Secondary prevention patterns in persons with pre-existing coronary artery disease: Are we getting it right?

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1 740596PSH / Proceedings of Singapore HealthcareAbdul Hafidz et al. research-article Original Article PROCEEDINGS OF SINGAPORE HEALTHCARE Secondary prevention patterns in persons with pre-existing coronary artery disease: Are we getting it right? Proceedings of Singapore Healthcare 1 5 The Author(s) 2017 Reprints and permissions: sagepub.co.uk/journalspermissions.nav DOI: journals.sagepub.com/home/psh Muhammad Imran Abdul Hafidz 1, Lily Diana Zainudin 2, Zhen-Vin Lee 1, Mohd Firdaus Hadi 1 and Ahmad Syadi Mahmood Zuhdi 1 Abstract Background: Cardiovascular diseases are the main cause of death globally. Individuals with evidence of coronary artery disease are at increased risk of further cardiovascular events. However, with good secondary prevention, which consists broadly of lifestyle changes, medical therapy and revascularisation, this risk can be reduced. The true extent of secondary prevention in individuals who are re-admitted with a myocardial infarction in such a high-risk cohort has never been explored in Malaysia. Methods: We performed a retrospective, observational study in a tertiary hospital in 100 individuals with previously diagnosed coronary artery disease admitted with a myocardial infarction from August 2016 to February Results: Twenty-nine per cent of patients were still smoking; 15% and 47% were not taking antiplatelet or beta-blocker therapy, respectively. A further 45% and 20% of patients were not on any renin angiotensin aldosterone inhibition or lipidlowering therapy, respectively. Conclusion: In our high-risk cohort, secondary prevention practices were sub-optimal. Poor physician patient communication was frequently listed as a major factor. Simple strategies taken at various levels of care should be implemented and audited to improve these practices. Keywords Secondary prevention, myocardial infarction, coronary artery disease, beta-blocker, ACE inhibitor Introduction Cardiovascular disease is the main cause of death in Malaysia, responsible for 36% of all deaths in Coronary artery disease (CAD), which is the major cause of cardiovascular morbidity and mortality, requires a multifaceted management plan with medical therapy, lifestyle change and revascularisation procedures. For patients who have suffered myocardial infarctions or have documented CAD, secondary prevention with evidence-based medicine is essential to reduce the risk of further cardiovascular events. Despite the proven benefits of these therapies, many studies have highlighted gaps in secondary prevention for this high-risk group. Malaysian Clinical Practice Guidelines (CPGs), along with American and European guidelines, are clear in their recommendations for secondary prevention. 2 Antiplatelet therapy, beta-blockers, inhibitors of the renin angiotensin aldosterone system (RAAS) and lipid-lowering therapy are all proven to be beneficial as secondary prevention and Grade I recommended with Class A evidence. In our experience, the practice of secondary prevention prescribing and compliance in our local Malaysian population are suboptimal. This finding has been found in other populations. Reasons for this are multifactorial but include poor prescribing knowledge, financial constraints and poor medication understanding. 1 Cardiology Unit, University of Malaya Medical Centre, Malaysia 2 Medical Faculty, Universiti Teknologi MARA (UiTM), Malaysia Corresponding author: Muhammad Imran bin Abdul Hafidz, Cardiology Department, University of Malaya Medical Centre, Lembah Pantai, Kuala Lumpur, Wilayah Persekutuan, Malaysia. imran.hafidz@gmail.com Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution- NonCommercial 4.0 License ( which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (

2 2 Proceedings of Singapore Healthcare Table 1. Subject characteristics (N=100). Variable n (%) Gender Male 75 (75) Female 25 (25) Age, years, mean (SD) 65.0 (11.3) Ethnicity Malay 39 Indian 33 Chinese 25 Other 3 Smoking status Current smoker 29 (29) Never smoked/ex-smoker 71 (71) Criterion of pre-existing CAD Previous angioplasty 48 (48) Previous myocardial infarction 22 (22) Previous CABG 14 (14) Angiography showing CAD 16 (16) Duration in days from initial diagnosis of CAD ( ) to re-admission, mean (SD) Admission diagnosis NSTEMI 79 (79) STEMI 21 (21) CAD: coronary artery disease; CABG: coronary artery bypass grafting; NSTEMI: non-st elevation myocardial infarction; STEMI: ST elevation myocardial infarction As far as we are aware, this is the first retrospective study exploring secondary prevention patterns in Malaysian patients with pre-existing CAD re-presenting with a myocardial infarction. Methods This was a retrospective study done to examine the demographics, medication, lipid profile and glycated