IL RISCHIO CARDIACO IN CHIRURGIA NON CARDIACA. Come sospendere la terapia antiaggregante nei cardiopatici prima di un intervento?

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1 IL RISCHIO CARDIACO IN CHIRURGIA NON CARDIACA Come sospendere la terapia antiaggregante nei cardiopatici prima di un intervento? Fondazione Arturo Pinna Pintor 12 dicembre 2011

2 Perché si usano gli antiaggreganti? Qual èil motivo specifico per il quale la persona che abbiamo di fronte sta prendendo antiaggreganti? Per prevenire trombosi arteriose 1.Prevenzione, primaria (raro) o nelle malattie aterosclerotiche secondaria 2.Prevenzione delle trombosi intrastent (coronarico)

3 Prevenzione primaria/secondaria Patrono C et al. Chest 2008;133:199S

4 Prevenzione primaria/secondaria Efficacia della terapia antipiastrinica Proportional effects of antiplatelet therapy on vascular events (myocardial infarction, stroke, or vascular death) in five main high risk categories. BMJ 2002;324:71-86

5 Prevenzione primaria/secondaria rischio emorragico These benefits were substantially larger than the excess risk of major extracranial bleeding, which was estimated to be three additional major extracranial bleeds per 1000 patients allocated antiplatelet therapy that is, an excess of about 1 such bleed per 1000 patients per year. BMJ 2002;324:71 86

6 ASA rischi/benefici * N di pazienti in cui si evita un evento avverso vascolare maggiore per 1000/anno N di pazienti in cui si causa un sanguinamento GE maggiore per 1000/anno Patrono C et al. Chest 2008;133:199S

7 Perché si usano gli antiaggreganti? Qual èil motivo specifico per il quale la persona che abbiamo di fronte sta prendendo antiaggreganti? 1.Prevenzione, primaria (raro) o secondaria 2.Prevenzione delle trombosi intrastent (coronarico)

8 DAPT Dual Anti Platelet Treatment superiore ad ASA The clinical benefit of dual antiplatelet therapy vs aspirin alone has been confirmed in patients undergoing PCI, 254 and in those presenting with an acute MI with ST-segment elevation within 12 h 256 to 24h 257 after the onset of symptoms Patrono C et al. Chest 2008;133:199S

9 DAPT superiore ad ASA Stent coronarici non medicati (BMS Bare Metal Stent), eventi a 30 giorni Grines CL et al. Circulation 2007;115:

10 DAPT rischio emorragico As expected, major bleeding was increased by dual antiplatelet therapy in both MATCH 255 and CHARISMA. 258 Patrono C et al. Chest 2008;133:199S

11 Berger et al. Circulation 2010, 121: :

12 Antiplatelet and Anticoagulation Therapy in Vitreoretinal Surgery Oh, J et al. American Journal of Ophthalmology, 2011;151:934

13 Surgical and other invasive procedures associated with a high bleeding risk Coronary artery bypass or heart valve replacement surgery. Intracranial or spinal surgery. Aortic aneurysm repair, peripheral artery bypass, and other major vascular surgery. Major orthopedic surgery, such as hip or knee replacement. Reconstructive plastic surgery. Major cancer surgery. Prostate and bladder surgery. Douketis JD et al, CHEST 2008; 133: S

14 High risk of Bleeding Criteria MATCH study (Clopidogrel ASA stroke) increased risk of bleeding: clinical evidence of severe hepatic insufficiency, current peptic ulceration, history of systemic bleeding, or other history of bleeding diathesis or coagulopathy Diener HC et al. Lancet 2004; 364:

15 Sospensione ASA individuals aged with a first prescription for aspirin ( mg/day) for secondary prevention of cardiovascular outcomes in Individuals were followed up for a mean of 3.2 years to identify cases of non-fatal myocardial infarction or death from coronary heart disease There were 876 non-fatal myocardial infarctions and 346 deaths from coronary heart disease. Compared with current users, people who had recently stopped taking aspirin had a significantly increased risk of non-fatal myocardial infarction or death from coronary heart disease combined (rate ratio 1.43, 95% confidence interval 1.12 to 1.84) and non-fatal myocardial infarction alone (1.63, 1.23 to 2.14). Garcia Rodriguez LA BMJ2011;343:4094

