STEMI 2014 YAHYA KIWAN. Consultant Cardiologist Head Of Cardiology Belhoul Specialty Hospital

Transcription

1 STEMI 2014 YAHYA KIWAN Consultant Cardiologist Head Of Cardiology Belhoul Specialty Hospital

2 Aspiration Thrombectomy Manual aspiration thrombectomy is reasonable for patients undergoing primary PCI. I IIa IIb III

3 UCR Uppsala Clinical Research Center Main results at 30 days Ole Fröbert, MD, PhD - on behalf of the TASTE investigators Departement of Cardiology Örebro University Hospital Sweden

4 Background Intracoronary thrombus aspiration may reduce distal embolization and improve reperfusion No previous randomized trial on thrombus aspiration has been powered for hard endpoints Current ESC recommendation: class IIa with a level of evidence B

5 TASTE trial enrollment flow chart Enrolled in Denmark N=247 All patients with STEMI in Sweden and Iceland undergoing primary or rescue PCI. N= * ) Erroneous enrollments N=15 Enrolled in TASTE N=7259 Randomized in TASTE N=7244 Not enrolled N=4697 N=3621 assigned to thrombus aspiration N=3623 assigned to conventional PCI N=3399 underwent thrombus aspiration N=222 underwent conventional PCI N=3445 underwent conventional PCI N=178 underwent thrombus aspiration N=1162 underwent thrombus aspiration N=3535 underwent conventional PCI N=3621 were followed up N=3623 were followed up N=1162 were followed up N=3535 were followed up

6 All-cause mortality at 30 days HR 0.94 ( ), P=0.63 Per protocol analysis based on actual treatment: HR 0.88 ( ), P=0.38

7 Reinfarction at 30 days HR 0.61 ( ), P=0.09 Per protocol analysis based on actual treatment: HR 0.67 ( ), P=0.19

8 Additional results Randomized in TASTE Not randomized in TASTE PCI Only Thrombus Aspiration Point Estimate (95% confidence interval) P Value PCI Only Thrombus Aspiration 30 days All cause death or myocardial infarction - no. (%) 140 (3.9) 121 (3.3) HR 0.86 ( ) (11.6) 134 (11.8) Stent thrombosis - no. (%) 19 (0.5) 9 (0.2) HR 0.47 ( ) (0.5) 5 (0.4) Target vessel revascularization - no. (%) 76 (2.2) 63 (1.8) HR 0.83 ( ) (2.3) 30 (2.6) Target lesion revascularization - no. (%) 57 (1.6) 43 (1.2) HR 0.75 ( ) (1.8) 25 (2.2) Index hospitalization Stroke or neurological complication - no. (%) 18 (0.5) 19 (0.5) OR 1.06 ( ) (0.9) 12 (1.0) Perforation or tamponade - no.(%) 14 (0.4) 13 (0.4) OR 0.93 ( ) (0.4) 7 (0.6) Heart failure - no.(%) 234 (6.5) 245 (6.8) OR 1.05 ( ) (10.0) 125 (10.8) Left ventricular function - no. (%) 0.33 Moderately reduced, LVEF 30-39% 495 (13.7) 526 (14.5) 523 (14.8) 190 (16.4) Severely reduced, LVEF <30% 157 (4.3) 137 (3.8) 255 (7.2) 102 (8.8)

9 Conclusions This large, prospective, registry-based randomized clinical trial showed: no reduction of mortality at 30 days no significant reduction of hospitalization for MI or of stent thrombosis at 30 days no reduction of other important clinical endpoints during hospitalization Our findings leave little role for manual thrombus aspiration as a routine adjunct to PCI in STEMI

10 STREAM TRIAL

11 STUDY AIM A strategy of early fibrinolysis followed by coronary angiography within 6-24 hours or rescue PCI if needed was compared with standard primary PCI in STEMI patients with at least 2 mm ST-elevation in 2 contiguous leads presenting within 3 hours of symptom onset and unable to undergo primary PCI within 1 hour.

