Division of Clinical Research & Training

St. John’s Research Institute Bangalore, India

01 Division of Clinical Research & Training

Our Mission

• To develop and conduct Clinical Research with special relevance to India and other developing countries • To achieve world class research standards at ‘realistic’ costs • To transform knowledge to better health through advocacy and policy change

Division of Clinical Research & Training St. John’s Research Institute St. John’s National Academy of Health Sciences, Bangalore-560 034 Karnataka; India Tel: +91-80-49467081/82/83/84 Fax: +91-80-49467090 For Enquiries, Please E-mail: [email protected]

02 About us

InstituteThe Division (SJRI of) Clinicalis one of Research four institutions and Training of the is aSt part John’s of St.National John’s AcademyResearch Institute,of Health established Sciences. inThe the otheryear 2000. institutions The St. John’s are St. Research John’s 1200 beds ranked one among the top ten Medical Colleges in India and St. John’s Medical College Hospital with , St. John’s Medical College

College of Nursing. From its inception 50 years ago (in 1963) St. John’s set before it an ideal of excellence in academic training as well as service to society.

In 2000,

St. John’s commitment to excellence in research led to setting up an Institute dedicated to research and capacity development.

The1. Clinical Research Research Institute andhas 8Training Divisions: by peer-reviewed grants while some 2. Epidemiology and Biostatistics are supported by Industry. leading journals including the Lancet, 3. Health and Humanities Our studies have been published in 4. Infectious Diseases JAMA, NEJM, Nature Cardiovascular, 5. Medical Informatics Journal,American JAPI, Heart etc. (See Journal, Pages) Circulation, European Heart Journal, Indian Heart 6. Mental Health and Neurosciences To focus on knowledge translational 7. Molecular Medicine research and training in health 8. Nutrition research methods, The Division of Clinical Research we recently and Training designs and conducts formed the Indian Cardiovascular national and international clinical Research and Advocacy Group (ICRAG) in collaboration with McMaster University, Canada and three other trials and observational studies in Institutions in India (Rajah Muthaiah, cardiovascular disease (CVD). Our Annamalainagar, Mahatma Gandhi ofcollaboration academic clinical includes researchers about 200 in Institute, Sevagram and Fortis Escorts institutions - the largest network HeartHospital, Lung Jaipur). Blood We Institute are recognised (NHLBI) as Nationala Center Instituteof Excellence of Health by the (NIH, National USA) India. We have recruited more than and United Health to counter chronic 60,000 subjectsitiated in different studies studies funded in just over a decade. Most of these are investigator-in diseases in developing countries. 03 Our Team

DCRT has a dedicated Dr.and Prem highly Paisqualified and Dr.Team Denis for theXavier. conduct of Clinical Research. The team is led by

Dr. Prem Pais M.D., Professor of Medicine Chief Mentor, Division of Clinical Research & Training Dr. Prem Pais, is one of India’s eminent clinical researchers in

preventive cardiology. He is on the review board of the Indian Council of Medical Research (ICMR) and a reviewer of the largeDavidson’s registries, Textbook case ofcontrol Internal studies Medicine. and clinical He is the trials steering that committee member and Principal Investigator of several

have identified risk factors and defined the evidence for the treatment of cardiovascular disease. Dr. Pais is the co-chair of the NIH Centre of Excellence to counter chronic diseases in Dr.developing Denis countries.Xavier M.D., M.Sc (Clin Epi) Vice Dean (PG) Professor and Head of Pharmacology, SJMC Head, Division of Clinical Research & Training

He has helped understand the risk factors for CVD (INTERHEART, INTERSTROKE case control studies), practice patterns and outcomes in CVD (CREATE, INSPIRE, RELY registries) and the effect of antiplatelet, anticoagulants, antihypertensive, lipid lowering drugs and a (POISE, VITATOPS, PROFESS, ASPIRE, OASIS, TIPS, TIPS-3, TIPS-K, HOPE-3, ARISTOTLE, RECREATE, AVVEROES). He was the Principal Investigator of the ‘Centre of Excellence’ award by the NHLBI (NIH, USA) and Academic Collaborators:United Health under their Global Health Initiative program

04 (2009-2014). He conducted knowledge translational studies and managing comprehensive training programs for about 1100 health professionals in health research methods. He was the Principal Investigator of the SPREAD trial evaluating the impact of community health worker based interventions in the secondary prevention of acute coronary syndromes (14 centers, 800 patients) and co-investigator of the PREPARE trial, a cluster RCT evaluating the impact of community health workers in primary prevention among rural communities. He was also the Principal Investigator of INSPIRE a 10,500 patient StrokeDr. Padmini Registry Devi from M.D.,all regions of India. Associate Professor of Pharmacology, SJMC

Co Investigator for MARS and AMEND program. A core member of the Health Research Methodologies training team. Her areas Dr.of interest Atiya includeFaruqui, MD and cardiovascular research. Associate Professor of Pharmacology, SJMC

Co-investigator in observational studies in cardiovascular disease- FRIENDS Study (primary care physicians) and SPECTRUM (secondary and tertiary care physicians); VISION Study (A cohort study in Peri-operative cardiac Ischaemia). She is currently involved in areas of health promotion, coordinating the development of a website,Dr. Mangala as well Rao, as working MD with primary care physicians. Assistant Professor of Pharmacology, SJMC

Co-investigator of a Systematic Review of all the cardiovascular studies conducted in India, involved in an observational study in primary care physicians (FRIENDS). She is the Project officer for the multi centric POISE 2 (PeriOpertive Ischemic Evaluation) trial. She is currently involved in looking at the practice patterns Government Collaborators:for chronic diseases among primary care physicians.

