Expert Opinion : Reperfusion Strategies in STEMI: Focus on current Guidelines and Late-breaking TRANSFER-AMI trial (ACC-2008)

Transcription

1 Cardiology Update Volume-1 Issue-2 May-June 2008 Editorial Board Editor Dr. Milan Chag (M) Co-Editor Dr. Mihir Tanna (M) Cardiologist Dr. Urmil Shah MD, DM (M) Dr. Hemang Baxi MD, DM (M) Dr. Anish Chandarana MD, DM (M) Dr. Ajay Naik MD, DM (Mumbai) DNB, FACC (M) Dr. Satya Gupta MD, DM, FIC (FRANCE) (M) Dr. Gunvant Patel MD, DM (M) Dr. Keyur Parikh MD (USA) FCSI (India) FACC, FESC, FSCAI (M) Cardiac Physicians Dr. Joyal Shah MD (M) Dr. Ravi Singhvie MD (M) Dr. Jayesh Bhanushali MD (M) Expert Opinion : Reperfusion Strategies in STEMI: Focus on current Guidelines and Late-breaking TRANSFER-AMI trial (ACC-2008) Topic : Clinical Cardiology Expert : Milan Chag, MD, DM, DNB Interviewer : Mihir Tanna, MD Dr. Mihir Tanna: It is unfortunate that the incidences of acute coronary syndromes are on the rise in our society and we tend to see a large number of young persons presenting with Myocardial infarction. Due to lack of awareness of the disease and its symptoms as well as socioeconomic constraints, patients defer from taking medical opinion at early stages of the disease, and hence almost 50 percent of patients of ours are ACS patients, almost half of them have acute STEMI. I am with Dr. Milan Chag, senior interventional cardiologist, who is one of the pioneers in establishing primary angioplasty program in the state. Dr. Mihir Tanna: Dr. Milan, What is the ultimate aim of treatment of STEMI? Message from Editor Management of STEMI, one of the most dreaded and life threatening event with very high mortality two decades ago has been systematically evolved over last two decades. Although 25% patients still die BEFORE they reach to hospital, in-hospital mortality has been substantially reduced from nearly 15% during pre-fibrinolytic era to nearly 5% in current primary PCI era (Figure 1). Latest concept of pharmacoinvasive approach may further change our day-to-day clinical practice. This concept was studied in randomized, multicenter TRANSFER-AMI trial which was presented in Annual ACC conference, March 2008 at Chicago, USA. This Collector's Issue discusses various reperfusion strategies in Indian context. I hope this will help to serve our critical patients in better, scientific way! Sincerely, Dr. Milan Chag

