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Semelhante a Management of AF and Role of NOACs
Semelhante a Management of AF and Role of NOACs (20)
Mais de Dr Vivek Baliga
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Management of AF and Role of NOACs
- 1. Dr Vivek Baliga MRCP PhD MBA Cardiologist and Physician Baliga Diagnostics, Bangalore
- 2. AF is the most common arrhythmic disorder which generates abnormal electrical signals in the atria, causing them to contract irregularly and quickly. Types of AF : Paroxysmal AF : is a recurrent arrhythmia that returns to its normal sinus rhythm in a few minutes, hours, or days (but within 7 days of onset) without intervention Persistent AF: AF lasts for more than 7 days and does not resolve spontaneously, requiring medical intervention, e.g., pharmacological therapy or direct cardioversion Permanent AF: is used to describe cases of long-standing arrhythmia (i.e., a year or longer), where interventions to restore sinus rhythm (cardioversion) have failed or have not been attempted. Common symptoms for AF: • Palpitation • Mild Chest pain • Lightheadedness • Dyspnea • Syncope Camm et al, ESC guidelines 2010. Eur Heart J.
- 3. • Diabetes • Heart failure • Obesity • Coronary artery disease • Hypertension • Ageing • Genetic predisposition
- 6. Bang et al. Journal of Stroke 2014;16(2):73-80 By 2040, higher % of elder patients (>65 years) will be in Asia in comparison of developed countries By 2050, more adults with AF in Asia in comparison of US
- 7. Mathur R, et al. Heart 2013;99:1087–1092
- 8. Mathur R, et al. Heart 2013;99:1087–1092. doi:10.1136/heartjnl-2013-303767 Significant increase in the risk of stroke among South Asian but not black people compared to white people (CHADS2 score OR 1.42, CHA2DS2VASc score OR 1.67, 95% CI 1.02 to 2.73). An epidemiological study of 6292 AF patients from UK
- 9. Incidence of ICH in different ethnic groups on warfarin: 18,867 patients hospitalized with first-time AF Shen AY, et al. J Am Coll Cardiol 2007;50:309-315. White Black Hispanic Asian 0 1 2 3 4 5 6 7 INR 2-3 Hazard ratio (95% CI) p value White 55% 1 - Black 48% 2.05 (1.25-3.36) 0.005 Hispanic 54% 2.06 (1.31-3.24) 0.002 Asian 54% 4.06 (2.48-6.66) <0.0001 Hazard ratio 9
- 11. ESC 2016 guidelines for AF management (e.g., b-blockers, cardioversion)
- 14. CIRCULATIONAHA.114.013243Published online before print July 29, 2015 • Stroke is the most serious complication of AF and is more disabling • There is 5 fold and 17 fold increase in the risk of stroke due to non-valvular AF (NVAF) and valvular AF respectively
- 15. Benjamin EJ Circulation 1998;98;946-952 PMID: 9737513;
- 18. Circulation. 2014;129:000–000.) Recommendations for Prevention of Thromboembolism in Patients With AF Recommendation COR LOE Antithrombotic therapy based on shared decision-making, discussion of risks of stroke and bleeding, and patient’s preferences I C Antithrombotic therapy selection based on risk of thromboembolism I B CHA2DS2-VASc score recommended to assess stroke risk I B
- 19. HAS-BLED risk criteria Score Hypertension 1 Abnormal renal or liver function (1 point each) 1 or 2 Stroke 1 Bleeding 1 Labile INRs 1 Elderly (eg, age >65 years) 1 Drugs or alcohol (1 point each) 1 or 2 CHA2DS2-VASc criteria Score Congestive heart failure/ left ventricular dysfunction 1 Hypertension 1 Age ≥75 years 2 Diabetes mellitus 1 Stroke/transient ischaemic attack/TE 2 Vascular disease (prior myocardial infarction, peripheral artery disease or aortic plaque) 1 Age 65–74 years 1 Sex category (ie, female gender) 1 • Irrespective of the HAS-BLED, the patient should be anti-coagulated; if CHA2DS2VASc score is high. • If HAS-BLED score is high prefer lower dose of NOACs.
- 21. Many Challenges with VKAs????