05 Dr. Deepak Kamath M.D., Assistant Professor of Pharmacology, SJMC

trials.Co-Investigator for the TIPS-3 polypill trial and IMPACT-AF. He is also the trial manager for APOLLO, HOPE-3 and other large

Godfreeda Denis B.Sc (Microbiology), MSc (Clinical Trials & Regulatory affairs)

Training from 2001. Her interest includes coordination of Senior Coordinator in the Division of Clinical Research and

multicentre drug trials, registries and observation studies in Cardiovascular disease. She also heads the monitoring group.

Nandini Mathur M.Sc (Microbiology)

coordinating large multicentre randomized clinical trials, Senior Study Coordinator from 2004 and has experience in

case control studies and registries. She is also the program coordinator of the Health Research Methodologies & Training under mentorship program conducted by the NIH-NHLBI- United Health funded Centre of Excellence as well as of Pfizer’s Preferred Research Centre.

06 Our Contribution

Clinical Research

1. Generated evidence from a developing country on risk factors and practice patterns for Acute MI • Indian Case control study and INTERHEART • CREATE Registry 2. Generated evidence on risk factors and treatments for • INTERSTROKE, INSPIRE 3. Contributed to Global RCTs that have impacted clinical practice • CREATE Study – use of LMWH & GIK in Acute MI • OASIS 5 & 6 – use of fondaparinux in ACS Trials • in RELY, Health ARISTOTLE System -Research Novel anticoagulants in atrial fibrillation

• ischemia PRoFESS – largest secondary stroke prevention study • POISE 1 & 2 –largest clinical trials evaluating treatments in perioperative

• TIPS -1, 2 & 3 –RCTs evaluating a “Polypill” • PREPARE-Randomized trial evaluating primary prevention strategies at the community level. • SPREAD - Randomized trial evaluating post discharge interventions in Training ACS patients.

• Research methodology course for medical professionals • Trial management course for research coordinators Industry • Clinical Collaborators: training for Biomedical Industry

07 Our Capacity for Clinical Research

• At about 200 sites across the country and about 500 investigators. coordinators and research • Team of trained & experienced and 500 across the country. assistants, about 50 at St. John’s

• Capacity to coordinate large multicentre global clinical trials International • Regulatory Approval - National & Clinical Research Assistants

• Investigational Product – Importation, storage, redistribution & accounting • A State of the Art Storage facility which is access controlled and temperature controlled to store • India.The store distributes drugs and materials to over 500 sites across

• Sample Storage

Clinical Trial Supplies

• A Bio-repository for long term storage of biological samples. It has the capacity to store 80,000 samples.

Sample Storage

08  Data Management

• Develop Case Report Forms • Set up database • Handle data from over 100 sites (receive forms, enter data, generate queries, resolve queries, rolling database lock) Data Management Team

 Bio Statistics

and methodologies, • Consultant for - study design

Questionnaire preparation and

database development

• Carries out - Sample size calculation,Data quality checks, Randomization Statistical analysisschedule and preparation,result Bio Statisctics Team

interpretation and contribute to manuscript preparation.

Two dedicated servers that can support databases. It has facilitated remote 150data sites capture across for the global country multicentre in data clinical trial. Over 15 Years trained capture, supported central databases with resolution of queries in case a report forms. Promasys, Wesystem. have This licenseduses the study life cycle versatile database management concept, creates data capture forms, build edit checks and overall enhances efficiency in data management.

Data Server 09 Research Training at DCRT

We conduct various training programs in Health Research Methods for Nationalphysicians Institutes and Research of Healthmanagement (NIH, for research support staff. We are a conduct training in health research methods.USA) Centre We are of Excellencealso recognized (CoE) as to a Year 2016 No of Partipants - 88

conduct training in clinical research.Preferred Research Centre (PRC) by Pfizer, to

To date, we have trained 1188 participants from 60 institutions Year 2015 spread across 33 cities in 7 countries. No of Partipants - 1. 2011,Two-year 2011-2013) Research training through mentorship (2009,

2. 2011)Two week course in Health Research Methodology (2009,

3. (2010,Two week 2012) course in Advanced Health Research Methodology 4. Six months in Undergraduate

2010, 2011, 2012, 2013) Research Mentorship (2009,

5. 2013)Three days course in Clinical Research Management (2011,

6. Three days course in Research 2012)Methodology & Good Clinical Practice for physicians (2010, 8. One day Nurses Research (20Workshop13) in collaboration with Global Research Nurses network 7. One week International course 9. Three day course on Data Management and Biostatistics for (2013,in Health 2014, Research 2015) Methodology & Evidence Based Medicine

