Cardiovascular diseases

Ambulatory monitoring is critical in accurately assessing blood pressure to calculate absolute cardiovascular risk. Recently, there has been debate about the need for ambulatory blood pressure monitoring (ABPM) in clinical decision making, promoting instead the use of an absolute cardiovascular disease (CVD) risk-based approach. While we fully endorse hypertension management based on absolute risk, inherent in this assessment is the accurate measurement of blood pressure (BP). ...

Geoffrey A Head BSc, PhD · Barry P McGrath MB BS, MD, FRACP · Mark R Nelson MB BS(Hons), PhD, FRACP · Michael Stowasser MB BS, MD, FRACP

About 80% of congenital heart disease (CHD) is multifactorial and arises through various combinations of genetic and environmental contributors. About 20% of cases can be attributed to chromosomal anomalies, Mendelian syndromes, non-syndromal single gene disorders or teratogens. Down syndrome and velocardiofacial syndrome are the most commonly seen syndromes in patients with CHD. To date, more than 30 genes have been linked to non-syndromal forms ...

Gillian M Blue MSc, GradDipGenCouns · Edwin P Kirk MB BS, PhD, FRACP · Gary F Sholler MB BS, FRACP · Richard P Harvey PhD · David S Winlaw MB BS, MD, FRACS

She was not told the meaning of absence why parents could not visit except on weekends — and then only for an hour. The 1906 Home Handbook of Domestic Hygiene and Rational Medicine outlines the treatment for rheumatic afflictions — hot blanket packs, repeated. She remembers those who wrapped her body in hairy blankets to preserve her rheumatic heart — remembers how the blankets electrified her body so ...

Jennifer Harrison

What is in our food should be on the labelTrans fatty acids (TFAs) are produced by the food industry during partial hydrogenation of edible vegetable oils, such as soybean oil, canola oil and cottonseed oil. This industrial process leads to oils that are more solid at room temperature and have better physical properties for food processing, including increased shelf life. Low levels of TFAs are ...

Gunveen Kaur PhD · David Cameron-Smith PhD · Andrew J Sinclair PhD

To the Editor: A 62-year-old woman was admitted on 10 January 2012 for cardiac monitoring after her implantable cardioverter–defibrillator (ICD) discharged four times over a few hours. She had a history of ventricular tachycardia due to ischaemic cardiomyopathy, and had had an ICD (D284DRG Maximo II DR, Medtronic, Minneapolis, Minn, USA) inserted 6 years earlier. Her ICD had ...

Bo Xu · Howard Connor · Robert Ziffer

A new drug with great promise, but be very aware of the risksDabigatran is the first new oral anticoagulant for the prevention of embolism in patients with non-valvular atrial fibrillation (AF) that has been recently ...

Ross I Baker BMedSc, FRACP, FRCPA · Paul Harper MD, FRCP, FRACP · Claire McLintock MB ChB, FRACP, FRCPA

Objective: To assess the use of Prothrombinex-VF powder for injection (PTX-VF) at Royal Perth Hospital and analyse the efficacy and safety profile of PTX-VF.Design, setting and patients: A prospective observational audit ...

Paul C Kruger MB BS · Annette S Le Viellez BSc(MedSci) · Richard P Herrmann MB BS, FRCPA, FRACP

To the Editor: Neal and Irwig1 argue that more precise measurement of blood pressure using ambulatory blood pressure monitoring is unlikely to deliver the clinical and economic benefits that could be achieved by switching to a risk-based strategy, such as that advocated by the National Vascular Disease Prevention Alliance.2 Moreover, they question: do you need to “know your numbers”? However, all risk-based strategies are based on numbers for blood pressure and various lipid parameters. Furthermore, despite a wealth of evidence that numbers-based approaches reduce cardiovascular events, I am not aware of any randomised controlled trial demonstrating the superiority, or even the equivalence, of a strategy based on 5-year absolute risk for cardiovascular prevention. Is a strategy based on 5-year absolute risk best for the individual patient? Clinicians treat lifetime risk,3 taking into account family history and, for women, the prospect of pregnancy. A low 5-year risk is not sufficient justification for withholding treatment of elevated lipids or blood pressure. Although the 44-year-old, male non-smoker without diabetes and with a systolic blood pressure of 170 mmHg may have a 5-year cardiovascular risk of 5%, clinicians will investigate and provide aggressive blood pressure treatment to reduce his lifetime risk. Treating according to the numbers will ensure that the choice of therapy offers the greatest risk reduction. Clinicians treat individuals, not populations. Management of the individual patient with cardiovascular risk is neither exclusively numbers-based nor exclusively risk-based, but a combination of the two approaches. We should use the approach that works best for the individual patient.

Duncan J Campbell

Despite the various functional tests and biomarkers available for evaluation of patients with coronary artery disease (CAD), we sometimes look for the reassurance of anatomical information by way of a coronary angiogram. However, as an invasive modality, it does carry some risks, and the proportion of patients with normal coronary angiograms has remained relatively stable at 15%. In recent years, the rapid development of computed ...