haemoglobin (HbA 1 c) levels (if diabetic) of individuals with pre-existing CAD admitted with a myocardial infarction (non-st and ST elevation myocardial infarction) admitted into University of Malaya Medical Centre (UMMC), Kuala Lumpur, Malaysia between August 2016 and February Individuals admitted with a myocardial infarction (MI) were identified from the admissions register on the cardiology wards. Within this list, individuals with pre-existing CAD were identified. Pre-existing CAD was defined as a previous MI or having undergone prior angioplasty, coronary artery bypass grafting (CABG) or a coronary angiogram showing CAD regardless of revascularisation status. All consecutive patients admitted during the period of study were included, which amounted to 100 patients. Current medication was taken as what was reported by the individual on admission regardless of whether this had been affected by prescription gaps or individual non-adherence. Lipid profiles and HbA 1 c levels were taken within the same admission. Results A total of 100 individuals were included. The mean age was 65.0 (SD = 11.3) years. Table 1 displays the subject characteristics. Most subjects were male and did not smoke. Most patients were ethnically Malay. The majority of subjects were admitted with a non-st elevation MI and had previous angioplasty as their criterion of pre-existing CAD. The mean duration from the initial diagnosis of CAD until re-admission with a MI was (SD = ) days. The majority of subjects were on either aspirin or clopidogrel monotherapy and beta-blockers. Most were also on angiotensin-converting enzyme inhibitors or angiotensin receptor blockers and taking lipid-lowering therapy. Table 2 summarises the pattern of secondary prevention therapy and Table 3 lists the cardiovascular risk factors. Discussion Individuals with documented CAD are categorised as very high risk for developing further cardiovascular events. This group includes those with previous MI, CAD diagnosed on coronary angiography and those who have undergone revascularisation procedures such as angioplasty and CABG. A multifaceted strategy of secondary prevention has been studied extensively and recommended in the Malaysian CPG and major cardiovascular guidelines from the European Society of Cardiology (ESC), United Kingdom National Institute of Clinical Excellence and the American Heart Association/ American College of Cardiology Foundation (AHA/ACCA). Class I recommendations include lifestyle modifications (exercise, weight management, smoking cessation), cardiac rehabilitation, control of risk factors (lipid profile, blood pressure, glycaemic control) and specific drug therapy (antiplatelet, RAAS antagonists, beta-blockers). Our study found a sub-optimal pattern of secondary prevention across the spectrum. There was a significant proportion of individuals still smoking (29%) despite smoking cessation having been shown to cause a major reduction of all cause mortality (relative risk (RR) = 0.64) and non-fatal MIs (RR = 0.68) in individuals with prior CAD. 3 Factors to stop smoking were unfortunately not determined in this study but referral to a cardiac rehabilitation programme or treatment at a hospital with inpatient smoking cessation

3 Abdul Hafidz et al. 3 Table 2. Secondary prevention therapy. Drug n (%) Antiplatelet therapy Dual antiplatelet therapy 32 (32) Aspirin monotherapy 42 (42) Clopidogrel monotherapy 10 (10) Other antiplatelet 1 (1) No antiplatelet therapy 15 (15) Beta-blocker Beta-blocker present 53 (53) No beta-blocker 47 (47) RAAS antagonists ACE inhibitor 41 (41) ARB 14 (14) No ARB or ACE inhibitor 45 (45) Lipid-lowering therapy Statin 79 (79) Other 1 (1) No lipid-lowering therapy 20 (20) RAAS : renin angiotensin aldosterone system; ACE: angiotensin-converting enzyme; ARB: angiotensin II receptor blocker Table 3. Cardiovascular risk factor profile. Variable Mean (SD) Presenting heart rate, beats/min (17.48) Presenting blood pressure, mmhg Systolic (26.09) Diastolic (14.52) Total cholesterol, mmol/l 4.49 (1.63) LDL, mmol/l 2.62 (1.37) HbA 1 c if diabetic, % 8.05 (2.07) LDL: low-density lipoprotein; HbA 1 c: glycated haemoglobin services has been associated with better cessation rates. 4 Pharmacotherapy, referral to smoking cessation services and avoidance of environmental smoke are steps recommended in guidelines. In the AHA/ACCA guidelines, asking about smoking status and giving cessation advice at every clinic visit have strong supporting evidence and are given a Class I grade of recommendation. 5 The mean low-density lipoprotein (LDL) level in our studied population was 2.62 mmol/l. Malaysian and AHA/ACCA guidelines published in 2011 recommend a target level of 2.6 mmol/l with an option of < 2.0 mmol/l. However, more recent guidelines from the ESC have recommended a stricter LDL goal of < 1.8 mmol/l for these individuals classified as very high risk for further cardiovascular events, which would deem the mean LDL level in our population as sub-optimal. 