oral anticoagulants sao paulo
TRANSCRIPT
Oral AnticoagulantsOral Anticoagulants
Antonio Raviele, MD, FESC, FHRS Antonio Raviele, MD, FESC, FHRS
SOBRAC 2015, Sao Paulo - Brazil, 4-6 November 2015 SOBRAC 2015, Sao Paulo - Brazil, 4-6 November 2015
ALFA – Alliance to Fight Atrial fibrillation, Mestre – Venice, ItalyALFA – Alliance to Fight Atrial fibrillation, Mestre – Venice, Italy
• Rationale for the use of OACs in AF pts• Different types of OACs• Clinical results for the prevention of TE • Net clinical benefit of the different OACs• Indications to antithrombotic treatment• Which OAC to start?• Which NOAC to prefer?
Main IssuesMain Issues
Ischemic Areas
Cerebral embolism as complication of AF
AF 4,5%AF 4,5%
Controls 0,2% - 1,4%Controls 0,2% - 1,4%
Annual Incidence in pts with AFAnnual Incidence in pts with AF
AF & Stroke
(The SPAF Investigators. AIM 1992; 116: 1 – 5)(The SPAF Investigators. AIM 1992; 116: 1 – 5)
Strokes related to Afib are more severe
The European Community Stroke Project
Lamassa M et al. Stroke (2001) 32: 392-398
Multi-centre, multi-national hospital-based registry involving 4462 patients hospitalized for first stroke
AFib diagnosed in 803 stroke patients (18%)
At 3 months, 32.8% of stroke patients with AFib were dead vs 19.9% of stroke patients without AFib
AFib increased by approximately 50% the probability of remaining disabled
AFib is Associated with Progressive Risk of StrokeAFib is Associated with Progressive Risk of Stroke• Independent predictor of stroke recurrence and severityIndependent predictor of stroke recurrence and severity
Simons, LA et al. Stroke (1998) 29: 1341
Cum
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ive
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rd o
f fat
al s
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1000
0.01
0.02
0.04
0.050.05
0.03
9080706050403020100
Months of follow-up
AF Present
AF Absent
• To teduce the risk of thromboembolic events
when this risk outweighs the risk of bleeding
associated with the use of OACs.
Rationale for OACs in AFRationale for OACs in AF
• Rationale for the use of OACs in AF pts• Different types of OACs• Clinical results for the prevention of TE • Net clinical benefit of the different OACs• Indications to antithrombotic treatment• Which OAC to start?• Which NOAC to prefer?
Main IssuesMain Issues
• Vitamin K Antagonists (VKA)
• No Vitamin K Antagonists OACs (NOACs) or
Direct OACs (DOACs)
Different types of OACsDifferent types of OACs
• Vitamin K Antagonists, such as warfarin, are the
traditional OACs and until 2009 have been the only
class of OACs available.
Vitamin K AntagonistsVitamin K Antagonists
Point of action of VKA in the coagulation cascade.
Steffel J , Braunwald E Eur Heart J 2011;32:1968-1976
• The Non-VKA OACs (NOACs) or Direct OACs
(DOACs) are new compounds developed in the recent
years.
NOACs or DOACsNOACs or DOACs
Point of action of novel oral anticoagulants in the coagulation cascade.
Steffel J , Braunwald E Eur Heart J 2011;32:1968-1976
• Rationale for the use of OACs in AF pts• Different types of OACs• Clinical results for the prevention of TE • Net clinical benefit of the different OACs• Indications to antithrombotic treatment• Which OAC to start?• Which NOAC to prefer?
Main IssuesMain Issues
Hart RG, et al. Ann Intern Med. 2007; 146: 857-867
- 64%
Adjusted-Dose Warfarin Compared with Placebo or No Treatment*
------
Hart RG, et al. Ann Intern Med. 2007; 146: 857-867
Safety Outcomes for Major Antithrombotic Comparisons*
Limitations of VKA therapyLimitations of VKA therapy
Ansell J, et al. Chest 2008;133;160S-198S. Umer Ushman MH, et al. J Interv Card Electrophysiol 2008;22:129-137.Nutescu EA, et al. Cardiol Clin 2008;26:169-187.
This explains
• the low use and the high discontinuation
rate of warfarin in the real world,
• the inadequate level of anticoagulation
reached in many patients
Underuse of warfarinUnderuse of warfarin
Management of AF in clinical practice: Management of AF in clinical practice: VKA prescriptionVKA prescription
N=11.409ATRIA Cohort, USA
Go AS, et al.JAMA 2003;290:2685
N=5.333EuroHeart SurveyNieuwlaat R, et al.
Eur Heart J 2005;26:2422
N=23.657Medicare Cohort, USABirman-Deych E, et al.Stroke 2006;37:1070
No OACs VKA
55%67%64% 55%67%64%
Mean % of Time spent in Therapeutic Range (TTR): INR 2.0-3.0
Hallgreen CE et al. Pharmacoepidemiol Drug Saf. 2014; ;23: :974-83
Wallentin L et al. The Lancet 2010; 376, 975-983
Mean % of TTR in RE-LYCountry- based variation in average TTR
Verheugt FWA et al. The Lancet 2015; 386, 303-310
The 4 large RCTs comparing NOACs with warfarin for stroke prevention in AF (71.683 pts)
Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a
meta-analysis of randomised trials
Christian T Ruff, Robert P Giugliano, Eugene Braunwald, Elaine B Hoffman, Naveen Deenadayalu, Michael D Ezekowitz, A John Camm, Jeffrey I Weitz, Basil S Lewis, Alexander
Parkhomenko, Takeshi Yamashita, Elliott M Antman.
