MARCH 2011 • Vol. 3 • No. 2

Journal of the Society of PhySicianS of hong Kong

ISSN 2072-4209

www.sophysicianshk.orgVisit the web site for our regular CME programmes for doctors

香港內科學會THE SOCIETY OF PHYSICIANS OF HONG KONG

• giving chemotherapy or intensive immunosuppression to Patients Who are also chronic hepatitis B carriers

DrLiangHinSuen,Raymond(梁憲孫醫生)

• new treatment Modalities in osteoporosis DrChanKwokWing,Fredriech(陳國榮醫生)

• Management of adverse gastrointestinal events in Patients on antiplatelet therapy, Part i: gastrointestinal Bleeding induced by Low-dose aspirin

DrNgFookHong(吳福康醫生)

• Percutaneous coronary intervention for Patients With acute Myocardial infarction

DrChanWaiKwong,Andy(陳偉光醫生);DrLeungWaiSuen,Albert(梁偉宣醫生);DrLeePuiYin(李沛然醫生);DrWongWingKwong,Raymond(黃榮光醫生);DrKwokMiuFong,Jennifer(郭妙芳醫生);DrWuCheeWo(胡志和醫生)

CONTENTS

14 giving chemotherapy or intensive immunosuppression to Patients Who are also chronic hepatitis B carriers

Dr Liang Hin Suen, Raymond (梁憲孫醫生)

18 new treatment Modalities in osteoporosis Dr Chan Kwok Wing, Fredriech (陳國榮醫生)

21 Management of adverse gastrointestinal events in Patients on antiplatelet therapy, Part i: gastro-intestinal Bleeding induced by Low-dose aspirin

Dr Ng Fook Hong (吳福康醫生)

24 Percutaneous coronary intervention for Patients With acute Myocardial infarction

Dr Chan Wai Kwong, Andy (陳偉光醫生); Dr Leung Wai Suen, Albert (梁偉宣醫生); Dr Lee Pui Yin (李沛然醫生); Dr Wong Wing Kwong, Raymond (黃榮光醫生); Dr Kwok Miu Fong, Jennifer (郭妙芳醫生); Dr Wu Chee Wo (胡志和醫生)

Journal of the Society of PhySicianS of hong Kong

MARCH 2011 • Vol. 3 • No. 2

www.sophysicianshk.org

香港內科學會THE SOCIETY OF PHYSICIANS OF HONG KONG

executive coMMittee

PRESIDENT

Dr Lam tat chung, Paul 林達聰醫生

VIcE PRESIDENT

Dr tsang Wah tak, Kenneth曾華德醫生

HoN. SEcRETaRy

Dr Shiu cho tak, Wesely邵祖德醫生

HoN. TREaSuRER

Dr Lam how Mo, ignatius 林孝武醫生

cHIEF EDIToR

Dr Lau chu Pak 劉柱柏醫生

EDIToRS

Dr chan hin Lee, henry 陳衍里醫生

Dr chan Kwok Wing, fredriech 陳國榮醫生

Dr chan Pui yiu, nicola 陳珮瑤醫生

Dr chan tak hin 陳德顯醫生

Dr chen yi tin 陳以天醫生

Dr Kung Wai chee, annie龔慧慈醫生

Dr Lam tat chung, Paul 林達聰醫生

Dr Leung Wai Keung 梁偉強醫生

Dr Li Siu Lung, Steven 李少隆醫生

Dr Shiu cho tak ,Wesely 邵祖德醫生

Dr tsang Wah tak, Kenneth 曾華德醫生

Dr Wong chun yu, Benjamin 王振宇醫生

EditorialThis year the H1N1 swine flu seems to have taken an exceptionally heavy toll, causing serious morbidity and mortality to the local population, including children and healthy adults. It is again a time when the medical profession needs to do its best to contribute to the health and safety of the community. We cogently ask all doctors, including frontline doctors, public health admin-istrators and research workers, to treat this as their priority, and help to put the epidemic under control.

Dr lau Chu Pak劉柱柏醫生FRCP, MD, FHKAM (Medicine)Chief Editor

Dr lam Tat Chung, Paul林達聰醫生FRCP, FHKAM (Medicine), FHKAM (Psychiatry)President

editorial office:UBM Medica

27th Floor, OTB Building, 160 Gloucester Road, Wan Chai, Hong KongT +852 2559 5888 F +852 2559 6910

advertising enquiries:Ms Chloe Wong

T +852 2155 8557e-mail: chloe.p.wong@ubm.com

© 2011 The Society of Physicians of Hong Kong. All rights reserved. No part of this publication may be reproduced in any language, stored in or introduced into a retrieval system, or transmitted, in any form or by any means (electronic, mechanical, photocopying, recording or otherwise), without the written consent of the copyright owner. Permission to reprint must be obtained from the publisher. Advertisements are subject to editorial acceptance and have no influence on editorial content or presentation. The Society of Physicians of Hong Kong does not guarantee, directly or indirectly, the quality or efficacy of any product or service described in the advertisements or other material which is commercial in nature.

Journal of The Society of Physicians of Hong Kong 14

Introduction

chronic hepatitis B virus (HBV) infection is endemic among Hong Kong Chinese. While the younger population has ben-

efited from universal HBV vaccination, at least half of the remaining population has had previous contact with the virus and can be identified by the presence of antibodies against the HBV core antigen in their serum (ie, HBcAb positive).1 Ten percent of the Hong Kong population is positive for the hepatitis B surface antigen

(HBsAg), and the remaining 40 percent has antibodies to HBsAg (ie, HBsAb positive).2 Therefore, when cytotoxic chemotherapy or intensive immunosup-pression is given, there is a 10% chance that the patient is HBsAg positive. For patients with lymphoma, the chance is even higher, at up to 20%.3,4 The clinical consequence of HBV reactivation can be very serious.5

Before active anti-HBV drugs were available, more than half of the chronic HBV patients had HBV reactivation fol-lowing chemotherapy for lymphoma.6-8 Reactivation commonly occurs several months after the commencement of treatment, and can be of variable severity, ranging from mild liver enzyme elevation to severe liver failure. Intensive immuno-suppression encourages viral replication in the liver. Upon immune recovery, immune-mediated viral killing leads to massive destruction of hepatocytes. The resulting mortality ranges from 5% to 20%, depending on the degree of immunosuppression.

Diagnosis and Management of HBV Reactivation

HBV reactivation typically occurs not im-mediately, but several months after the start of chemotherapy or intensive im-munosuppression in HBsAg-positive patients. There is an elevation of liver transaminases. This may become icteric in severe cases. Prothrombin time pro-longation is a poor prognostic sign. The event is typically preceded by a surge in the serum HBV DNA level.9 The se-verity of the reactivation depends on both the viral load and the degree of immunosuppression. Other causes of

liver derangement, such as hepatotoxic drugs and other infections, need to be excluded. A high serum HBV DNA level is diagnostic.