12 MEDIAN TIMES TO TREATMENT (min) Sx onset 1st Medical contact Randomize IVRS Rx TNK min Sx onset 1st Medical contact Randomize IVRS 78 min difference Rx PPCI = Hour 2 Hours 178 min

13 PCI Hospital Ambulance/ER STUDY PROTOCOL STEMI <3 hrs from onset symptoms, PPCI <60 min not possible, 2 mm ST-elevation in 2 leads RANDOMIZATION 1:1 by IVRS, OPEN LABEL Strategy A: pharmaco-invasive Strategy B: primary PCI <75y:full dose Aspirin Clopidogrel: LD 300 mg + 75 mg QD Enoxaparin: 30 mg IV + 1 mg/kg SC Q12h ECG at 90 min: ST resolution 50% YE S angio >6 to 24 hrs PCI/CABG if indicated After 75y: 20% ½ dose of TNK the planned recruitment, the TNK Aspirin dose was Clopidogrel: reduced 75 mg QD by 50% Enoxaparin: among 0.75 mg/kg patients SC Q12h 75 years of age. N O immediate angio + rescue PCI if indicated no lytic Antiplatelet and antithrombin treatment according to local standards Standard primary PCI Primary endpoint: composite of all cause death or shock or CHF or reinfarction up to day 30

14 PATIENTS TIMI FLOW RATES 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% P<0.001 P= TIMI before PCI TIMI after PCI Pharmacoinvasive (N=944) PPCI (N=948)

15 CLINICAL OUTCOMES Before amendment (N=379) After amendment (N=1503)

16 STROKE RATES Pharmaco-invasive PPCI P-value TOTAL POPULATION (N=1892) Total stroke 15/939 (1.60%) 5/946 (0.53%) 0.03 fatal stroke 7/939 (0.75%) 4/946 (0.42%) 0.39 Haemorrhagic stroke 9/939 (0.96%) 2/946 (0.21%) 0.04 fatal haemorrhagic stroke 6/939 (0.64%) 2/946 (0.21%) 0.18 POST AMENDMENT POPULATION (N=1503) Total stroke 9/747 (1.20%) 5/756 (0.66%) 0.30 fatal stroke 3/747 (0.40%) 4/756 (0.53%) >0.999 Haemorrhagic stroke 4/747 (0.54%) 2/756 (0.26%) 0.45 fatal haemorrhagic stroke 2/747 (0.27%) 2/756 (0.26%) >0.999

17 MEDIAN TIMES TO TREATMENT (min) Sx onset 62 1st Medical contact Randomize IVRS 29 9 Rx TNK 36% Rescue PCI at 2.2h 100 min 64% non-urgent cath at 17h Sx onset 1st Medical contact Randomize IVRS Rx PPCI n= Hour 2 Hours 178 min

18 CONCLUSIONS A strategy of fibrinolysis with bolus tenecteplase and contemporary antithrombotic therapy given before transport to a PCI-capable hospital coupled with timely coronary angiography : circumvents the need for an urgent procedure in about two thirds of fibrinolytic treated STEMI patients. is associated with a small increased risk of intracranial bleeding. is as effective as primary PCI in STEMI patients presenting within 3 hours of symptom onset who cannot undergo primary PCI within one hour of first medical contact.

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20 Cardiovascular Death, MI, or Stroke STEMI PRIMARY EFFICACY ENDPOINT: 30 Days 2% ITT: HR 0.71 (95% CI ) P=0.042 Placebo 2.3% 1.7% Rivaroxaban 1% 0% 0 5 mitt: HR 0.71 (95% CI ) P= Days

21 Cardiovascular Death, MI, or Stroke STEMI PRIMARY EFFICACY ENDPOINT 10% ITT: HR 0.81 (95% CI ) P=0.019 Placebo N= % 8% 8.4% 6% Rivaroxaban N=5128 4% 2% 0% mitt: HR 0.85 (95% CI ) P= Days

22 CONCLUSION STEMI Treatment with very low dose rivaroxaban (2.5 mg BID) offers an effective strategy to reduce thrombotic events in patients following a STEMI.

