Rischio Cardiovascolare e Rischio Emorragico

Transcript

1 Corso di Aggiornamento Gestione dei Farmaci Antiaggreganti e Anticoagulanti in specifici Contesti Clinici 15 marzo 2011 Aula G-Ospedale Infermi Rimini Rischio Cardiovascolare e Rischio Emorragico Giancarlo Piovaccari, Nicoletta Franco Dipartimento Malattie Cardiovascolari

2 68 Million Americans with CVD Stroke 4.4 million PAD 8.4 million HTN 50 million Leading cause of death ww And many moredeaths to come!! annually in US Heart 16.8 million CHF 4.6 mill AMI 7.2 mill Angina 6.3 mill

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5 Platelet shape change and aggregation

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7 Patofisiologia delle SCA SCA con persistente sopraelevazione ST (STEMI) SCA senza persistente sopraelevazione ST (NSTEMI)

8 Le Sd CORONARICHE ACUTE

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13 Improvement in Mortality La riduzione della Mortalità per Infarto negli Anni Day Mortality (%) % Bed Riposo arest letto 15 Anni 80 13%-15% Defibrillazione Defibrillation Defibrillation 10 Hemodynamic Hemodynamic Monitoraggio monitoring monitoring 5 0 Anni 70 Emodinamico 5.0%- 6.5% Beta-bloccanti ASA, PTCA Aspirin, Aspirin, PTCA, PTCA, Lysis Lysis Fibrinolisi β-blockade β-blockade Pre-CCU Era CCU Era Pre UNITA CORONARICA UNITA CORONARICA PTCA, percutaneous transluminal coronary angioplasty. Reperfusion Era LA RIPERFUSIONE

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22 Aumento del rischio emorragico dosaggi elevati o eccessivi di farmaci antitrombotici durata del trattamento associazione di più farmaci antitrombotici cambio tra differenti farmaci anticoagulanti età avanzata ridotta funzione renale basso peso corporeo sesso femminile valori basali di emoglobina procedure invasive

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24 Bleeding ed incremento di Mortalità

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26 Analisi multivariata per emorragie maggiori in pz con NSTEMI

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32 Bleeding Risk Score per PCI : Variabili cliniche

33 Severe bleeding occurred in 1.7% of the clopidogrel group versus 1.3% on placebo (P0.087) moderate bleeding occurred in 2.1% versus 1.3%, respectively (P0.001) The risk of bleeding was greatest the first year

34 Kaplan-Meier curves for moderate or severe bleeding in the first year

35 Kaplan-Meier curves for moderate or severe bleeding after the 1 year in pts with no bleeding events in the 1 year

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37 JAMA 2004

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39 Siti di Sanguinamento

40 Accesso per Procedura Interventistica: Femorale Radiale

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46 Siti di Sanguinamento non in Relazione PCI

47 *Puncture-site bleeding in 1489 pts who underwent a PCI Surgical bleeding in 2189 pts who had at least 1 surgical procedure.

48 Over one million PCI procedures are performed annually Antithrombotic therapy has become more aggressive (more complex lesions, Drug eluting stents) Current antithrombotic regimens may induce new gastrointestinal (GI) bleeding or exacerbate chronic episodic GI bleeding GI bleeding is associated with significant morbidity and mortality Prevention and management of GI bleeding in this patient population With the increasing adoption of radial access as compared to femoral artery approach, GI bleeding may be the most common type of bleeding associated with PCI

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50 Evaluation of bleeding risk, according to the presence or absence of predictors Baseline characteristics must be taken into account, particularly age, female sex and low body weight Renal function has to be evaluated by calculating creatinine clearance and/or GFR Previous history of bleeding must be recorded, and recent or ongoing bleeding must be searched for

51 Bleeding was once considered to be inherent to the therapeutic approach required to treat ACS patients Bleeding has a strong impact on outcome in terms of excess risk for death, MI and stroke at 30 days and long term Blood transfusion may also have a deleterious effect The interruption of active treatment, and activation of coagulation and inflammation in case of bleeding, as well as the depletion of 2,3-DPG and nitric oxide in preserved blood, and the stimulation of immunologic reactions after transfusion, may be some potential explanations