10 health professionals (2014). o da undergraduate medical student’s 10. Tw ys workshop for setting University, Canada. We initiated a (NPTU’s)up Non-Communicable (2014) diseases Prevention and Training units mentorship program at MGIMS, Sevagram and at St. John’s which completed 6 batches (2009-2015). 11. Three days training program We are a pre vetted site for the 2015)on clinical diabetes and Health Research Methodology (2014, Fogarty Fellowship program. Health professionals can apply to conduct research at St. John’s with financial 12. One day program on Accreditation and technical support from the Fogarty for Clinical Research-Awareness center based in the USA. and expectation (2015) Federation emerging leader think The PRC activities at St. John’s are 13. tankOne week seminar seminar (2016) on World Heart overseen by a Steering Committee which includes members from St. John’s and Pfizer India Ltd. The 14. One week International course in training activities include two short- term courses for Clinicians in Health Health Research Methodology & Research Methods and Good Clinical MostEvidence of our training Based Medicine is conducted (2016) in Practice (GCP), and Site Research Coordinators in Clinical Research collaboration with PHRI, McMaster Management and GCP.

11 Ongoing Studies

1. TIPS-3 - A clinical trial of polypill 9. CANTOS- RCT of subcutaneous in primary prevention setting to India-1,200)canakinumab in the post-MI with reduce cardiovascular outcomes elevated hsCRP (Global- 17,200/ (Global – 5000/India– 2000) 2. MACE Registry- A nation wide 10. PROGRESS- Policy and peeR (India-10,000+)observational study in Acute Sitesmentor in 3 intervention South Asian proGramscountries Coronary Syndrome (ACS) on cardiovascular disease at work 3. AMEND PHASE II- An ongoing (India- 3,000)

management strategies) to program (research, patient 11. AUGUSTUS- Apixaban versus (India-10,000) Vitamin K Antagonist in Patients prevent & manage CVDs in India with Atrial Fibrillation and Acute Coronary Syndrome and/ 4. STABILITY-RCT to evaluate the Inida-or Percutaneous400) Coronary effects of chronic treatment with Intervention (Global 4,600/ 15,828/darapladib India-398) in high-risk patients with chronic CHD(Global – 12. TREAT- Compare ticagrelor with clopidogrel in STEMI patients 5. IMPACT- A clustered randomized India-600)treated with fibrinolytic therapy controlled trial to improve stroke within 24 hours (Global- 4,000/ in patients with atrial fibrillation India-494)by improving treatment with 13. BP Home Monitoring- Perception anticoagulants (Global –1800/ of patients and healthcare providers on patients’ self enhance adherence to treatment 6. HF-CHW- Health workers to management of : and self care among heart failure A pilot mixed methods study (Global- 150/ India- 25) patients (India-30) 14. PANACEA-HF- Piloting a quality 7. ODYSSEY- A phase III trial to improvement intervention for evaluate the lipid lowering failureoptimal (India- medical 230) management efficacy of a monoclonal antibody of patients with chronic Heart that blocks PCSKA receptors (Global-18,000/ India-521) 8. MANAGE- Randomized clinical trial of Dabigatran in peri operative myocardial infraction 12 (Global-1750/ India- 250) Completed Studies

1. HOPE-3 - A trial to evaluate 9. CREATE – RCT of Reviparin and hydrochlorothiazidethe safety and efficacyand their of /or AHJ GIK 2004) Vs placebo in AMI (Global – rosuvastatin and cadesartan/ 20,201/India – 8060, JAMA 2004

combinations in middle aged 10. POISE - Metoprolol vs placebo in people, who are at intermediate Peri Operative Ischemia (Global risk for vascular events (Global– –8351/India – 777, Lancet 2008) 11,000/India – 2000) 11. CURRENT - RCT of standard 2. MACE Registry - A nation wide vs high dose of clopidogrel observational study in Acute in unstable angina or non-ST Coronary Syndrome (ACS) (India segment elevation (Global – 12. PrePare - A cluster randomized trial – 10,000+) 25000 /India –2250) 3. VISION - A large cohort study to evaluate major vascular events in to evaluate primary prevention 4000,patients JAMA undergoing 2012) non-cardiac strategies at the community level surgery (Global- 40,000/India – to promote treatment adherence to prevent cardiovascular disease 4. AMEND - An ongoing program (India – 27,000) (research, patient management 13. CREATE ACS Registry - To strategies) to prevent & manage examine the treatment patterns CVDs in India (India – 10,000) to determine etiologies, clinical Lancetand outcome 2008 of ACS patients in 5. INSPIRE - An observational study India (Global and India – 20,468,

