16 Maggio 2015
Camogli
“Caso Clinico”
Dott. Sergio Agosti
Cardiologo,
Ospedale Novi Ligure (AL)
www.docvadis.it/agostisergio
[email protected]
la storia del signor B.D.
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il signore ha 80 anni
è in ottima forma (peso 77 kg)
la memoria è così e così
accudisce la moglie paraplegica
la moglie gli raccomanda di andar dal dottore
anamnesi
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pregresso NSTEMI (5 anni prima) con FE normale
è iperteso controllato da un sartano (135/85 mm Hg)
diabetico in terapia con metformina (glicata 6.8%)
assume metoprololo 50 mg x 2, ASA 100 mg, atorvastatina 20 mg,
insufficienza renale III stadio (eCrCl 48 ml/min)
da una settimana lamenta modesta dispnea da sforzo
si rivolge al medico curante per il riscontro di «battito irregolare»
Il signor B. D.
Cosa prescrive il medico al paziente?
Domanda 1
Valgono le risposte multiple
• warfarin?
• esami ematochimici?
• visita cardiologica?
• visita cardiologica urgente?
• invio in PS?
• visita aritmologica con ECG?
Risposta1
• warfarin?
• esami ematochimici?
• visita cardiologica?
• visita cardiologica urgente?
• invio in PS?
• visita aritmologica con ECG
113 anni fa
113 anni fa
Un mese più tardi: l’ecg del signor B.D.
Go, A. S. et al. JAMA 2001;285:2370-2375.
Qual’è il CHADASVASC di questo paziente?
Domanda 2
Qual’è il CHA2DS2-VASc score di questo paziente?
Uomo
IRC III stadio
Peso: 80 kg
Iperteso
PA: 135/85 mmHg
Diabetico
NSTEMI con FE normale
80 anni
1.CHA2DS2-VASc = 1
2.CHA2DS2-VASc = 2
3.CHA2DS2-VASc = 3
4.CHA2DS2-VASc = 5
The CHA2DS2-VASc score of this patient
CHA2DS2-VASc1
Score
Congestive heart failure/LV dysfunction
1
Hypertension
1
Aged ≥75 years
2
Diabetes mellitus
1
Stroke/TIA/TE
2
Vascular disease (prior MI, PAD, or aortic
plaque)
1
Aged 65-74 years
1
Sex category (i.e. female gender)
1
Maximum score
9
LV: left ventricular; TIA: transient ischemic attack; INR: international normalized ratio; MI: myocardial infarction
aVascular disease includes myocardial infarction, complex aortic plaque, and peripheral artery disease
1. Lip et al. CHEST. 2010;137:263–272.
The CHA2DS2-VASc score of this patient
CHA2DS2-VASc1
Score
Congestive heart failure/LV dysfunction
1
Hypertension
1
Aged ≥75 years
2
Diabetes mellitus
1
Stroke/TIA/TE
2
Vascular disease (prior MI, PAD, or aortic
plaque)
1
Aged 65-74 years
1
Sex category (i.e. female gender)
1
Maximum score
9
LV: left ventricular; TIA: transient ischemic attack; INR: international normalized ratio; MI: myocardial infarction
aVascular disease includes myocardial infarction, complex aortic plaque, and peripheral artery disease
1. Lip et al. CHEST. 2010;137:263–272.
Risposta 2
Qual’è il CHA2DS2-VASc score di questo paziente?
Uomo
IRC III stadio
Peso: 80 kg
Iperteso
PA: 135/85 mmHg
Diabetico
NSTEMI con FE normale
80 anni
1.CHA2DS2-VASc = 1
2.CHA2DS2-VASc = 2
3.CHA2DS2-VASc = 3
4.CHA2DS2-VASc = 5
Cosa prescrive l’aritmologo a questo paziente?
Domanda 3
• enoxaparina + warfarin?
• warfarin?
• un NAO?
• ecocardiogramma?
• invio al centro TAO?
• cardioversione elettrica?
• amiodarone?
Risposta 2
• enoxaparina + warfarin?
• warfarin?
• un NAO?
• ecocardiogramma
• invio al centro TAO
• cardioversione elettrica
• amiodarone
Domanda numero zero
• perché non il dabigatran?