52 Prevention of bleeding has become equally as important as prevention of further ischaemic events in pts suffering from ACS The risk factors for bleeding are well known, and should be taken into account in the choice of appropriate drugs and procedures Attention should be paid to use of drugs or drug combinations, and dosages that may favour bleeding A radial approach should be favoured over a femoral approach, if an invasive strategy is required Renal function should be taken into account, as it is a major contributor to bleeding risk

53 Triplice Terapia

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55 Follow-Up Clinical Results in Studies Comparing Triple Therapy Versus Dual Antiplatelet Therapy in Pts Requiring Oral Anticoagulation and Undergoing PCI

56 Risk of all-cause mortality in patients receiving TT or DT

57 Risk of major bleeding in the first 6 months FUP

58 Terapia antiaggregante ed Inibitori della Pompa Protonica

59 1.1% 2.9% Event rate

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61 Clopidogrel con o senza omeprazolo nella malattia coronarica: i risultati dello studio COGENT Nei pazienti con malattia coronarica che ricevono doppia terapia antiaggregante, è stata osservata una riduzione statisticamente significativa del sanguinamento gastrointestinale a seguito di terapia con PPI non risulta esservi un interazione fra PPI e clopidogrel clinicamente significativa dal punto di vista cardiovascolare questi risultati non escludono la possibilità di una differenza clinicamente rilevabile in termini di eventi cardiovascolari a causa dell uso di PPI.

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65 Characteristics of patients being at high or low risk for suffering Stent Thromboses after withdrawal of antiplatelet drugs

66 Provvedimenti per ridurre l impatto del rischio emorragico un sanguinamento minore deve essere gestito preferibilmente senza sospendere il trattamento attivo L evenienza di un sanguinamento maggiore comporta la necessità di sospendere e/o inibire entrambe le terapie (antiaggregante piastrinica e anticoagulante), a meno che non si possa controllare adeguatamente il sanguinamento con interventi specifici sull emostasi

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68 Corso di Aggiornamento Gestione dei Farmaci Antiaggreganti e Anticoagulanti in specifici Contesti Clinici 15 marzo 2011 Aula G-Ospedale Infermi Rimini Rischio Cardiovascolare e Rischio Emorragico Giancarlo Piovaccari, Nicoletta Franco Dipartimento Malattie Cardiovascolari

69 68 Million Americans with CVD Stroke 4.4 million PAD 8.4 million HTN 50 million Leading cause of death ww And many moredeaths to come!! annually in US Heart 16.8 million CHF 4.6 mill AMI 7.2 mill Angina 6.3 mill

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72 Platelet shape change and aggregation Figure 4

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74 Patofisiologia delle SCA SCA con persistente sopraelevazione ST (STEMI) SCA senza persistente sopraelevazione ST (NSTEMI)

75 Le Sd CORONARICHE ACUTE

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77

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80 Improvement in Mortality La riduzione della Mortalità per Infarto negli Anni Day Mortality (%) % Bed Riposo arest letto 15 Anni 80 13%-15% Defibrillazione Defibrillation Defibrillation 10 Hemodynamic Hemodynamic Monitoraggio monitoring monitoring 5 0 Anni 70 Emodinamico 5.0%- 6.5% Beta-bloccanti ASA, PTCA Aspirin, Aspirin, PTCA, PTCA, Lysis Lysis Fibrinolisi β-blockade β-blockade Pre-CCU Era CCU Era Pre UNITA CORONARICA UNITA CORONARICA PTCA, percutaneous transluminal coronary angioplasty. Reperfusion Era LA RIPERFUSIONE

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89 Aumento del rischio emorragico dosaggi elevati o eccessivi di farmaci antitrombotici durata del trattamento associazione di più farmaci antitrombotici cambio tra differenti farmaci anticoagulanti età avanzata ridotta funzione renale basso peso corporeo sesso femminile valori basali di emoglobina procedure invasive

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91 Bleeding ed incremento di Mortalità