practice patterns and outcomes of 14. POISE - Metoprolol vs placebo in in India (India – 10,500) Peri Operative Ischemia (Global – 6. SPREAD - A randomized trial 8351/India – 777, Lancet 2008) comparing post discharge 15. PRoFESS - RCT of Dipyridamole, interventions by CHWs to Clopidogrel & Telmisartan in standard care in ACS patients ischemic stroke (Global – 20,333 (India – 800) /India – 1,620, NEJM 2008) study the risk factors for AMI in 7. ICMR - A case control study to 16. TIMACS - RCT of timing of Intervention in ACS (Global – Indians (India – 2000) 3031 /India – 31, AHA 2008) study of risk factors for AMI in 8. INTERHEART - A case control 17. OASIS 5 - RCT of fondaparinux Vs enoxaparin in unstable/ 2004all regions / JAMA of 2006) the world (Global– NEJMnon-ST-segment 2006) elevation MI 29,972 / India – 3000, Lancet (Global-20,078 /India – 522, 13 18. OASIS 6 - RCT of Fondaparinux Vs 26. APOLLO - A randomized controlled placebo in STEMI (Global-12,092 trial of aliskiren in the prevention /India –1444, JAMA 2007) of major cardiovascular events in elderly people (Global – 11,000/ 19. RELY - RCT of dabigatrin Vs India – 1600) NEJM,warfarin Lancet) in atrial fibrillation (Global – 18113 /India – 578, 27. APPRAISE 2 - A trial to evaluate 1078)apixaban in patients with recent ACS (Global – 10,000/India – 20. VITATOPS - RCT of multi-vitamins vs placebo in secondary stroke prevention (Global – 8167 /India 28. RELY-AF Registry – An – 1421, Int J of Stroke, 2007) observational study to determine predisposing conditions & 21. AVVEROES - RCT of apixaban Vs regional variations in atrial ASA to prevent stroke in atrial fibrillation/ flutter (Global fibrillation patients who had –15,000/India – 2500) 203,failed NEJM or are 2011) unsuitable for Vit- K antagonist (Global – 5000 /India– 29. ASPIRE - A randomized controlled trial of low-dose after initial anticoagulation to prevent 22. ARISTOTLE - RCT to evaluate the recurrence of venous apixaban in preventing stroke thromboembolism (Global – and systemic embolism in atrial 2000/India – 400) fibrillation (Global – 18,000/ India– 601, NEJM 2011) 30. FRIENDS - A Prospective Study of Practice Patterns and Outcomes 23. RECREATE - RCT of Intensive normoglycemia in acute MI in Chronic Disease in an Urban insulin therapy targeting 2000) Family Practice Setting (India – (Global – 287/India – 273, Diab Care 2011) 31. SPECTRUM - Situational analysis of the practice patterns in 24. RIVAL - RCT of radial versus Angina or cardiovascular disease in all femoral PCI Access in Unstable regions of India (India – 1300) 2012) (Global – 7000/India – 340, JAMA 32. OASIS-8/ FUTURA - RCT to evaluate standard Vs low dose control study to determine the adjunctive i.v. UFH in patients 25. INTERSTROKE - A case undergoing PCI (Global – 2000 / emerging risk factors for stroke India – 500, JAMA 2010) importance of conventional and Lancet 2011) 33. MARS - A five arm RCT of (Global – 24,000/India – 5000, amlodipine + metoprolol XL 400,& amlodipineBlood Pressure as 2011) individual components in Indians (India – 14 34. POLYCAP - A 9 arm RCT of a 35. TIPS-K - RCT of low strength POLYCAP Vs its components in polycap & of low strength K+ 2009)subjects with at least one CV supplementation in patients risk factors (India – 2053, Lancet with stable CVD/ ischemic heart disease (India –500)

Abbrevations:

ACS: Acute Coronary Syndrome, CHW: Community Health Worker, CVD: Cardio Vascular Disease, RCT: Randomized Controlled Trial, AMI: Acute Myocardial Infarction, MI: Myocardial Infarction, STEMI: ST-Elevation MI, UFH: Unfractionated Heparin, ASA: Aspirin, PCI: Percutaneous LMWH: Low Molecular Weight Heparin GIK: Glucose Insulin Potassium Intervention, K+: Pottassium)

15 Selected Publications

1. inPais Indians: P, Pogue case-control J, Jayprakash study. S, Yusuf Lancet S, 1996.et al; 9. rationaleHankey GJ, and Algra design A, Xavier of randomised D, et al; VITATOPS, trial of PMID:Risk factors 8709733. for acute myocardial infarction the VITAmins TO prevent stroke trial: transient ischaemic attack or stroke Int J Stroke.B-vitamin 2007 therapy PMID: 18705976. in patients with recent 2. Yusuf, S., Hawken, S., Ôunpuu, S., Dans, T., Avezum, A., Lanas, F., Pais P et al. Effect of potentially modifiable risk factors associated 10. Cook D, Moore-Cox A, Xavier D, et al; Lancetwith myocardial 2004 - 937-952. infarzction PMID:15364185 in 52 countries Randomized trials in vulnerable populations. (the INTERHEART study): case-control study, Clin Trials. 2008; PMID: 18283082. 11. Oldgren J, Wallentin L, Afzal R, Pais P, Xavier 3. Yusuf S, Mehta SR, Pais P, Xavier D, et al; D, Yusuf S; OASIS-6 Investigators. Effects of CREATE-ECLA investigators and steering fondaparinux in patients with ST-segment committee. Challenges in the conduct of 2008elevation PMID: acute 18084015. myocardial infarction not large simple trials of important generic receiving reperfusion treatment. Eur Heart J. questions in resource-poor settings: the CREATE and ECLA trial program evaluating 12. Xavier D, Devereaux PJ, Pais P, Yusuf myocardialGIK (glucose, infarction. insulin andAmHeart potassium) J. 2004 and HeartS. Polypharmacotherapy J. 2008 PMID: 19359761. for primary Dec;148(6):1068low-molecular-weight 78. PMID:15632895. heparin in acute prevention of cardiovascular disease. Indian