Gary Y H Liew MB BS, FRACP · Michael P Feneley MD, FRACP · Stephen G Worthley MD, PhD, FRACP

Non-surgical intervention has many benefits. A recent article published in the Journal1 was widely reported in the popular press, with statements such as the following being quoted: public health messages encouraging people to eat healthy food and to exercise are unlikely to have long-term impact on their weight....

Daniel J Green PhD · Andrew J Maiorana PhD

Plotting the trajectory of some common artery conditions.

on behalf of the REACH Registry Investigators

Do you need to “know your numbers”? “Know your numbers” was the public catchcry on World Hypertension Day 2011, and doctors were once again admonished to measure their patients’ blood pressure levels. The National Institute for Health and Clinical Excellence (NICE) in the United Kingdom has gone one step further and now recommends that all patients in whom hypertension is suspected be offered ambulatory blood pressure monitoring to confirm the diagnosis.1 A recent report suggested this approach is cost-effective,2 although other research findings suggest that the precise measurement of blood pressure may not be very important when selecting whom to treat.3-4 Indeed, a recent report suggested that age alone might be a sufficient basis for decision making.5 What then is the role of ambulatory blood pressure monitoring in clinical practice? The past few decades have seen huge advances in our understanding of how blood pressure causes illness. At the heart of these advances has been the recognition that blood pressure causes disease in a progressive way across a broad range of blood pressure levels, and not just when an individual crosses a diagnostic threshold for “hypertension”.1 “Hypertension” cut-points, as variously set over the past half century, are now recognised as arbitrary levels on a continuous scale; and while they were a pragmatic solution at the time, their limitations are now widely understood.6 The development of risk-based approaches to allocating blood pressure-lowering treatment has been equally important.7 Under the risk-based model, the effects of blood pressure, age, sex, blood lipid levels and the presence or absence of smoking and diabetes all play a role in the decision whether or not to treat the patient with blood pressure-lowering therapy. Further, it is the blood pressure level, not the presence or absence of hypertension, that is incorporated into the decision-making process. Compared with traditional hypertension control programs, strategies that allocate blood pressure-lowering treatment based on measures of risk are projected to avert more disease for fewer people treated and at lower cost.8 Risk-based strategies are superior in this way because they direct treatment towards those most likely to gain from therapy. A diagnosis of hypertension on its own is a poor discriminator of risk, and assessment based on multiple risk factors is much better for identifying those who will benefit.8 The discriminatory power of risk-based strategies is only marginally improved by more precise measurement of the risk factors.3 The usual day-to-day variability of blood pressure for an individual is large, which means that many, many measurements are required to define an individual’s blood pressure level with real precision.9 This is a real problem when trying to categorise a patient as above or below a hypertension cut-point, but less important when blood pressure is treated continuously and is just one of half a dozen factors influencing the treatment decision. In deciding the potential value of ambulatory blood pressure monitoring to clinical practice, it is important to understand that showing that ambulatory blood pressure is more strongly associated with risk is not in itself sufficient. To be of real clinical value, it must also more reliably select those who will benefit from intervention. Recent economic analyses2 showed that routine ambulatory blood pressure measurement was superior compared with strategies based on home or clinic measurements because it made more reliable diagnoses of hypertension and saved treatment costs. However, the analysis did not report how ambulatory blood pressure performed compared to a risk-based approach. This is a serious shortcoming, because it is in this context that NICE makes its recommendations.8 Furthermore, in those cost-effectiveness analyses, ambulatory measurements were assumed to have perfect sensitivity and specificity for the diagnosis of hypertension, and blood pressure-lowering treatment was assumed to provide no benefit to individuals classified as non-hypertensive. Both are dubious assumptions that work substantively in support of strategies based on ambulatory measurements, and, when varied, will change the conclusions drawn.2 Making more measurements to get a better estimate of an individual’s true blood pressure is an inherently appealing concept deeply rooted in clinical practice. But as the evolving evidence shows, it’s not that simple. However precisely blood pressure is measured, it is unlikely to ever be as good a discriminator as an assessment based on multiple risk factors. And while the widespread use of ambulatory blood pressure measurement will more reliably pin down someone’s true blood pressure and better define who has hypertension, it is very unlikely to deliver the clinical and economic benefits that could be achieved by switching to a risk-based strategy.8 The National Vascular Disease Prevention Alliance has released an Australian risk assessment tool10 that supports a risk-based strategy, and management guidelines will follow. Rapid nationwide uptake of this approach to deciding who to treat has the potential to revolutionise the prevention of blood pressure-related diseases. Against this background, ambulatory blood pressure measurement will remain an excellent research tool but will add little to clinical decision making for most patients.

