ASA/Trombyl

Indikation:

Kontraindikation:

  • Läs alltid även på FASS.se
  • Blödningsanemi, magsår, tidigare GI-blödning
  • vissa operationer (ökad blödningsrisk)
  • ASA-allergi (läs dock sidan om ASA-allergi!)
  • ASA rekommenderas inte för cancerpatienter med <10 000 trombocyter (ESC 2023 Class IIIC) 2
  • Glukos-6-fosfatdehydrogenasbrist (G6PD) : ASA kan möjligen orsaka en hemolytisk kris hos patienter med G6PD (favism), en sjukdom som förekommer hos ca 1/350 nyfödda barn i Sverige. Det är dock omdebatterat om ASA är helt kontraindicerat hos G6PD-patienter som har en stark indikation för ASA, konsensus saknas.34 5 En RCT om ASA för strokeprevention hos G6PD-patienter pågår.

Dosering:

  • Laddningsdos 320 mg (150-320mg) p.o. Laddningsdos kan även ges i.v. (250 mg)6.
  • Underhållsdos 75 mg 1×1 dagligen p.o. 7

Behandlingstid:

Vid AKS och stabil angina tills vidare (utsättning vid kontraindikation eller om patient utvecklar en OAK-indikation).

Kontroller:

Vid klinisk misstanke på anemi.

Kommentar:

I.v. laddning lämplig för patienter som inte kan svälja tabletter (chock, hjärtstop etc).

Länk till FASS.se här

ASA-historisk utveckling

(originalpublikationen- en disputation från 2019 – är på engelska):

The history of antiplatelet drugs began with Acetylsalicylic Acid (ASA). An essential step in platelet activation (initiated by platelet adhesion to collagen or von Willebrand factor) is platelets’ synthesis and release of the prostaglandin Thromboxane A2 and ADP.

ASA irreversibly blocks platelets’ cyclooxygenase by acetylation and thus reduces the production of the platelet-aggregation-stimulating Thromboxane A28 (Thromboxane was named after its platelet aggregation property at Karolinska Institute in the 1970s).9 10 Bark and leaves from the willow tree, Salix, (see Linné) 11 were used as anti-inflammatory and painkilling drugs for more than 3,000 years12  and recommended by Hippocrates 2,400 years ago13 for use as analgetics in childbirth, and analgesia and anti-inflammation were even the indications for the drug Aspirin after the synthetic production of ASA (acetylated salicylate) in Germany at the turn of the 19th to the 20th century.14 The initially extracted salicylate, named after the tree Salix, had severe gastric side effects, illustrated by the fact that its current indication is usage as a keratolytic for warts.15 Before synthetic production, meadowsweet (spiraea ulmaria) was used for the production of ASA due to its higher concentration of salicylates, hence the name Aspirin was selected (acetyl spirsäure with the at-the-time popular suffix –in, as in Heroin by the same company Bayer or as in the U.S. Heparin).16

The effect of ASA on platelet aggregation first became known in the 1960s17 18 19 and the first major study with clinical cardiovascular endpoints was conducted in the late 1970s to prove ASA was effective in the secondary prevention of stroke. 20 In 1983, an RCT showed a reduction of the rate of MI or death by 50% in patients with unstable angina treated with ASA, as compared to a placebo.21 In 1984, an RCT proved ASA was effective in preventing early and late saphenous vein graft occlusion after CABG, 22while in 1985, a Canadian multicenter RCT confirmed a 51% risk reduction (cardiac death or MI) in unstable angina23, and three years later, the ISIS-2 trial showed a significantly improved survival rate (25 prevented deaths for every 1,000 patients taking one month of ASA) and fewer re-infarctions and strokes in STEMI patients taking ASA alone or initially in combination with streptokinase.24 25 

A medicine used for thousands of years could half the risk of death and MI. Based on this fantastic data, ASA has from the 1990s to today been a standard acute and secondary preventive treatment for all subtypes of acute coronary syndromes. 

