Canadian Antiplatelet Therapy Guidelines: 2014 Update James D. Douketis MD, FRCP(C)
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1 Canadian Antiplatelet Therapy Guidelines: 2014 Update James D. Douketis MD, FRCP(C) Department of Medicine, St. Joseph s Healthcare Hamilton and McMaster University, Hamilton, Canada
2 Disclosures for: James D. Douketis Potential Financial Conflicts of Interest* Consultant/advisory board participant: AGEN Biomedical, Astra-Zeneca, Bayer, Biotie, Boehringer-Ingelheim, Bristol-Myers-Squibb, Leo Pharma, Medicines Co., Ortho-Janssen, Portola, Pfizer, Sanofi Potential Intellectual Conflicts of Interest Steering Committee/Applicant: BRIDGE Trial (NIH), Perioperative NOAC study (CIHR) Adjudication Committee, ATTRACT Trial (NIH), DODS (CIHR) Director and Secretary, THSNA Director and President, Thrombosis Canada
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4 Topics Included in CCS Antiplatelet ACS/PCI stable CAD cerebrovascular disease peripheral arterial disease Guidelines Use of antiplatelet drugs in the outpatient setting for: heart failure chronic kidney disease pregnancy and Iactation perioperative management bleeding management drug interactions primary prevention Tanguay diabetes JF, et al. Can J Cardiol 2013 Nov; 29(11): Bell AD, et al. Can J Cardiol 2011 May-Jun;27
5 Case Vignette No yr old male presents with dyspnea since hospital discharge following heart attack 3 weeks ago describes intermittent breathlessness usually at rest not associated with: chest pain, palpitations, ankle swelling, cough or wheeze Able to continue with usual activities
6 NSTEMI 3 weeks prior to current visit managed with PCI (2 drug eluting stents) discharged after 3 days with uneventful course Comorbid conditions: hypertension hyperlipidemia Current medications: ECASA 81 mg OD ticagrelor 90 mg BID metoprolol 50 mg BID rosuvastatin 20 mg OD irbesartan/hctz 300 mg/12.5 mg OD
7 Which is the likely cause(s) of dyspnea? A. recurrent cardiac ischemia B. anxiety C. medication side effect D. cardiac arrhythmia E. pulmonary disease
8 Antiplatelet Drugs: Mechanisms of Action P2Y 12 receptor antagonists: - clopidogrel - ticagrelor - prasugrel P2Y12 receptor GPIIb/ IIIa (Fibrinog en Receptor) COX 1 Activatio n Collage n Thromb in TXA 2
9 Standard of therapy for secondary cardiac prevention in combination with ASA Lower bleeding rates vs. prasugrel and ticagrelor Indicated for: all ACS / PCI stroke PAD Management Tips for Clopidogrel Indicated for long term monotherapy in secondary prevention for all vascular beds
10 Management Tips for Clopidogrel Less efficacy in secondary cardiac prevention vs. ticagrelor and prasugrel Associated with drug induced rash in ~5% usually generalized, urticarial treated with oral steroid without stopping drug Depends on CYP2C19 for activation ~ 24% of population have CYP2C9 loss of function alleles resulting in reduced capacity to activate clopidogrel CYP2C19 inhibited by many PPIs Cheema AN, et al J Am Coll Cardiol 2011;
11 Management Tips for Ticagrelor and Prasugrel Both provide improved efficacy vs. clopidogrel NNT = ~50 over clopidogrel following ACS/PCI to prevent 1 CV death, non-fatal MI or non-fatal stroke Both have increased risk of bleeding vs. clopidogrel Neither indicated as monotherapy ECASA, 81 mg, should be co-prescribed
12 Management Tips for Ticagrelor Dyspnea in 14% of patients (vs. 8% with clopidogrel) not associated with cardiorespiratory compromise likely central ADP-related event usually resolves spontaneously Ventricular pauses and bradycardia caution with β-blockers and non DHP CCB caution in patients with heart block or sinus node disorders Associated with slight increase in uric acid, creatinine
13
14 Case Vignette No yr old male with T2DM, HTN, high cholesterol presents with crescendo typical CP for 3 days Meds: ramipril, ASA, simvastatin, metformin No bleeding diathesis, no history of TIA or stroke Exam: BP 150/85, HR 80 (sinus), no CHF, S4
15 CBC, electrolytes: normal Creatinine: 112 μmol/l Troponin I: 1.2 μg/l (4 th generation assay) ECG: NSR, 1mm horizontal ST depression V1-V3 CXR: normal (no CHF) Diagnosed with high risk Non-ST Elevation Acute Coronary Syndrome (NSTEACS) Undergoes coronary angiography and drugeluting stent implantation
16 Which antiplatelet regimen(s) are recommended by the Canadian Cardiovascular Society following NSTEACS and coronary stent? 1)ASA + clopidogrel 2)ASA + ticagrelor 3)ASA + prasugrel 4)Any of the above 5)None of the above
