Fibrinolytic Therapy for STEMI Patricia Howard,
Transcription
Fibrinolytic Therapy for STEMI Patricia Howard,
Fibrinolytic Therapy for STEMI Patricia Howard, Pharm. D., BCPS, AQ Cardiology Professor and Vice Chair Pharmacy Practice Professor Cardiovascular Medicine University of Kansas Medical Center Presenter Disclosure Information Patricia Howard, PharmD Fibrinolytics for STEMI FINANCIAL DISCLOSURE: No relevant financial relationship exists UNLABELED/UNAPPROVED USES DISCLOSURE: None to disclose 2 Acute Coronary Syndromes* 1.57 Million Hospital Admissions in US 70 % UA/NSTEMI† 1.10 million Admissions/year 30% STEMI 470,000 Admissions/year Heart Disease and Stroke Statistics – 2013 Update. Circulation 2013;127:143-152 Spectrum of ACS No ST elevation Stable angina Unstable angina NSTEMI ST elevation STEMI ACUTE CORONARY SYNDROMES Tissue damage after Infarction (wavefront inside to outside of muscle) Timeline for Loss of Viable Myocardium after Infarction Normal heart: elliptical Larger infarcts lead to greater damage, extensive remodeling and poorer outcomes Remodeling results in more spherical shape with hypertrophy, collagen deposition and fibrosis STEMI Early Reperfusion is the most Critical Step Plan A: Mechanical Primary PCI • Highly Effective but……….. • Available at only 25% of U.S. hospitals Plan B: Pharmacologic (fibrinolytics) • Lesser efficacy but…. • Widely available at U.S. hospitals and can be administered in the field 9 PCI vs Lytics: Comparison from Clinical Trials Keeley et al. Lancet 2003;361:13-20 Outcomes with PCI vs tPA in Real World Setting Percent NRMI 2 Cohort: n=2,958, lytic eligible, no shock at presentation PTCA 8 6 5.2 5.4 t-PA 6.2 5.6 4 2 0 In-hospital mortality P=NS In-hospital mortality or nonfatal stroke P=NS Tiefenbrunn AJ, et al. J Am Coll Cardiol. 1998;31:1240-1245. Time from Symptom Onset to Treatment Predicts 1-year Mortality after Primary PCI Relative Risk for 1 year mortality increases 8% with Each 30 minute delay to Reperfusion DeLuca et al. Circulation 2004;109:1223-1225 A hypothetical patient develops chest pain at 1000 h. As commonly happens, the patient does not call for help immediately, and phones the emergency number only because of persistent pain at 1130 h. Paramedics arrive at 1145 h—the first medical contact. They do a full assessment and an ECG, which shows obvious anterior ST-segment elevation. This assessment takes 25 min. The patient lives in a semirural area, and the time to hospital is about 65 min. If the paramedics radio ahead the patient could be on the cath table with a vascular sheath deployed within 40 min of arrival at the hospital door. These fairly commonplace events equate to a total ischemic time of 235 min and FMC to device time of 130 min. Adapted from Gershlick et al. Lancet 2013;382:624-32 In many parts of the US, achieving timely mechanical reperfusion is nearly impossible • The patient - Failure to promptly recognize symptoms - Hesitation to seek medical attention • Time to transport - Mandated delivery to the closest hospital, regardless of PCI capabilities - Long transport in rural areas • Decision process on arrival - Clot-busting drugs vs. PCI - Off hours - Transfer to PCI facility • Time to implement treatment strategy - Procedural factors - Team assembly Reperfusion Algorithm for STEMI *Patients with cardiogenic shock or severe heart failure initially seen at a non–PCI-capable hospital should be transferred for cardiac catheterization and revascularization as soon as possible, irrespective of time delay from MI onset (Class I, LOE: B). †Angiography and revascularization should not be performed within the first 2 to 3 hours after administration of fibrinolytic therapy. ACCF/AHA 2013 guidelines 2013 ACCF/AHA Guideline for the