- 22. If INR value is less than 2.0, then more chance of development of Stroke If INR value is more than 3.0 then more chance of development of Intra-Cranial Hemorrhage Thromb Res 2006;117:493–499 Narrow therapeutic Window
- 23. Mazzaglia G Thromb Haemost. 103(5):968-75, 2010. PMID 20216987. OACs 27% APs 31% Not treated 37% APs +OACs 6% Prescription rate for AF diagnosed patients… OACs APs Not treated APs +OACs In study of 5,400 patients, at end of 1 year, only 42% of patients were persistent with VKAs therapy At 2nd year follow up, patients persisting with VKAs dropped further to only 24%
- 25. Fixed dosing/no dose adjustment in a range of patients, including elderly patients Oral, once-daily administration No requirement for frequent INR monitoring A rapid onset and offset of action No food and drug interactions A favorable benefit–risk profile Novel Oral Anticoagulants – NOACs
- 27. New Anticoagulants A long time coming… 1954 2009 RE-LY 2010 ROCKET - AF 2011 ARISTOTLE 2013 ENGAGE AF TIMI
- 28. 28 NOACs : PK PD comparison
- 29. Major Dose Adjustments For Noacs In Renal Failure Patients BID = twice daily; EU = European Union; OD = once daily Pradaxa® : EU SmPC, 2012; Xarelto: EU SmPC, 2012; Eliquis: EU SmPC, 2012 NOACs are not recommended in patients with CrCl <15 mL/min and Hemodialysis
- 30. 30 Rivaroxaban is only NOACs having Once Daily dose regimen and has minimal dose adjustment in comparison of other NOACs ROCKET AF1 RE-LY2 ARISTOTLE3 Rivaroxaban Dabigatran Apixaban 20 mg od (15 mg od) 110 mg bid or 150 mg bid (randomized to two separate arms) 5 mg bid (2.5 mg bid) Dose adjustment for patients with: •Moderate renal impairment CrCl : 15-49 ml/min •HAS-BLED ≥3 • For 110mg BD dose: • Elderly patients ≥80 years • Concomitant use of interacting drugs such as verapamil, amiodarone • HAS-BLED ≥3 • Moderate renal impairment: CrCl 30-49 mL/min Dose adjustment for patients fulfilling ≥2 of the following criteria at baseline: •Age ≥80 years •Body weight ≤60 kg •Serum creatinine ≥1.5 mg/dl (133 µmol/l) 1. Patel MR et al, 2011; 2. Connolly SJ et al, 2009; 3. Lopes RD et al, 2010;
- 31. Efficacy end point N= number of events (RRR )↓ ROCKET-AF (Rivaroxaban) RE-LY (Dabigatran) ARISTOTLE (Apixaban) 20mg/15mg 110mg Dose 150mg Dose 5mg/2.5mg Patient population (n) 7061# 6015 6076 9120 Stroke or Systemic embolism 189 (21% ↓)* 182 (09% ↓)* 134 (34% ↓)* 212 (21% ↓)* Haemorrhagic stroke 29 (41% ↓)* 14 (62% ↓)* 12 (74% ↓)* 40 (49% ↓)* Ischaemic stroke 149 (6% ↓) 159 (11% ↑ ) 111 (24% ↓)* 162 (8% ↓) MI 101 (19% ↓) 86 (35% )↑ 89 (38% )↑ 90 (12% ↓) All cause mortality 208 (15% ↓) 446 (9%↓ ) 438 (12% ↓) 752 (11% ↓) * Composite of stroke, non-CNS SE, and vascular death 346 (14% ↓)* - - - #Safety population – on-treatment analysis * p-value significant Thrombosis;Volume 2012, Article ID 108983, 10 pages
- 32. Risk of myocardial infarction and acute coronary syndrome across 7 studies of Dabigatran Dabigatran was significantly associated with a 33% higher risk of MI or ACS in various clinical trials (p value= 0.03) Uchino K et al. Arch Intern Med. 2012;172(5):397-402.
- 33. Safety end point N= number of events (RRR )↓ ROCKET-AF (Rivaroxaban) RE-LY (Dabigatran) ARISTOTLE (Apixaban) 20mg/15mg 110mg Dose 150mg Dose 5mg/2.5mg Patient population (n) 7061# 6015 6076 9120 Major-Non major- clinically significant bleed 1475 (3% ↑) 1740 (22%↓) * 1977 (9%↓) * 613 (32%↓) * Fatal bleed 27 (50%↓)* 145 (32%↓) * 175 (19↓) * 199 (39%↓) * ICH 55 (33% ↓)* 27 (69%↓) * 36 (60%↓) * 52 (48%↓) * GI bleed 224 (46% ↑)* 133 (10% ↑) 182 (50% ↑) * 105 (11%↓) Thrombosis;Volume 2012, Article ID 108983, 10 pages #Safety population – on-treatment analysis * p-value significant
- 34. ROCKET AF : Rivaroxaban in reduction of MI events Mahaffey KW et al. Eur Heart J 2013;doi:10.1093/eurheartj/eht428 • Primary efficacy and safety outcomes in patients with prior MI were consistent with the overall ROCKET AF results • While taking Rivaroxaban, patients had fewer ischaemic cardiac events compared with patients assigned to warfarin
- 35. European Guidelines : Oacs In AF Patients With ACS And/Or Undergoing PCI Rivaroxaban (2.5mg, BD) is only approved oral anti-coagulant for Post ACS patients along with DAPT (ASA + Clopidogrel)
- 36. Am Heart J. 2015 Apr;169(4):472-8.e5
- 38. Overall co-morbid conditions are less with NVAF patients in routine practice of Rivaroxaban Less incidences of thrombo-embolic event rates in routine practice of Rivaroxaban Less incidences of bleeding events Camm AJ et al. European Heart Journal doi:10.1093/eurheartj/ehv466 XANTUS trial : Real world evidence of Rivaroxaban in NVAF patients