2 2 Dr. Milan Chag: Aim is to establish complete and sustained epicardial flow (TIMI 3) along with complete myocardial tissue perfusion (TMP III) as early as possible. This results in maximum salvage of myocardium, preservation of LV function and improvement in long-term survival. Dr. Mihir Tanna: Before patient reaches hospital for reperfusion therapy (fibrinolytic or primary PCI), what should be the First Line Therapy? Dr. Milan Chag: First Line Therapy should include: Aspirin: mg (Chewed), mg to continue Clopidogrel: 300 mg load, 75 mg to continue Atorvastatin: 80 mg stat, mg to continue Beta blocker: Metoprolol- unless contraindicated UFH or Enoxaparine: 60 U/kg, 12 U/kg/hr of UFH or 30 mg IV bolus followed by 1 mg/kg, bid (if age >75 yr: No bolus, O.75 mg/kg, bid) of Enoxaparine. Dr. Mihir Tanna: Can we give UFH or LMWH before or along with fibrinolytic? Dr. Milan Chag: Yes. This reduces chances of reocclusion of culprit artery (which occurs in ~10%). Enoxaparine is preferable to UFH as there is no risk of heparin induced thrombocytopenia and there is additional 20% risk reduction in death or MI at 30 days compared to UFH ( EXTRACT TIMI 25 trial) Dr. Mihir Tanna: What should be the preferable reperfusion strategy- Fibrinolysis or Primary PCI? Dr. Milan Chag: This is very important issue - I follow and recommend ACC/AHA guidelines of STEMI (Updated in 2007). If presentation is less than 3 hours and there is no delay to an invasive strategy, there is no preference for either strategy: Fibrinolysis is generally preferred if- 1. Early presentation ( < 3 hours from symptom onset and delay to invasive strategy) 2. Invasive strategy is not an option if 3. Delay to invasive strategy: Cath lab occupied or not available Vascular access is difficult No access to skilled PCI lab Prolonged transport > 60 minutes Door-to-balloon (first medical contact to balloon) time > 90 minutes Invasive strategy is generally preferred if- 1. Skilled PCI lab is available with surgical backup Door-to-balloon < 90 minutes 2. High Risk from STEMI Cardiogenic shock, Killip class = 3 3. Contraindications to fibrinolysis, including increased risk of bleeding and ICH 4. Late presentation i.e. > 3 hours from onset of symptom 5. Diagnosis of STEMI is in doubt Dr. Mihir Tanna: What should be the approach if presentation is after 3 hours of chest pain? Dr. Milan Chag: In that case, primary PCI is clearly better than fibrinolysis. However, if PCI is not feasible, fibrinolysis is still indicated till 12 hours (better than placebo). Dr. Mihir Tanna: Why this 3 hour time setting is important? Dr. Milan Chag: If we analyze 30 days mortality for both reperfusion strategies fibrinolysis clearly separates for worse after 3-4 hours of time delay (figure 2). At that point, primary PCI has significant mortality benefit. Dr. Mihir Tanna: Regarding the use of a fibrinolytic agent, does the saying OLD IS GOLD holds true? I mean, are Streptokinase/Urokinase still the agents of first choice? Dr. Milan Chag: No, OLD IS NOT GOLD! In fact, urokinase is the least studied drug for its use in STEMI. Possible correct dose may be lac units which is hardly given in real world clinical scenario. It is not even FDA approved. Success rate (achievement of TIMI III flow) with STK is only 31% compared to 54% with accelerated tpa and 63% with TNK-tPA (figure 3). Compared to tpa, TNK-tPA is 14 times more fibrin specific (less bleeding), 80 times more resistant to PAI-1, more effective in late presentation (> 4 hours, ASSENT-2 trial) and has long half-life needing just 5 seconds bolus as single, weight adjusted dose! This clearly makes TNK-tPA the best available agent. Dr. Mihir Tanna: 5 second bolus sounds exciting. Can it be given in pre-hospital settings?

3 Dr. Milan Chag: Of course yes! Meta-analysis of all prehospital versus in-hospital fibrinolysis trials clearly suggests significant benefit and safety in favor of pre-hospital fibrinolysis. Bolus dose in just 5 seconds makes TNK-tPA ideal for pre-hospital settings. Dr. Mihir Tanna: If fibrinolysis fails, what should we do? Is there any role of repeat fibrinolysis? Dr. Milan Chag: Controlled trials have proved that there is no role of repeat fibrinolysis immediately after failed fibrinolysis (ST-segment resolution < 50% after 60 min). It increases chances of bleeding also. Such patients should be transferred for rescue PCI as soon as possible. Dr. Mihir Tanna: Is there any other subset of patients who should also be transferred for Rescue PCI? Dr. Milan Chag: Yes, there are other high risk patients who also need Rescue PCI if they have Cardiogenic shock or Severe congestive heart failure and/or pulmonary edema (Killip class III) or Hemodynamically compromising ventricular arrhythmias. These groups of patients carry high mortality with continued conservative therapy. Dr. Mihir Tanna: Is there any way to judge risk of STEMI or chances of success with fibrinolytic therapy? Dr. Milan Chag: Yes, we can judge that by TIMI risk score (Figure 4). As the TIMI score increases, mortality risk increases and chance of success with fibrinolytics decreases. For any time window presentation, primary PCI is better than fibrinolysis for high TIMI risk score patients. Dr. Mihir Tanna: If high TIMI risk score patient (e.g. Diabetic patient with extensive anterior MI with tachycardia and hypotension) presents to non-pci capable center after 4 hours of chest pain, what should be our approach? Dr. Milan Chag: This is very high risk patient. Fibrinolysis will have low success rate. Early invasive approach will be the best strategy. After first line therapy, such patient should be transferred with GPIIbIIIa inhibitor on board to PCI capable center for Emergency Facilitated PCI. Dr. Mihir Tanna: If such patient with high TIMI risk score presents within 3 hours at Non-PCI capable center. What should be our approach? Dr. Milan Chag: Such patient should receive the most effective fibrinolytic agent (TNK-tPA,) as early as possible and transferred to PCI capable center without waiting for lytic response. Transfer for routine early PCI within 6 hours of fibrinolysis is known as pharmaco-invasive strategy. Dr. Mihir Tanna: What is the background or rationale behind Pharmacoinvasive approach? Dr. Milan Chag: Logic behind this novel approach may be summarized as follows: 1. Treatment delay due to transfer from non-pci capable to PCI capable center can reduce or eliminate the benefits of primary PCI 2. STEMI patients presenting to Non-PCI centers usually receive fibrinolysis. Successful fibrinolysis will be present in 30-60% cases depending upon type of fibrinolytic agent used. Waiting to see its response or wait till complications occur will further delay the process to open artery. 3. The role and optimal timing of routine early PCI after fibrinolysis was not well established till recent TRANSFER-AMI trial. Dr. Mihir Tanna: What is TRANSFER-AMI trial? Dr. Milan Chag: It is a multicenter, randomized trial (Trial of 3

