slide1 n.
Download
Skip this Video
Loading SlideShow in 5 Seconds..
Giovanni Maria Santoro S. C. Cardiologia Ospedale San Giovanni di Dio Firenze PowerPoint Presentation
Download Presentation
Giovanni Maria Santoro S. C. Cardiologia Ospedale San Giovanni di Dio Firenze

Loading in 2 Seconds...

play fullscreen
1 / 35

Giovanni Maria Santoro S. C. Cardiologia Ospedale San Giovanni di Dio Firenze - PowerPoint PPT Presentation


  • 1120 Views
  • Uploaded on

Gestione del paziente con stent coronarico. Il mantenimento della doppia antiaggregazione a lungo termine. Giovanni Maria Santoro S. C. Cardiologia Ospedale San Giovanni di Dio Firenze. Efficacy of Dual Antiplatelet Therapy in Reducing Coronary Events after Stenting.

loader
I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
capcha
Download Presentation

PowerPoint Slideshow about 'Giovanni Maria Santoro S. C. Cardiologia Ospedale San Giovanni di Dio Firenze' - nanette


An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript
slide1

Gestione del paziente con stent coronarico. Il mantenimento della doppia antiaggregazione a lungo termine

Giovanni Maria Santoro

S. C. Cardiologia

Ospedale San Giovanni di Dio

Firenze

slide3

Early stent thrombosis in patients treated with BMS

Subacute stent thrombosis

24 h - 1 month

Acute stent thrombosis < 24 h

Cutlip et al. Circulation 2001;103:1967-71

slide4

Stent Thrombosis of DES

Data from a large two institutional cohort study

Cumulative incidence at 3 yrs 2.9%

Predictors of stent thrombosis

ACS HR 2.28 95% CI 1.29-4.03

Diabetes HR 2.07 95% CI 1.07-3.83

Daemen J et al. Lancet 2007;369:667-668

independent predictors of stent thrombosis
Independent predictors of stent thrombosis

Iakovou I, Colombo A, et al. JAMA 2005; 293:2126-30

slide9

Long-term dual antiplatelet therapy

Main open issues

  • Clopidogrel low responsiveness
  • Perioperative management
  • Chronic oral anticoagulation
  • Interaction with PPIs
slide11

Definite/Probable DES thrombosis at 6-month FU

  • 804 unselected consecutive pts with CAD (2/3 UA/STEMI) with DES implanted, on ASA and clopidogrel (600 mg loading dose + 75 mg/day chronically for almost six months)

P < .0001

% stent

thrombosis

8.6 (n=9)

3.1 (n=25)

2.3 (n=16)

Clop-nonResp

(n=105, 13%)

Clop-Resp

(n=699, 87%)

All pts

(n=804)

Buonamici et al. J Am Coll Cardiol 2007;49:2312

slide13

Long-term dual antiplatelet therapy

Main open issues

  • Clopidogrel low responsiveness
  • Perioperative management
  • Chronic oral anticoagulation
  • Interaction with PPIs
the perioperative dilemma
The perioperative dilemma

Risk of discontinuing antiplatelet therapy and increasing the possibility of perioperative stent thrombosis

Risk of continuing antiplatelet therapy and increasing the possibility of surgical bleeding

slide15

Coronary stent thrombosis and noncardiac surgery

  • noncardiac surgery increases the risk of stent thrombosis
  • early surgery carries significantly greater risk than delayed surgery
  • the risk increases when antiplatelet therapy is discontinued
slide16

DELAY SURGERY

ACC/AHA 2007 Guidelines on Perioperative Cardiovascular Evaluation and Care for Noncardiac Surgery

minimize the risk of stent thrombosis
MINIMIZE THE RISK OF STENT THROMBOSIS

Continue dual antiplatelet therapy

during and after surgery

Risk of bleeding

Continue aspirin, stop clopidogrel and

restart it soon after surgery

Stop clopidogrel and aspirin and “bridge”

with a short-acting GP IIb-IIIa inhibitor

Heparin probably ineffective because stent thrombosis is primarily a platelet-mediated phenomenon.

slide18

Long-term dual antiplatelet therapy

Main open issues

  • Clopidogrel low responsiveness
  • Perioperative management
  • Chronic oral anticoagulation
  • Interaction with PPIs
the triple dilemma of triple therapy
The triple dilemma of triple therapy

Risk of discontinuing clopidodrel and increasing the possibility of stent thrombosis

Risk of continuing warfarin + aspirin

+ clopidogrel and increasing the possibility of bleeding

Risk of discontinuing warfarin and increasing the possibility of stroke or thromboembolic events

triple therapy and major bleeding
Triple therapy and major bleeding

@ ≥ 12 months

13.3%

@ 30 days

6.0%

@ 6 months

13.3%

Rubboli et al. Ann Med 2008;40:428-36

slide21

What to do in patients with DES who need warfarin?