13. Xavier D, Pais P, P J Devereaux, Changchun 4. Yusuf S, Mehta SR, Xavier D, Pais P, Zhu J, Liu Thanikachalam,Xie, D Prabhakaran, K K K Haridas,Srinath Reddy, T M RajeevJaison, L, et al; CREATE Trial Group Investigators. Gupta, Prashant Joshi, Prafulla Kerkar, S Effects of reviparin, a low-molecular-weight heparin, on mortality, reinfarction, and andSudhir outcomes Naik, A of K acute Maity, coronary Salim Yusufsyndromes et al; strokes in patients with acute myocardial CREATE registry investigators. Treatment PMID:infarction 15671427. presenting with ST-segment registry data. Lancet. 2008 PMID: 18440425. elevation. JAMA. 2005 Jan 26;293(4):427-35. in India (CREATE): a prospective analysis of

5. Mehta SR, Yusuf S, Díaz R, Zhu J, Pais P, 14. Devereaux PJ, Yang H, Yusuf S, Xavier D, Pais P, Xavier D, et al; CREATE-ECLA Trial Group et al. Effects of extended-release metoprolol Investigators. Effect of glucose-insulin- controlledsuccinate intrial. patients Lancet. undergoing2008 May PMID: non- potassium infusion on mortality in patients 18479744.cardiac surgery (POISE trial): a randomised controlledwith acute trial. ST-segment JAMA. 2005 elevation PMID:15671428. myocardial infarction: the CREATE-ECLA randomized 15. Sacco RL, Diener HC, Yusuf S, Pais P et al; PRoFESS Study Group. Aspirin and extended- 6. andYusuf the S, risk Hawken of myocardial S, Ounpuu infarction S, et al;in recurrent stroke. N Engl J Med. 2008 PMID: INTERHEART Study Investigators. 18753638.release dipyridamole versus clopidogrel for case-control study. Lancet. 2005 PMID: 16271645.27,000 participants from 52 countries: a 16. Yusuf S, Diener, Pais P, et al; PRoFESS Study Group. Telmisartan to prevent recurrent on the management of coronary artery stroke and cardiovascular events.N Engl J 7. Karthikeyan G, Xavier D, Pais P. Perspectives disease in India. Heart. 2007 PMID: Med. 2008 Sep 18;359(12):1225-37. Epub 17933988. 2008 Aug 27.PMID: 18753639;Central PMCID: PMC2714258. 17. Xavier D, Pais P, Sigamani A, Pogue J, Afzal 8. Díaz R, Goyal A, Xavier D, Pais P, Yusuf S, R, Yusuf S; Indian Polycap Study (TIPS) myocardialet al; Glucose-insulin infarction. JAMA. potassium 2007 therapyPMID: Investigators. The need to test the theories 18042917.in patients with ST-segment elevation behind the Polypill: rationale behind the Indian Polycap Study. Nat Clin Pract Cardiovasc Med. 2009 PMID: 19104516. 16 18. Diener HC, Sacco RL, Yusuf S, Pais P et al; Effects 27. O’Donnell MJ, Xavier D, Liu L, Yusuf S et al; of aspirin plus extended-release dipyridamole INTERSTROKE investigators. Risk factors for versus clopidogrel and telmisartan on study):ischaemic a case-control and intracerebral study. haemorrhagicLancet. 2010 disability and cognitive function after recurrent PMID:stroke 20561675. in 22 countries (the INTERSTROKE stroke in patients with ischaemic stroke in the Prevention Regimen for Effectively Avoiding LancetSecond Neurol. Strokes 2008 (PRoFESS) PMID: 18757238. trial: a double- 28. Diener HC, Connolly SJ, Xavier D, Yusuf S; for blind, active and placebo-controlled study. the RE-LY study group. Dabigatran compared with warfarin in patients with atrial 19. Goyal A, Mehta SR, Xavier D, Pais P, Yusuf S, fibrillation and previous transient ischaemic et al; Glucose levels compared with diabetes 21059484.attack or stroke: a subgroup analysis of the J.history 2009 PMID: in the 19332208. risk assessment of patients RE-LY trial. Lancet Neurol. 2010, PMID: with acute myocardial infarction. Am Heart 29. Eva Lonn, Jackie Bosch Prem P, Xavier D, 20. Joshi P, Islam S, Pais P, Reddy S, Dorairaj Yusuf S ; The polypill in the Prevention of forP, Kazmi early K,myocardial Pandey MR, infarction Haque S,in MendisSouth Cardiovascular Diseases: Key Concepts, S, Rangarajan S, Yusuf S. Risk factors Current Status, Challenges, and Future countries. JAMA 2009. PMID: 17227980. Directions. Circulation 2010. Asians compared with individuals in other 30. Devereaux P.J. Xavier D, Sigamani A, Yusuf S, et Patientsal; Characteristics Undergoing and Noncardiac Short-Term Surgery: Prognosis a 21. Yusuf S, Pais P, Xavier D, Sigamani A, Mohan cohortof Perioperative study. Ann MyocardialIntern Med. Infarction 2011.PMID: in V, Gupta R, Thomas N. Effects of a polypill 21502650. (Polycap) on risk factors in middle-aged trial.individuals Lancet. without 2009 PMID: cardiovascular 19339045. disease (TIPS): a phase II, double-blind, randomised 31. John H Alexander, Renato D Lopes, Stefan syndrome,James, Prem NEJM Pais, 2011. et PMID: al; Apixaban 21780946 with 22. Connolly SJ, Ezekowitz MD, Yusuf S, Xavier D,; Antiplatelet therapy after acute coronary RE-LY Steering Committee and Investigators. 