Management of HBV reactivation is mainly supportive.10 Antiviral therapy such as lamivudine or newer agents such as entecavir should be given to halt the process. However, antiviral therapy is not always effective when the HBV viral load is high and the immunosup-pression is intense. A liver transplant may be considered for severe cases. For those who have recovered from HBV reactivation, the cytotoxic chemo-therapy for the original cancer may be delayed, and the treatment result may be compromised.

Prevention of HBV Reactivation Following Immunosuppression

Anti-HBV therapy should be given pro-phylactically to all HBsAg-positive pa-tients receiving therapy that results in significant immunosuppression.11 This includes all blood cancer patients re-ceiving cytotoxic chemotherapy, as well as those on long-term steroids or immu-nosuppression after organ transplants. Lamivudine is commonly used and is effective. However, drug resistance may develop after prolonged use, especially after more than 1 year of therapy. Newer agents such as entecavir may have less of this problem, and are preferred when prolonged immunosuppression is ex-pected, such as following bone marrow transplantation.12 The antiviral treatment should be continued for at least 6 months after stopping all immunosup-pression. Premature stopping may result in late reactivation.13

giving chemotherapy or intensive immunosuppression to Patients Who are also chronic hepatitis B carriers

Key words: Hepatitis B virus (乙型肝炎病毒), chemotherapy (化療), immunosuppression (免疫抑制治療), bone marrow transplantation (骨髓移植)

Dr liang Hin Suen, Raymond (梁憲孫醫生)MB BS(HK), MD(HK), FRCP(Lond), FRCP(Edin), FRCP RCPS(Glasg), FRACP, FHKCP, FHKAM(Medicine)

Head, Department of Medicine and Director, Comprehensive Oncology Centre, Hong Kong Sanatorium and Hospital

15 Journal of The Society of Physicians of Hong Kong

HBV Reactivation in Patients With occult HBV Infection

Forty percent of the Hong Kong Chinese population is HBsAg negative but positive for both HBsAb and HBcAb, indicating immunity following prior HBV infection. The reactivation risk is much lower in this group of patients, but it may still occur if their HBsAb titre is low and the immuno-suppression is intensive. This includes pa-tients receiving bone marrow transplant or monoclonal antibody therapy, such as rituximab or alemtuzumab. The same prophylactic anti-HBV therapy may be considered. If not, these patients should be closely monitored with regular testing of their liver transaminases, HBV status and HBV DNA level. Antiviral treatment should be promptly instituted at first sign of reactivation.14

Haematopoietic Stem Cell Transplantation

Because of the intensive and prolonged immunosuppression, the risk of HBV reactivation is extremely high following both autologous and allogeneic haemato-poietic stem cell transplantation (HSCT). At-risk patients should be put on prophy-lactic anti-HBV therapy. As immunosup-pression is expected to be prolonged and there is fear of drug resistance, newer agents such as entecavir appear to have an advantage because of the lower risk of

drug resistance.15-22

For allogeneic HSCT, the donor’s HBV status is important. If an HBsAb- and HBcAb-positive donor is used for an HBsAg-positive recipient, adoptive immune transfer of HBV immunity from donor to recipient may result in HBsAg serological clearance in the recipient post-transplant. The use of HBsAg-positive donors should be avoided as far as possible for HBsAg-negative recipients, especially if the recipient is HBsAb negative. If absolutely unavoidable and life saving, early use of anti-HBV therapy for both the donor and the recipient can significantly reduce the risk of infecting the recipient.23-28

Conclusion

HBV reactivation is a serious but pre-ventable condition. At-risk patients must be identified. Prophylactic use of antiviral therapy is the standard of care.29

References:1. Chang MH, Chen CJ, Lai MS, et al. Universal hepatitis B vaccination

in Taiwan and the incidence of hepatocellular carcinoma in children. Taiwan Childhood Hepatoma Study Group. N Engl J Med 1997;336:1855-1859.

2. Liang R, Lau GK, Kwong YL. Chemotherapy and bone marrow transplan-tation for cancer patients who are also chronic hepatitis B carriers: A review of the problem. J Clin Oncol 1999;17:394-398.

3. Lok AS, Liang R, Chiu EK, Wong KL, Chan TK, Todd D. Reactivation of hepatitis B virus replication in patients receiving cytotoxic therapy: Report of a prospective study. Gastroenterology 1991;100:182-188.

4. Liang R, Lok AS, Lai CL, Chan TK, Todd D, Chiu EK. Hepatitis B infection in patients with lymphomas. Hematol Oncol 1990;8:261-270.

5. Lalazar G, Rund D, Shouval D. Screening, prevention and treatment of viral hepatitis B reactivation in patients with haematological malig-nancies. Br J Haematol 2007;136:699-712.

6. Faggioli P, De Paschale M, Tocci A, et al. Acute hepatic toxicity during cyclic chemotherapy in non-Hodgkin’s lymphoma. Haematologica 1997;82:38-42.

7. Lau GK. Hepatitis B reactivation after chemotherapy: Two decade of clinical research. Hepatol Int 2008;2:152-162.

8. Hui CK, Bowden S, Jackson K, et al. Clinical significance of intrahepatic

hepatitis virus covalently closed circular DNA in chromic hepatitis B patients who received cytotoxic chemotherapy. Blood 2005;105:2616-2617.

9. Lau GK, Leung YH, Fong DY, et al. High HBV DNA viral load is the most significant risk factor for hepatitis B reactivation in hepatitis B surface antigen positive patients treated with autologous hematopoietic cell transplantation. Blood 2002;99:2324-2330.

10. Coiffier B. Hepatitis B virus reactivation in patients receiving chemo-therapy for cancer treatment: Role of lamivudine prophylaxis. Cancer Invest 2006;24:548-552.

11. Lau GK, Yiu HH, Fong DY, et al. Early is superior to deferred preemptive lamivudine therapy for hepatitis B patients undergoing chemotherapy. Gastroenterology 2003;125:1742-1749.

12. Hui CK, Sun J, Au WY, et al. Occult hepatitis B virus infection in hema-topoietic stem cell donors in a hepatitis B virus endemic area. J Hepatol 2005;42:813-819.

13. Hui CK, Cheung WW, Zhang HY, et al. Kinetics and risk of de novo hepatitis B infection in HBsAg-negative patients undergoing cytotoxic chemotherapy. Gastroenterology 2006;131:59-68.

14. Uhm JE, Kim K, Lim TK, et al. Changes in serologic markers of hepatitis B following autologous hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2007;13:463-468.

15. Lau GK, He ML, Fong DY, et al. Preemptive use of lamivudine reduces hepatitis B exacerbation after allogeneic hematopoietic cell transplan-tation. Hepatology 2002;36:702-709.

16. Peters MG, Han Hw H, Martin P, et al. Adevovir dipivoxil alone or in com-bination with lamivudine in patients with lamivudine-resistant chronic hepatitis B. Gastroenterology 2004;126:91-101.

17. Cheng PN, Chang TT. Entecavir: A potent antiviral with minimal long-term resistance in nucleoside-naive chronic hepatitis B patients. Expert Rev Anti Infect Ther 2008;6:569-579.