Bruce C Neal MB ChB, MRCP, PhD · Les Irwig MB BCh, PhD

Patients with cardiovascular disease may be especially prone to the adverse effects of complementary medicines Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in Australia.1 Given the chronic nature of CVD, medical management is the most common mode of care, and medications are prescribed to most patients with CVD.2 In general practice, treatment of CVD accounts for almost one in five encounters, with hypertension the most commonly treated risk factor, followed by lipid disorders.2 Although effective management of CVD depends on a range of factors, one that is often neglected is the use of complementary medicine (CM). While CM can potentially benefit patients with CVD, it can have an adverse impact on the effectiveness of conventional CVD therapies in two main ways: through drug interaction or through reduced adherence to conventional therapies. In Australia, CM is defined as the use of medicines containing herbs, vitamins, minerals, nutritional supplements and homoeopathic medicines.3 The popularity of CM has increased in recent years,4 and in people with CVD, rates of use have been estimated at up to 42%, with up to 21% of these patients taking herbal supplements.5 The most common types of CM taken by people with CVD are multivitamins and minerals (34% of surveyed cardiac patients), calcium (22%), vitamin E (20%) and vitamin C (14%). The most common herbal agents used are mint or lemon balm (11%), nettle (8%), green tea (7%), echinacea (6%) and garlic (6%). The use of coenzyme Q10 (3%), fish oil or omega-3 fatty acids (2%) and hawthorn (1%) are surprisingly low.5 Although CM is often considered safe by patients, harmful effects associated with its use do exist. The use of CM alongside prescription medications has the potential of reducing the effectiveness or increasing the potency of therapy. These effects may be compounded in people with CVD for several reasons. First, CM users tend to consume more than one CM product concurrently over periods of months to years.5 Second, the likelihood of interference with prescribed therapy is increased since certain medications, such as digoxin and warfarin, have a narrow therapeutic window. Patients with CVD also tend to be elderly, are likely to suffer from multiple comorbidities and therefore are likely to be using multiple long-term medications.5 Several studies in people with CVD indicate that not only do a significant proportion use CM concurrently with prescribed therapy, but about half do not inform treating doctors about their use.5 The relatively widespread use of CM in people with CVD means it is vital that doctors are aware of CM use. Some commonly observed interactions between CM and conventional CVD medications and possible mechanisms are summarised in the Box. Apart from the possibility of drug interactions, the bioactive components of CM products can also directly cause adverse effects. Some examples of CM that are used in the treatment of CVD (and their adverse effects) include Aloe vera (diarrhoea and potassium depletion), fenugreek (diarrhoea and hypoglycaemia), garlic (inhibition of platelet function), ginseng (insomnia), ephedra (stroke and myocardial infarction), Ginkgo biloba (bleeding) and red yeast rice (myopathy and rhabdomyolysis).7 More generally, there are safety issues associated with the quality of CMs. These relate to the lack of standard dosing, which in part is due to variations in potency, depending on where plants are grown; the possibility of contamination by pesticides and heavy metals during cultivation; and the possibility of contamination by bacteria in the storage, transport or manufacturing processes.7 The second main mechanism in which CM use may impact on effective management of CVD is through reduced adherence to prescription medications. However, a limited number of studies investigating the impact of CM on cardiovascular medication adherence show inconsistent results. Some studies report a lower adherence to prescription medications among cardiovascular patients taking CM, while others found the opposite.5 Importantly, we found in our review that CM use was not disclosed by cardiac patients up to 65% of the time. The main reasons were fear of clinician disapproval and because clinicians had not asked about CM use.5,9 This strongly suggests that clinicians need to take a less judgemental and more proactive approach to encourage patient discussion of CM use, regardless of adherence to conventional treatment. What, then, are the identifying characteristics of a CM user? In the general population, use of CM is associated with higher levels of education and income10 but poorer self-reported health status. Although few differences have been found between cardiac patients who are CM users compared with non-users,5 it appears that people with chronic disease are more likely to use CM, especially if they have multiple comorbidities.10 As well as being aware of the potential impact of CM on prescribed therapy, clinicians should also be aware of the reasons patients use CM. About half of CM users with CVD believe that CM is of greater benefit than conventional treatment, or perceive that the CM used has proven benefits for their condition.5 Many CM users also believe that there are fewer side effects associated with “natural” therapies.5 CM therefore meets a real or perceived need for health care, and serves an important psychological function in enabling patients to manage their own health.11 Given the increasing prevalence of both CM use and CVD, it is likely that clinicians will see more cases of patients who are using CM either specifically for their cardiovascular condition or towards improving general health. Regardless of personal viewpoint, CM is now an integral part of the therapeutic armamentarium used by the Australian population. Thus, there is a need to better inform doctors about CM use and the associated potential for adverse reactions and herb–drug interactions. There are significant gaps in clinician knowledge of the risks and benefits associated with CM use, and clinicians report feeling ill-equipped to respond to patient enquiries about CM.12 Medical schools overseas, such as those in Asia, France, Germany, Switzerland and some in the United States, have incorporated CM into their medical curricula. Awareness of CM needs to be integrated into routine medical practice, such as by asking patients about CM as part of a medication review. CM modules should be included in continuing professional education programs for general practitioners and specialists alike. The key issues and complexities of CM that should be understood include the differing definitions of CM in different countries, such as the American and Australian classifications, and the processes underlying its regulation. In Australia, for example, the Therapeutic Goods Administration regulates CM products, and the difference between “listed” medicines (which are not evaluated for efficacy) versus “registered” medicines is important.3 There is growing research on the efficacy of select CMs for various conditions. Results from robust studies show that omega-3 fatty acids may assist in the treatment of hypertriglyceridaemia,13 reduce the incidence of thrombotic stroke14and coronary heart disease,15 and may prevent sudden cardiac death in patients with prior myocardial infarction.16 Coenzyme Q10 supplements appear to reduce the symptom of statin-induced myalgia17 and may have favourable effects in those with heart failure.18 Physical therapies such as qi gong also appear helpful for hypertension19 and are likely to be beneficial in some patient groups as alternatives to higher intensity physical activity. Furthermore, considerable efforts are being made to investigate the efficacy of CM in CVD prevention and risk factor reduction. Research bodies such as the National Institutes of Health in the US and the National Institute of Complementary Medicine in Australia are supporting studies investigating the effects of hawthorn leaf in milder forms of heart failure, the use of disodium edetate (EDTA) chelation therapy to treat coronary artery disease, vitamin D3 for prevention of CVD and melatonin for lowering hypertension. Further research is required to strengthen the evidence base for these and other CM therapies; however, certain CMs may prove to be efficacious for people with CVD, and critical awareness of this work is necessary for effective clinical practice. The use of CM is common among patients with cardiovascular conditions and a high proportion of patients using CM believe they have remedial benefits. Many CM users also believe that CM is as safe as or safer than their prescribed treatments, and are often unwilling to inform their doctors of their use of CM products. Commonly used CM products have the potential to interfere with the intended action of prescription medications although clinician knowledge of these interactions may be limited. We have restricted our discussion to patients with CVD, although the importance of considering CM in medical management applies equally to other patient groups, especially those with chronic disease. We emphasise the need for education about CM, so clinicians become more aware of patients’ CM use, become more knowledgeable about CM, and more capable of advising their patients about this issue. Letter p 660 Potential interactions of commonly used CM with cardiovascular medications6-8 CM (prevalence of use*) Possible herb–drug interactions and mechanism of action Coenzyme Q10 (3%) May partially antagonise antiplatelet effect of clopidogrel and decrease response to warfarin Vitamin E (20%) Contains curbicin, which antagonises the effect of vitamin K on coagulation, which, with clopidogrel, may increase the risk of bleeding and potentiate warfarin effects Garlic (6%) Additive antiplatelet effects may occur with clopidogrel and other anticoagulants Ginkgo biloba (4%) Ginkgo inhibits platelet aggregation and increases the effect of warfarin Fish oil (2%) Increases the effect of antiplatelet agents and vitamin K-dependent coagulation Concomitant use of warfarin and fish oils may increase risk of bleeding Vitamin D (4%) Improves calcium absorption, which increases the toxic effect of digoxin St John’s wort (2%) Reduces the effectiveness of statins, warfarin and digoxin through induction of hepatic enzymes and P-glycoprotein Hawthorn (1%) Increases the inotropic effects of digoxin Ginseng (4%) Has an additive effect with antiplatelet agents Decreases the effect of anticoagulants Glucosamine/chondroitin (4%) Increases the effect of anticoagulants Capsicum (5%) Increases the effect of antiplatelet agents Bilberry (1%) Increases the effect of anticoagulants Aloe vera (4%) Increases the effect of antiplatelet agents Produces hypokalaemia, leading to increased toxic effect of digoxin; enhances the effect of digoxin Liquorice (prevalence of use unknown) Mineralocorticoid effects promote potassium excretion. Causes hypokalaemia when used with some antihypertensive agents CM = complementary medicine. * Prevalence of use is based on figures from a systematic review of the literature combining data from multiple studies.5

