Διαρθρωτική Πολιτική 2014 -2020 Νέοι Κανονισμοί ΕΥΣΣΑΑΠ - Ιούλιος 2012
Νέοι αλόριθμοι xκίμησης θρομβο xμβολικού και...
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Νέοι αλγόριθμοι εκτίμησης θρομβοεμβολικού και αιμορραγικού κινδύνου σε ασθενείς με κολπική μαρμαρυγή Ιωάννης Α. Χαβελές, MD A‘ Kαρδιολογικό τμήμα Γ.Ν.Α " Ο Ευαγγελισμός "
Transcript of Νέοι αλόριθμοι xκίμησης θρομβο xμβολικού και...
Νέοι αλγόριθμοι εκτίμησης
θρομβοεμβολικού και αιμορραγικού
κινδύνου σε ασθενείς με κολπική
μαρμαρυγή
Ιωάννης Α. Χαβελές, MDA‘ Kαρδιολογικό τμήμα
Γ.Ν.Α " Ο Ευαγγελισμός "
Af epidemiology
• From a public health perspective, Af is the most important cardiac arrhythmia
• One in four people aged 55 years or older can be expected to develop AF in their lifetime; its prevalence increasing from 0.3% to those under 55 years to 10% in those over 85 years of age
• The most devastating consequence of AF is stroke, with AF patients overall having a risk fivefold that of an age- and sex-matched patient in sinus rhythm
Atrial fibrillation: profile and burden of an evolving epidemic in the 21st century.Ball J, Carrington MJ, McMurray JJ, StewartS.Int J Cardiol. 2013 Sep;167(5):1807-24. Epub 2013
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Miyakasa Y, et al. Circulation. 2006; 114:119-125.
Atrial Fibrillation U.S. Prevalence
16 millionUS
Prevalence
1 in 4 lifetime risk in men and women ≥ 40 years old
Scoring Systems in Atrial Fibrillation
• Given that anticoagulant therapy has both risks (principally bleeding) and benefits (a reduced risk of thrombosis).
• Many authors have attempted to produce scoring systems which estimate the risks of these outcomes
• No one scoring system is universally accepted or highly predictive (in individual patients)
Stroke Risk in Atrial Fibrillation Working Group. Stroke. 2008 Jun;39(6):1901-10. Pub Med PMID: 18420954.
Stroke Risk Predictor Scoring (SRPS)
• A variety of systems have been published• Newer scores are under examination
• All use selected clinical characteristics to predict the risk of stroke
• Most widely used is the CHA2DS2-VASc score
• All scores provide a rough estimate of risk of thrombosis in a population at similar risk as patient being reviewed
Stroke Risk in Atrial Fibrillation Working Group. Stroke. 2008 Jun;39(6):1901-10. Pub Med PMID: 18420954.
Nonvalvular Atrial Fibrillation
Prior
Stroke/TIAAge
> 75 years
Hypertension Female Diabetes Heart Failure LVEF
Hart RG et al. Neurology 2007; 69: 546.
Stroke Rates Without AnticoagulationAccording to Isolated Risk Factors
Part I
STROKE SCORES
CHADS2: Risk of Stroke2001-ACC, AHA, Canadian CS
able to select moderate and high risk pts but 2% risk in score 0
CHADS2Score
# Patients(n = 1733)
# Strokes(n = 94)
NRAF Crude Stroke Rate per 100 Patient-yrs
NRAF Adjusted Stroke Rate
(95% CI)†
0 120 2 1.2 1.9 (1.2-3.0)
1 463 17 2.8 2.8 (2.0-3.8)
2 523 23 3.6 4.0 (3.1-5.1)
3 337 25 6.4 5.9 (4.6-7.3)
4 220 19 8.0 8.5 (6.3-11.1)
5 65 6 7.7 12.5 (8.2-17.5)
6 5 2 44.0 18.2 (10.5-27.4)
Scoring: 1 point: Congestive heart failure, HTN, < 75 years, and DM2 points: Stroke history or transient ischemic attack† Expected stroke rate per 100 pt-yrs from the exponential survival model, assuming aspirin not taken
Gage BF, Waterman AD, Shannon W, Boechler M, Rich MW, Radford MJ. JAMA. 2001 Jun 13;285(22):2864-70. Pub Med PMID: 11401607.