- 42. • Outcomes with Rivaroxaban and Apixaban were consistent with ROCKET-AF and ARISTOTLE trial • Rivaroxaban is more commonly used for SPAF • Significant ICH reduction by both NOACs vs Warfarin • Reduction of 39% (Rivaroxaban) and 37% (Apixaban) in combined end point of ischemic stroke and ICH (vs. Warfarin) • Apixaban is causing more Ischemic stroke than warfarin Coleman Cl et al. J of Inter Electrophysiology. 2016. 45:253
- 43. Management Of Bleeding With Noacs Europace (2015) 17, 1467–1507
- 44. Rivaroxaban treated participants, anti–factor Xa activity was reduced by 92% among those who received an andexanet bolus (27 participants), as compared with 18% among those who received placebo (14 participants) (P<0.001) Apixaban-treated participants, anti– factor Xa activity was reduced by 94% among those who received an andexanet bolus (24 participants), as compared with 21% among those who received placebo (9 participants) (P<0.001), Siegel D et al. NEJM. Nov, 2015
- 46. Europace (2015) 17, 1467–1507
- 47. 1. Lailberte F et al. Advances in Therapy August 2012, Volume 29, Issue 8,pp 675-690 2. Nelson WW et al Curr Med Res Opin.2015;31(10):1831-40
- 48. PINNACLE Registry NOACs usage is increased by 24% .. Rivaroxaban is more commonly used in NVAF Conclusions: In a large quality improvement registry of outpatients with AF, prescription of OAC therapy increased with a higher CHADS2 score and CHA2DS2-VASc score. JAMA Cardiol. doi:10.1001/jamacardio.2015.0374. Published online March 16, 2016.
- 49. JAMA Cardiol. doi:10.1001/jamacardio.2015.0374. Published online March 16, 2016.
- 50. Characteristics Selection criteria Preferred Agent High risk of bleeding (HAS BLED >3) Drug / dose having lowest incidence of bleedings Dabigatran / Apixaban Prior h/o of GI bleed Agent reported with lowest GI bleeds Apixaban High risk of Ischemic stroke, low bleeding risk Agent with best reduction of Ischemic stroke Dabigatran / Rivaroxaban / Apixaban CAD, Prior h/o MI, Acute MI Consider drug which improves mortality in ACS patients Rivaroxaban Renal impairment Consider drug which has less elimination through renal Rivaroxaban / Apixaban GI disorders Consider an agent with least GI side effects Rivaroxaban / Apixaban Prior h/o Stroke Consider an agent with max reduction of secondary stroke Rivaroxaban / Apixaban Patient compliance (Less frequency of intake) Consider an agent with once daily dose Rivaroxaban AFpatientcharacteristics
- 52. Facebook Page – IAE Karnataka Website: iaekarnataka.org
Notas do Editor
- Stroke is one of the commonest complication with AF. out of 10 thromboembolic events in AF, 9 were stroke and 1 was extra-cranial systemic embolic event (SEE). While 20% strokes in AF are fatal or leads to disability in approximately 80% of patients. So for primary prevention of stroke it’s risk assessment is mandatory before starting treatment with OACs.
- VKAs are commonly used drugs for management of SPAF since almost 50 years. And VKAs are very effective for reducing stroke by 38-64%. But still it has many challenges for routine treatment of SPAF.
- Commnest challenge of treatment with Warfarin is to maintain INR level between 2.0-3.0. As it has narrow therapeutic window and if INR value is going below 2.0 which has more chance of develop stroke and if it goes beyond 3.0 then there will be more chance of intra cranial hemorrhage.
- a study of 5400 patients was published in 2010 by G Mazagilla et al and it showed that in AF diagnosed patient only 37% patients were taking OACs only and during follow up it was found that at end of 1 year only 42% of patients were persistent with VKAs therapy. 2nd year follow up only 24% patients were on treatment.
- Rivaroxaban has least dose adjustment as compare to Dabigatran and Apixaban. In maroity SPAF cases Rivaroxaban is given 20mg OD while CrCl less than 49ml/min dose is 15mg OD. While For Dabigatran & Apixaban apart from renal condition, Weight, Age and bleeding criterias are also considered for dose aadjustment. Also once daily dose of Rivaroxaban has an advantage from compliance point of view.
- All 3 NAOCs are reducing Primary stroke rate as compare to warfarin significantly. Including Hemorrhagic stroke and Mortality rates are also low in NOACs. In AF patient with usages of NOACs MI events are also less while in Dabigatran MI events are numerically very high as compare to Warfarin. If AF patient has h/o MI then mortality rate is increasing upto 40% so in this condition use of Dabigatran should be with precaution.
- All NOACs has similar major bleeds and significant less fatal bleed & ICH as compare to warfarin. Rivaroxaban had highest CHADS2 score which was 3.5 and even in this condition bleeding rates are similar with other NOACs. GL bleed events more with Riva and Dabi drugs while apixaban has less GI bleeds.
- PIONEER AF PCI is ongoing trial which will give more clarity that which dose of Rivaroxaban should be added with DAPT therapy when patient is undergoing for PCI.