Cardiovascular Pharmacology

Cardiovascular Pharmacology

i n d i a n h e a r t j o u r n a l 6 4 ( 2 0 1 2 ) S 1 2 8 eS 1 3 1 Available online at www.sciencedirect.com journal homepage: www.elsevier.com/lo...

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i n d i a n h e a r t j o u r n a l 6 4 ( 2 0 1 2 ) S 1 2 8 eS 1 3 1

Available online at www.sciencedirect.com

journal homepage: www.elsevier.com/locate/ihj

64th Annual CSI Conference and SAARC Cardiac Congress DECEMBER 06e09, 2012, NEW DELHI, INDIA Cardiovascular Pharmacology Poster Presentation Thrombolysis in massive pulmonary embolism: Our clinical experience Brijesh Agrawal, Snehil Mishra, Irfan Khan, Pranjal Patil, Rajendra Chavan, Dhirender Singh, Vinay Kumar, Pritesh Punjabi, Sohan Sharma, Sachin M. Mukhedkar, Madhusudan A. Yemul, Sandeep N. Patil, Jaywant M. Nawale, Ajay S. Chaurasia TNMC and BYL Nair Ch. Hospital, Mumbai, India Aim: To evaluate the efficacy of thrombolysis in massive pulmonary embolism. Materials & Methods: The hospital course of 24 patients treated for massive pulmonary embolism demonstrated by CTpulmonary angiography, 2D ECHO & ECG findings, over a period of 2 years, was reviewed. The embolism was termed massive in the presence of hemodynamic instability &/or RV dysfunction on 2D ECHO &/or CT findings of significant main pulmonary or proximal right or left pulmonary artery obstruction. The average age of patients was 47 years with a range of 23 to 84 years. All patients with no contraindications were thrombolysed with Streptokinase followed by the course of anticoagulation. Echocardiography was performed before & after therapy & presence of thrombus in pulmonary artery, Pulmonary Artery Systolic Pressure (PASP) as well as evidence of Right ventricular dysfunction were noted. Results: Of the 24 patients, 20 patients were thrombolysed, while 4 had contraindications to thrombolysis. In the thrombolytic arm, 4 patients died with 1 of these 4 dying as a result of intracranial haemorrhage. In the group of patients not thrombolysed, 3 out of 4 patients died. The echocardiographic features such as PASP & ventricular dysfunction improved in 12 of the 20 patients thrombolysed & the improvement persisted on follow up. None of the patients who were not thrombolysed showed any improvement in Echocardiographic features. Conclusion: Mortality due to massive pulmonary embolism was remarkably high (75%) in patients who were not thrombolysed, while patients who could be thrombolysed had 20% mortality. Thrombolysis also led to improvement in echocardiographic parameters, which was sustained on follow up. Incidence of

The author underlined is the Presenting author. http://dx.doi.org/10.1016/j.ihj.2012.10.031

life threatening bleeding following thrombolysis was low (5%). Thus our study confirmed the efficacy of thrombolysis in patients with hemodynamic compromise & a likely benefit even in those only with RV dysfunction &/or CT features of massive embolism. Name of Corresponding Author: Brijesh Agrawal; Designation: Senior Resident, Department of Cardiology; Address for Correspondence: Topiwala National Medical College & BYL Nair Charitable Hospital, Mumbai 400008l; Telephone 022 23081758; Fax 022 23542540; Mobile 8767586093; Email: [email protected].

Safety and efficacy of eptifibatide as antithrombotic agent in pharmacoinvasive therapy D.P. Sinha, S. Sau, C.M. Zumder, C. Misra, J. Ghosh Department of Cardiology, IPGME&R and SSKM Hospital, Kolkata, India Introduction: Primary PCI is the preferred method of revascularisation in STEMI if it can be performed in time. However in our country negligible percent of patient can achieve the scheduled door to balloon time of <90 minutes. Use of gp2b3a inhibitor as antithrombotic agent is class1 indication in primary PCI. But their use in pharmaco invasive arm is shaded by increase risk of bleeding. Abciximab is effective but very costly. In our country, considering the socio-economic status of the population a cheap though effective antithrombotic agent is required for successful procedure. Aims and objectives: To determine the safety and efficacy of pharmaco-invasive reperfusion strategy utilising full dose of thrombolytics combined with PCI and intra and postoperative eptifibatide use as sole antithrombotic agent in STEMI, presenting in our hospital or referred from outside. Materials and methods: Prospective data obtained from patient attending in our hospital with AMI thrombolysed outside or in our hospital within the schedule time period of 24 hrs of acute event. Streptokinase was used as thrombolytic agent. They all received the loading dose of aspirin 325 mg, either Clopidrogrel 600 mg /prasugrel 60 mg, no heparin, intra & post procedural bolus & maintenance dose of eptifibatide according to weight adjusted