CHA2DS2-VASc
Lip GY, Nieuwlaat R, Pisters R, Lane DA, Crijns HJ. Chest. 2010 Feb;137(2):263-72. Pub Med PMID: 19762550.
Risk Factor Score
Congestive heart failure/LV dysfunction 1
Hypertension 1
Age ≥ 75 y 2
Diabetes mellitus 1
Stroke/TIA/TE 2
Vascular disease (prior
myocardial infarction, peripheral artery disease, or aortic plaque)1
Age 65-74 y 1
Sex category(i.e. female gender)
1
2009 Birmingham Schema Expressed as a Point-Based Scoring SystemIdentifying trully lower riskESC+ASIA PASIFIC HRS
LV = left ventricular; TE = thromboembolism
CHA2DS2-VASc
CHA2DS2-VASc Score #
#TEEvents
TE Rate During 1 yr (95% CI)
TE Rate During 1 yr, Adjusted for
Aspirin RX
0 103 0 0% (0-0) 0%
1 162 1 0.6% (0.0-3.4) 0.7%
2 184 3 1.6% (0.3-4.7) 1.9%
3 203 8 3.9% (1.7-7.6) 4.7%
4 208 4 1.9% (0.5-4.9) 2.3%
5 95 3 3.2% (0.7-9.0) 3.9%
6 57 2 3.6% (0.4-12.3) 4.5%
7 25 2 8.0% (1.0-26.0) 10.1%
8 9 1 11.1% (0.3-48.3) 14.2%
9 1 1 100% (2.5-100) 100%
Total 1,084 25 P Value for trend 0.003
Lip GY, Nieuwlaat R, Pisters R, Lane DA, Crijns HJ. Chest. 2010 Feb;137(2):263-72. Pub Med PMID: 19762550.
Stroke or Other TE at One Year
CHA2DS2-VASc and CHADS2 Score 0–1
1 Year Follow-up 12 Years Follow-up
Person Yrs Events Stroke rate (95%CI) Person Yrs Events Stroke rate (95%CI)
CHADS2 score 0–1 40,272 1,405 3.49 (3.31–3.68) 187,200 4,599 2.46 (2.39–2.53)
CHA2DS2-VASc = 0 6,919 58 0.84 (0.65–1.08) 39,500 299 0.76 (0.68–0.85)
CHA2DS2-VASc = 1 8,880 159 1.79 (1.53–2.09) 45,926 662 1.44 (1.34–1.56)
CHA2DS2-VASc = 2 11,863 435 3.67 (3.34–4.03) 51,595 1,489 2.89 (2.74–3.04)
CHA2DS2-VASc = 3 11,473 660 5.75 (5.33–6.21) 45,799 1,933 4.22 (4.04–4.41)
CHA2DS2-VASc = 4 1,137 93 8.18 (6.68–10.02) 4,380 216 4.93 (4.32–5.64)
CHADS2 score = 0 17,327 275 1.59 (1.41–1.79) 92,531 1182 1.28 (1.21–1.35)
CHA2DS2-VASc = 0 6,919 58 0.84 (0.65–1.08) 39,500 299 0.76 (0.68–0.85)
CHA2DS2-VASc = 1 6,811 119 1.75 (1.46–2.09) 35,079 504 1.44 (1.32–1.57)
CHA2DS2-VASc = 2 3,347 90 2.69 (2.19–3.31) 16,710 353 2.11 (1.90–2.34)
CHA2DS2-VASc = 3 250 8 3.20 (1.60–6.40) 1,242 26 2.09 (1.43–3.07)
CHADS2 Score = 1 22,945 1,130 4.92 (4.65–5.22) 94,669 3417 3.61 (3.49–3.73)
CHA2DS2-VASc = 1 2,069 40 1.93 (1.42–2.64) 10,847 158 1.46 (1.25–1.70)
CHA2DS2-VASc = 2 8,516 345 4.05 (3.65–4.50) 34,885 1136 3.26 (3.07–3.45)
CHA2DS2-VASc = 3 11,223 652 5.81 (5.38–6.27) 44,557 1907 4.28 (4.09–4.48)
CHA2DS2-VASc = 4 1,137 93 8.18 (6.68–10.02) 4,380 216 4.93 (4.32–5.64)
Refines stroke risk stratification in AF patients: nationwide cohort
Olesen JB, Torp-Pedersen C, Hansen ML, Lip GY. Thromb Haemost. 2012 Jun;107(6):1172-9. Pub Med PMID: 22473219.