16 Sospensione della DAPT: cause e rischi In one multicenter study of patients with acute myocardial infarction treated with DES, 13.6% of patients discontinued dual anti-platelet therapy by 30 days 11. Patients who discontinued therapy before 30 days had a higher rate of re-hospitalization and mortality when compared with those who continued therapy. Factors contributing to dual antiplatelet discontinuation included anemia or need for surgery, but importantly also included many socioeconomic factors (such as education level, cost for prescriptions, understanding of instructions, and misinformation from healthcare professionals). 11. Spertus JA, et al. Circulation 2006;113: , in Hodgson Catheterization and Cardiovascular Interventions 2007

17 Sospensione antiaggreganti Risk-Adjusted Instantaneous Incidence Rates of Death or Acute Myocardial Infarction Over Time After Stopping Treatment With Clopidogrel Ho PM et al. JAMA. 2008;299:

18 Cumulative incidence of stent thrombosis in patients who continued (black) and those who discontinued clopidogrel therapy (red). Schulz S et al. Eur Heart J 2009;30:

19 Number of patients incurring stent thrombosis during 4 years of follow-up. On clopidogrel Off clopidogrel Schulz S et al. Eur Heart J 2009;30:

20 Thienopiridine discontinuation, Stent Thrombosis, Mortality In a large observational cohort study of patients treated with DES, stent thrombosis occurred in 29% of patients in whom antiplatelet therapy was discontinued prematurely. 9 hazard ratio of 161 for subacute stent thrombosis and a hazard ratio of 57 for late (30 days) stent thrombosis. In a single-site study of 652 patients treated with sirolimus DES, premature discontinuation of clopidogrel was associated with an30-fold greater risk of stent thrombosis, with 25% of patients who discontinued clopidogrel therapy within the first month suffering stent thrombosis. 17 Park et al 13 reported on 1911 consecutive patients with DES followed up for a median of 19.4 months. Five (7.8%) of 64 patients with premature interruption of aspirin, clopidogrel, or both experienced stent thrombosis. Spertus and colleagues 19 The mortality rate of those who stopped thienopyridine therapy was 7.5% compared with 0.7% in those who had not stopped therapy (hazard ratio 9.0, P ). Pfisterer et al 20 randomized 746 patients (1133 lesions) to DES versus bare-metal stents after discontinuation of clopidogrel at 6 months, late stent thrombosis (2.6% versus 1.3%) and death or nonfatal MI (4.9% versus 1.3%) occurred more frequently in the DES group. Grines CL et al. Circulation 2007;115:

21 Clopidogrel Use and Long-term Clinical Outcomes After Drug-Eluting Stent Adjusted Cumulative Mortality Rates Using the 6-Month Landmark Analysis. Per to a i DES l uso di clopidogrel al di là dei 6 mesi èassocia minore mortalità Eisenstein, E. L. et al. JAMA 2007;297:

22 Dual antiplatelet therapy for a period longer than 12 months in patients who had received DES was not significantly more effective than aspirin monotherapy Park et al. N Engl J Med 2010;362:

23 Grines CL et al. Circulation 2007;115:

24 Fattori di rischio per trombosi di DES a) Rischio di sospendere > trombosi Malattia coronarica Stent non medicati Stent medicati Rivascolarizzazione chirurgica Hodgson Catheterization and Cardiovascular Interventions 2007