4 4 Routine ANgioplasty and Stenting after Fibrinolysis to Enhance Reperfusion in Acute Myocardial Infarction) which was presented at ACC 2008 meet. In this trial, patients with STEMI were randomized to a pharmacoinvasive strategy (emergent transfer for PCI within 6 hours of fibrinolysis) or to standard treatment after fibrinolysis (which included rescue PCI as required for ongoing chest pain and <50% resolution of ST-elevation at minutes or if patients were hemodynamically unstable). For standard treatment patients who did not require Rescue PCI, Elective Cardiac Catheterization within the first 2 weeks were encouraged, but not mandated. All patients received standard-dose tenecteplase (TNK) and aspirin mg. PCI of culprit lesion was performed if there is greater than 70% stenosis or high-risk features were present i.e. (thrombus, ulceration, dissection). Stents were used whenever technically feasible. Dr. Mihir Tanna: What were the results of TRANSFER AMI trial (Pharmacoinvasive therapy)? Dr. Milan Chag: Results were outstanding and can be summarized as follows (Figure 5, Table-1): 1. For high-risk STEMI patients receiving fibrinolysis at non-pci centers, urgent transfer and PCI within 6 hours and it is associated with 6% absolute (and 46% relative) reduction in ischemic complications at 30-days and no excess in major bleeding complications, compared with standard treatment. 2. Transfers to PCI centers should be initiated immediately after fibrinolysis without waiting to see whether reperfusion is successful. 3. Regional systems should be developed to ensure timely transfers of STEMI patients to PCI centers. Dr. Mihir Tanna: What is take home message from TRANSFER- AMI? Dr. Milan Chag: 6 hours after fibrinolytic is a very practical time frame to achieve. The 90 minutes door-to-balloon time (first medical contact to balloon time) for primary PCI is not achievable in many parts of the world, but I think a six-hour window is very practical and realistic. This allows use of other blood thinners (if needed) without causing increased bleeding risk. 6% absolute (and 46% relative) reduction in ischemic complications at 30-days is remarkable and may change our practice guidelines. Dr. Mihir Tanna: I agree it is quite encouraging! Lastly, can you please tell what should be Discharge prescription for STEMI patients? Dr. Milan Chag: That is very important. In general, this is what I prescribe: Aspirin: mg/day for 1 year, then mg/day Clopidogrel: 75 mg/day for at least 1 year or longer Beta- Blockers: to all, unless contraindicated ACE Inhibitors: to all, especially if LVEF< 40% or with hypertension, diabetes, or chronic kidney disease, unless contraindicated. ARB: if intolerant to ACE inhibitors Aldosterone Blockade: if LVEF of = 40% and have either diabetes or HF, unless contraindicated Statin: to all, lifelong; goal LDL-C < 70 mg/dl Blood pressure control: goal <130/80 mm Hg Diabetes management: goal: HbA1c < 7% Physical activity: minutes 7 days per week; minimum 5 days per week 2 Weight management: goal: BMI 18.5 to 24.9 kg/m Waist circumference: Women: < 35 in. (89 cm)men: < 40 in. (102 cm) Smoking Goal: Complete cessation. No exposure to environmental tobacco smoke. Table 1. Outcome at 30-Day Follow-Up Standard Pharmacoinvasive P Value Treatment Strategy (n=498) (n=512) Primary endpoint* 16.6% 10.6% Reinfarction 6.0% 3.3% Recurrent Ischemia 2.2% 0.2% *Composite of death, reinfarction, recurrent ischemia, congestive heart failure, and cardiogenic shock