NEWER STROKE SCORES
• R2 CHADS2
• ATRIA
• GARFIELD-AF score
• ABC
• mCHA2DS2-VASc etc.
I. R2 CHADS2 score• Renal dysfunction was incorporated in the R2CHADS2 risk score by adding
2 additional points for eGFR<60/ml/min/1.73 m2
• ROCKET-AF 2012
II. ATRIA SCOREanticoagulation and risk factor in atrial fibrillation-2013
Rate of stroke/systemic embolismaccording to CHA2DS2-VASc score of
0 versus 1-9:
0.2% 1.1%
III. GARFIELD-AF (Global anticoagulation registry in the field)
• Data from 38,984 patients from the GARFIELD-AF registry, Fox et al compared the predictive ability of the GARFIELD-AF score to that of the CHA2DS2-VASc score
• Better predicted all-cause mortality (0.78 C vs. 0.66) and haemorrhagic stroke/major bleeding (0.67 C vs. 0.61 C) whereas its predictive ability of ischaemic stroke/embolism was similar (both 0.63)
• However, for low-risk patients, the GARFIELD-AF score had superior prediction ability for all-cause mortality (0.72 C statistic vs. 0.56 C statistic), ischaemic stroke/systemic embolism (0.62 vs. 0.56), and haemorrhagic stroke/major bleeding (0.72 vs. 0.57)
IV. THE ABC SCORE
The ABC (Age, Biomarkers, Clinical history) stroke risk score: a biomarker-based risk score for predicting stroke in atrial fibrillation.
Age
Biomarkers (NT-proBNP, cTnI-hs)
Clinical history (prior stroke/TIA).
ABC SCORE (0-30)
ABC STROKE SCORE• The ABC-stroke score was well calibrated and yielded
higher c-indices than the widely used CHA2DS2-VASc score in both the derivation cohort (0.68 vs. 0.62, P < 0.001) and the external validation cohort (0.66 vs. 0.58, P < 0.001)
• Moreover, the ABC-stroke score consistently provided higher c-indices in several important subgroups.
• Subclinical cardiovascular dysfunction
• Dynamic risk factor/ monitoring.
Internal validation of the ABC-stroke score and comparison with CHA2DS2-VASc
• The ABC-stroke score that included cTnI-hsconsistently achieved higher c-indices when compared with the CHA2DS2-VASc score in subgroups without prior stroke (0.66 vs. 0.59, P , 0.001). It also achieved well in patients with a low time ( 65%) in therapeutic range (TTR) (0.67 vs. 0.62, P¼ 0.014).
• Within both low- and high-risk CHA2DS2-VASc score cohorts, the ABC-stroke risk score was well calibrated and further stratified patients into subgroups with observed 1-year event rates close to the 1-year predicted by the ABC-stroke score
Performance and Validation of a Novel Biomarker-Based Stroke Risk Score for Atrial Fibrillation
Jonas Oldgren, Ziad Hijazi, Johan Lindbäcket.al
http://dx.doi.org/10.1161/CIRCULATIONAHA.116.022802Published Ahead of Print: August 28, 2016
CONCLUSIONS• A novel risk score for predicting stroke or
systemic embolism using two biomarkers (NT-proBNP and cTn-hs) and information on age and prior stroke/TIA, named ABC-stroke score (Age, Biomarkers, Clinical history), was developed in a large cohort and validated in a smaller cohort of patients with AF.
• The ABC-stroke risk score consistently performed better than presently used clinically based risk scores in terms of risk prediction and risk stratification, and may provide improved decision support in patients with AF.