18. Lau GK, Lee CK, Liang R. Hepatitis B and bone marrow transplantation. Crit Rev Oncol Hematol 1999;31:71-76.

19. Lau GK, Liang R, Chiu EK, Lee CK, Lam SK. Hepatic events after bone marrow transplantation in patients with hepatitis B infection: A case- controlled study. Bone Marrow Transplant 1997;19:795-799.

20. Ma SY, Au WY, Ng IO, et al. Hepatic graft-versus-host disease after hematopoietic stem cell transplantation: Clinicopathologic features and prognostic implication. Transplantation 2004;27:1252-1259.

21. Ma SY, Au WY, Ng IO, et al. Role of liver biopsy in the management of liver dysfunction after hematopoietic stem cell transplantation in hepatitis B virus-prevalent patient population. Transplantation 2003;76:169-176.

22. Ma SY, Lau GK, Cheng VC, Liang R. Hepatitis B reactivation in patients positive for hepatitis B antigen undergoing autologous hematopoietic stem cell transplantation. Leuk Lymphoma 2003;44:1281-1285.

23. Lau GK, Lie AK, Kwong YL, et al. A case-controlled study on the use of HBsAg positive donors for allogeneic hematopoietic stem cell transplan-tation. Blood 2000;96:452-458.

24. Hui CK, Lie A, Au WY, et al. Effectiveness of prophylactic anti-HBV therapy in allogeneic hematopoietic stem cell transplantation with HBsAg positive donors. Am J Transplant 2005;5:1437-1445.

25. Lau GK, Liang R, Lee CK, et al. Clearance of persistent hepatitis B virus infection in Chinese bone marrow transplant recipients whose donors were antihepatitis B core and antihepatitis B surface antibody positive. J Infect Dis 1998;178:1585-1591.

26. Lau GK, Lok AS, Liang RH, et al. Clearance of hepatitis B surface antigen after bone marrow transplantation: Role of adoptive immunity transfer. Hepatology 1997;25:1497-1501.

27. Lau GK, Suri D, Liang R, et al. Resolution of chronic hepatitis B and anti-HBs seroconversion in humans by adoptive transfer of immunity to hepatitis B core antigen. Gastroenterology 2002;122:614-624.

28. Lau GK, Yuen ST, Au WY, Wu PC, Liang R. Histological changes during clearance of chronic hepatitis B virus infection by adoptive immune transfer. J Gastroenterol Hepatol 1999;14:262-268.

29. Liang R. How I treat and monitor viral hepatitis B infection in patients receiving intensive immunosuppressive therapies or undergoing hema-topoietic stem cell transplantation. Blood 2009;113:3147-3153.

THE SoCIETY oF PHYSICIANS oF HoNG KoNGSunday Symposium in Dermatology • April 17, 2011

10:00 am – 4:30 pm / Lunch 1:00 – 2:00 pmThe Langham Hotel, Peking Road, TST

Programme Director: Dr Hau Ka Lam (侯嘉林醫生), Specialist in DermatologySponsors: Beaufour-Ipsen International and Janssen Pharmaceutica

Non-members: $50

Further information can be seen on the Web: www.SOPHYSICIANSHK.orgFirst come first served. Pre-registration is required.

Journal of The Society of Physicians of Hong Kong 18

Postmenopausal osteoporosis is characterized by a state of high bone turnover leading to decreased bone mass. Agents

that reduce bone resorption are effective in stabilizing bone architecture and re-ducing fracture rate in patients with os-teoporosis. Thus, antiresorptive therapy plays a central role in management of the disease. Bisphosphonates are the most commonly used antiresorptive agents for the management of osteoporosis. They are effective in suppressing osteoclast function and reducing osteoclast survival, but their prolonged half-life in bone and potential adverse effects are issues of concern. Novel biological therapies are being developed.

Receptor-activated Nuclear Factor kB Neutralization

Receptor-activated nuclear factor kB ligand (RANKL) and macrophage colony-stimulating factor are factors derived from osteoblasts, and are necessary for the formation, function and survival of osteoclasts. RANKL binds to its receptor, RANK, on osteoclasts and osteoclast pre-cursors to induce osteoclastogenesis. (Figure 1) Naturally occurring osteo-protegerin (OPG) binds to RANKL and prevents its activity. The RANK-RANKL-OPG system has been found to play a critical role, not only in the pathophys-iology of postmenopausal osteoporosis, but also in the bone resorption associated with skeletal metastasis, hypercalcaemia of malignancy, and glucocorticoid-induced osteoporosis.

Denosumab is a human monoclonal antibody directed against RANKL, which

new treatment Modalities in osteoporosis

constitutes a new class of antiresorptive agents. It is probably the first therapeutic agent in osteoporosis that is directly derived from a major breakthrough in our understanding of bone biology.

By blocking RANKL, denosumab is effective in decreasing the formation of osteoclasts. Denosumab, when admin-istered subcutaneously at 60 mg every 6 months for 2 years, increases vertebral and hip bone mineral density (BMD) in postmenopausal women vs placebo.1 A phase III trial named FREEDOM (Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6 Months) enrolled 7,808 patients between 60 and 90 years of age with a BMD T score ranging from -2.5 to -4.0.2 Compared with placebo, denosumab reduced the incidence of vertebral fractures by 68% after 3 years, and a significant reduction in fractures was noted as early as after 1 year of treatment. In addition, it reduced hip fractures by 40%, and the cumulative incidence of nonvertebral fractures by 20%. (Figure 2)

Key words: osteoporosis (骨質疏鬆症), RaNKL (破骨細胞分化因子), monoclonal antibody (單克隆抗體), denosumab

Dr Chan Kwok Wing, Fredriech (陳國榮醫生)

MBBS(HK), MRCP(UK), FHKCP, FHKAM (Med), FRCP(E), FRCP(G)

Specialist in Endocrinology, Diabetes & Metabolism

figure 1. Pathophysiology of postmenopausal osteoporosis

Bone

Osteoblasts

RANK ligand

Activated osteoclast

Osteoclast precursor

Reduced oestrogen levels in postmenopausal women

Increased RANK ligand expression

Increased osteoclast formation

Increased osteoclast activity and survival

Excessive bone resorptionRANK = receptor-activated nuclear factor kB

19 Journal of The Society of Physicians of Hong Kong

The incidence of adverse events was not significantly different between denosumab and placebo except for eczema, flatulence and cellulitis. Cellulitis was considered a serious adverse event which occurred in 0.3% (n=12) of the pa-tients in the denosumab arm vs <0.1% (n=1) in the placebo arm.

Treatment with denosumab for 3 years also increased lumbar spine BMD by 9.2% and hip BMD by 6.0%. In addition, it suppressed levels of the serum resorption marker, C-telo-peptide, by 86% at 1 month, 72% at 6 months, and 72% at 36 months. In a head-to-head study in treatment-naïve subjects, denosumab produced signifi-cantly greater gains in BMD at the total hip, lumbar spine and other sites than weekly 70 mg alendronate therapy.3 Even in those who had received prior alendronate therapy, transitioning to de-nosumab was found to increase BMD and reduce bone turnover markers to a greater extent than continued alendronate therapy.