i n d i a n h e a r t j o u r n a l 6 4 ( 2 0 1 2 ) S 1 2 8 eS 1 3 1

dose. Wide range of age from 32-83 yrs, both high and low risk STEMI, both diabetic and nondiabetic patient included in the study. All of the patients present within two to twelve hrs of AMI. Procedures were done at mean six hrs of thrombolysis. End point event monitored were stroke, major bleeding, reinfarction, stent thrombosis, SCD due to other complication within one month, rescue PCI Results and observations: 62 patients were studied from month May 2011 till date.49 were male and 13 were female. Majority were in 50-59 yrs age group in both male and female (25 and 7respectively). All patients received 1st bolus of eptifibatide after PTCA wire crossed the lesion.7 patients had no reflow and among them 3 had TIMI 2 flow at the of the procedure. Post procedure 3 (4.8%) had minor bleed and 1 (1.6%) had major bleed requiring blood transfusion. 2 (3.2%) patients had subacute stent thrombosis who died during hospital stay. No Stroke, procedural AMI was reported. Conclusion: There was no excess bleeding, ischaemic complications or mortality in this group although heparin was not used. Thus it can be concluded that Use of eptifibatide as sole antithrombotic agent in patient undergoing pharmacoinvasive therapy is safe and effective Abbrebiations: AMI-Acute myocardial infarction. STEMI-ST Elevation Myocardial Infarction. PCI-Percutaneous coronary intervention, SCD-Sudden Cardiac Death Name of Corresponding Author: Prof. D.P. Sinha; Designation: Professor of Cardiology; Address for Correspondence: Department of Cardiology, ICVS, IPGME&R and SSKM Hospital, KOLKATA-20; Mobile 9433018443; Email: [email protected].

Role of platelets in thrombosis; newer antiplatelet therapies: An overview Gundu H. R. Rao, Professor Lillehei Heart Institute, University of Minnesota, USA Platelet hyper-function plays a very important role in the pathogenesis of atherosclerosis, thrombosis and stroke. Hyperactive platelets also are implicated in precipitating acute vascular events in clinical complications associated with type-2 diabetes. Blood platelets interact with a variety of soluble agonists such as epinephrine, adenosine diphosphate (ADP), and many insoluble cell matrix components, including collagen, fibronectin and biomaterials used for medical devices and drug delivery. These interactions stimulate specific receptors on the plasma membrane and initiate the activation of intracellular enzymes. Ionized calcium is the primary bio-regulator and varieties of biochemical mechanisms modulate the level and availability of free calcium. Elevation of cytosolic calcium stimulates phospholipases and release arachidonic acid (AA) from platelet membranes. Free AA is transformed to bioactive pro-aggregatory metabolites like prostaglandin endoperoxides and thromboxanes. Aspirin inhibits the formation of these active metabolites, whereas Plavix (Clopidogrel) inhibits ADP mediated activation of platelets. Aspirin, Plavix and their combinations are the choice of anti-platelet drugs available for secondary prophylaxis at this time. In spite of such prophylactic measures, significant numbers of patients on these therapies are at risk for acute vascular events, indicating the limitations of these therapeutic modalities. In this overview, I will discuss platelet physiology, pharmacology, risk assessment, risk management, anti-platelet therapies,

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expectations and limitations of anti-platelet therapies and some aspects of prevention strategies. Name of Corresponding Author: Gundu H. R. Rao Ph D; Designation: Emeritus Professor; Address for Correspondence: Unit 306, North Tower, 12500 Park Potomac Ave, Potomac, MD, USA 20854; Telephone 301 444 4545; Mobile 952 594 5248; Email: gundurao9@gmail. com