Part II
BLEEDIND SCORES
Bleeding Risk Scores
• Variety of scoring systems developed to predict risk of bleeding in patients initiating anticoagulants, as with stroke risk
• Less predictive than stroke risk scores, in general
• Each score incorporates clinical characteristics and provides estimate of risk of bleeding in a population similar to patients being considered
• Unclear whether to include risk scores in decision making for individual patients
Bleeding Risk Scores Widely Used in AF
• HAEMORR2HAGES
• HASBLED
• ATRIA Score
• mOBRI
• Shireman
• ORBIT
• NEWER
1.Gage BF, et al. Am Heart J. 2006 Mar;151(3):713-9. PMID: 16504638. Pub Med PMID:16504638.2.Pisters R, Lane DA, Nieuwlaat R, de Vos CB, Crijns HJ, Lip GY. Chest. 2010 Nov;138(5):1093-100. PMID:20299623.3.Fang MC, et al. J Am Coll Cardiol. 2011 Jul 19;58(4):395-401. Pub Med PMID:21757117.
Bleeding Risk Scores in AF
ATRIA HAS-BLED HEMORR2HAGES
Anemia1 3 Hypertension4 1Hepatic10 or Renal disease2
11
Severe renal disease2 3Abnormal Renal5 or Liver function6
11
Ethanol abuse 1
Age ≥75 yrs 2 Stroke 1 Malignancy 1
Any prior hemorrhage 1 Bleeding 1 Older Age (>75 yrs) 1
Hypertension3 1 Labile INR8 1Reduced platelet number or function11 1
Elderly (>65 yrs) 1 Rebleeding12 2
Drugs9 or Alcohol
11
Hypertension4 1
Anemia13 1
Genetic factors14 1
Excessive fall risk15 1
Stroke 1
Apostolakis S, Lane DA, Guo Y, Buller H, Lip GY. J Am Coll Cardiol 2012;60:000–000. 2012 Jul 24. [Epub ahead of print] Online Appendix. PMID: 22858389.
1. Hemoglobin <13 g/dl men; <12 g/dl women2. Estimated glomerular filtration rate <30 ml/min or dialysis-dependent3. Diagnosed hypertension4. Systolic blood pressure >160 mmHg5. Presence of chronic dialysis or renal transplantation or serum creatinine ≥200 mmol/L6. Chronic hepatic disease (eg cirrhosis) or biochemical evidence of significant hepatic derangement (eg bilirubin 2 x upper limit of normal, in
association with aspartate aminotransferase/alanine aminotransferase/alkaline phosphatase >3 x upper limit normal, etc.)8. Unstable/high INRs or poor time in therapeutic range (eg <60%)9. Concomitant use of drugs, such as antiplatelet agents, non-steroidal anti-inflammatory drugs, or alcohol abuse etc. 10. Cirrhosis, two-fold or greater elevation of AST or APT, or albumin <3.6 g/dl11. Platelets <75,000, use of antiplatelet therapy (eg daily aspirin) or NSAID therapy; or blood dyscrasia12. Prior hospitalization for bleeding13. Most recent hematocrit <30 or hemoglobin <10 g/dl14. CYP2C9*2 and/or CYP2C9*315. Alzheimer's dementia, Parkinson's disease, schizophrenia, or any condition predisposing to repeated falls
OBRI SCOREOutpatient Bleeding Risk Index
• age ≥65 years,
• previous stroke,
• gastro-intestinal bleed,
• ≥1 of the following comorbidities [recent MI, haematocrit <30%, creatinine >1.5 mg/dl, or diabetes mellitus] with 1 point for presence of each risk factor and 0 if absent.
• Low risk: 0, intermediate risk: 1–2, high risk: ≥3.
References : 1. Beyth RJ, Quinn LM, Landefeld CS. Prospective evaluation of an index for predicting the risk of major bleeding in outpatients treated with warfarin. Am J Med. 1998;105:91–9. 2. Aspinall SL, DeSanzo BE, Trilli LE, et al. Bleeding Risk Index in an anticoagulation clinic. Assessment by indication and implications for care. J Gen Intern Med. 2005 November; 20(11): 1008–1013.
