaglandins. Analgesic and antipyretic doses of 500–1000 mg inhibit COX systemically and behave like other nonselective NSAIDs with respect to renal hemodynamics and BP.
Management
Antiplatelet aspirin doses of 75–100 mg are compatible – no adjustment needed. Analgesic and antipyretic doses of 500–1000 mg should be limited to the shortest possible course, with paracetamol preferred. In patients over 75 and/or with eGFR below 60 mL/min, analgesic-dose aspirin should be avoided. For NSAID courses longer than 5 days, check creatinine, potassium, and BP at 7–10 days ( Drug Safety Communication, July 2015).
Mechanism
Aspirin's NSAID effect reduces prostaglandin-dependent renal perfusion and blunts the diuretic and natriuretic action of spironolactone. Antiplatelet doses of 75–100 mg barely affect renal prostaglandin synthesis. Analgesic and antipyretic doses of 500–1000 mg and above suppress renal prostaglandin synthesis systemically – similar to ibuprofen and naproxen. HF patients may decompensate. Additionally, additive GI bleeding risk (synergistic gastrotoxicity from COX inhibition plus the erosive action of aspirin).
Management
In HF, low antiplatelet aspirin doses of 75–100 mg are acceptable – clinically meaningful diuretic blunting is unlikely. Analgesic and antipyretic doses of 500–1000 mg and above are contraindicated in HF NYHA II–IV and/or eGFR below 60 mL/min ( 2016 and HF 2024 guidelines) – replace with paracetamol. For worsening edema or a 2 kg or greater weight gain over 3 days, check creatinine and seek medical review.
Mechanism
Additive antithrombotic effect at two levels: warfarin inhibits clotting factors while aspirin blocks platelet aggregation and simultaneously damages gastric mucosa (antiprostaglandin effect). Major GI bleeding and hemorrhagic stroke risk rise 2–3-fold.
Management
Routinely avoid the combination. It is justified only with clear indications: mechanical valve plus recent ACS, recent stenting in atrial fibrillation. In those cases, use aspirin 75–81 mg/day, add a PPI (pantoprazole, not omeprazole), and keep the INR at the lower end of the target range.
Mechanism
Older experimental data suggested that NSAIDs combined with fluoroquinolones increase CNS excitability and seizure risk (via fluoroquinolone-mediated GABA-A receptor antagonism with possible NSAID potentiation). Clinically meaningful seizure frequency is rare but the risk is elevated in older patients, CKD, and prior epilepsy.
Management
In patients without epilepsy and with normal eGFR, the combination is acceptable, particularly at antiplatelet aspirin doses. With prior epilepsy or eGFR below 30 mL/min, choose a non-fluoroquinolone.
Sources
Mechanism
Ибупрофен может занимать сайт COX-1 на тромбоцитах и блокировать антитромботический эффект низкодозового аспирина.
Management
Ибупрофен принимать не ранее чем через 8 часов после аспирина или за 30 минут до. По возможности заменить на парацетамол.
Sources
FDA pregnancy categories were retired in 2015 (PLLR). Full analgesic doses are avoided throughout pregnancy and strictly contraindicated after 30 weeks due to premature closure of the ductus arteriosus. Low-dose aspirin (81–150 mg daily) for preeclampsia prevention in high-risk women is started at week 12 and continued until delivery per USPSTF 2021, ACOG Committee Opinion 743, NICE NG133, and WHO 2011 (the previous «stop at week 36» rule has been dropped — there is no evidence supporting earlier discontinuation).
Excreted in breast milk. Low antiplatelet doses (75–100 mg) are acceptable during breastfeeding. High analgesic doses are not recommended.
acetylsalicylic acid is evaluated for the following indications with varying evidence strength: Established ASCVD, secondary prevention (evidence tier A), Primary cardiovascular prevention with aspirin (evidence tier C). See the full indication matrix with dosing and citations above on this page.
Common side effects of acetylsalicylic acid (≥ 1 in 100): Dyspepsia, heartburn, Increased bleeding tendency (epistaxis, bruising), Nausea. See the Safety section for uncommon and serious reactions.
FDA pregnancy categories were retired in 2015 (PLLR). Full analgesic doses are avoided throughout pregnancy and strictly contraindicated after 30 weeks due to premature closure of the ductus arteriosus. Low-dose aspirin (81–150 mg daily) for preeclampsia prevention in high-risk women is started at week 12 and continued until delivery per USPSTF 2021, ACOG Committee Opinion 743, NICE NG133, and WHO 2011 (the previous «stop at week 36» rule has been dropped — there is no evidence supporting earlier discontinuation).
Excreted in breast milk. Low antiplatelet doses (75–100 mg) are acceptable during breastfeeding. High analgesic doses are not recommended.
acetylsalicylic acid is contraindicated in: Active GI bleeding; Severe thrombocytopenia; Hemorrhagic diathesis; Aspirin allergy or aspirin-exacerbated respiratory disease; Severe hepatic failure. Full list in the Safety section.