DO NOT STOP CLOPIDOGREL PREMATURELY

  • Add warfarin to clopidogrel and aspirin if < 1 month after BMS or < 1 year after DES implantation.
  • Limit the time of triple therapy as much as possible, containing aspirin dose to ≤100 mg and targeting INR to 2.0-2.5.
  • A combination of warfarin and one antiplatelet agent seem to be a better choice for long-term treatment after stent implantation.
  • Since the most frequent bleeding site is gastro-intestinal, strategies to reduce GI events are recommended.
slide22

Long-term dual antiplatelet therapy

Main open issues

  • Clopidogrel low responsiveness
  • Perioperative management
  • Chronic oral anticoagulation
  • Interaction with PPIs
clopidogrel and ppis the ocla study
Clopidogrel is a prodrug; requires conversion by the liver primarily via CYP3A4 and CYP2C19 to an active metabolite

PPIs are strong inhibitors of CYP2C19 activity

Clopidogrel and PPIs – The OCLA study

PRI: Platelet Reactivity Index – change at day 7 from baseline

clopidogrel

clopidogrel + omeprazole

p<0.0001

Gilard et al. J Am Coll Cardiol 2008;51:256-60.

slide25

Risk of All-Cause Mortality and Recurrent ACS

in Patients Taking Clopidogrel and PPI

Of 8205 patients with ACS taking clopidogrel after hospital discharge,

63.9% (n=5244) were prescribed PPI at discharge

Clopidogrel + PPI

Clopidogrel / noPPI

Ho et al. JAMA. 2009;301(9):937-944.

slide26

The COGENT Trial

  • Multicenter, international, randomized, double-blind, placebo-controlled trial
  • Comparison of a fixed-dose combination of clopidogrel (75 mg) and omeprazole (20 mg), with clopidogrel (75 mg) alone.
  • All patients were to receive enteric coated aspirin at a dose of 75 to 325 mg.
  • 3627 patients included, median follow-up 133 days (max 366 days)
slide27

Placebo: 67 events, 1821 at riskTreated: 69 events, 1806 at risk

HR = 1.0295% CI = 0.70; 1.51

Adjustment through Cox Proportional Hazards ModelAdjusted to Positive NSAID Use and Positive H. Pylori Status

slide28

HR = 0.9695% CI = 0.59; 1.56

Placebo: 37 events, 1851 at riskTreated: 36 events, 1839 at risk

Adjustment through Cox Proportional Hazards ModelAdjusted to Positive NSAID Use and Positive H. Pylori Status

slide29

HR = 0.9595% CI = 0.59; 1.55

Placebo: 67 events, 1821 at riskTreated: 69 events, 1806 at risk

Adjustment through Cox Proportional Hazards ModelAdjusted to Positive NSAID Use and Positive H. Pylori Status

slide30

HR = 0.5595% CI = 0.36; 0.85

p=0.007

Placebo: 67 events, 1895 at riskTreated: 38 events, 1878 at risk

conclusions
Conclusions
  • COGENT is the first, randomized assessment of clopidogrel and PPIs on clinical events
  • The data provide strong reassurance that there is no clinically relevant adverse cardiovascular interaction between clopidogrel and omeprazole
  • The results support the use of prophylactic PPIs, although the optimal strategy to reduce GI events in patients on antithrombotic therapy is still needed to define.
slide33

Primary endpoint stratified by use of a PPI

PPI use at randomization (n= 4529)

Clopidogrel

Prasugrel

CV death, MI or stroke

CLOPIDOGREL PPI vs no PPI: Adj HR 0.94, 95% CI 0.80-1.11

PRASUGREL PPI vs no PPI: Adj HR 1.00, 95% CI 0.84-1.20

Days

O’Donoghue ML, Braunwald E, Antman EM, et al. Lancet. 2009.

major bleeding risk triple therapy vs double therapy
Major bleeding risk Triple therapy vs Double therapy

Major bleeding Relative Risk 4.16 (95% CI 2.08-8.33)

Sourgounis et al. Circulation 2009;119:1682-88

slide35

Noncardiac surgery and risk of stent thrombosis

  • incomplete endhotelialization of the stent
  • rebound after interruption of antiplatelet therapy

- increased platelet adhesion and aggregation

- increased inflammatory prothrombotic state

  • increased prothrombotic and inflammatory state associated with surgery

- sympathetic activation

- increased inflammatory mediator release

- increased platelet adhesiveness and persistently high platelet counts

- increase release of procoagulant factors

- decreased/impaired fibrinolysis