Hosen Kiat MB BS, FRACP, FACC · Yu Sun Bin BSc(Hons) · Suzanne Grant BApplSc(TCM), MPS, PhD · Dennis Hsu-Tung Chang MB BS, MSc, PhD

Rowan Nicks was born in New Zealand on 24 February 1913. He studied medicine at the University of Otago in Dunedin and, on graduation in 1937, worked as an intern at Auckland City Hospital. After his internship, he moved to the United Kingdom to further his surgical studies, working as a demonstrator in anatomy at Middlesex Hospital, London. Rowan served as a Surgeon Lieutenant in the Royal Navy during the Second World War. In 1945, he was appointed Officer of the Order of the British Empire and became a Fellow of the Royal College of Surgeons. After the war, he turned his attention to cardiothoracic surgery, and worked at Royal Brompton Hospital, London. In 1947, he returned to New Zealand to pioneer cardiothoracic surgery at Greenlane Hospital in Auckland. In 1956, Rowan was appointed Staff Specialist in Cardiothoracic Surgery at Royal Prince Alfred Hospital in Sydney. He was involved in the beginning of open-heart surgery in New South Wales in 1957 and played a leading role in the design and development of the first automatic cardiac pacemaker. After the death of his wife Mary in 1969, Rowan travelled widely, visiting hospitals in Africa and India in particular. This was the beginning of his second career as a significant philanthropist. After his official retirement in 1973, Rowan continued to travel and work in hospitals in East Africa, India and Malaysia, as well as in remote Aboriginal communities in Australia. Rowan established a series of scholarships and fellowships for young surgeons from Africa, India, Asia, the United Kingdom and Ireland, and the Western Pacific region. In 2005, he established the Rowan Nicks Russell Drysdale Fellowship in Australian Indigenous Health and Welfare. Throughout his life, Rowan had a sustaining love of nature and gardening. In his later years, he developed his interest in chamber music, symphony and opera. Rowan died on 26 May 2011, and is survived by his extended family in Australia and New Zealand.