Denosumab does not accumulate in skeletal tissues and is not cleared by kidneys. The method of adminis-tration may improve adherence to the regimen. Moreover, its effect is po-tentially reversible upon cessation of treatment, as proven by the fast return of the bone turnover markers to baseline levels or above soon after the injection is stopped.

Cathepsin K Inhibitors

Cathepsin K is a lysosomal cysteine protease preferentially expressed by os-teoclasts that degrades type 1 collagen. Loss-of-function mutations in the gene encoding cathepsin K (CTSK) cause pycnodysostosis, a rare disease charac-terized by osteopetrosis, short stature and bone fragility.4 Osteoclasts from patients with pycnodysostosis are characterized by large vacuoles of undigested collagen and defective bone resorption. Thus, several cathepsin K inhibitors, including odanacatib, balicatib and relacatib, have been developed. They have good bio-availability and are effective in reducing bone resorption.

As cathepsin K is also expressed in epithelial cells and fibroblasts, skeletal

selectivity is important in minimizing the nonskeletal side effects. In a phase II trial, odanacatib at 10, 25 or 50 mg once weekly for 2 years increased vertebral and hip BMD in postmenopausal women with osteoporosis; at a 50 mg dose, it increased vertebral BMD by 5.7% compared with placebo.5 Odanacatib is being tested for fracture risk reduction in a phase III trial to be completed in 2012.

Src Kinase Inhibitors

Src kinase is a nonreceptor tyrosine kinase and a member of the Src family of protein kinases. Src has a role in os-teoclast survival and activity. Src inac-tivation in mice causes osteopetrosis. In Src null mutants, osteoclasts fail to form ruffled border and do not resorb bone. Saracatinib is a novel oral com-petitive inhibitor of Src kinase shown to inhibit bone resorption in vitro. A recent phase I study was performed in healthy men, with results showing no significant adverse events.6 Further phase II and phase III trials are needed to assess its efficacy and safety.

Novel Anabolic Therapies

Currently, the only anabolic agent ap-proved by the US FDA for treatment of osteoporosis is teriparatide, a 1-34

amino acid fragment of human para-thyroid hormone (PTH 1-34). A limitation of PTH is the need for daily subcutan-eous administration. Alternative delivery systems such as oral, transdermal and even intranasal routes of administration have been tested. The main challenge is how to deliver a consistent and reliable dose without any potential side effects on the nasal and bronchial epithelium. Another approach is the stimulation of endogenous PTH secretion by agents that interfere with the calcium sensing receptor on the parathyroid cells. Oral calcilytic agents stimulate endogenous PTH secretion in rodents and are being tested in humans.7

Enhancing Wnt Signalling in the Skeleton

Activation of the Wnt signalling pathway induces osteoblastic cell differentiation, and loss-of-function mutation of Wnt coreceptors cause profound bone loss, whereas gain-of-function mutations result in increased bone mass.8 Wnt binding to receptors and low-density li-poprotein receptor–related protein (LRP) 5 and 6 coreceptors leads to stabilization of b-catenin and its translocation to the nucleus, where it associates with nuclear factors to regulate gene transcription. The activity of Wnt is modulated by extra-cellular antagonists that act by binding to

Placebo Denosumab

Frac

ture

inci

denc

e (%

)

New vertebral

68% reduction (p<0.001)

Hip

40%reduction (p=0.04)

Nonvertebral

20%reduction (p=0.01)

8

6

4

2

0

figure 2. Denosumab significantly reduced risk of osteoporotic fractures at vertebral, hip and nonvertebral sites

Adapted from reference 2.

Journal of The Society of Physicians of Hong Kong 20

Wnt itself, or by preventing its interaction with its receptors or coreceptors.

Sclerostin, a protein secreted by os-teocytes, is a natural antagonist against Wnt signalling. Humanized monoclonal antibodies to sclerostin cause enhanced Wnt signalling and increased bone mass in rodents and nonhuman primates.9 A phase I study in humans demonstrated that a single administration of sclerostin antibodies resulted in an increase in BMD and biochemical markers of bone formation lasting 3 months.

Conclusion

New antiresorptive agents that are effi-cacious, tolerable and easy to administer are needed. It will definitely increase

patients’ acceptance of and compliance with treatment. Anabolic agents will have a place in the management of severe osteoporosis and in specific forms of disease characterized by decreased bone formation and remodelling.

Despite the advance in treatment, more than 80% of patients with osteo-porosis or fractures remain untreated. Concerted efforts in motivating ap-propriate patients to receive treatment are the key to resolving the problem. Current high-profile media coverage of the uncommon side effects of osteo-porosis medications might have scared patients and their healthcare providers of treatment. Some of the myths and mis-understanding should be clarified with patients, and judicious administration of drugs under regular monitoring and

follow-up is an effective solution.

References:1. BoneHG,BologneseMA,YuenCK,etal.Effectsofdenosumabonbone

mineral density and bone turnover in postmenopausal women. J ClinEndocrinolMetab2008;93:2149-2157.

2. Cummings SR, San Martin J, McClung MR, et al; FREEDOM Trial.Denosumabforpreventionoffracturesinpostmenopausalwomenwithosteoporosis.NEnglJMed2009;361:756-765.

3. Brown JP, Prince RL, Deal C, et al. Comparison of the effect ofdenosumabandalendronateonBMDandbiochemicalmarkersofboneturnoverinpostmenopausalwomenwithlowbonemass:Arandomizedblindedphase3trial.JBoneMinerRes2009;24:153-161.

4. Ho N, Punturieri A, Wilkin D, et al. Mutations of CTSK result in pyc-nodysostosisviaareductionincathepsinKprotein.JBoneMinerRes1999;14:1649-1653.

5. BoneHG,McClungMR,RouxC,etal.Odanacatib,acathepsinKinhibitorforosteoporosis:Atwo-yearstudyinpostmenopausalwomenwithlowbonedensity.JBoneMinerRes2010;25:937-947.

6. HannonRA,ClarckG,RimmerM,etal.EffectsoftheSrckinaseinhibitorsaracatinib (AZD0530)onboneturnover inhealthymen:ArandomizeddoubleblindplacebocontrolledmultipleascendingdosephaseItrial.JBoneMinerRes2010;25:463-471.

7. Gowen M, Stroup GB, Dodds RA, et al. Antagonizing the parathyroidcalcium receptor stimulates parathyroid hormone secretion and boneformationinosteopenicrats.JClinInvest2000;105:1595-1604.

8. WestendorfJJ,KahlerRA,SchroederTM.Wntsignalinginosteoblastsandbonediseases.Gene2004;341:19-39.

9. LiX,OminskyMS,WarmingtonKS,etal.Sclerostinantibodytreatmentincreasesboneformation,bonemassandbonestrengthinaratmodelofpostmenopausalosteoporosis.JBoneMinerRes2009;24:578-588.