Cardiovascular manifestations of acute organophosphorus poisoning S. Laudari and Patowary B.S. DM Resident Cardiology, Professor of Medicine, College of Medical Sciences, Bharatpur, Nepal, India Aims and Objectives: This study is aimed to study the different cardiovascular manifestations and complications of acute organophosphorus (OP) poisoning. Materials and Methods: This is a hospital based prospective study of 115 acute OP poisoning patients presenting in casualty, intensive care unit and medical wards of CMS-Teaching Hospital, Bharatpur (Nepal) during November 2008 to October 2011. All the data were entered into pre-structured proforma and then analyzed by SPSS 15.00. Results: Majority of the patients had cardiac manifestations in the form of sinus tachycardia (57/115¼49.57%). Sinus bradycardia was observed in only 3 (2.61%) patients. The common complications were: non-cardiogenic pulmonary edema in 23 (20%); electrocardiographic abnormalities including prolonged Q-Tc interval in 21 (18.26%); cardiac arrhythmias in 12 (10.43%); ST-T changes in 10 (8.70%) and atrioventricular conduction defects in 5 (4.35%). Hypertension was detected in 23 (20%) patients and hypotension in 6 (5.22%). Sixteen (13.91%) patients needed respiratory support because of acute respiratory failure. Five patients had polymorphic ventricular tachycardia. Three patients died from ventricular fibrillation. The overall mortality during this study was 8 (6.95%) mainly contributed by WHO Class I compounds like methylparathion and dichlorvos. Conclusions: Cardiac complications are commonly encountered after acute OP poisoning especially with WHO Class I compounds during the first few hours. Hypoxia, respiratory failure, acid base disturbances mainly metabolic/mixed acidosis, dyselectrolytemia and over atropinisation were the major contributing factors. Intensive supportive treatment and early specific therapy with atropine and pralidoxime to counteract muscarinic and nicotinic effects in intensive care unit will definitely help to reduce the mortalities and morbidities. Name of Corresponding Author: Dr Shankar Laudari, DM Resident, Cardiology; Designation: College of Medical Sciences, Bharatpur, Nepal; Address for Correspondence: Telephone 977 1 56523609; Fax 97756521527; Mobile 9779845112909; Email: [email protected]

Efficacy of high dose atorvastatin after PTCA and its tolerance in Indian patients K.V. Pranav Kumar, K. Tamilarasu, P. Ramasamy, P. Arun Kumar, G. Rajendiran, J.S. Bhuvaneswaran PSG Institute of Medical Sciences and Research, Coimbatore, India

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Aim & Objective: To study the efficacy of high dose atorvastatin in reducing LDL levels after PTCA and to study its tolerance in Indian patients. Methods: The study was done on 30 patients who underwent PTCA in PSG hospitals, Coimbatore from June 2012 to July 2012. Lipid levels were checked after 1 week of receiving 80mg of atorvastatin after undergoing PTCA. Outcome was measured in terms of number of patients who reached LDL levels of 100 or lower. Occurrence of any side effects of atorvastatin and SGOT/SGPT levels were noted at one week. Results: Out of 30 patients included in the study, at the end of 1 week of therapy with 80mg of atorvastatin, 66% (n¼20) of the patients had LDL level of <70, 23% (n¼7) had levels of 71-100 and only 10% (n¼3) had levels >100. Of the 3 patients with LDL levels >100, the range was 101 to 102. There was no significant elevation in SGPT and SGOT levels with average value being 29 and 22 respectively. 26% (n¼8) responded positively for adverse effects of atorvastatin. Side effects reported were minor and included muscle and joint pain and none of them were severe enough to discontinue therapy. Conclusion: High dose atorvastatin is very efficacious in reducing LDL levels in a short period of time and is well tolerated in Indian patients. Name of Corresponding Author: Dr. Pranav Kumar K.V; Designation: 2nd year Resident ( DM Cardiology); Address for Correspondence: PSG Hospital, Coimbatore; Tel./Fax: 0422 2365000 Mobile þ91 9003346211; Email: [email protected].