John Masterton · and Brian Morgan

Earlier concerns put to rest as new evidence confirms their safety and efficacy The three sentinel developments in percutaneous coronary intervention (PCI) have been the groundbreaking use of balloon angioplasty from 1977, the widespread uptake of bare metal stents (BMS) in the early 1990s, and the era of drug-eluting stents (DES) commencing in 2002. DES greatly reduce the incidence of vessel restenosis, and this has allowed the application of PCI to increasingly complex coronary anatomy that had previously been untreatable due to prohibitive restenosis rates. Uptake of this technology was immediate and widespread, with near ubiquitous use (95%) of DES for PCI in the Australian private sector by 2005 despite a fourfold higher cost and uncertain incremental cost-effectiveness over BMS.1 However, the initial unbridled optimism was tempered by case reports of “very late” stent thrombosis, and then shattered by the release of data at the 2006 World Congress of Cardiology in Barcelona suggesting DES were associated with higher mortality rates.2 This dramatically shook confidence in the use of this new technology with an immediate effect on DES use worldwide.3 In early 2007, the widely reported Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial, in which outcomes were similar for medically and percutaneously treated patients with stable angina, further challenged the interventional paradigm.4 Criteria for drug-eluting stent use in Victorian state hospitals6 One or more of: Diabetes mellitus Chronic renal failure Small diameter target vessel (< 2.5 mm diameter) Long target lesion (> 20 mm in length) Ostial lesion Bifurcation lesion Chronic total occlusion Previous coronary artery bypass grafting In-stent restenosis So what was the effect on Australian DES use? In this issue of the Journal, the Melbourne Interventional Group (MIG) present their registry data for DES use in selected Melbourne public hospitals over a 4-year period spanning this crucial time.5 Even though there was already a selective policy in place restricting DES use to patients with lesions at high risk of restenosis (Box), DES implantation fell from a peak of 54% of all stents used between April 2004 and March 2005 to 32% in 2007–2008.5 Even more dramatic falls in DES use (91% to 34%) have been reported in the Melbourne private sector over this period.7 The change in DES use in public hospitals demonstrated by the MIG is revealing, as they have previously reported underuse of DES and calculated that greater than 65% of patients undergoing stent implantation met the criteria for selective use of DES.8 Of further interest is the decrease in the absolute number of patients undergoing PCI, and in particular elective PCI, that is perhaps related to the release of the COURAGE study. It is likely that the change in practice reflects uncertainty over safety of DES at that time. It is therefore reassuring that data reported from the MIG registry affirm the safety and efficacy of DES, with DES use being the only independent predictor of better clinical outcomes at 12 months (driven, as expected, by reduced target vessel revascularisation rates). Given this finding, we would have expected to have seen deterioration in clinical outcomes during the period of low DES use. Surprisingly, this did not happen — the MIG investigators report that the reduction in DES shown by their data was not associated with an adverse effect on overall clinical outcomes. One possible explanation for this is that there was concurrent change in several other variables including referral patterns, stent technologies, implantation techniques, and adjunctive pharmacological therapy (eg, increased use of dual antiplatelet therapy). These changes may have acted favourably on clinical outcomes, masking an adverse impact of reduced DES use. The inability to separate out these confounding influences is one of the limitations of registry data. Following the Barcelona Congress, there was a rigorous reappraisal of the available studies using patient-level data, review by regulatory authorities (including the Australian Therapeutic Goods Administration) and further randomised trials. The safety and efficacy of DES were reaffirmed. Analyses showed they were not associated with an increased rate of myocardial infarction or death, but were associated with a reduction in need for revascularisation of up to 70% compared with BMS.9,10 Moreover, there has been an evolution to “second generation” stent platforms with very low stent thrombosis and restenosis rates,11 and greater understanding of the importance of dual antiplatelet therapy. Indeed, new registry data have provocatively shown a mortality benefit with liberal utilisation of DES.12 So who should receive a DES? If there was no cost difference, it would be appropriate to implant DES in the majority of patients. The main exceptions would be patients unlikely to tolerate 12 months of dual antiplatelet therapy because of increased bleeding risk, an anticipated need for elective surgery, or poor medication compliance. However, a significant cost differential remains and, therefore, rationing to those most likely to benefit (Box) is appropriate. This will, nonetheless, still result in much higher DES utilisation rates than those documented in the MIG registry in 2007. The reassurance that DES are safe has had an effect on practice at our institution, with implantation rates increasing from 43% to 70% over the past 3 years, bringing us back in line with the proportion of patients reported to meet selective utilisation criteria in Victoria.8 The information presented by the MIG gives a fascinating insight into physician behaviour by documenting the local change of practice that followed concerns regarding DES. Confidence has been restored by evidence affirming DES safety, the introduction of “second generation” platforms, and a better understanding of the importance of optimal medical therapy. It would be interesting to see how these more recent developments have affected DES use, and we look forward to ongoing insights from this important local registry.