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24 Results of the OPTIMIZE trial presented at TCT 2013 New study demonstrates potential benefits of shorter-term dual antiplatelet therapy in patients treated with a second generation drug-eluting stent SAN FRANCISCO, CA OCTOBER 31, A new study demonstrates that some patients may not need to receive prolonged anti-clotting therapy after drug-eluting stent (DES) implantation with the Endeavor zotarolimus-eluting stent, and that shortening the duration could reduce bleeding risks and treatment costs. The OPTIMIZE clinical trial findings were presented today at the 25th annual Transcatheter Cardiovascular Therapeutics (TCT) scientific symposium. Sponsored by the Cardiovascular Research Foundation (CRF), TCT is the world's premier educational meeting specializing in interventional cardiovascular medicine. Current guidelines recommend long-term (12 month) dual antiplatelet therapy (DAPT) after DES implantation, but the clinical benefits of this regimen remain unclear, especially with newer generation DES. The OPTIMIZE trial enrolled 3,120 patients with largely stable coronary artery disease in a prospective, randomized (1:1) multicenter clinical evaluation that compared shortterm (3 month) and long-term (12 month) dual antiplatelet therapy. All patients underwent PCI with Endeavor zotarolimus-eluting stents, a second-generation DES. The primary endpoint was a composite of Net Adverse Clinical and Cerebral Events (NACCE), which included death from any cause, myocardial infarction, stroke or major bleeding at one year followup.

25 After one year, NACCE rates for patients receiving short-term DAPT were similar to those who received the longer, standard DAPT (6.1 percent vs. 5.9 percent respectively), establishing non-inferiority of the shorter-term therapy (non-inferiority p-value = 0.002). After 90 days, both groups showed comparable rates of NACCE, stent thrombosis and revascularization. Patients in the long-term DAPT group also showed a trend towards increased bleeding events. "To date, OPTIMIZE is the only DAPT duration study using a single second-generation DES, and these promising findings could help shorten antiplatelet therapy time and reduce related complication risks for patients receiving select drug-eluting stents," said lead investigator Fausto Feres, MD of the Instituto Dante Pazzanese de Cardiologia in São Paulo, Brazil. "These outcomes may be especially relevant for patients who are at a high risk of bleeding complications following PCI, such as the elderly and patients with a history of hemorrhagic events."

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37 Antiplatelet Therapy to Support Primary PCI for STEMI I IIa IIb III It may be reasonable to administer intravenous GP IIb/IIIa receptor antagonist in the precatheterization laboratory setting (e.g., ambulance, ED) to patients with STEMI for whom primary PCI is intended. I IIa IIb III It may be reasonable to administer intracoronary abciximab to patients with STEMI undergoing primary PCI. I IIa IIb III Continuation of a P2Y 12 inhibitor beyond 1 year may be considered in patients undergoing DES placement.

38 Adjunctive Antithrombotic Therapy to Support Reperfusion With Primary PCI *The recommended maintenance dose of aspirin to be used with ticagrelor is 81 mg daily.

39 Adjunctive Anticoagulant Therapy With Fibrinolysis I IIa IIb III I IIa IIb III I IIa IIb III I IIa IIb III Patients with STEMI undergoing reperfusion with fibrinolytic therapy should receive anticoagulant therapy for a minimum of 48 hours, and preferably for the duration of the index hospitalization, up to 8 days or until revascularization if performed. Recommended regimens include: a. UFH administered as a weight-adjusted intravenous bolus and infusion to obtain an activated partial thromboplastin time of 1.5 to 2.0 times control, for 48 hours or until revascularization; b. Enoxaparin administered according to age, weight, and creatinine clearance, given as an intravenous bolus, followed in 15 minutes by subcutaneous injection for the duration of the index hospitalization, up to 8 days or until revascularization; or c. Fondaparinux administered with initial intravenous dose, followed in 24 hours by daily subcutaneous injections if the estimated creatinine clearance is greater than 30 ml/min, for the duration of the index hospitalization, up to 8 days or until revascularization.