Comparative study of prasugrel and clopidogrel in patients undergoing PCI in Indian population. Prabhu S., Inania R., Bansal N.O. Sir J. J., Hospital, Mumbai, India Aims and Objective: To compare the efficacy and safety of prasugrel with clopidogrel in patients with acute coronary syndrome under going PCI. Methods: To compare prasugrel, a new thienopyridine, with clopidogrel, we randomly assigned 370 patients (185 in each group) with moderate to high risk acute coronary syndromes with age less than 75 years with scheduled percutaneous coronary intervention to receive prasugrel (a 60 mg loading dose and a 10 mg daily maintenance dose) or clopidogrel (a 300 mg loading dose and a 75 mg daily maintenance dose). Mean body weight was 64 kg. The primary efficacy endpoint was death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The key safety end point was major bleeding. Results: The primary efficacy endpoint occurred in 9.1% of patients receiving clopidogrel and 6.4% of patients receiving prasugrel. We also found significant reductions in the prasugrel group in the rates of myocardial infarction (8.1% for clopidogrel vs 5.4% for prasugrel), urgent target vessel revasularisation (4.3% for clopidogrel vs 2.7% for prasugrel). Major bleeding was observed in 2.1% of patients receiving prasugrel and 1.6% of patients receiving clopidogrel. Also greater in the prasugrel group was the rate of life threatening bleeding (2.1% vs 1.6%), bleeding requiring transfusion, (4.3% vs 3.2%) and overall bleeding risk (5.4% with prasugrel and 3.2% with clopidogrel). Conclusion: Our data support the hypothesis that the greater inhibition of adenosine diphosphate-induced platelet aggregation by means of prasugrel, a potent oral P2Y12 inhibitor, is more

Death from cardiovascular causes, nonfatal MI, or nonfatal stroke Nonfatal MI Target vessel revascularisation Stent thrombosis Major or minor TIMI bleeding Life threatening bleeding Intracranial bleeding Bleeding requiring transfusion

Prasugrel %(n)

Clopidogrel %(n)

6.4 (12)

9.1 (17)

5.4 2.7 1.08 5.4 2.1 1.08 4.3

(10) (5) (2) (10) (4) (2) (8)

8.1 4.3 3.2 3.2 1.6 0.5 3.2

(15) (8) (6) (6) (3) (1) (6)

effective at preventing ischemic events than is the inhibition conferred by a standard regimen of clopidogrel. However, this beneficial effect is accompanied by a slight increase in the rate of major bleeding. When considering the choice of antiplatelet regimens for the treatment of patients with acute coronary syndromes who are undergoing PCI, clinicians need to weigh the benefits and risks of intensive inhibition of platelet aggregation. Name of Corresponding Author: Sandesh Prabhu; Designation: Senior Resident, DM Cardiology; Address for Correspondence: Department of Cardiology, Sir J J hospital, Byculla, Mumbai; Telephone: 02223738947 Fax: 02223735599 Mobile: 9892654409; Email: [email protected].

Pattern and prevalence of cardiovascular disease in indoor psychiatric patients in an industrial city of eastern India Subodh Kumar and K. N. Thakur Bokaro General Hospital, Bokaro Steel City, India Various psychiatric conditions and stress related disorders have been evaluated as risk factors for the development and expression of cardiovascular disease. The issue of prevention of cardiac problems in psychiatric patients has been poorly attended by the clinicians in this part of the country. Aims and objects: The present study aims to see the pattern and prevalence of cardiovascular disease in adult psychiatric patients admitted in the psychiatry ward of the Bokaro General Hospital in 4-month duration period. Methods: In this study all the 122 adult psychiatric patients admitted in the psychiatry ward of the hospital by the psychiatrists were selected for the examination during a random 4-month period, April to July, 2012. Pattern and prevalence of cardiovascular disease in these patients were ascertained with the help of a clinical psychologist (presenting author), the treating psychiatrists, and the case record files. Sociodemographic and clinical data-sheet and especially designed psychosocial risk factors schedule of cardiovascular disease were applied to the subjects. Results and conclusions: The obtained data are being analyzed. Results and conclusions of the study and their implications for prevention of cardiac risk factors in this clinical population will be discussed at the time of presentation. Name of Corresponding Author: Subodh Kumar; Designation: Senior Clinical Psychologist; Address for Correspondence: Q. No. 3039, Sector- 5B, Bokaro Steel City, Jharkhand-827006; Ph. 08986873068 Mobile: 09798701542; Email: [email protected].