THE SOCIETY OF PHYSICIANS OF HONG KONGSUNDAY SYMPOSIUM • MAY 8, 2011

Time Topic Speaker / moderator

11:00 am – 1:00 pm Conservative renal therapy Chairman: Dr Mak Chun Kei (麥振基醫生), FRCP

Epidemiology of renal diseases in Hong Kong Dr Gordon Siu (蕭睿邦醫生), FHKCP

Reducing the progression of renal diseases Dr Jonathan CU Yung (熊啟恩醫生), FHKAM

1:00 pm – 2:00 pm Lunch

2:00 pm – 4:30 pm Palliative renal medicine Chairman: Dr Ng Kwok Keung (吳國強醫生), FRCP

Reasons for palliative medicine, legal aspects, communication with patients

Dr Au Tak Cheung (區德璋醫生), FRCP

Medical treatment in palliative renal medicine Dr Lo Kin Yee (盧建宜醫生), FHKAM

Clinics in palliative medicine Dr Ho Chung Ping (何仲平醫生), FRCP

Co-organizer: The Integrated Dialysis Facilities (HK) Ltd

Place: The Langham Hotel, 8 Peking Road, TST, KLNEnquiry: Dr Ho Chung Ping (tel: 2771 1366; e-mail: cpho@hkma.org)CME points under applicationFirst come first served basis. Pre-registration is required.Fee: Non-members please pay $50 on admission. (Do not mail your cheque.)No confirmation will be sent for registration. Unsuccessful applicants will be notified.Sponsor: Boehringer Ingelheim (HK) Ltd.

Registration form: Fax to 2827 0162 Attention: Ms Helena Leung of BoehringerWeb registration and further details: www.SOPHYSICIANSHK.org

I wish to attend Sunday Symposium on May 8, 2011 ($50)Free for Members and Associate Members on presentation of valid membership cards.

21 Journal of The Society of Physicians of Hong Kong

Introduction

antiplatelet therapy is effective in reducing the incidence of cerebrovascular accident, myo-cardial infarction and death from

vascular causes in individuals with symp-tomatic atherothrombotic diseases.1 Low-dose aspirin is most commonly used. The other commonly employed antiplatelet drug is clopidogrel. The man-agement of gastrointestinal bleeding (GIB) related to clopidogrel alone or dual antiplatelet therapy will be discussed in a coming issue.

This review aims to examine the epidemiology and management of adverse upper gastrointestinal events in patients receiving low-dose aspirin. The safety of long-term proton-pump inhibitor (PPI) therapy will be discussed.

low-dose Aspirin

Low-dose aspirin, commonly defined as 75–325 mg daily, is efficacious for primary and secondary prevention of car-diovascular or cerebrovascular events.1 The effects of different doses have been analyzed.2 The doses of 75–150 mg daily are at least as effective as higher daily doses for long-term treatment. However, doses below 75 mg daily appear to be less effective.

Epidemiology of Upper Gastrointestinal Bleeding With low- dose Aspirin

In a large 5-year observational cohort study, hospitalization for GIB in 27,694 patients using aspirin was compared with that in the overall country population of 490,000 people.3 For aspirin users, the incidence was 0.60% per year. The ad-justed standardized incidence rate ratio of hospitalization for upper GIB in the low-dose aspirin group was 2.6.

Risk Factors for Upper Gastrointestinal Bleeding

A large number of studies have evaluated risk factors for upper GIB with non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs). However, data on low-dose aspirin are much more limited, and some are just inferred from the randomized con-trolled trials. Factors that increase the risk of upper GIB related to low-dose aspirin include prior history of ulcers (odds ratio,

OR=2.0) or GIB (OR=6.5), higher dose of aspirin, corticosteroid use (OR=5.3), an-ticoagulant therapy, selective serotonin reuptake inhibitor (SSRI) therapy, ad-dition of NSAID therapy (OR=7.7), cyclo-oxygenase-2 (COX-2)–selective inhibitor4 or clopidogrel (OR=1.9),5 alcohol con-sumption (OR=2.8),6 and Helicobacter pylori infection (OR=4.7).7 However, the formulation of low-dose aspirin has no impact on the rate of upper GIB.8 In a large-scale cohort study consisting of 27,694 low-dose aspirin users, the risk was similar among users of non-coated vs coated low-dose aspirin.3

Prevention of Peptic Ulcer Disease Induced by low-dose Aspirin

To reduce upper GI complications, the lowest effective dose of aspirin should be used. The role of cotherapy with gastroprotective drugs and eradication of H pylori in the prevention of aspirin-associated GIB are further discussed.

Eradication of H pyloriAmong low-dose aspirin users with H pylori infection and a history of upper GIB, Chan et al reported that eradication of H pylori was equivalent to treatment with

Management of adverse gastrointestinal events in Patients on antiplatelet therapy, Part i: gastro-intestinal Bleeding induced by Low-dose aspirin

Key words: Gastrointestinal bleeding (腸胃出血), aspirin (阿士匹靈)

Dr Ng Fook Hong (吳福康醫生)Specialist in Gastroenterology & Hepatology

MB,BS(HK), MD (HK), MRCP(UK), FRCP (London), FRCP (Edinburgh), FRCP(Glasgow), FHKCP, FHKAM (Medicine)

Honorary Assistant Professor, Department of Medicine, University of Hong Kong

Honorary Consultant in Gastroenterology and Hepatology, Ruttonjee Hospital

“The formulation of low-dose aspirin has no impact on the rate

of upper GIB”

Journal of The Society of Physicians of Hong Kong 22

omeprazole (20 mg/day) in preventing recurrent ulcer bleeding.9 The probability of recurrent bleeding during the 6-month period was 1.95% for patients who received eradication therapy and 0.95% for patients who received omeprazole. The American College of Gastroen-terology recommended testing for and eradication of H pylori in patients with a history of ulcer disease before starting chronic antiplatelet therapy.10 However, H pylori eradication alone might not be sufficient in high-risk patients.

Proton-pump InhibitorAmong patients with ulcer bleeding and H pylori infection, the use of PPI in addition to eradication therapy can significantly reduce the risk of ulcer com-plications further. Lai et al reported that treatment with lansoprazole (30 mg/day) in addition to the eradication of H pylori infection significantly reduced re-current upper GIB in patients continued on aspirin (100 mg/day).11 During the study period of 12 months, recurrent GIB occurred in 14.8% of patients receiving eradication therapy alone vs 1.6% of pa-tients receiving eradication therapy and lansoprazole (adjusted hazard ratio=9.6).

In patients with major peptic ulcer bleeding, the timing of resuming aspirin plus PPIs is uncertain. In a randomized controlled study, patients were treated with aspirin or placebo for 8 weeks im-mediately after endoscopic haemostatic therapy.12 It was found that continuous aspirin therapy might increase the risk of recurrent bleeding, but significantly reduced mortality rates attributable to vascular complications. However, larger trials are needed to confirm these findings.