Christopher J K Hammett MBChB, FRACP, FCSANZ · Peter J Stewart MB BS, FRACP, FCSANZ · John J Atherton PhD, FRACP, FCSANZ

Objectives: To describe temporal trends in the use of evidence-based medical therapies and management of patients with acute coronary syndromes (ACS) in Australia and New Zealand.Design, setting and participants: Our analysis of the Australian and New Zealand cohort of the Global Registry of Acute Coronary Events (GRACE) included patients with ST-segment-elevation myocardial infarction (STEMI) and non-ST-segment-elevation ACS (NSTEACS) enrolled continuously between January 2000 and December 2007 from 11 metropolitan and rural centres in Australia and New Zealand.Results: 5615 patients were included in this analysis (1723 with STEMI; 3892 with NSTEACS). During 2000–2007 there was an increase in the use of statin therapy, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and thienopyridines (P < 0.0001 for each). Among patients with STEMI, there was an increase in emergency revascularisation with PCI (from 11% to 27% [P < 0.0001]), and inhospital coronary angiography (from 61% to 76% [P < 0.0001]). Among patients with NSTEACS, there was an increase in revascularisation with PCI (from 20% to 25% [P = 0.004]). Heart failure rates declined substantially among STEMI and NSTEACS patients (from 21% to 12% [P = 0.0002], and from 13% to 4% [P < 0.0001], respectively) as did rates of hospital readmission for ischaemic heart disease at 6 months (from 23% to 9% [P = 0.0001], and from 24% to 15% [P = 0.0001], respectively).Conclusions: From 2000 to 2007 in Australia and New Zealand, there was a fall in inhospital events and 6-month readmissions among patients admitted with ACS. This showed an association with improved uptake of guideline-recommended medical and interventional therapies. These data suggest an overall improvement in the quality of care offered to contemporary ACS patients in Australia and New Zealand.

Bernadette Aliprandi-Costa RN · Isuru Ranasinghe MB BS, MMed · Vincent Chow MB BS · Shruti Kapila MB BS · Craig Juergens MB BS, FRACP, FCSANZ · Gerard Devlin MBChB, FRACP, FCSANZ · John Elliott MBChB, FRACP, FCSANZ · Jeff Lefkowitz MB BS, FRACP, FCSANZ · David B Brieger MB BS, PhD, FRACP

Objective: To evaluate percutaneous coronary intervention (PCI) practice trends and 12-month outcomes in Australia in the era of drug-eluting stents (DES).Design, setting and patients: Prospective study of consecutive patients undergoing 9204 PCIs between 1 April 2004 and 31 March 2008 at seven Victorian public hospitals.Main outcome measures: Temporal trends in baseline characteristics and in-hospital and 12-month clinical outcomes including death, myocardial infarction (MI), target vessel revascularisation (TVR) and composite major adverse cardiac events (MACE), from year to year.Results: Between 2004–2005 and 2007–2008, the mean age of patients undergoing PCI was stable (65 ± 12 years), and comorbidities such as hypertension, hyperlipidaemia, peripheral arterial disease and stroke increased (P < 0.05). There were fewer elective and more urgent PCIs, especially for MI < 24 hours (17.6% in 2004–2005 to 27.2% in 2007–2008, P < 0.01). Overall stent use remained high (mean, 94.6%), but use of DES declined steadily (53.9% in 2004–2005 to 32.0% in 2007–2008, P < 0.01), despite increases in complex lesions. Planned clopidogrel therapy of ≥ 12 months after insertion of DES increased from 54.7% in 2004–2005 to 98.0% in 2007–2008 (P < 0.01). The overall procedural success rate was high (mean, 95.9%), and 12-month rates of mortality (3.8%), MI (4.8%), TVR (6.8%) and stent thrombosis (1.8%) remained low. Selective use of DES was an independent predictor of freedom from MACE at 12 months (odds ratio, 0.68; 95% CI, 0.56–0.81).Conclusions: Use of DES declined steadily from 2004–2005 to 2007–2008, despite increasing patient risk profile and lesion complexity. Procedural success remained high and 12-month adverse outcomes remained low, with increasing use of prolonged dual antiplatelet therapy.