25 Fattori di rischio per trombosi di DES Möllmann H et al. Heart 2010;96:986e991.

26 Fattori di rischio per trombosi di DES Hodgson Catheterization and Cardiovascular Interventions 2007

27 Stent Thrombosis After Noncardiac Surgery Kaluza et al 25 reported on 40 patients treated with bare-metal stents who underwent noncardiac surgery within 6 weeks of stent implantation. Seven patients had an MI, of which 6 were fatal. In 5 of 7 cases, thienopyridine therapy (ticlopidine) had been withheld before surgery. In a similar analysis of 47 patients who underwent noncardiac surgery within 90 days of bare-metal stent implantation, 6 of the 7 patients in whom thienopyridine therapy was discontinued died in a manner suggestive of stent thrombosis Kaluza GL, J Am Coll Cardiol. 2000;35: Sharma AK, Catheter Cardiovasc Interv. 2004;63: In Grines CL et al. Circulation 2007;115:

28 Stent, Antipiastrinici, Chirurgia non cardiaca Mayo 2003 Wilson SH et al. J Am Coll Cardiol 2003;42:234 40

29 Stent, Antipiastrinici, Chirurgia non cardiaca Sanguinamenti? Mayo 2003 Antithrombotic Regimen Aspirin and a Thienopyridine (n = 54) Aspirin and Last Thienopyridine 10 Days Before Surgery (n = 29) Aspirin and Warfarin (n = 4) Aspirin Alone (n = 104) No Therapy for >10 Days (n = 13) p Value Excessive surgical bleeding, n N of patients transfused, n (%) (42.6%) 5 (17.2%) 1 (25%) 33 (31.7%) 5 (38.5%) 0.54 Wilson SH et al. J Am Coll Cardiol 2003;42:234 40

30 Stent, Antipiastrinici, Chirurgia non cardiaca Quali eventi avversi e quando? Mayo 2003 Wilson SH et al. J Am Coll Cardiol 2003;42:234 40

31 Coronary Stent (BMS) Thrombosis and Noncardiac Surgery Authors Year Type Time Period Patients, n DES, % Time From PCI to Surgery Mortality Rate, * % (95% CI) Kaluza et al Retr, NR <42 d 21.4 Wilson et al Retr, NR <60 d 3.4 Sharma et al Retr, NR <90 d 18.4 Reddy et al Retr, NR Leibowitz et 2006 Retr, NR <90 d 14.6 al 13 Vicenzi et al Prosp, NR <1 y 5.7 Compton et 2006 Retr, NR al 14 PCI indicates percutaneous coronary intervention; Retr, retrospective; Prosp, prospective; and NR, nonrandomized. *Mortality rates were calculated using the adjusted Wald interval. Riddell J W et al. Circulation 2007;116:e378-e382

32 Sospensione preoperatoria di clopidogrel Gaglia & Waksman European Heart Journal , 2358

33 Stent, Antipiastrinici, Chirurgia non cardiaca Schouten O, et al. J Am Coll Cardiol 2007;49:122

34 Stent, Antipiastrinici, Chirurgia non cardiaca Schouten O, et al. J Am Coll Cardiol 2007;49:122

35 Stent, Antipiastrinici, Chirurgia non cardiaca Mortalità e infarto correlano con intervento 30 gg e sospensione DAPT Schouten O, et al. J Am Coll Cardiol 2007;49:122

36 Non cardiac surgery in pts with stents MACCE & Bleeding Prospective, multicentre, observational cohort study of 1134 consecutive patients with coronary stents. MACCE and haemorrhagic complications were observed in 124 (10.9%) and 108 (9.5%) patients, respectively. Average time delay from invasive procedure to event of and days. Independent preoperative correlates for MACCE were complete OAT interruption for more than 5 days prior to surgery, preoperative haemoglobin <10 g/dl, creatinine clearance of <30 ml/min and emergency or high-risk surgery. Independent factors for haemorrhagic complications were preoperative haemoglobin <10 g/dl, creatinine clearance between 30 and 60 ml/min, highrisk surgery, and a delay from stent implantation to surgery <3 months Albaladejo P et al. Heart 2011;97:1566

37 Non cardiac surgery Albaladejo P et al. Heart 2011;97:1566

38 Non cardiac surgery MACCE after discontinuation of antiplatelet High risk: intra thoracic, intraperitoneal, suprainguinal vascular Albaladejo P et al. Heart 2011;97:1566