ESC 2012 Guideline recommendations1
CHA2DS2-VASc
Recommendation
0
No antithrombotic therapy
1
OAC therapy with
• Adjusted-dose VKA (INR 2–3); or
• A direct thrombin inhibitor (dabigatran); or
• An oral factor Xa inhibitor (e.g. rivaroxaban, apixaban)
…should be considered
≥2
OAC therapy with
• Adjusted-dose VKA (INR 2–3); or
• A direct thrombin inhibitor (dabigatran); or
• An oral factor Xa inhibitor (e.g. rivaroxaban, apixaban)
…is recommended
Class*
Level†
I
B
IIa
A
I
A
*Class of recommendation; †Level of evidence; OAC, oral anticoagulant
1. Camm et al. Eur Heart J 2012;33:2719–2747.
CHADS2VASc score
Fattori di rischio
tromboembolico
Punteggio
attribuito a
singolo fattore
Punteggio
CHA2DS2-VASC
complessivo
Rischio di ictus
annuo rapportato al
punteggio
complessivo
0
0
0%
C
Scompenso cardiaco
congestizio/disfunzione
ventricolare sinistra (<40%)
1
1
1.3%
H
Ipertensione arteriosa
1
2
2.2%
A2
Età ≥75 anni
2
3
3.2%
D
Diabete mellito
1
4
4.0%
S2
Ictus/TIA/tromboembolismo
2
5
6.7%
V
Malattia vascolare –pregresso
infarto miocardico,
arteriopatia periferica, placca
aortica
1
6
9.8%
A
Età 65-74 anni
1
7
9.6%
SC
Sesso femminile
8
6.7%
9
15.2%
1
Lip GYH et al. Chest.2010:137:263-72
ESC 2012 Guideline recommendations1
Recommendations for prevention of thromboembolism
in NVAF—NOACs
Class*
Level†
IIa
A
Where OAC is recommended, one of the NOACs, either:
• A direct thrombin inhibitor (dabigatran); or
• An oral factor Xa inhibitor (e.g. rivaroxaban, apixaban)
…should be considered rather than adjusted-dose VKA
(INR 2–3) for most patients with NVAF, based on their net clinical benefit
*Class of recommendation; †Level of evidence; OAC, oral anticoagulant
1. Camm et al. Eur Heart J 2012;33:2719–2747.
STROKE OR SYSTEMIC EMBOLISM
NNT 173
Ruff CT,Lancet, December 4, 2013
MAJOR BLEEDING
Ruff CT,Lancet, December 4, 2013
Dabigatran in numeri….
• 60000 pz nei trials
•2170 articoli - studi clinici (PUBMED)
•Almeno 260000 pz nei registri
(Minisentinel, Medicare, registro AHA)
•50000 pz in GLORIA
•Oltre 3 milioni di pz trattati nel mondo
Medicare analysis: results
Incidence rate per 1000 personyears
Adjusted HR
(95% CI)
Dabigatran
Warfarin
Ischaemic stroke
11.3
13.9
0.80 (0.67-0.96)
Intracranial haemorrhage
3.3
9.6
0.34 (0.26-0.46)
Major gastrointestinal
bleeding
34.2
26.5
1.28 (1.14-1.44)
Acute myocardial infarction
15.7
16.9
0.92 (0.78-1.08)
Mortality
32.6
37.8
0.86 (0.77-0.96)
Dabigatran was associated with a lower risk of ischaemic stroke, intracranial
haemorrhage and death than warfarin.
Risk of MI was similar for dabigatran and warfarin.
Primary findings for dabigatran are based on analysis of both 75 mg and 150 mg
together without stratification by dose. Warfarin is the reference group. CI = confidence
interval; HR = hazard ratio; MI = myocardial infarction;
Available at: www.fda.gov/Drugs/DrugSafety/ucm396470.htm (accessed May 2014)
Medicare analysis: results
Incidence rate per 1000 personyears
Adjusted HR
(95% CI)
Dabigatran
Warfarin
Ischaemic stroke
11.3
13.9
0.80 (0.67-0.96)
Intracranial haemorrhage
3.3
9.6
0.34 (0.26-0.46)
Major gastrointestinal
bleeding
34.2
26.5
1.28 (1.14-1.44)
Acute myocardial infarction
15.7
16.9
0.92 (0.78-1.08)
Mortality
32.6
37.8
0.86 (0.77-0.96)
Dabigatran was associated with a lower risk of ischaemic stroke, intracranial
haemorrhage and death than warfarin.