The Lancet 2014; 383: 955-962
Ruff CT et al. The Lancet 2014; 383: 955-962
Stroke or Systemic Embolic Events
Secondary efficacy and safety outcomes
Ruff CT et al. The Lancet 2014; 383: 955-962
Advantages of therapy with NOACsAdvantages of therapy with NOACs
Ruff CT et al. The Lancet 2014; 383: 955-962
Ansell J Circulation 2012;125:165-170
• Rationale for the use of OACs in AF pts• Different types of OACs• Clinical results for the prevention of TE • Net clinical benefit of the different OACs• Indications to antithrombotic treatment• Which OAC to start?• Which NOAC to prefer?
Main IssuesMain Issues
Should this patient be treated with OACsShould this patient be treated with OACs
??
Critical questionCritical question
OAC / Net Clinical BenefitOAC / Net Clinical Benefit
Potential benefit of ischemic
stroke prevention
Potential risk of serious
bleeding, in particular ICH
OAC / Net Clinical BenefitOAC / Net Clinical Benefit
(Isoff OAC – Ison OAC) – 1.5 x (ICHon OAC –ICHon OAC)
number of IS avoided by OACs - number of ICH attributable to OACs x 1.5 number of IS avoided by OACs - number of ICH attributable to OACs x 1.5
to account for the generally more disastrous effects of an intracranial bleed compared with an ischemic stroke
Friberg L, et al. Circulation 2012; 125: 2298-2307
Circulation 2012; 125: 2298-2307
Thromb Haemost 2011; 106: 739-749
Thromb Haemost 2012; 107: 584-589
Net Clinical Benefit for Oral Anticoagulation, Aspirin, or No Therapy in Nonvalvular Atrial Fibrillation Patients With 1 Additional Risk Factor of the CHA2DS2-VASc Score (Beyond Sex).Lip GY, Skjøth F, Rasmussen LH, Nielsen PB, Larsen TB.
J Am Coll Cardiol. 2015 ; 66: 488-90.
Olesen JB et al. Thromb Haemost 2011; 106: 739-749
Net Clinical Benefit for Oral Anticoagulation, Aspirin, or No Therapy in Nonvalvular Atrial Fibrillation Patients With 1 Additional Risk Factor of the CHA2DS2-VASc Score (Beyond Sex)
Lip GYH et al. J Am Coll Cardiol. 2015; 66: 488-490.
Banerjie A et al. Thromb Haemost 2012; 107: 584-589
Stroke rate per yearStroke rate per year
Threshold for starting OAC therapyThreshold for starting OAC therapy
taking into account that NOACs reduce by 50% the
annual incidence of ICH compared to warfarin
Warfarin: 1.7%Warfarin: 1.7%NOACs: 0.9% NOACs: 0.9%
• Rationale for the use of OACs in AF pts• Different types of OACs• Clinical results for the prevention of TE • Net clinical benefit of the different OACs• Indications to antithrombotic treatment• Which OAC to start?• Which NOAC to prefer?
Main IssuesMain Issues
Lip GYH, Lane DA. JAMA 2015; 313:1950-1962
Algorithm for Risk Stratification and Selection of Anticoagulation Therapy for Stroke Prevention in AF
• Rationale for the use of OACs in AF pts• Different types of OACs• Clinical results for the prevention of TE • Net clinical benefit of the different OACs• Indications to antithrombotic treatment• Which OAC to start?• Which NOAC to prefer?
Main IssuesMain Issues
Figure 1. Percent of patients free from stroke over time, stratified by time spent in therapeutic range (INR 2.0–3.0).
FD Richard Hobbs et al. European Journal of Preventive Cardiology 2015;2047487315571890
Lip GYH, Lane DA. JAMA 2015; 313:1950-1962
Lip GYH, Lane DA. JAMA 2015; 313:1950-1962
Algorithm for Risk Stratification and Selection of Anticoagulation Therapy for Stroke Prevention in AF
• Rationale for the use of OACs in AF pts• Different types of OACs• Clinical results for the prevention of TE • Net clinical benefit of the different OACs• Indications to antithrombotic treatment• Which OAC to start?• Which NOAC to prefer?
Main IssuesMain Issues
Choice of the NOAC
No head-to-head comparisons exist between the different NOACs
So it is difficult to provide definitive recommendations on which
NOAC should be used in the single patient.
Indeed, NOACs are all individually noninferior to warfarin in terms
of efficacy for stroke prevention in patients with AF
However, some patient and drug characteristics may help in
decision making
Choosing the right drug to fit the patient when selecting oral anticoagulation for stroke prevention in atrial fibrillation
Shields AM, Lip GYH. Journal of Internal Medicine 2015; 278,:1-18
Conclusions (1)
• VKA are very effective drugs in preventing TEE in pts with AF.
• NOACs are at least as effective (if not more effective) than VKA,
and associated with significantly lower risk of serious bleeding, i.e
intracranial hemorrhages.
• The favorable net clinical benefit of the different OACs prompts
their use in the majority of pts with AF, with the only exception of
those at low risk of stroke, i.e males with CHA2DS2-VASc score = 0
and females with CHA2DS2-VASc score = 1.
Conclusions (2)
• The SAME-TT2R2 score system may be used to decide which OAC
(warfarin or NOACs) to start in newly diagnosed non anticoagulated
pts.
• Although no head-to-head comparisons exist between the different
NOACs, some patient and drug characteristics may help in selecting
which drug to use in single patients.