H2 Receptor AntagonistsH2 receptor antagonists (H2RA) can reduce the risk of GIB in patients taking low-dose aspirin. A case-control study (372 cases, 381 controls) demonstrated that the use of H2RA or PPI was signifi-cantly associated with a reduction in risk of upper GIB.13 Furthermore, a recent randomized controlled study using endo-scopic endpoint at the 12th week dem-onstrated that famotidine (20 mg twice daily) was superior to placebo in pre-venting gastric and duodenal ulcers, as

well as erosive oesophagitis in low-risk patients taking low-dose aspirin.14

H2RA are less effective than PPI in the prevention of recurrent ulcers. Re-cently, a double-blind randomized con-trolled study demonstrated that GIB was significantly more common in the high-dose famotidine group than the panto-prazole group (7.7% vs 0%; p=0.0289), as was recurrent dyspepsia caused by ulcer or erosion (12.3% vs 0%; p=0.0031).15

Safety of long-term PPI Therapy

The main concerns with the long-term safety of PPI therapy include risk of gastric cancer due to prolonged hyper-gastrinaemia, and the possible asso-ciation with gastric atrophy. However, clinical evidence on the association between chronic use of PPI and GI cancer is lacking.16 Possible associations with hip fractures and community- acquired pneumonia have also been suggested,17,18 but these were not well proven due to the presence of biases in confounding factors. Similarly, the recent suggestion that PPIs cause acute inter-stitial nephritis is not confirmed by case-control studies.19

Chronic hypochlorhydria does appear to increase gastric and/or du-odenal bacterial growth, and has the potential to increase the risk of enteric infections.20 Furthermore, the absorption of protein-bound vitamin B12 can be impaired by PPI therapy,21 although the possibility of progression to overt vitamin B12 deficiency is uncertain.

Conclusion

The relative risk of major GIB with low-dose aspirin is increased by around two to three times compared with untreated controls. The annual incidence of hospi-talization for GIB is around 0.6% in aspirin users. The predictors of GIB include previous ulcers or GIB, corticosteroid use, anticoagulant therapy, addition of non-aspirin NSAID, COX-2–selective inhibitor and SSRI, H pylori infection, alcohol consumption, advanced age,

and probably increasing doses of aspirin. Coadministration of a PPI is the most effective for the prevention of aspirin- associated ulcer complications. In fact, the American College of Gastroen-terology recommends the long-term use of PPIs instead of double-dose H2RA for the prevention of recurrent injury related to low-dose aspirin use.21

References1. Antiplatelet Trialists’ Collaboration. Collaborative overview of ran-

domized trials of antiplatelet therapy, I: Prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various cat-egories of patients. BMJ 1994;308:81-106.

2. Antithrombotic Trialists’ Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myo-cardial infarction, and stroke in high risk patients. BMJ 2002;324:71-86.

3. Sorensen HT, Mellemkjær L, Blot W, et al. Risk of upper gastrointestional bleeding associated with use of low-dose aspirin. Am J Gastroenterol 2000;95:2218-2224.

4. Laine L. Review article: Gastrointestinal bleeding with low-dose aspirin – what’s the risk? Aliment Phamacol Ther 2006;24:897-908.

5. Peters RJ, Mehta SR, Fox KA, et al; Clopidogrel in Unstable angina to prevent Recurrent Events (CURE) Trial Investigators. Effects of aspirin dose when used alone or in combination with clopidogrel in patients with acute coronary syndromes: Observations from the Clopidogrel in Unstable angina to prevent Recurrent Events (CURE) study. Circulation 2003;108:1682-1687.

6. Kaufman DW, Kelly JP, Wiholm BE, et al. The risk of acute major upper gastrointestinal bleeding among users of aspirin and ibuprofen at various levels of alcohol consumption. Am J Gastroenterol 1999;94:3189-3196.

7. Lanas A, Fuentes J, Benito R, Serrano P, Bajador E, Sáinz R. Helicobacter pylori increases the risk of upper gastrointestinal bleeding in patients taking low-dose aspirin. Aliment Pharmacol Ther 2002;16:779-786.

8. Walker J, Robinson J, Stewart J, Jacob S. Does enteric-coated aspirin result in a lower incidence of gastrointestinal complications compared to normal aspirin? Interact Cardiovasc Thorac Surg 2007;6:519-522.

9. Chan FKL, Chung S, Suen BY, et al. Preventing recurrent upper gastro-intestinal bleeding in patients with Helicobacter pylori infection who are taking low-dose aspirin or naproxen. N Engl J Med 2001;344:967-973.

10. Bhatt DB, Scheiman J, Abraham NS, et al; American College of Car-diology Foundation; American College of Gastroenterology; American Heart Association. ACCF/ACG/AHA 2008 Expert consensus document on reducing the gastrointestinal risks of antiplatelet therapy and NSAID use. Am J Gastroenterol 2008;103:2890-2907.

11. Lai KC, Lam SK, Chu KM, et al. Lansoprazole for the prevention of recur-rences of ulcer complications from long-term low-dose aspirin use. N Engl J Med 2002;346:2033-2038.

12. Sung JJ, Lau JY, Ching JY, et al. Continuation of low-dose aspirin therapy in peptic ulcer bleeding: A randomized trial. Ann Intern Med 2010;152:1-9.

13. Lanas A, García Rodríguez LA, Arroyo MT, et al; Investigators of the Asociación Española de Gastroenterología (AEG). Effect of antisecretory drugs and nitrates on the risk of ulcer bleeding associated with non- steroidal anti-inflammatory drugs, antiplatelet agents, and anticoag-ulants. Am J Gastroenterol 2007;102:507-515.

14. Taha AS, McCloskey C, Prasad R, Bezlyak V. Famotidine for the pre-vention of peptic ulcers and oesophagitis in patients taking low-dose aspirin (FAMOUS): A phase III, randomised, double-blind, placebo- controlled trial. Lancet 2009;374:119-125.

15. Ng FH, Wong SY, Lam KF, et al. Famotidine is inferior to pantoprazole in preventing recurrence of aspirin-related peptic ulcers or erosions. Gas-troenterology 2010;138:82-88.

16. Klinkenberg-Knol EC, Nelis F, Dent J, et al; Long-Term Study Group. Long-term omeprazole treatment in resistant gastroesophageal reflux disease: Efficacy, safety, and influence on gastric mucosa. Gastroen-terology 2000;118:661-669.

17. Yang YX, Lewis JD, Epstein S, Metz DC. Long-term proton pump inhibitor therapy and risk of hip fracture. JAMA 2006;296:2947-2953.

18. Laheij RJ, Sturkenboom MC, Hassing RJ, Dieleman J, Stricker BH, Jansen JB. Risk of community-acquired pneumonia and use of gastric acid-suppressive drugs. JAMA 2004;292:1955.

19. Simpson IJ, Marshall MR, Pilmore H, et al. Proton pump inhibitors and acute interstitial nephritis: Report and analysis of 15 cases. Nephrology (Carlton) 2006;11:381-385.

20. Leonard J, Marshall JK, Moayyedi P. Systematic review of the risk of enteric infection in patients taking acid suppression. Am J Gastroenterol 2007;102:2047-2056.