Risk of MI was similar for dabigatran and warfarin.
Primary findings for dabigatran are based on analysis of both 75 mg and 150 mg
together without stratification by dose. Warfarin is the reference group. CI = confidence
interval; HR = hazard ratio; MI = myocardial infarction;
Available at: www.fda.gov/Drugs/DrugSafety/ucm396470.htm (accessed May 2014)
Medicare analysis: results
Incidence rate per 1000 personyears
Adjusted HR
(95% CI)
Dabigatran
Warfarin
Ischaemic stroke
11.3
13.9
0.80 (0.67-0.96)
Intracranial haemorrhage
3.3
9.6
0.34 (0.26-0.46)
Major gastrointestinal
bleeding
34.2
26.5
1.28 (1.14-1.44)
Acute myocardial infarction
15.7
16.9
0.92 (0.78-1.08)
Mortality
32.6
37.8
0.86 (0.77-0.96)
Dabigatran was associated with a lower risk of ischaemic stroke, intracranial
haemorrhage and death than warfarin.
Risk of MI was similar for dabigatran and warfarin.
Primary findings for dabigatran are based on analysis of both 75 mg and 150 mg
together without stratification by dose. Warfarin is the reference group. CI = confidence
interval; HR = hazard ratio; MI = myocardial infarction;
Available at: www.fda.gov/Drugs/DrugSafety/ucm396470.htm (accessed May 2014)
Medicare analysis: results
Incidence rate per 1000 personyears
Adjusted HR
(95% CI)
Dabigatran
Warfarin
Ischaemic stroke
11.3
13.9
0.80 (0.67-0.96)
Intracranial haemorrhage
3.3
9.6
0.34 (0.26-0.46)
Major gastrointestinal
bleeding
34.2
26.5
1.28 (1.14-1.44)
Acute myocardial infarction
15.7
16.9
0.92 (0.78-1.08)
Mortality
32.6
37.8
0.86 (0.77-0.96)
Dabigatran was associated with a lower risk of ischaemic stroke, intracranial
haemorrhage and death than warfarin.
Risk of MI was similar for dabigatran and warfarin.
Primary findings for dabigatran are based on analysis of both 75 mg and 150 mg
together without stratification by dose. Warfarin is the reference group. CI = confidence
interval; HR = hazard ratio; MI = myocardial infarction;
Available at: www.fda.gov/Drugs/DrugSafety/ucm396470.htm (accessed May 2014)
EFFICACY AD SAFETY
SECONDARY ENDPOINTS
ICH NNT 141
Ruff CT, Lancet, December 4, 2013
Ictus emorragico (TF receptor)
Mackmann, Anesth Analg. 2009 May; 108(5):1447-52
The role of tissue factor and factor VIIa in hemostasis.
Stroke ed embolia sistemica
nell’insufficienza renale moderata
Hart R. et al. Nat. Rev. Nephrol. 2012;8:569
ESC 2012 Guideline recommendations1
*Class of recommendation; †Level of evidence; OAC, oral anticoagulant
1. Camm et al. Eur Heart J 2012;33:2719–2747.
RE-LY, ROCKET-AF, ARISTOTLE
Popolazioni studiate
6076
6015
6022
150mg BID
110mg BID
W
5619
20mg OD
15mg OD
1462
7081
W
8692
5mg BID
2.5mg BID
W
428
9081
Connolly et al. NEJM 2009; 361:1139-51; Patel et al. NEJM 2011; 365:883-91; Granger et al. NEJM 2011; 365:981-92; Fox et al. European Heart Journal
2011; 32:2387-2394
Lip, Thromb Haemost 2014; 111
Lip, Thromb Haemost 2014; 111
Lip, Thromb Haemost 2014; 111
Domanda 4
Il nostro paziente dovrà iniziare una terapia
anticoagulante per la FANV.