6 The mean HbA 1 c level in diabetic individuals in our cohort was 8.05%, also above target levels of < 7.0% recommended in guidelines. Blood pressure targets of 140/90 mmhg were, however, met in our cohort. Medication therapy is a major part of secondary prevention. Unfortunately, there was a poor rate of prescription and adherence rates in all medication classes. Antiplatelet therapy was absent in 15% of individuals; 47% and 45% of our cohort were not taking beta-blockers or RAAS antagonists. Lipidlowering therapy was found in only 80% of individuals. Poor adherence increases mortality rates in this high-risk cohort. For example, statin non-adherence is associated with a 25% mortality increase whereas mortality rates have been found to halve with good adherence to beta-blockers. 7,8 Discontinuation of clopidogrel within 12 months of an acute coronary syndrome was also associated with a significant increase in mortality rates. 9 Based on these findings, the importance of good secondary prevention therapy rates is obvious for reduction in events. Several causes were identified in most of our cases, which reflect other observational studies. 10 They can be broadly divided into patient, physician and organisational causes. Patients frequently reported medication side effects, financial cost and polypharmacy as common reasons for nonadherence. A review of available repeat prescription scripts identified gaps in prescription of evidence-based medicines although reasons for these were not obvious from notes. Poor physician awareness of secondary prevention regimes, failure to set treatment goals and shortage of time have been identified from other studies as contributing factors. Lack of hospital clinical guidelines, prescribing audit activities and oversubscription of clinic services may be organisational factors compounding this problem. Overall the most common factor quoted by individuals in our cohort was poor communication between physician and patient. This was determined qualitatively through patient reasons for non-adherence during admission clerkings. Unclear benefits and emphasis on secondary prevention, lack of agreed treatment goals, information on side effects of medication and lack of smoking cessation advice were all listed as examples of poor communication. Communication and adherence have been shown to be closely associated. 11 Improvement in secondary prevention will reduce morbidity and reduce mortality. Many studies have proven the economic benefit of effective secondary prevention strategies Table 4 displays possible steps that have been introduced elsewhere to improve secondary prevention practices We recognise that steps like referrals to smoking cessation or cardiac rehabilitation may be challenging due to lack of providers in our healthcare system. Nonetheless we have introduced simple and practical improvements in our own hospital that we believe are also achievable for smaller hospitals. Increased participation of a pharmacist during ward rounds, a discharge checklist ensuring the prescription of secondary prevention medication and a more extensive discharge summary are among the new improvements that are currently being audited but have shown early promise. As with all retrospective studies, our study has weaknesses. Our small number of studied individuals and potential for reporting bias limit its potential for generalisation. Despite this, it does have its advantages. To our knowledge, this is the first study done in a Malaysian population exploring secondary prevention in this high-risk group. Furthermore, it has shown that secondary prevention in this Malaysian cohort is sub-optimal and reflects the findings of other observational studies done elsewhere Conclusion Secondary prevention is important in reducing morbidity and mortality in individuals with pre-existing CAD. These include

4 4 Proceedings of Singapore Healthcare Table 4. Proposed steps to improve secondary prevention in cardiovascular disease. Perspective Specific steps Patient Gain ownership of own medication plans. Adhere to and participate in recommended regimes. Physician Adhere to guideline-based therapy. 15 Seek opportunities to improve and update knowledge on new evidence or practices. Improve physician patient communication. Encourage decision-making and questions regarding disease and therapy. Give clear instructions on discharge summaries on medication doses, clinic follow-ups and referrals to services such as smoking cessation and cardiac rehabilitation. 16 Communicate plans with primary care providers. Work with pharmacists for medication reviews. 17 Organisation Promote audit activities to ensure compliance with published clinical guidelines. 18 Appoint clinical champions who can influence practices of other colleagues. 