21. Marcuard SP, Albernaz L, Khazanie PG. Omeprazole therapy causes malabsorption of cyanocobalamin (vitamin B12). Ann Intern Med 1994;120:211-215.

Journal of The Society of Physicians of Hong Kong 24

Percutaneous coronary intervention for Patients With acute Myocardial infarction

Key words: Percutaneous coronary intervention (經皮膚冠狀動脈介入手術), acute myocardial infarction (急性心肌梗塞)

Dr Chan Wai Kwong, Andy (陳偉光醫生)MBBS(HK), MRCP(UK), FHKAM(Med), FHKCP, FRCP(Lond), FRCP(Edin), FRCP(Glasg), FRCP(Irel)

Hong Kong Heart Rescue

Dr leung Wai Suen, Albert (梁偉宣醫生)MBBS(HK), MRCP(UK), FHKAM(Med), FHKCP, FRCP(Edin), FRCP(Glasg)

Hong Kong Heart Rescue

Dr lee Pui Yin (李沛然醫生)MBBS(HK), MRCP (UK), FHKCP, FHKAM (Med)

Hong Kong Heart Rescue

Dr Wong Wing Kwong, Raymond (黃榮光醫生)MBBS(HK), MRCP(UK), FHKAM(Med), FHKCP, FRCP(Edin)

Hong Kong Heart Rescue

Dr Kwok Miu Fong, Jennifer (郭妙芳醫生)MBChB(HK), MRCP(UK), FHKAM(Med), FHKCP

Hong Kong Heart Rescue

Dr Wu Chee Wo (胡志和醫生)MBBS(HK), MRCP (UK), FHKAM, FHKCP, FRCP(Edin)

Hong Kong Heart Rescue

Case Study

Miss Chan, a 61-year-old lady, presented with severe chest pain of acute onset. She was sent to the accident and emergency department (AED) within 2 hours of symptom onset. Electrocardiogram done at AED showed acute anterior myocardial infarction. She was then transferred to the cardiac catheter-ization laboratory. Emergency coronary angiogram showed occluded proximal left anterior descending artery. (Figure 1) Ad hoc percutaneous coronary intervention (PCI) was done to reopen and stent the occluded proximal left anterior descending artery. (Figure 2) The coronary flow was completely re-established. She was stable and discharged 2 days afterwards.

figure 1. Before Pci

figure 2. after Pci

25 Journal of The Society of Physicians of Hong Kong

Discussion

The above case illustrates a typical patient with acute myocardial infarction (AMI). AMI is myo-cardial necrosis usually caused by

sudden thrombotic occlusion of the epi-cardial coronary artery. This acute cardiac condition is associated with significant morbidity and mortality. Timely appro-priate treatment can greatly reduce com-plications and mortality. Therefore, early appropriate diagnosis of AMI to allow timely life-saving treatment will not only protect our patients, but also protect us as physicians from potential medicolegal consequences. Missed diagnosis of AMI is not an uncommon cause of medicolegal proceedings in Western countries.

AMI is usually not difficult to di-agnose if a patient presents with typical severe chest pain and ST elevation on electrocardiogram. However, undi-agnosed or missed diagnosis of AMI is not uncommon even in AEDs.1 The absence of chest pain and lack of ST ele-vation were found to be the main reasons for inappropriate diagnosis of AMI. In fact, elderly patients with AMI might present with dyspnoea and syncope rela-tively more commonly than their younger counterparts.2 Therefore, family phy-sicians, AED physicians or other doctors taking care of elderly patients should be well aware of these possible variable presentations to avoid delayed or missed diagnosis.

Hong Kong is a relatively small place geographically. It was found that over 85% of AMI patients presented to hospitals within 12 hours of symptom onset.3 A delay in presentation time of more than 6 hours was only significantly associated with seeking general practi-tioners’ advice before entering hospital.4 In other words, most patients presented to hospitals within a time frame when life-saving treatment can be instituted.

The most important treatment of AMI is to open up the occluded coronary artery as soon as possible because delayed reperfusion may not be able to salvage the at-risk myocardium. There are two possible ways to reperfuse the occluded coronary arteries, pharmaco-logically by intravenous thrombolytic

therapy or mechanically by PCI. Throm-bolytic therapy was used for many years with a reasonable success rate and an acceptable complication rate. Previous local data showed that around 25% of patients receiving thrombolytic therapy developed bleeding complications.5

In recent years, PCI is being adopted more and more frequently as the primary reperfusion strategy for AMI patients because of its superior results. A meta-analysis by Keeley et al published in 2003 has demonstrated the superiority of PCI over thrombolytic therapy in improving not just the short-term but also the long-term morbidity and mortality of AMI patients.6 Death, nonfatal myocardial infarction, recurrent myocardial ischaemia and stroke (total and haemorrhagic) were all reduced with PCI compared with thrombolytic therapy. Moreover, the mortality benefit with PCI was persistent among various patient subgroups.7 Because of these convincing superiority results of PCI in AMI patients, various recent international guidelines – including the American College of Cardiology/American Heart Association Guideline for the management of patients with ST-elevation myocardial infarction (STEMI),8 and the European Society of Cardiology 2008 STEMI Guideline on reperfusion strategies9 – emphasized that each community should develop a system of care to ensure that appropriate STEMI patients receive timely PCI.

In real-world situations, it appears that the percentage of STEMI patients undergoing primary PCI (ie, PCI as primary reperfusion strategy for STEMI) is unsatisfactory. There are a number of logistic issues. Sufficient cardiac cath-eterization laboratories and experienced interventional cardiology staff are just prerequisites for successful primary PCI service. Ambulance involvement, and

involvement of AED physicians, family physicians and the whole community are required to build up an efficient and effective system of care so as to avoid delays in treatment. This is very important but difficult to achieve.

Published data and findings pre-sented at various international cardiology conferences suggest wide variations in primary PCI rates among different countries in different continents. Widimsky reported a great difference in rates of use of PCI as primary reperfusion therapy among European countries at the Annual Congress of the European Society of Car-diology in 2008.10 It ranged from 95% in the Netherlands, 45% in Finland, to just 9% in the UK. However, UK is catching up very quickly. Seddon M et al pointed out that PCI will become the primary re-perfusion treatment for more than 90% of the population in the UK over the next 2 to 3 years.11

According to the American Heart Association’s Heart Disease and Stroke Statistics 2010 Update, 8.5 million indi-viduals in the United States had AMI in 2006.12 The National Registry of Myo-cardial Infarction 3 revealed a primary PCI rate of 24.4% in 1999, whereas the rate of use of thrombolytic therapy was 47.9%.13

In Australia, the proportion of AMI patients aged 40–90 years who un-derwent PCI during acute admission increased from a crude rate of 2% in 1993–1994 to 12% in 1999–2000.14 There was a substantial increase in the use of PCI among AMI patients aged 75–90 years (from <0.5% in 1993–1994 to around 4% in 1999–2000).