5 Cardiology Update Case Presentation Chief Complaint: Chest discomfort History of Present Illness: A 48-year-old female presented with anginal chest discomfort of one day duration The patient experienced multiple episodes, each lasting no longer than a few minutes except for the latest one, which persisted for hours. Past Medical History: Thyroid gland irradiation for possible thyroid cancer, migraine headaches, degenerative disk disease status post-cervical/thoracic/lumbar spine fusion. Physical Findings Blood Pressure: 110/69 mm Hg Pulse: 63 bpm General Appearance: Well-nourished female in no distress RS : Clinically NAD CVS : Clinically NAD Abd : Clinically NAD Lab/Diagnostic Tests Cardiac enzymes were negative. Stress Thallium Study was performed and showed a small anteroapical area of ischemia. An echocardiogram showed no evidence of valvular or ventricular abnormalities. Left ventricular ejection fraction was 60%-65%. Cardiac catheterization demonstrated luminal irregularities in all coronaries without significant stenosis. The flow was thrombolysis in myocardial infarction (TIMI)-2 to TIMI-3 in all territories. Our next Issue : "Chest Pain Unit" Month : July-August Editor : Dr. Urmil Shah Quiz of the month The questions 1 & 2 you are required to answer are from Case Presentation: 1. Which of the following most likely explains the slow coronary flow? A. Coronary embolization B. Dilated coronaropathy C. Myocarditis D. Endothelial dysfunction E. Coronary steal syndrome 2. Which of the following therapies would be beneficial to the patient? A. Aspirin B. Statin therapy C. Angiotensin-converting enzyme inhibitors D. All of the above E. None of the above The questions 3 to 10 you are required to answer are from Clinical Cardiology: 3. Which of the following anti anginal drug acts by altering energy substrate metabolism of the cardiac myocyte? A. Nicorandil B. Ranolazine C. Iso sorbide mononitrate D. Diltiazem 4. Which is the most cardioselective B blocker amongst the following? A. Nebivolol B. Bisoprolol C. Metoprolol D. Atenolol 5. Which of the following parameter does NOT help in assessing the severity of mitral stenosis? A. Intensity of S1. B. EF slope on Echo C. Planimetered valve area on Echo D. Intensity of diastolic murmur 5

6 6 6. Which of the following congentital defects is not amenable to percutaneous intervention? A. ASD B. VSD C. PDA D. Valvular Pulmonic Stenosis E. Mitral Stenosis 7. Which of the following is the most sensitive diagnostic modality for evaluation of viable myocardium? A. Dobutamine stress Echo B. Stress thallium C. PET scan D. Cardiac MRI 8. In a hemodynamically unstable acute pulmonary embolism, within what period of time after the initial event could the initiation of streptokinase infusion considered? A. Upto 24 hours B. Upto 1 week C. Upto 2 weeks D. Upto 1 month year old man was undergoing work up for anaemia. All his reports were normal except for a positive stool occult blood. Patient was to undergo G. I. scopy. ECG taken before that revealed large QRS voltages. Hence, patient underwent an echo examination which showed a concentric LVH with LVEF of 50%, a thickened calcified aortic valve with Peak and mean gradients across the valves of 86 and 60 mm Hg, mild AR. Normal other valves. What would be the plan of management for his asymptomatic cardiac condition? A. Medical management B. CAG followed by AVR with a metallic valve+/- CABG C. CAG followed by AVR with a bioprosthetic valve +/- CABG D. Balloon Aortic Valvuloplasty 10. What would be the most likely diagnosis from the following Echo parameters? Mild Bi atrial enlargement Mild Pulmonary Hypertension Mild MR and TR Trans mitral inflow velocity respiratory variation > 25% A. Cardiac Tamponade B. Restrictive Cardiomyopathy C. Constrictive Pericarditis D. Right Ventricular Infarct Put a cross inside the correct answer in the given answer sheet Only one best answer for each question Three top answerers will get prizes with their name, address and photo published in next issue Everybody who answers All 13 questions, and mails the answers in, will still get a Certificate of CME (1 Hour) from the 3 C CON Accomplishment of Dr. Mihir Tanna Dr. Mihir Tanna, after completion of his MD Medicine from Pramukh Swami Medical college in 2005, joined SAL hospital as an ICCU registrar. After 6 months of registrarship, he joined the DNB cardiology course. At present he is working as a DNB Fellow (Final year) at SAL Hospital under Dr. Milan Chag. During his cardiology tenure he has gained one of the largest experience in various fields of cardiology viz invasive and non invasive cardiology.