19 lifestyle changes, medication therapy and revascularisation strategies. Unfortunately, similar to findings in other countries, secondary prevention practices in our cohort were suboptimal. This was multifactorial; however, poor communication between physician and patient was frequently quoted. Simple strategies at the individual, physician and organisational levels can be taken to improve practices, which would reduce the cardiovascular disease impact on our society. Acknowledgements Data is available upon request from the corresponding author. Ethical approval for this study was obtained from the UMMC Medical Research Committee (MREC) ID number: Informed consent was not required for this study. Author contribution Author 1: conceptualisation, data collection, data analysis and writing of the manuscript; author 2: conceptualisation, writing and editing the manuscript; author 3: data collection, data analysis and interpretation; author 4: data collection, data analysis and interpretation; author 5: conceptualisation, data interpretation and editing the manuscript. Declaration of conflicting interests The authors declare that there are no conflicts of interest. Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. References 1. World Health Organization. Malaysia: Country Statistics, (2017, accessed 29 May 2017). 2. Academy of Medicine of Malaysia. Clinical practice guidelines (CPGs), (2000, accessed 29 May 2017). 3. Critchley J and Capewell S. Smoking cessation for the secondary prevention of coronary heart disease. Cochrane Database Syst Rev 2004; 1: CD Dawood N. Predictors of smoking cessation after a myocardial infarction. The role of institutional smoking cessation programs in improving success. Arch Intern Med 2008; 168: Smith S, Benjamin E, Bonow R, et al. AHA/ACCF secondary prevention and risk reduction therapy for patients with coronary and other atherosclerotic vascular disease: 2011 update: A guideline from the American Heart Association and American College of Cardiology Foundation. Circulation 2011; 124: Catapano A, Graham I, De Backer G, et al ESC/EAS guidelines for the management of dyslipidaemias. Eur Heart J 2016; 37: Rasmussen J, Chong A and Alter D. Relationship between adherence to evidence-based pharmacotherapy and long-term mortality after acute myocardial infarction. JAMA 2007; 297: Wei L, Flynn R, Murray G, et al. Use and adherence to betablockers for secondary prevention of myocardial infarction: Who is not getting the treatment? Pharmacoepidemiol Drug Saf 2004; 13: Boggon R, van Staa T, Timmis A, et al. Clopidogrel discontinuation after acute coronary syndromes: Frequency, predictors and associations with death and myocardial infarction a hospital registry-primary care linked cohort (MINAP-GPRD). Eur Heart J 2011; 32: Piepoli M, Corrà U, Dendale P, et al. Challenges in secondary prevention after acute myocardial infarction: A call for action. Eur J Prev Cardiol 2016; 23: Haskard Zolnierek K and DiMatteo M. Physician communication and patient adherence to treatment. Med Care 2009; 47: Basu S, Bendavid E and Sood N. Health and economic implications of national treatment coverage for cardiovascular disease in India: Cost-effectiveness analysis. Circ Cardiovasc Qual Outcomes 2015; 8: Franco O. Cost effectiveness of statins in coronary heart disease. J Epidemiol Community Health 2005; 59: Hay J, Yu W and Ashraf T. Pharmacoeconomics of lipid-lowering agents for primary and secondary prevention of coronary artery disease. Pharmacoeconomics 1999; 15: Brindis R and Sennett C. Physician adherence to clinical practice guidelines: Does it really matter? Am Heart J 2003; 145: Halvorsen S, Jortveit J, Hasvold P, et al. Initiation of and long-term adherence to secondary preventive drugs after acute myocardial infarction. BMC Cardiovasc Disord 2016; 16: Bailey T, Noirot L, Blickensderfer A, et al. An intervention to improve secondary prevention of coronary heart disease. Arch Intern Med 2007; 167:

5 Abdul Hafidz et al Hurst D. Audit and feedback had small but potentially important improvements in professional practice. Evid Based Dent 2013; 14: Flodgren G, Parmelli E, Doumit G, et al. Local opinion leaders: Effects on professional practice and health care outcomes. Cochrane Database Syst Rev 2011; 8: CD Kotseva K, Wood D, De Bacquer D, et al. EUROASPIRE IV: A European Society of Cardiology survey on the lifestyle, risk factor and therapeutic management of coronary patients from 24 European countries. Eur J Prev Cardiol 2015; 23: Lee H, Cooke C and Robertson T. Use of secondary prevention drug therapy in patients with acute coronary syndrome after hospital discharge. J Manag Care Pharm 2008; 14: Eagle K, Kline-Rogers E, Goodman S, et al. Adherence to evidence-based therapies after discharge for acute coronary syndromes: An ongoing prospective, observational study. Am J Med 2004; 117:

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