According to 2007 data of the Sin-gapore Myocardial Infarction Registry (SMIR), there were 2,008 patients with STEMI; 883 patients received primary PCI, and 224 had thrombolytic therapy. In Japan, the Registry of Miyagi Study Group for AMI showed a primary PCI rate of 75% among 41 hospitals in 1998–2000.15

There are some limitations with the above data. Firstly, these published data or presentations are not up-to-date. Secondly, there has been an amazingly rapid increase in primary PCI rate in many places in recent years. Moreover, it is also noted that the primary PCI rate of local

“Elderly patients with AMI might present with dyspnoea and

syncope relatively more commonly”

Journal of The Society of Physicians of Hong Kong 26

hospital networks is usually higher than that of national registries.

In Hong Kong, there were around 5,000 AMI patients in 2007.16 Compared with many developed countries overseas, Hong Kong appears to be lagging behind slightly in primary PCI development. At the moment, most public hospitals cannot provide 24/7 (24 hours a day, 7 days a week) continuous primary PCI services for all eligible STEMI patients. The insufficiency of experienced staff, especially nursing staff, is one of the several important reasons. In private hospitals, primary PCI service is available and feasible, but ambulance transfer is an issue of concern. It has been announced recently that ambulances will only take emergency patients to the nearest AED in public hospitals. As stated in various recent international guidelines, the com-munity should really develop a system of care to ensure that STEMI patients in need receive timely life-saving PCI. Perhaps all parties involved, including

the public and private sectors, should discuss and collaborate with each other to formulate an effective primary PCI service system.

AMI is a severe acute cardiac condition. Timely primary PCI can save life and reduce complications. Time is muscle. Every effort should be made to shorten the delay in treatment. An effective system of care for AMI patients in Hong Kong is urgently needed.

References:1. Chan WK, Leung KF, Lee YF, Hung CS, Kung NS, Lau FL. Undiagnosed

acute myocardial infarction in the accident and emergency department: Reasons and implications. Eur J Emerg Med 1998;5:219-224.

2. Chan WK, Chan TF, Yue CS, Ma L. A five year study of comparison of characteristics and in-hospital complications of acute myocardial in-farction between elderly and younger patients. Am J Geriatr Cardiol 1999;8:21-25.

3. Chan WK, Yung CY, Leung EMF. Clinical profiles of acute myocardial in-farction in elderly Chinese. Age and Ageing 1998;27(suppl 1):6.

4. Leung KF, Chan WK, Chu CM, Yue CS, et al. Why do patients with acute myocardial infarction present late: Our experience over seven years. Journal of the Hong Kong College of Cardiology 1999;7:47.

5. Chan WK, Chiu A, Yue CS. Prevalence of various complications of throm-bolytic therapy in patients with acute myocardial infarction: Experience in a local regional hospital. Journal of the Hong Kong College of Car-diology 1996;4:77-80.

6. Keeley EC, Boura JA, Grines CL. Primary angioplasty versus intravenous thrombolytic therapy for acute myocardial infarction: A quantitative review of 23 randomised trials. Lancet 2003;361:13-20.

7. Zahn R, Schiele R, Schneider S, et al. Primary angioplasty versus in-

travenous thrombolysis in acute myocardial infarction: Can we define subgroups of patients benefiting most from primary angioplasty? Results from the pooled data of the maximal individual therapy in acute myo-cardial infarction registry and the myocardial infarction registry. J Am Coll Cardiol 2001;37:1827-1835.

8. Kushner FG, Hand M, Smith SC, et al. 2009 focused updates: American College of Cardiology / American Heart Association Guidelines for the management of patients with ST-elevation myocardial infarction (updating the 2004 Guideline and 2007 Focused Update) and American College of Cardiology / American Heart Association / Society for Car-diovascular Angiography and Interventions Guidelines on percutaneous coronary intervention (updating the 2005 Guideline and 2007 Focused Update). J Am Coll Cardiol 2009;54:2205-2241.

9. Van de Werf F, Bax J, Betriu A, et al; ESC Committee for Practice Guidelines (CPG). Management of acute myocardial infarction in patients presenting with persistent ST-segment elevation: The Task Force on the Management of ST-Segment Elevation Acute Myocardial Infarction of the European Society of Cardiology. Eur Heart J 2008;29:2909-2945.

10. Widimsky, et al. Presented at: European Society of Cardiology Congress 2008. Munich, Germany; 30 August – 3 September 2008.

11. Seddon M, Gray H. Early reperfusion treatment for ST-elevation myo-cardial infarction: National guidance. Clinical Medicine 2010;10:215-217.

12. American Heart Association. Heart Disease and Stroke Statistics - 2010 Update. Dallas, Texas: American Heart Association; 2010. Available at: http://www.americanheart.org/presenter.jhtml?identifier=3000090. Accessed 21 January 2011.

13. Rogers WJ, Canto JG, Lambrew CT, et al. Temporal trends in the treatment of over 1.5 million patients with myocardial infarction in the U.S. from 1990 through 1999: The National Registry of Myocardial In-farction 1, 2 and 3. J Am Coll Cardiol 2000;36:2056-2063.

14. Mathur S. Epidemic of coronary heart disease and its treatment in Australia. Cardiovascular Disease Series No. 20. AIHW Cat. No. CVD 21. Canberra: Australian Institute of Health and Welfare; 2002. Available at: http://www.aihw.gov.au/publications/index.cfm/title/7865. Accessed 21 January 2011.

15. Sakurai K, Watanabe J, Iwabuchi K, et al. Comparison of the efficacy of reperfusion therapies for early mortality from acute myocardial infarction in Japan: Registry of Miyagi Study Group for Acute Myocardial Infarction (Ms AMI). Cir J 2003;67:209-214.

16. Department of Health. Department of Health Annual Report 2007/2008. Available at: http://www.dh.gov.hk/english/pub_rec/pub_rec_ar/pdf/ 0708/DOH_TABLES/tabA19.pdf. Accessed 13 January 2011.

Nycomed (Hong Kong) LimitedUnits 3706-08, 37/F AIA Tower, 183Electric Road, North Point, Hong KongTel: +852 2133 9800Fax: +852 2856 2728

VIBE StudyNew Data

Harris ST,

Further information availableIBandronate Efficacy (VIBE) database fracture study, 2009; 44 : 758-765.Bone

Risk of fracture in women treated with monthly oral ibandronate or weekly bisphosphonates: The eValuation ofet al.,Reference 1:

Comparable

Comparable

Weekly bisphosphonateMonthly ibandronate

*Analysis includes monthly ibandronate n=1,811 and weekly bisphosphonate n=14,648

In elderly patients (aged ≥65 years old)*Monthly BONVIVA® vs weekly bisphosphonates

72%

35%

Significantly lower in BONVIVA

group by (p=0.030)

Significantly lower inBONVIVA group by

(p=0.033)

Vertebral

Hip

Nonvertebral

Any clinical

Unadjusted incidence of fracture (%)

0.0 0.5 1.0 1.5 2.0 2.5 3.0