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A Comparative Evaluation of the Safety and Tolerability of the combination of Aspirin and Prazugrel with Aspirin and Clopidogrel in Post PCI patients Tom Devasia*, Supurna Dhar**, Swapna S.**, Thashma P.P.**, Yeshwanth Rao** * Dept of Cardiology, Kasturba Medical College Hospital, Manipal, Karnataka **Faculty, Dept. Of Pharmacology, KMC-IC, Manipal, Karnataka Background: Prasugrel, a new thienopyridine antiplatelet agent is indicated for the reduction of thrombotic cardiovascular events (including stent thrombosis) in patients with acute coronary syndrome (ACS) who are to be managed with primary or delayed percutaneous coronary intervention PCI . Prasugrel may be given concurrently with aspirin for post PCI patients. A potential concern of prazugrel therapy is its safety, particularly bleeding. The use of aspirin and clopidogrel in combination has become part of the standard clinical care of patients with coronary artery disease. The aim of this study is to compare the safety of 2 antiplatelet combinations (prasugrel + aspirin vs clopidogrel + aspirin) in post PCI patients. Methodology: Seventy three eligible patients were enrolled in the study and randomised based on the body weight (33 patients in <60 kg category & 40 in >60kg category) into arms - prazugrel/ aspirin (17 in <60 kgs, 20 in >60kgs) & clopidogrel/aspirin (17 in <60kgs & 20 in >60kgs). Haemoglobin levels were estimated before (0 week) and after (12 weeks) the study. Any other adverse effects were observed during the study. Results: The mean and the standard deviation between Hb values before and after antiplatelet combination therapy showed no significant difference (p¼0.94 & 0.93 in <60 kg, p¼0.56 & 0.81 in >60 kg resply) in both the groups. No other adverse effects were observed. Conclusion: The safety profile of the newer antiplatelet drug prazugrel (in combination with aspirin) is similar to the current standard combination of clopidogrel and aspirin.

Oral Presentation Outcome of high dose tirofiban bolus only versus bolus plus infusion strategy during primary PCI in Acute Myocardial Infarction (AMI) T. Ghose, R. Kachru, R. Gupta, A. Hussain, S.D. Karloopia, K.K. Shahi, U. Kaul Fortis Flt. Lt. Rajan Dhall Hospital, New Delhi, India

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Single centre studies have shown that high dose tirofiban (25 mcg/ kg) bolus only during elective percutaneous coronary intervention (PCI) is safe, feasible and has comparable short and intermediate term out come. Outcome data of such an approach in primary PCI is rare. In this retrospective analysis, we compared the in hospital and 30 days MACE amongst all the patients undergoing primary PCI with tirofiban bolus (Group A) and bolus plus infusion (Group B) usage between June 2006 to June 2012. Standard antiplatelet protocol was followed. Inj. Tirofiban bolus was administered as intravenous/intracoronary bolus (25 mcg/kg over 3 min) or bolus plus infusion (0.15 mcg/kg/min over 16-18 hours). Inj. Heparin was administered to keep the intraprocedural ACT between 250-300 seconds. Thrombosuction (Thrombuster II, Kaneka Corporation, Japan) was done. Intracoronary NTG and/or Nicorandil were administered routinely based on the haemodynamics. Either balloon dilatation followed by stent implantation or direct stenting was performed. In trans radial approach the sheaths (6F, Avanti, Cordis) were removed in lab and pneumatic radial compression device (TR band, Terumo, Japan) was applied. In transfemoral approach the sheath (6F, 7F, Cordis) were removed at ACT < 160 sec. Baseline demographic profile was comparable between two groups. Post procedural TIMI III flow was achieved in 48 (94%) in group A compared to 190 (95.4%) in group B (P¼NS). Post procedural TMP flow was grade 1 in 1 (2%) vs 3 (1.5%), TMP grade 2 flow was in 24 (47.05%) vs 76 (38.1%) and TMP grade 3 flow was 26 (50.9%) vs 120 (60.3%) patients in group A and B respectively (P¼NS). Mean left ventricular ejection fraction was 38þ12% vs 39þ14% in group A & B respectively (P¼NS). Death was recorded in 1 (1.9%) vs 2 (1.0%) in Group A & B respectively (P¼NS). Myocardial infarction occurred in 5 (9.8%) vs 6 (3.0%) in Group A & B respective (P¼NS). TVR occurred in 3 (5.9%) vs 2 (1.0%) in Group A & B respectively. TIMI Major bleeding occurred in 6 (11.7%) vs 8 (4.02%) in Group A & B respectively (P¼NS). TIMI Minor bleeding occurred in 10 (11.7%) vs 12 (4.02%) in Group A & B respectively (P¼NS). Any bleeding occurred in 16 (31.3%) vs 20 (10.05%) in Group A & B respectively (P¼NS). High dose tirofiban bolus only dose in the setting of primary PCI is safe, useful and is associated with similar outcome when compared with bolus plus infusion strategy. Large prospective randomized controlled trial is warranted. Name of Corresponding Author: Dr. Tapan Ghose; Address for Correspondence: 6020/D-6 Vasant Kunj, New Delhi 110070 Mobile 9811695113; Email: [email protected].