40 Adjunctive Antiplatelet Therapy With Fibrinolysis I IIa IIb III In patients with STEMI who receive fibrinolytic therapy: aspirin should be continued indefinitely and I IIa IIb III clopidogrel (75 mg daily) for at least 14 days I IIa IIb III o and up to 1 year

41 Indications for PCI of an Infarct Artery in Patients Who Were Managed With Fibrinolytic Therapy or Who Did Not Receive Reperfusion Therapy *Although individual circumstances will vary, clinical stability is defined by the absence of low output, hypotension, persistent tachycardia, apparent shock, high-grade ventricular or symptomatic supraventricular tachyarrhythmias, and spontaneous recurrent ischemia.

42 Adjunctive Antithrombotic Therapy to Support Reperfusion With Primary PCI (cont.) *The recommended maintenance dose of aspirin to be used with ticagrelor is 81 mg daily. Balloon angioplasty without stent placement may be used in selected patients. It might be reasonable to provide P2Y 12 inhibitor therapy to patients with STEMI undergoing balloon angioplasty alone according to the recommendations listed for BMS. (LOE: C).

43 PCI of a Noninfarct Artery Before Hospital Discharge I IIa IIb III PCI is indicated in a noninfarct artery at a time separate from primary PCI in patients who have spontaneous symptoms of myocardial ischemia. I IIa IIb III PCI is reasonable in a noninfarct artery at a time separate from primary PCI in patients with intermediate- or high-risk findings on noninvasive testing.

44 Adjunctive Antithrombotic Therapy to Support Reperfusion With Primary PCI (cont.)

45 Adjunctive Antithrombotic Therapy to Support PCI After Fibrinolytic Therapy (cont.) The recommended ACT with no planned GP IIb/IIIa receptor antagonist treatment is s (HemoTec device) or s (Hemochron device).

46 PCI of an Infarct Artery in Patients Who Initially Were Managed With Fibrinolysis or Who Did Not Receive Reperfusion Therapy Delayed PCI of a totally occluded infarct artery greater than 24 hours after STEMI should not be performed in asymptomatic patients with 1- or 2-vessel disease if they are hemodynamically and electrically stable and do not have evidence of severe ischemia. I IIa IIb III No Benefit

47 Beta Blockers I IIa IIb III I IIa IIb III Oral beta blockers should be initiated in the first 24 hours in patients with STEMI who do not have any of the following: signs of HF, evidence of a low output state, increased risk for cardiogenic shock,* or other contraindications to use of oral beta blockers (PR interval >0.24 seconds, second- or third-degree heart block, active asthma, or reactive airways disease). Beta blockers should be continued during and after hospitalization for all patients with STEMI and with no contraindications to their use. *Risk factors for cardiogenic shock (the greater the number of risk factors present, the higher the risk of developing cardiogenic shock) are age >70 years, systolic BP <120 mm Hg, sinus tachycardia >110 bpm or heart rate <60 bpm, and increased time since onset of symptoms of STEMI.

48 Anticoagulation I IIa IIb III I IIa IIb III Anticoagulant therapy with a vitamin K antagonist should be provided to patients with STEMI and atrial fibrillation with CHADS2* score greater than or equal to 2, mechanical heart valves, venous thromboembolism, or hypercoagulable disorder. The duration of triple-antithrombotic therapy with a vitamin K antagonist, aspirin, and a P2Y 12 receptor inhibitor should be minimized to the extent possible to limit the risk of bleeding. *CHADS2 (Congestive heart failure, Hypertension, Age 75 years, Diabetes mellitus, previous Stroke/transient ischemic attack (doubled risk weight)) score. Individual circumstances will vary and depend on the indications for triple therapy and the type of stent placed during PCI. After this initial treatment period, consider therapy with a vitamin K antagonist plus a single antiplatelet agent. For patients treated with fibrinolysis, consider triple therapy for 14 days, followed by a vitamin K antagonist plus a single antiplatelet agent.

49 Guideline Comparison ESC ACC TICA, PRASO (PPCI) 1 B 1B CLOPIDO (PPCI) 1C 1B ENOXI (PPCI) 1C NONE BETABLOCKERS 2a B 1 B RIVAROXIBAN FONDAPAR(LYSIS) 2b B NONE