Management of STEMI • Reperfusion therapy should be administered to all eligible patients with STEMI with symptom onset within the prior 12 hours (Class I:A) • Primary PCI is the recommended method of reperfusion when it can be performed in a timely fashion by experienced operators (Class I:A) • In the absence of contraindications, fibrinolytic therapy should be administered to patients with STEMI at non–PCI-capable hospitals when the anticipated FMC-to-device time at a PCIcapable hospital exceeds 120 minutes because of unavoidable delays (Class I:B) • When fibrinolytic therapy is indicated or chosen as the primary reperfusion strategy, it should be administered within 30 minutes of hospital arrival (Class I:B) Fibrinolysis Goals: reestablish perfusion by opening the artery minimize infarct size and salvage myocardium Lytics activate Fibrinolytics: Activate Plasminogen Fibrin-bound Plasminogen Fibrin-bound Plasmin Fibrin split prod Dissolves clot Circulating Plasminogen Circulating Plasmin Degrades Fibrinogen V, VIII, others Systemic bleeds Fibrinolytic Agents Available in US • streptokinase (SK) • alteplase (TPA or rTPA) • reteplase (rPA) • tenecteplase (TNK) Characteristics of Ideal Fibrinolytic Drugs • Fibrin Selective: greater selectivity reduces the risk of systemic bleeding • Longer Half-Life: generally enhances efficacy • Non-antigenic • Ease of administration: faster drug delivery and less nursing time TIMI Flow as Indicator of Reperfusion (Thrombolysis in Myocardial Infarction) Levels of coronary blood flow assessed during PCI Graded 0-3 0 1 2 3* no perfusion dye penetration but no distal perfusion partial reperfusion – delayed or slow normal flow * Correlates with survival and improved LV function Comparison of Fibrinolytic Agents Property SK TPA rPA Fibrin select. Half-life min. Antigenic Dosing method* Wt. Adjusted -15-25 yes IVF no +++ ++ 4-8 13-16 no no SB/IVF DB yes no TIMI 2 or 3 flow % TIMI 3 flow % 60-68 32 73-84 54 84 60 * IVF=intravenous infusion; SB=single bolus; DB=double bolus TNK ++++ 20-25 no SB yes 85 63 Is the Patient Eligible for Fibrinolysis? • • • • ECG consistent with STEMI Time from symptom onset less than 12 hours Estimated time FMC to device > 120 min No evidence of cardiogenic shock, PE or recurrent VT/VF • No known contraindications to lytics • Acceptable Bleeding risk Absolute Contraindications Who should NOT get Fibrinolytics? • • • • • • • • • • • • Any prior ICH Known structural cerebral vascular lesion (e.g., arteriovenous malformation) Known malignant intracranial neoplasm (primary or metastatic) Ischemic stroke within 3 mo EXCEPT acute ischemic stroke within 4.5 h Suspected aortic dissection Active bleeding or bleeding diathesis (excluding menses) Significant closed-head or facial trauma within 3 mo Intracranial or intraspinal surgery within 2 mo Severe uncontrolled hypertension (unresponsive to emergency therapy) For streptokinase, prior treatment within the previous 6 mo ACCF/AHA 2013 Guideline Relative Contraindications Must weigh benefits/risks • • • • • • • • • • • • History of chronic, severe, poorly controlled hypertension Significant hypertension on presentation (SBP > 180 mm Hg or DBP > 110 mm Hg) History of prior ischemic stroke > 3 mo Dementia Known intracranial pathology not covered in absolute contraindications Traumatic or prolonged (> 10 min) CPR Major surgery (< 3 wk) Recent (within 2 to 4 wk) internal bleeding Noncompressible vascular punctures Pregnancy Active peptic ulcer Oral anticoagulant therapy ACCF/AHA 2013 guideline Fibrinolytic Dosing for STEMI (1 of 2) SK: 1.5 MU infused over 60 min rTPA: Front Loaded: max 100 mg over 90 min 15 mg IV bolus 0.75 mg/kg over 30 min (max. 50 mg) 0.5 mg/kg over 60 min (max. 35 mg) Fibrinolytic Dosing for