Litteratur

Platelets in atherothrombosis 26

2023 ESC Guidelines for the management of acute coronary syndromes.27

Referenser

  1. Avsnitt 6.1 in: Byrne RA et al; ESC Scientific Document Group. 2023 ESC Guidelines for the management of acute coronary syndromes. Eur Heart J. 2023 Oct 12;44(38):3720-3826. doi: 10.1093/eurheartj/ehad191. PMID: 37622654. ↩︎
  2. Byrne RA, Rossello X, Coughlan JJ, Barbato E, Berry C, Chieffo A, Claeys MJ, Dan GA, Dweck MR, Galbraith M, Gilard M, Hinterbuchner L, Jankowska EA, Jüni P, Kimura T, Kunadian V, Leosdottir M, Lorusso R, Pedretti RFE, Rigopoulos AG, Rubini Gimenez M, Thiele H, Vranckx P, Wassmann S, Wenger NK, Ibanez B; ESC Scientific Document Group. 2023 ESC Guidelines for the management of acute coronary syndromes. Eur Heart J. 2023 Oct 12;44(38):3720-3826. doi: 10.1093/eurheartj/ehad191. PMID: 37622654. ↩︎
  3. Kafkas NV, Liakos CI, Mouzarou AG. Antiplatelet and invasive treatment in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency and acute coronary syndrome. The safety of aspirin. J Clin Pharm Ther. 2015 Jun;40(3):349-52. doi: 10.1111/jcpt.12262. Epub 2015 Mar 25. PMID: 25807896. ↩︎
  4. Feghaly J, Al Hout AR, Mercieca Balbi M. Aspirin safety in glucose-6-phosphate dehydrogenase deficiency patients with acute coronary syndrome undergoing percutaneous coronary intervention. BMJ Case Rep. 2017 Oct 9;2017:bcr2017220483. doi: 10.1136/bcr-2017-220483. PMID: 28993349; PMCID: PMC5652485. ↩︎
  5. Li J, Chen Y, Ou Z, Ouyang F, Liang J, Jiang Z, Chen C, Li P, Chen J, Wei J, Zeng J. Aspirin Therapy in Cardiovascular Disease with Glucose-6-Phosphate Dehydrogenase Deficiency, Safe or Not? Am J Cardiovasc Drugs. 2020 Dec 14. doi: 10.1007/s40256-020-00460-8. Epub ahead of print. PMID: 33313989. ↩︎
  6. Avsnitt 6.1 in: Byrne RA et al; ESC Scientific Document Group. 2023 ESC Guidelines for the management of acute coronary syndromes. Eur Heart J. 2023 Oct 12;44(38):3720-3826. doi: 10.1093/eurheartj/ehad191. PMID: 37622654. ↩︎
  7. 75-100mg, Avsnitt 6.1 in: Byrne RA et al; ESC Scientific Document Group. 2023 ESC Guidelines for the management of acute coronary syndromes. Eur Heart J. 2023 Oct 12;44(38):3720-3826. doi: 10.1093/eurheartj/ehad191. PMID: 37622654. ↩︎
  8. Zipes DP, Libby P, Bonow RO, Mann DL, Tomaselli GF and Braunwald E. Braunwald’s heart disease : a textbook of cardiovascular medicine; 2019, Opie LH and Gersh BJ. Drugs for the Heart : Expert Consult – Online and Print. Saint Louis: Elsevier Health Sciences; 2014 ↩︎
  9. Fitzgerald DJ and Fitzgerald GA. Historical lessons in translational medicine: cyclooxygenase inhibition and P2Y12 antagonism.Circulation research. 2013;112:174-94 ↩︎
  10. Hamberg M, Svensson J and Samuelsson B. Thromboxanes: a new group of biologically active compounds derived from prostaglandin endoperoxides. Proceedings of the National Academy of Sciences of the United States of America. 1975;72:2994-8 ↩︎
  11. Linné Cv and Salvius L. Caroli Linnaei … Species plantarum :exhibentes plantas rite cognitas, ad genera relatas, cum differentiis specificis, nominibus trivialibus, synonymis selectis, locis natalibus, secundum systema sexuale digestas. Holmiae :: Impensis Laurentii Salvii; 1753 ↩︎
  12. Fuster V and Sweeny JM. Aspirin: a historical and contemporary therapeutic overview. Circulation. 2011;123:768-78 ↩︎
  13. Mueller RL and Scheidt S. History of drugs for thrombotic disease. Discovery, development, and directions for the future. Circulation. 1994;89:432-49 ↩︎