17 .and for how long? 1) 1 month 2) 3 months 3) 6 months 4) 1 year 5) Indefinite What if he had instead received a BMS? 1) Same duration as with a drug eluting stent 2) Shorter duration 3) Longer duration
18 Antiplatelets for Secondary Prevention in the Year Following PCI: NSTEACS 1. We recommend ASA 81 mg OD indefinitely in all patients with NSTEACS (Strong Recommendation, High Quality Evidence). For patients allergic to or intolerant of ASA, indefinite therapy with clopidogrel 75 mg OD is recommended. (Strong Recommendation, High Quality Evidence)
19 Recommendations for Antiplatelet Therapy for PCI for a Non-ACS Indication We recommend ticagrelor 90 mg BID over clopidogrel 75 mg daily for 12 months and ASA 81 mg daily in patients with moderate to high-risk NSTE-ACS managed with either PCI, CABG or medical therapy alone. (Strong Recommendation, High Quality Evidence) We recommend clopidogrel 75 mg daily for at least 12 months and ASA 81 mg daily indefinitely in patients receiving PCI with BMS or DES for non-acs indication. (Strong Recommendation, High Quality
20 Recommendation is for DAPT for 1 year for all ACS patients whether they are treated Change in Philosophy in Antiplatelet Therapy for ACS: Update Choice of antiplatelet agent dependent on situation: ACS-PCI: ticagrelor or prasugrel instead of clopidogrel elective PCI, non-acs: clopidogrel medical therapy only: clopidogrel or ticagrelor post-cabg: clopidogrel or ticagrelor
21 Case Vignette No. 3 3 months after receiving a DES, your patient has to undergo prostatectomy for cancer. He has been advised to discontinue his antiplatelet therapy for the surgery. He asks you, his family doctor, if this is safe?
22 Your response: 1. Yes, you can interrupt clopidogrel after 3 months post PCI but continue ASA 2. No, you must continue clopidogrel + ASA for a minimum of 1 year regardless of the surgery What if he has a bare metal stent? 1. Yes, you can stop the clopidogrel after 3 months post PCI but continue the ASA 2. No, you must continue clopidogrel + ASA for a minimum of 1 year regardless of the surgery
23 New Recommendation We suggest that in patients with a secondgeneration DES who cannot tolerate clopidogrel for 12 months (e.g., bleed risk or non-cardiac surgery), the minimum duration of therapy may be 3 months. (Weak Recommendation, Low Quality Evidence) Discontinuation of dual antiplatelet therapy in patients with implanted stents prior to 1 year is hazardous. Ensure there has been a consultation with a physician expert in the management of coronary disease.
24 New Recommendations (continued) We recommend that in patients with a BMS who are unable to tolerate clopidogrel for 12 months (e.g., bleed risk or non-cardiac surgery), the minimum duration of therapy should be 1 month (Strong Recommendation, High Quality Evidence) In patients at very high risk of bleeding, the minimum duration of treatment may be 2 weeks (Weak Recommendation, Low Quality Evidence)
25 but what about the POISE-2 Trial? Design blinded 2 2 factorial RCT ASA vs. placebo clonidine vs. placebo Eligiblity criteria: patients ( 45 yrs) with or at risk of CV disease having non-cardiac surgery Excluded patients: BMS <6 weeks before surgery DES <1 year before surgery took ASA within 72 hrs before surgery Devereaux PJ, et al. N Engl J Med 2014;370:1494
26 POISE-2: Efficacy Results (primary outcomes) Outcome ASA (n=4,99 8) Placebo (n=5,012 ) HR (95% CI) death or nonfatal MI 351 (7.0) 355 (7.1) 0.99 ( ) Note: Only ~4% of patients had cardiac stents, m Devereaux PJ, et al. N Engl J Med 2014;370:1494
27 POISE-2: Efficacy Results (patient Subgroup Analyses of the Primary Outcome. sub-groups) Devereaux PJ, et al. N Engl J Med 2014;370:1494
28 POISE-2: Safety Results (primary Outcome outcomes) ASA (n=4,998 ) Placebo (n=5,012) HR (95% CI) Major bleeding 230 (4.6) 188 (3.8) 1.23 ( ) Lifethreatening 87 (1.7) 73 (1.5) 1.19 ( ) bleeding Stroke 16 (0.3) 19 (0.4) 0.84 ( )
29 Take-away Messages Ticagrelor recommended for secondary prevention after NSTE-ACS treated with PCI, CABG or medically clopidogrel recommended for non-acs indications (elective PCI, elective CABG, PAD) After PCI/stent, duration of antiplatelet therapy determined by stent type; less with newer stents DES: 3-12 months BMS: 1-3 months
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