19717844.Dabigatran versus warfarin in patients with 32. Kavsak, P. a, Walsh, M., Srinathan, S., Sigamani atrial fibrillation. N Engl J Med. 2009 PMID: A, Xavier D et al. High sensitivity troponin T concentrations in patients undergoing 23. Goyal A, Mehta SR, Díaz R, Xavier D, PMID:noncardiac 21640092 surgery: A prospective cohort Pais P, Yusuf S, et al; Differential clinical study. Clinical biochemistry, 2011 May 24. outcomes associated with hypoglycemia 19948980.and hyperglycemia in acute myocardial 33. Christopher B. Granger, John H. Alexander, infarction. Circulation. 2009 PMID: NEJMJohn J.V.August, Prem 2011. Pais, PMID: et al; 21870978 Apixaban versus Warfarin in Patients with Atrial Fibrillation 24. Philippe Gabriel Stege, Sanjit S. Jolly, Shamir R. Mehta, Rizwan Afzal, Denis Xavier, Hans-Jurgen 34. Devereaux PJ, Chan MT, Sigamani A, Yusuf Rupprecht, Jose L. Lopez-Sendon, Andrzej S et al; Association between postoperative budaj, Rafael Campbell joyner, Janice Pogue, JAMA.troponin June levels 2012 and PMID:22706835 30-day mortality among Salim Yusuf; Low-Dose vs Standard-Dose patients undergoing noncardiac surgery. Unfractionated Heparin for The Percutaneous Coronary Percutaneous Coronary Intervention in Acute Coronary Syndromes Treated 35. Yusuf S, Pais P, Sigamani A, Xavier D, Afzal With Fondaparinux: The FUTURA/OASIS-8 R, Gao P, Teo KK et al; Comparison of Risk Randomized Trial. JAMA 2010. Factor Reduction and Tolerability of a Full- Dose Polypill (With Potassium) Versus Low- 25. O’Donnell M, Xavier D, Pias P, Yusuf S et al; Dose Polypill (Polycap) in Individuals at Rationale and design of INTERSTROKE: a PMID:2278706High Risk of Cardiovascular Diseases: TIPS- global case-control study of risk factors for 20389123. 2 Circ Cardiovasc Qual Outcomes Jul 2012 stroke. Neuroepidemiology. 2010; PMID: 36. Hankey GJ, Eikelboom JW, Yi Q, Lees KR, Chen 26. Gupta R, Guptha S, Joshi R, Xavier D; C, Xavier D, Navarro JC. Treatment With B Translating evidence into policy for Vitamins and Incidence of Cancer in Patients cardiovascular disease control in India. Health With Previous Stroke or Transient Ischemic 17 Res Policy Syst. 2011. PMID:21306620. Attack: Stroke. 2012 Apr 3. 37. StrategyDenis Xavier, for Alben Sigamani, Deepak Y. 44. Botto F, Alonso-Coello P, Chan MT, Villar Kamath, Prem Pais. Polypill Is an Important JC, Xavier D, Srinathan S, Guyatt G,Cruz the Prevention of Cardiovascular P, Graham M, Wang CY, Berwanger O, Disease Risk. Journal of Clinical and Pearse RM, Biccard BM, Abraham V, Preventive Cardiology April 2012, No. 2 Malaga G, Hillis GS, Rodseth RN, Cook D, 38. Timothy A. Brighton, John W. Eikelboom, 24534856.P, Nagele P, Raina P, Yusuf S, Devereaux PJ, VISION, Anesthesiology. 2014, Mar; PMID: Kristy Mann, Rebecca Mister, Wendy Hague, Denis Xavier, Rafael Diaz, Adrienne Kirby, John 2012.Simes et al; Low-Dose Aspirin for Preventing 45. P.J. Devereaux, M. Mrkobrada, D.I. Recurrent Venous Thromboembolism, NEJM Sessler, A. Sigamani, D. Xavier, S. Pettit, S. Chrolavicius, and S. Yusuf et al, for the EnglandPOISE-2 Journal Investigators. of Medicine, Aspirin 31 March in Patients 2014. 39. Fathima FN, Joshi R, Agrawal T, Hegde S, PMID:Undergoing 24679062. Noncardiac Surgery. The New Xavier D, Misquith D, Chidambaram N, Kalantri SP, Chow C, Islam S, Devereaux PJ, Gupta R, Pais P, Yusuf S. Rationale and design of the Primary pREvention strategies at the 46. P.J. Devereaux, D.I. Sessler, K. Leslie, A. Sigamani, D. Xavier, S. Pettit, S. diseases.community Am levelHeart toJ. 2013. Promote Adherence of treatments to pREvent cardiovascular Chrolavicius, and S. Yusuf et al, for the EnglandPOISE-2 Investigators.Journal of Medicine, Clonidine March in Patients 31st Thomas T, Murthy S, Sharma K, Bosco 2014.Undergoing PMID: 24679061 Noncardiac Surgery. The New 40. Devi P, Xavier D, Sigamani A, Pandey S,