  14. Mueller RL and Scheidt S. History of drugs for thrombotic disease. Discovery, development, and directions for the future. Circulation. 1994;89:432-49 ↩︎
  15. Mueller RL and Scheidt S. History of drugs for thrombotic disease. Discovery, development, and directions for the future. Circulation. 1994;89:432-49 ↩︎
  16. Mueller RL and Scheidt S. History of drugs for thrombotic disease. Discovery, development, and directions for the future. Circulation. 1994;89:432-49 ↩︎
  17. Mueller RL and Scheidt S. History of drugs for thrombotic disease. Discovery, development, and directions for the future. Circulation. 1994;89:432-49 ↩︎
  18. Fuster V and Sweeny JM. Aspirin: a historical and contemporary therapeutic overview. Circulation. 2011;123:768-78 ↩︎
  19. Fitzgerald DJ and Fitzgerald GA. Historical lessons in translational medicine: cyclooxygenase inhibition and P2Y12 antagonism. Circulation research. 2013;112:174-94 ↩︎
  20. Group CCS. A randomized trial of aspirin and sulfinpyrazone in threatened stroke. The New England journal of medicine. 1978;299:53-9 ↩︎
  21. Lewis HD, Jr., Davis JW, Archibald DG, Steinke WE, Smitherman TC, Doherty JE, 3rd, Schnaper HW, LeWinter MM, Linares E, Pouget JM, Sabharwal SC, Chesler E and DeMots H. Protective effects of aspirin against acute myocardial infarction and death in men with unstable angina. Results of a Veterans Administration Cooperative Study. The New England journal of medicine. 1983;309:396-403 ↩︎
  22. Chesebro JH, Fuster V, Elveback LR, Clements IP, Smith HC, Holmes DR, Jr., Bardsley WT, Pluth JR, Wallace RB, Puga FJ and et al. Effect of dipyridamole and aspirin on late vein-graft patency after coronary bypass operations. The New England journal of medicine. 1984;310:209-14 ↩︎
  23. Cairns JA, Gent M, Singer J, Finnie KJ, Froggatt GM, Holder DA, Jablonsky G, Kostuk WJ, Melendez LJ, Myers MG and et al. Aspirin, sulfinpyrazone, or both in unstable angina. Results of a Canadian multicenter trial. The New England journal of medicine. 1985;313:1369-75  ↩︎
  24. Baigent C, Collins R, Appleby P, Parish S, Sleight P, and Peto R. ISIS-2: 10-year survival among patients with suspected acute myocardial infarction in randomized comparison of intravenous streptokinase, oral aspirin, both, or neither. The ISIS-2 (Second International Study of Infarct Survival) Collaborative Group. BMJ (Clinical research ed). 1998;316:1337-43 ↩︎
  25. Randomized trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2. ISIS-2 (Second International Study of Infarct Survival) Collaborative Group. Lancet (London, England). 1988;2:349-60 ↩︎
  26. Ruggeri ZM. Platelets in atherothrombosis. Nat Med. 2002 Nov;8(11):1227-34. doi: 10.1038/nm1102-1227. PMID: 12411949. ↩︎
  27. Byrne RA, Rossello X, Coughlan JJ, Barbato E, Berry C, Chieffo A, Claeys MJ, Dan GA, Dweck MR, Galbraith M, Gilard M, Hinterbuchner L, Jankowska EA, Jüni P, Kimura T, Kunadian V, Leosdottir M, Lorusso R, Pedretti RFE, Rigopoulos AG, Rubini Gimenez M, Thiele H, Vranckx P, Wassmann S, Wenger NK, Ibanez B; ESC Scientific Document Group. 2023 ESC Guidelines for the management of acute coronary syndromes. Eur Heart J. 2023 Oct 12;44(38):3720-3826. doi: 10.1093/eurheartj/ehad191. PMID: 37622654. ↩︎

Last Updated on December 23, 2023 by Christian Dworeck

Christian Dworeck
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