39 Non cardiac surgery Albaladejo P et al. Heart 2011;97:1566

40 Length of clopidogrel therapy Gaglia&Waksman, European Heart Journal , 2358

41 Sospensione della DAPT This advisory stresses the importance of 12 months of dual antiplatelet therapy after placement of a drug-eluting stent It also recommends postponing elective surgery for 1 year, and if surgery cannot be deferred, considering the continuation of aspirin during the perioperative period in high-risk patients with drug-eluting stents. Grines CL et al. Circulation 2007;115:

42 Come sospendere la terapia antiaggregante nei cardiopatici prima di un intervento? Prima: Il cardiologo che si accinge ad eseguire una PCI deve accertare se nell immediato futuro (12 mesi) del paziente sia previsto un intervento chirurgico e di che tipo; dovrà quindi concordare con paziente e chirurgo la strategia opportuna: rimandare la PCI, ricorrere and una angioplastica semplice senza stent o impiegare stent non medicati con 4-6 settimane di DAPT

43 Come sospendere la terapia antiaggregante nei cardiopatici prima di un intervento? Dopo una PCI con DES, i fattori di cui tenere conto sono Tipo stent usato (e altre variabili procedurali note al cardiologo) Tempo trascorso dall impianto dello stent (6 settimane-1 anno) Variabili cliniche (età avanzata, diabete, insuff. renale, bassa frazione di eiezione) Tipo di chirurgia (basso rischio: odontoiatrica, dermatologica, oculistica (cataratta), angiografie, endoscopie) Le reciproche relazioni di tali fattori sono ben riassunte da Riddell e Korte

44 Coronary Stent Thrombosis and Noncardiac Surgery Riddell J W et al. Circulation 2007;116:e378-e382

45 Come sospendere la terapia antiaggregante nei cardiopatici prima di un intervento? Korte W et al, Thrombosis and Haemostasis 2011;105:743

46 Come sospendere la terapia antiaggregante nei cardiopatici prima di un intervento? Se prevenzione primaria: As the peri-operative use of aspirin is associated with increased blood loss and blood product use and as patients undergoing primary prophylaxis show no manifestation of any cardiovascular disease, this expert group suggests that aspirin given for primary prevention should be stopped 5 7 days before any type of surgery 46, 47. Korte W et al, Thrombosis and Haemostasis 2011;105:743

47 Come sospendere la terapia antiaggregante nei cardiopatici prima di un intervento? Se prevenzione secondaria: This expert group recommends the continuation of aspirin (or clopidogrel) monotherapy for secondary prevention during most types of surgery. Only in patients undergoing surgical procedures in areas of closed space (e.g. intracranial neurosurgery, posterior chamber of the eye, medullary canal etc.) or when major bleeding complications are to be expected, stopping monotherapy with aspirin or clopidogrel 5 7 days pre-operatively should be evaluated on a case by case basis. Korte W et al, Thrombosis and Haemostasis 2011;105:743

48 Come sospendere la terapia antiaggregante nei cardiopatici prima di un intervento? se DAPT per stent / sindrome coronarica acuta: The guidelines of international cardiologic societies (ACC/AHA and ESC) (55 58) recommend dual antiplatelet therapy for a period of four to six weeks after elective PCI with bare-metal stents (BMS); 12 months are recommended when drug-eluting stents (DES) are used. 12 months of dual antiplatelet therapy also after NSTEMI and STEMI Korte W et al, Thrombosis and Haemostasis 2011;105:743

49 Surgical and other invasive procedures associated with a high bleeding risk The peri-operative bleeding risk is related to the type of surgery: minor surgical interventions like dental procedures, cataract surgery, dermatologic operations, as well as angiographic diagnostic procedures or diagnostic endoscopies can apparently be performed under full anti-platelet therapy if no additional bleeding risks exist. A clear increase in haemorrhagic risk with dual antiplatelet therapy, however, has to be acknowledged in vascular, visceral and transbronchial surgery (27 29). Korte W et al, Thrombosis and Haemostasis 2011;105:743

50 Periop management antiplatelets Korte W et al, Thrombosis and Haemostasis 2011;105:743