B, Mehta K, Joshi S, Gupta R, Singh G, 47. Deepak Y Kamath, Denis Xavier, Alben Hiremath J, Ds C, Nambiar A, Pais P. Effect Sigamani, Prem Pais: High sensitivity of fixed dose combinations of metoprolol C-reactive protein hsCRP) & cardiovascular and amlodipine in essential : disease: An Indian perspective. Indian J MARS--a randomized controlled trial. Blood 268 Med Res 142, September 2015, pp 261- Pressure 2011 Suppl 2:5-12. Epub 2011 Oct 13. PubMed : 21992003. Michael Hanna, Jack Ansell, Elaine M Hylek, 48. JohnChristopher H Alexander, B Granger, Laine RenatoThomas, D Junyuan Lopes, 41. Lars Wallentin, Renato D. Lopes, Michael Hanna, Lain Thomas, Anne Hellkamp, Sunil Nepal, Denis Xavier. Efficacy and Safety Wang, M Cecilia Bahit, Freek Verheugt, Jack of Apixaban Compared With Warfarin at Lawrence Denis Xavier, Lars Wallentin: Different Levels of Predicted International Clinical events after transitioning from 2013;127:2166-2176Normalized Ratio Control for Stroke apixaban versus warfarin To warfarin at the Prevention in Atrial Fibrillation Circulation. end of the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial 42. David A. Garcia, Lars Wallentin, Renato D. Fibrillation (ARISTOTLE) trial: American Lopes, Laine Thomas, John H. Alexander, Heart Journal January 2015 Volume 169, Elaine M. Hylek, Patrick Commerford, Denis Issue 1, Pages 25–30 Xavier, Dragos Vinereanu, Hongqiu Yang, 49. Mangala Rao, Denis Xavier, Padmini Devi, and Christopher B. Granger et al; Apixaban Alben Sigamani, Atiya Faruqui, Rajeev versus warfarin in patients with atrial Gupta, Prafulla Kerkar, Rajendra Kumar Jain, fibrillation according to prior warfarin use: Rajnish Joshi, N Chidambaram, Daya Sagar American Heart Journal, Sept. 2013 treatmentsRao, S Thanikachalam, and outcomes SS Iyengar,of coronary Kiron 43. Hankey GJ. Ford AH, Yi Q, Eikelboom JW, Lees arteryVerghese, disease V Mohan, in Indians:Prem Pais: A Prevalence,systematic KR, Chen C, Xavier D, Navarro JC, Ranawaka UK, Uddin W, Ricci S, Gommans J, Schmidt R, Almeida OP, Van Bockxmeer FM. Effect review. Indian heart journal, August 2015, of B-Vitamins and Lowering Homocysteine vl 67,pp 302-310 on Cognitive Impairment in Patients with 50. Prem Pais, Deepak Y Kamath, Alben Previous Stroke or Transient Ischemic Sigamani, Denis Xavier. Prevention of Meta-AnalyAttack: A Prespecifiedsis. Stroke. Secondary2013 Analysis of Cardiovascular Disease: The Polypill Concept; A Randomized, PlaceboControlled Trial and Pathophysiology and Pharmacotherapy of Cardiovascular Disease,2015,pp613-632. 18 51. Eva Lonn, Jackie Bosch, Janice Pogue, Alvaro 56. Yusuf S, Bosch J, Dagenais G, Zhu J, Xavier MatyasAvezum, Keltai, Irina Chazova,Katalin Keltai, Antonio Kamlesh Dans, Rafael Kunti D, Liu L, Pais P, López-Jaramillo P, Leiter LA, Diaz, George J Fodor, Claes Held, Petr Jansky, Dans A, Avezum A, Piegas LS, Parkhomenko A, Keltai K, Keltai M, Sliwa K, Peters RJ, Held C, Jae-Hyung Kim, Lawrence Leiter, Basil Lewis, Chazova I, Yusoff K, Lewis BS, Jansky P, Khunti Lisheng Liu, Patricio Lopez-Jaramillo, Prem K, Toff WD, Reid CM, Varigos J, Sanchez- Pais, Alexandr Parkhomenko, Ron JG Peters, Vallejo G, McKelvie R, Pogue J, Jung H, Gao Leopoldo S Piegas, Christopher M Reid, Kares, P, Diaz R, Lonn E; HOPE-3 Investigators. Sliwa, William D Toff, John Varigos, Denis Cholesterol Lowering in Intermediate-Risk Xavier, Khalid Yusoff, Jun Zhu, Gilles Dagenais, Persons without Cardiovascular Disease.N Salim Yusuf, Novel Approaches