Bryan P Yan MB BS, FRACP, FACC · Andrew E Ajani MB BS, FRACP, MD · David J Clark MB BS, FRACP · Stephen J Duffy MB BS, PhD, FRACP · Nick Andrianopoulos MB BS, MBiostat · Angela L Brennan RN, CCRN · Philippa Loane BSc · Christopher M Reid BA, MSc, PhD

To the Editor: A review by Harper and Lefkovits favoured increased use of prehospital thrombolysis (PHT) for the management of ST-elevation myocardial infarction (STEMI).1 The acknowledged importance of early reperfusion and the ready application of PHT make this a sound recommendation for settings that are remote from percutaneous coronary intervention (PCI) centres. However, the recommendation of using PHT for patients presenting within 2 hours of symptom onset in metropolitan areas is more controversial. Recent enthusiasm for this strategy has been buoyed by the 5-year data from the randomised CAPTIM study that compared PHT with primary PCI.2 This French study, conducted from 1997 to 2000, was prematurely terminated after recruiting 840 of the planned 1200 patients. There was no difference in the primary composite end point at 30 days. A post-hoc analysis subsequently reported that among the 460 patients randomly assigned to PHT or PCI within 2 hours of symptom onset, there was a trend towards lower mortality among those receiving PHT (2.2% [five patients] v 5.7% [13 patients] at 30 days; P = 0.058).3 By 5 years, an additional eight patients receiving PHT and 12 patients receiving primary PCI had died, resulting in a P value of 0.04 for mortality difference.2 This result reflected one component of a composite end point in a post-hoc subgroup analysis from a prematurely terminated, underpowered trial. Harper and Lefkovits comment that French registry data support the CAPTIM findings. However, data from a more than 10-fold larger Swedish registry do not.4 Important to the successful implementation of PHT is the transport of patients directly to PCI centres where early angiography can be performed if required. However, PCI and fibrinolysis do not make good bedfellows — a lesson learnt through the counterintuitive results of facilitated PCI trials, which showed no benefit and some harm when offering thrombolysis as a prelude to PCI.5,6 This adverse interaction is ameliorated if PCI is deferred for 3 to 24 hours after thrombolysis; however, there is a real risk that early PCI will be overused when STEMI patients arrive rapidly at a staffed PCI facility after receipt of PHT. We need stronger evidence than currently exists to be sure that, in metropolitan settings, the temptation for zealous application of PCI after PHT does not effectively result in over-application of a facilitated PCI strategy, with untoward consequences. In metropolitan regions, the current focus on reducing delays from onset of symptoms to percutaneous revascularisation should remain. Based on the evidence to date, PHT may be a cost-effective but not clinically superior alternative for reperfusion, and should be encouraged as the strategy of choice in circumstances when logistic or resource constraints limit ready access to primary PCI.

David B Brieger

A recently published critique of a set of Australian clinical practice guidelines (CPG) highlighted problematic issues in guideline development concerning conflicts of interest of guideline panellists, validity and strength of recommendations, and involvement of end users and external stakeholders. Management of financial or intellectual conflicts of interest requires: full disclosure; limitations on industry or agency financial support during guideline development; a representative panel that includes conflict-free members; and only conflict-free panellists to be involved in drafting guideline recommendations. Guideline panels should consider adopting the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system to assist in determining the validity and strength of recommendations. Guideline panels should seek formal feedback from external stakeholders and end users. Enacting such policies aims to lend greater transparency and credibility to CPG, limit protracted and unhelpful interpretive debates, and promote wider use of CPG.

Ian A Scott FRACP, MHA, MEd · Gordon H Guyatt MD, MSc, FRCP(C)

To the Editor: Harper and Ko recently suggested radically changing the way we investigate patients with stable coronary artery disease (CAD), stating that they should initially undergo computed tomography coronary angiography (CTCA), with subsequent stress testing if CTCA shows atherosclerosis.1 To save costs, they recommend excluding stress nuclear myocardial perfusion imaging (MPI) because it has similar accuracy to stress echocardiography and involves ionising radiation. To suggest that the available evidence supports CTCA as the first-line investigation of stable CAD is premature, and likely to cause more therapeutic confusion than it resolves. Of particular concern is the assertion that all patients with any detectable atherosclerosis on CTCA should undergo intensive medical therapy for CAD. The clinical significance of mild atherosclerosis detected on CTCA in patients with chest pain that is unlikely to be of cardiac origin is uncertain, with no clinical studies demonstrating a benefit of medical management for CAD based on CTCA findings. Conversely, were such patients investigated first with a stress test, those with a negative test could be reassured that their chest pain is not cardiac and their intermediate-term prognosis is excellent. Importantly, the directive for unproven lifelong medical therapy for CAD is averted. It is also incorrect to imply that different stress-testing modalities may be seen as equivalent because they have comparable diagnostic accuracies, because their strengths and weaknesses remain complementary. This allows referring physicians to choose the modality that most suits the individual patient. For example, stress echocardiography is more operator-dependent, with known limitations in patients with obesity, airways disease, arrhythmias, poorly controlled hypertension, and contraindications for β-blocker cessation. It also cannot be fused with CTCA images, as myocardial perfusion images can.2 While we agree that measurement of fractional flow reserve (FFR) is an extremely important advance in interventional cardiology, it has the limitation of underestimating ischaemia in patients with small-vessel disease (eg, patients with diabetes).3 We agree that demonstrating ischaemia is the critical component in the decision to perform either percutaneous coronary intervention or coronary artery bypass graft surgery — and until now the largest body of evidence has been accumulated with MPI.4 Moreover, demonstration of regional ischaemia on MPI associated with an angiographic stenosis obviates the need for FFR. Electrocardiographic stress testing alone cannot provide these localising data. The advent of CTCA promises to reshape how we assess and manage CAD in the future, but today we should be guided by the clinical evidence, and be mindful not to put the cart before the horse.