La sua CAD è stabile, ha avuto un NSTEMI 5 anni prima.
Il nostro paziente può sospendere l’ASA?
1. Si,
l’ASA può essere sospesa
2. No,
l’ASA deve essere continuata
Dabigatran: SCA
RE-LY®: analisi di sottogruppo per uso concomitante di antiaggreganti1,2
Nello studio RE-LY®:3,4
– Il 38.4% dei pazienti ha ricevuto un trattamento concomitante con ASA
oppure clopidogrel durante lo studio
– Il 4.5% dei pazienti sono stati trattati con ASA+clopidogrel
–
L’utilizzo concomitante di antiaggreganti aumenta il rischio di
sanguinamento maggiore di 1.6 volte in tutti i gruppi di trattamento
Il rischio assoluto è più basso con Dabigatran 110mg BID
I risultati del RE-LY con due dosaggi efficaci e sicuri consentono ai
medici di personalizzare la terapia nei singoli pazienti in rapporto ai loro
fattori di rischio ed alle loro preferenze
1. Douketis JD et al. Thromb Res 2011;127:513–7; 2. Johnson SG et al. Chest
2007;131:1500–7; 3. Connolly SJ et al. N Engl J Med 2009; 361:1139–51; 4.
Dans AL et al. Circulation 2013;127:634–40
EHRA guidance on concomitant ASA1
Stable CAD patients developing AF should receive anticoagulation,
depending on their CHA2DS2-VASc score
Anticoagulation without additional antiplatelet agents is considered
sufficient for most AF patients with stable CAD (acute coronary
syndrome ≥1 year ago; elective bare-metal stent ≥1 month; drugeluting stent ≥6 months)
The advantages of NOACs over VKA for NVAF are likely to be
preserved in stable CAD patients. NOACs may be an appropriate and
effective alternative to VKAs
1. Heidbüchel et al. Europace 2013;15:625–51.
Guidance from 2014 consensus document
(ESC / EHRA / EAPCI / ACCA / HRS / APHRS)1
In patients with stable vascular disease (e.g. with no acute ischaemic
events or PCI/stent procedure in the preceding 1 year), OAC
monotherapy (well-controlled VKA or a NOAC) should be used, and
concomitant antiplatelet therapy should not be prescribed on a
routine basis
Combination of OAC plus single antiplatelet therapy (preferably
clopidogrel 75 mg/day, or as an alternative, aspirin 75–100 mg/day) may
be sometimes continued in very selected cases, e.g. stenting of the left
main, proximal left anterior descending, proximal bifurcation, recurrent
MIs, etc
ESC: European Society of Cardiology; EHRA: European Heart Rhythm Association; EAPCI: European Association of Percutaneous
Cardiovascular Interventions; ACCA: European Association of Acute Cardiac Care; HRS: Heart Rhythm Society; APHRS: Asia-Pacific Heart
Rhythm Society
1. Lip et al. European Heart Journal; first published
online August 25, 2014.
Domanda 4
Il nostro paziente dovrà iniziare una terapia
anticoagulante per la FANV.
La sua CAD è stabile, ha avuto un NSTEMI 5 anni prima.
Il nostro paziente può sospendere l’ASA?
1. Si,
l’ASA può essere sospesa
2. No,
l’ASA deve essere continuata
Il signor B.D., sei mesi dopo?
Domanda 4
• TTR?
• esami ematochimici?
• visita cardiologica?
• cardioversione?
• terapia in atto?
• esami programmati?
Risposta 4
• TTR -> 57% (3 episodi di INR sotto i 2)
• esami ematochimici -> no
• visita cardiologica -> al quarto mese
• cardioversione -> no
• esami programmati -> ecg da sforzo
come finisce la storia
del signor B.D.?
• dice di avere sempre un po’ di affanno
• la memoria è molto peggiorata
• ha interrotto volontariamente l’anticoagulazione
• ha ripreso l’ASA
• non si presenta alla visita di controllo
• nessuno gli ha mai consigliato un NAO…
A 6 mesi dall’inizio della storia
GRAZIE PER L’ATTENZIONE
www.docvadis.it/agostisergio