in Primary Engl J Med. 2016 Apr 2 Cardiovascular Disease Prevention: The HOPE- 57. LeiterYusuf LA,Piegas S, Lonn E,LS, Pais Parkhomenko P, Bosch J,A, López-Keltai 3 Trial Rationale, Design and Participants’ Jaramillo P, Zhu J, Xavier D, Avezum A, Baseline Characteristics: Canadian Journal of Cardiology, 2015, 32(3): 311-8 M, Keltai K, Sliwa K, Chazova I, Peters RJ, 52. Prem Pais, Deepak Y. Kamath, Alben Held C, Yusoff K, Lewis BS, Jansky P, Khunti Sigamani, Denis Xavier: Prevention of K, Toff WD, Reid CM, Varigos J, Accini JL, Cardiovascular Disease: The Polypill Concept; McKelvie R, Pogue J, Jung H, Liu L, Diaz R, Pathophysiology and Pharmacotherapy of Dans A, Dagenais G; HOPE-3 Investigators. Cardiovascular Disease, 2015, pp 613-632. Blood-Pressure and Cholesterol Lowering in 53. Xavier D, Gupta R, Sigamani A, Kamath DY, Persons without Cardiovascular Disease.N Devereaux PJ, George N, Joshi R, Pogue J, Engl J Med. 2016 Apr 2 Pais P, Yusuf S. Community health worker 58. Krishna Kumar Sharma, Rajeev Gupta, based intervention for adherence to drugs Mukul Mathur, Vishnu Natani, Sailesh Lodha, and lifestyle change after Acute Coronary Sanjeeb Roy, Denis Xavier. Non-physician MarchSyndrome: 2016. a pilot randomized controlled health workers for improving adherence to trial. Lancet Diabetes and Endocrinology medications and healthy lifestyle following acute coronary syndrome: 24-month follow- 54. Gerald S. Bloomfield, Denis Xavier, up study. Indian Heart Journal, 2016. Deshirée Belis, Dewan Alam, Patricia Davis, 59. Meena P Rao, Andrea O Ciobanu, Renato D Prabhakaran Dorairaj, Hassen Ghannem, Lopes, Kathleen A Fox, Ying Xian, Sean D Robert H. Gilman, Deepak Kamath, Sylvester Pokorney, Hussein R Al-Khalidi, Jei Jiang, Kimaiyo, Naomi Levitt, Homero Martinez, Deepak Y Kamath, Otavio Berwanger, Gabriela Mejicano, J. Jaime Miranda, Tracey Denis Xavier, Cecilia M Bahit, Carlos Tajer, KatherinePerez Koehlmoos, A. Sacksteder, Cristina Rabadán-Diehl,Krisela Steyn, Dragos Vinereanu, Yong Huo, Christopher Manuel Ramirez-Zea, Adolfo Rubinstein, B Granger; A clustered randomized trial to AF):IMProve design treatment and rationale. with AntiCoagulanTs American Heart in Nikhil Tandon, Rajesh Vedanthan, Tracy Journal,patients 2016. with Atrial Fibrillation (IMPACT- Wolbach, Yangfeng Wu, Lijing L. Yan. Training and Capacity Building in LMIC for Research in Heart and Lung Diseases 60. Denis Xavier, Rajeev Gupta, Deepak The NHLBI- UnitedHealth Global Health Kamath, Alben Sigamani, P J Devereaux, Centers of Excellence Program, GLOBAL Nisha George, Rajnish Joshi, Janice Pogue, HEART,VOL.11,NO.1,2016March. toPrem drugs Pais, and Salim lifestyle Yusuf:: change Community after healthacute 55. Vilma E Irazola, Laura Gutierrez, Gerald worker-based intervention for adherence Bloomfield, Rodrigo M Carrillo-Larco, Prabhakaran Dorairaj, Thomas Gaziano, coronary syndrome:a multicentre, open, Naomi S Levitt, J Jaime Miranda, Antonio randomised controlled trial, The SPREAD Bernabe Ortiz, Krisela Steyn, Yangfeng Wu, Trial, Lancet Diabetes Endocrinol, Feb 2016. Denis Xavier, Lijing L Yan, Jiang He, Adolfo Rubinstein. Hypertension prevalence, awareness, treatment and control in selected LMIC communities: results from the NHLBI/ MarchUHG network 2016. of Centres of Excellence for chronic diseases,Global Heart, Volume 11, 19 DIVISION OF CLINICAL RESEARCH & TRAINING St. John’s Research Institute, Bangalore

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