7 Answer Sheet of the Quiz Question No. A B C D E Question-1 Question-2 Question-3 Question-4 Question-5 Question-6 Question-7 Question-8 Question-9 Question-10 Put a cross inside the correct answer Only one best answer for each question Three top answerers will get prizes with their name, address and photo published in next issue Everybody who answers all the 10 questions and mails the answers will still get a Certificate of CME of One Hour ( 1 Hour) from 3 C CON Please send your answers by post to below address before 15 June, 2008 The Heart Care Clinic 201, Balleshwar Avenue, Opp Rajpath Club, S.G. Highway, Bodakdev, Ahmedabd Phones : , , , Fax : , Mobiles : , , info@heartcareclinic.org Registration Form for Echocardiography Fellowship Course Make cheques payable to "Care Cardiovascular Consultants Pvt. Ltd. and send to the below address The Heart Care Clinic, 201, Balleshwar Avenue, Opp Rajpath Club, S. G. Road, Bodakdev, Ahmedabad Phones : , , Mobiles : , Dr. Mr. Mrs. Ms. Last Name First Middle Name Degree Speciality Address City State Pin Code Mobile Rs. 5,000/- will also include "3-C Con 2009" Registration Which month you would like to register for Course (Please tick any one option) Registration Fees : INR 5000 Practising Physicians INR 3000 Residents / Interns / Nurses / Allied Health Professionals Time : 9.00 am to 5.00 pm (Monday to Saturday) Place : The Heart Care Clinic Dates of Echocardiography Course 26th - 31st May, rd - 28th June, th July - 2nd August, th - 30th August, th - 27th September, th - 25th October, th - 29th November,

8 Cardiology Update Top Answerers of the March-April issue Dr. Anil Barupal Dr. Bhardwaj Joshi Dr. Vijay Bhatt Dr. R. N. Gandhi M.D. (Resident) M.D. (Medicine) M.D.F.I.A.M.S. M.D. Resident of JLN Hospital Urvang Medical Hospital Gayatri Heart Clinic Anand Hospital Ajmer, Rajasthan Surat, Gujarat Jamnagar, Gujarat Mansa, Gujarat Dear Colleague, At the Heart Care Clinic we are starting (A) Pulmonary Hypertension Clinic exclusively for Patients with 1. Severe Primary Pulmonary Hypertension (rare but very disabling and fatal disease) 2. Pulmonary Hypertension secondary to (a) Collagen vascular disease or (b) HIV or (c) Other disease Patients who are on conventional treatment for Pulmonary Hypertension and either not responding or worsening will be provided the following services free of cost: a. Free Consultation b. Free Echocardiography c. Free follow-up for next 1 year d. Free VQ scan (If indicated) (B) Heart Failure Clinic exclusively for Patients with severe LV Dysfunction with EF < 35%. Patients who have: (a) Dilated Cardiomyopathy (b) Hypertensive Heart Failure (c) Non Ischemic severe Heart Failure (d) Ischemic severe Heart Failure (e) All severe Heart Failure Patients Patients will be provided the following services one time free of cost: (a) Free consultation (b) Free Echocardiography with CD All the patients will be appropriately sent back to you for further management. Newer modalities of treatment, drugs, devices, guidance of stem cell therapy and supportive care will be offered to the patient & family. For further details call at The Heart Care Clinic or any of the Cardiologists 8