STEMI (2 of 2) rPA: 10 U bolus over 2 min; repeat in 30 min TNK: Weight based single bolus over 5 sec <60 kg 30 mg 60-69 kg 35 mg 70-79 kg 40 mg 80-89 kg 45 mg > 90 kg 50 mg Adjunct Antiplatelet Therapy • To prevent platelet activation and aggregation • Aspirin : 162-325 mg daily • Clopidogrel: – < 75 yrs 300 mg loading dose – > 75 yrs omit loading dose – Maintenance dose: 75 mg daily Adjunct Anticoagulant Therapy • To prevent additional clot formation Heparin: weight adjusted bolus to achieve aPTT 1.5-2.0 times control for > 48h Typical: 60 U/kg bolus (max 4000 U, then 12 U/kg/hr (max 1000 U/hr) OR LMWH (e.g. enoxaparin) < 75 yr: IV bolus 30 mg; wait 15 min then 1 mg/kg q 12 hr > 75 yr: No bolus; 0.75 mg/kg q 12 hr Patients with Cr Cl < 30 ml/min: 1 mg/kg daily Fibrinolytics: Bleeding Risks • Minor bleeding (20%) — Surface or superficial: invaded or disturbed sites (e.g., injection site, venous cutdowns, arterial punctures including catheterization site, location of recent surgical intervention) • Major bleeding (2-3%) —typically Internal: gastrointestinal, genitourinary, retroperitoneal, pericardial and intracranial • Intracranial bleeding (1%) Monitoring for Adverse Events • Monitor ECG for arrhythmias • Monitor BP and pulse e.g. q 15 min for 2 hr, then q 30 min for 6 hr, then hourly for 16 hr (total of 24 hr) • Bedrest; Minimize handling and moving patient • No unnecessary punctures, IM injections, catheters, invasive procedures for 24 hr • Monitor for bleeding; check secretions for blood • Assess for signs of neurologic dysfunction • Monitor for allergy (<1%) /anaphylaxis (<0.1%) Management of bleeding complications • Attempts should be made to manage minor bleeds without stopping treatment via compression and other supportive strategies • Major life-threatening bleeds or possible ICH: Stop the Fibrinolytic and call for immediate medical expertise Discontinue other anticoagulants/antiplatelets (Heparin can be reversed with Protamine) Achieving the Target DTN Time < 30 min • Availability of drug onsite or in ER • Mix the drug while completing assessment • Procedures for determining weight, calculating dose, administration of lytic and adjunct therapy (UH or LMWH, ASA etc.) • Monitoring plan: signs and symptoms of bleeding or neurological dysfunction, labs needed etc. • Protocols must be in place!! Assessing Reperfusion • Relief of chest pain • Resolution of ST elevation • Reperfusion arrhythmias • Note: all these are imprecise but lack of >50% resolution of ST elevation in the worst lead 60-90 min after treatment is strong indicator of need for rescue PCI Indications for Transfer for Angiography after Fibrinolytic Therapy • Immediate transfer for cardiogenic shock or severe acute HF • Urgent transfer for failed fibrinolysis or reocclusion • 3-24 hr after fibrinolysis in stable patients as part of invasive strategy ACCF/AHA 2013 Guidelines In this age of Mechanical Reperfusion, Fibrinolytics remain an Effective Alternative • “the appropriate and timely use of some form of reperfusion therapy is likely more important than the choice of therapy” (ACC/AHA guidelines) • Only a minority of US hospitals can perform primary PCI • Difficulties achieving FMC to device time goals • After approx. 20 minutes of occlusion, thousands of cells begin to die every minute In conclusion, through effective partnerships, proper planning, infrastructure development, protocols and education we can significantly improve the care of STEMI patients in Kansas Early recognition, early reperfusion and continuous quality improvement is key Initiatives such as Kansas Mission: Lifeline and Project 10-30 (10 min to read ECG and 30 min DIDO or DTN times) provide valuable tools and resources that SAVE LIVES and IMPROVE QUALITY OF LIFE