92

93 Analisi multivariata per emorragie maggiori in pz con NSTEMI

94

95

96

97

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99 Bleeding Risk Score per PCI : Variabili cliniche

100 Severe bleeding occurred in 1.7% of the clopidogrel group versus 1.3% on placebo (P0.087) moderate bleeding occurred in 2.1% versus 1.3%, respectively ( P0.001) The risk of bleeding was greatest the first year

101 Kaplan-Meier curves for moderate or severe bleeding in the first year

102 Kaplan-Meier curves for moderate or severe bleeding after the 1 year in pts with no bleeding events in the 1 year

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104 JAMA 2004

105

106 Siti di Sanguinamento

107 Accesso per Procedura Interventistica: Femorale Radiale

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109

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111

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113 Siti di Sanguinamento non in Relazione PCI

114 *Puncture-site bleeding in 1489 pts who underwent a PCI Surgical bleeding in 2189 pts who had at least 1 surgical procedure.

115 Over one million PCI procedures are performed annually Antithrombotic therapy has become more aggressive (more complex lesions, Drug eluting stents) Current antithrombotic regimens may induce new gastrointestinal (GI) bleeding or exacerbate chronic episodic GI bleeding GI bleeding is associated with significant morbidity and mortality Prevention and management of GI bleeding in this patient population With the increasing adoption of radial access as compared to femoral artery approach, GI bleeding may be the most common type of bleeding associated with PCI

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117 Evaluation of bleeding risk, according to the presence or absence of predictors Baseline characteristics must be taken into account, particularly age, female sex and low body weight Renal function has to be evaluated by calculating creatinine clearance and/or GFR Previous history of bleeding must be recorded, and recent or ongoing bleeding must be searched for

118 Bleeding was once considered to be inherent to the therapeutic approach required to treat ACS patients Bleeding has a strong impact on outcome in terms of excess risk for death, MI and stroke at 30 days and long term Blood transfusion may also have a deleterious effect The interruption of active treatment, and activation of coagulation and inflammation in case of bleeding, as well as the depletion of 2,3-DPG and nitric oxide in preserved blood, and the stimulation of immunologic reactions after transfusion, may be some potential explanations

119 Prevention of bleeding has become equally as important as prevention of further ischaemic events in pts suffering from ACS The risk factors for bleeding are well known, and should be taken into account in the choice of appropriate drugs and procedures Attention should be paid to use of drugs or drug combinations, and dosages that may favour bleeding A radial approach should be favoured over a femoral approach, if an invasive strategy is required Renal function should be taken into account, as it is a major contributor to bleeding risk

120 Triplice Terapia

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122 Follow-Up Clinical Results in Studies Comparing Triple Therapy Versus Dual Antiplatelet Therapy in Pts Requiring Oral Anticoagulation and Undergoing PCI

123 Risk of all-cause mortality in patients receiving TT or DT

124 Risk of major bleeding in the first 6 months FUP

125 Terapia antiaggregante ed Inibitori della Pompa Protonica

126 1.1% 2.9% Event rate

127

128 Clopidogrel con o senza omeprazolo nella malattia coronarica: i risultati dello studio COGENT Nei pazienti con malattia coronarica che ricevono doppia terapia antiaggregante, è stata osservata una riduzione statisticamente significativa del sanguinamento gastrointestinale a seguito di terapia con PPI non risulta esservi un interazione fra PPI e clopidogrel clinicamente significativa dal punto di vista cardiovascolare questi risultati non escludono la possibilità di una differenza clinicamente rilevabile in termini di eventi cardiovascolari a causa dell uso di PPI.

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132 Characteristics of patients being at high or low risk for suffering Stent Thromboses after withdrawal of antiplatelet drugs

133 Provvedimenti per ridurre l impatto del rischio emorragico un sanguinamento minore deve essere gestito preferibilmente senza sospendere il trattamento attivo L evenienza di un sanguinamento maggiore comporta la necessità di sospendere e/o inibire entrambe le terapie (antiaggregante piastrinica e anticoagulante), a meno che non si possa controllare adeguatamente il sanguinamento con interventi specifici sull emostasi

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