SHIREMAN SCORE
=[0.49 × age ≥70] + [0.32 × female gender] + [0.58 × remote bleed] + [0.62 × recent bleed] + [0.71 × alcohol/drug abuse] + [0.27 × diabetes] + [0.86 × anaemia] + [0.32 × antiplatelet] with 1 point for the presence of each condition and 0 if absent. Low risk: ≤1.07, intermediate risk: >1.07 to <2.19, high risk: ≥2.19.
Major bleeding events by risk category in 4824 AF patients with HAS-BLED, ATRIA, Shireman, HEMORR2HAGES, mOBRI, and
ORBIT scores, in related to the derivate western population.
NEWER BLEEDING SCORES
• ORBIT
• ABC BLEEDING SCORE
• OTHER (eg NAIGA)
I. ORBIT SCORE• Among 7411 ORBIT-AF patients taking OAC, the rate of
major bleeding was 4.0/100 person-years. • The full continuous model (12 variables) and five-factor
ORBIT risk score (older age [75+ years], reduced haemoglobin/haematocrit/history of anaemia, bleeding history, insufficient kidney function, and treatment with antiplatelet) both had good ability to identify those who bled vs. not (C-index 0.69 and 0.67, respectively).
• These scores both had similar discrimination, but markedly better calibration when compared with the HAS-BLED and ATRIA scores in an external validation population from the ROCKET-AF trial.
The ORBIT bleeding score: a simple bedside score to assess bleeding risk in atrial fibrillation You have access (CC)Emily C. O'Brien, DaJuanicia N. Simon, DOI: http://dx.doi.org/10.1093/eurheartj/ehv476 ehv476
ORBIT
The ORBIT bleeding score: a simple bedside score to assess bleeding risk in atrial fibrillation You have access (CC)Emily C. O'Brien, DaJuanicia N. Simon, DOI: http://dx.doi.org/10.1093/eurheartj/ehv476 ehv476
SPECIFITY
The ORBIT bleeding score: a simple bedside score to assess bleeding risk in atrial fibrillation You have access (CC)Emily C. O'Brien, DaJuanicia N. Simon, DOI: http://dx.doi.org/10.1093/eurheartj/ehv476 ehv476
II. ABC BLEEDING SCORE• The ABC bleeding risk score achieved a higher c-
index than the two comparator scores at 0.71 vs 0.62 for the HAS-BLED and 0.68 for the ORBIT.
• The ABC bleeding score also outperformed the HAS-BLED and ORBIT scores concerning the predictive value of intracranial hemorrhages.
• The ABC-bleeding score, using age, history of bleeding, and three biomarkers (haemoglobin, cTn-hs, and GDF-15 or cystatin C/CKD-EPI) should be useful as decision support on anticoagulation treatment in patients with atrial fibrillation.
Dr Ziad Hijazi,Jonas Oldgren, Johan Lindbäck et al., on behalf of the ARISTOTLE and RE-LY Investigator The novel biomarker-based ABC (age, biomarkers, clinical history)-bleeding risk score for patients with atrial fibrillation: a derivation and validation study
LANCET volume 387, no 1003, p2302–2311, 4 June 2016
III. OTHER SCORES
Kobayashi N, Yamawaki M,Nakano M. et.al:
A new scoring system (DAIGA) for predicting
bleeding complications in atrial fibrillation patients after drug-eluting stent implantation with triple antithrombotic therapy
Int J Cardiol. 2016 Aug 22;223:985-991. doi: 10.1016/j.ijcard.2016.08.310. [Epub ahead of print].
CONCUSIONS• Novel risk scores for predicting stroke (SPRS),
systemic embolism and bleeding in patients with atrial fibrillation are under examination
• For SPRS CHAD2VASC2 is the most common score and modifiable and not modifiable risk factors for bleeding are used in anticoangulated patients
• The dynamic ABC-stroke risk score consistently performed better than presently used clinically based risk scores, in terms of risk prediction and risk stratification, and may provide improved decision support in patients with AF especially in several important subgroups.
Thank you for your attention!