Victor Kalff · Stephen J Duffy · Andrew J Taylor

To the Editor: Harper and Ko have ignored significant facts regarding myocardial perfusion scintigraphy and made unsubstantiated conclusions regarding computed tomography coronary angiography (CTCA) and fractional flow reserve (FFR).1 Their investigation algorithm for suspected and known stable coronary artery disease (CAD) is flawed. By definition, stable CAD patients cannot be categorised into a “suspected CAD” subgroup. CTCA is not an appropriate first-line investigation for patients presenting with atypical chest pain or equivalent syndromes. Being purely anatomical, CTCA cannot determine the functional significance of CAD, rendering it ineffective in intermediate disease. Furthermore, CTCA often overestimates stenoses due to partial voluming and blooming. Guidelines from the United Kingdom National Institute for Health and Clinical Excellence (NICE) state that “questions remain about the ability of multislice CT coronary angiography to accurately identify stenoses of functional significance ... in people with stable chest pain”.2 Harper and Ko’s algorithm will lead to more investigation, provide no differentiation over and above Step 2 (functional imaging), and increase radiation dose, contrast burden and delays between presentation and definitive treatment. The real potential of CTCA lies in its ability to non-invasively assess plaque burden and therefore help rationalise long-term pharmacotherapy in high-risk, asymptomatic patients. However, because there is a lack of evidence for this approach, it has been largely ignored and instead the CTCA community has been “sidetracked” into comparing CTCA with functional imaging. Harper and Ko claim that additional costs from the inevitable increase in CTCA scans would be “minor in comparison to the savings”. This is unproven, and not supported by NICE.2 For atypical symptoms, Harper and Ko recommend “the less expensive ECG [electrocardiogram] exercise test” to risk-stratify patients; however, stress ECG testing is poor at predicting the degree of myocardium at risk, a key factor in risk-stratifying patients. The exercise ECG lacks specificity, leading to unnecessary invasive testing, and many patients are unable to comply. NICE has abandoned exercise ECG testing completely.2 The authors state that a “wealth of data has validated the accuracy of FFR”. The original papers demonstrating a significant FFR of 0.75 were based on perfusion imaging.3,4 The review cited quotes a lower sensitivity and specificity of FFR compared with perfusion scintigraphy, and lists scintigraphy as the “clinical gold standard of ischemia”.5 This is because scintigraphy is the most sensitive technique for identifying functionally significant CAD, as it detects the first abnormality in the ischaemic cascade (reduced myocardial perfusion). Furthermore, the exact level of FFR significance (0.75 v 0.80) is debated. In practice, there is a large degree of operator “discretion” in deciding to revascularise, irrespective of the FFR value, which is often “intermediate” in itself. Harper and Ko question the cost of scintigraphy; however, it is more than $300 cheaper than FFR measurement. They overstate the cost of a standard guidewire by threefold.1 In just one study of over 5000 patients (three times the population of a recent FFR meta-analysis6), increasingly abnormal perfusion scans predicted death and myocardial infarction. There was a reduction in death following revascularisation according to defect severity.7 The nuclear substudy of the COURAGE trial confirmed this.8 No study of CTCA or FFR has been able to predict survival with revascularisation, as the technology is unable to define area at risk. Despite this, Harper and Ko conclude that the Medicare rebate for nuclear testing should be abolished. The authors state that “instituting these changes would undoubtedly result in improved outcomes and substantial savings”. This comment is opinionated, inflammatory and not based on current evidence. The only reasonable conclusion is that before a rebate for CTCA is even proposed, it should be proven diagnostically and prognostically equivalent to myocardial perfusion scintigraphy in predicting ischaemia.

William J van Gaal · Kevin Allman

To the Editor: Although Harper and Ko’s effort at proposing an algorithm1 to reduce unnecessary cardiac catheterisation and stenting is laudable, it is concerning that they advocate investigating patients with stable coronary artery disease (CAD) using computed tomography coronary angiography (CTCA), with an algorithm, furthermore, that has not been validated in terms of patient outcomes. The COURAGE trial demonstrated that percutaneous coronary intervention (PCI) provided no survival advantage or reduction in myocardial infarction over 5 years of follow-up compared with optimal medical management in patients with chronic stable angina.2 PCI provided a relative symptomatic benefit only within the first 3 years. Therefore, it is debatable whether imaging most of these stable patients — much less catheterising them — provides any enduring favourable patient outcomes. For those who do require intervention, fractional flow reserve (FFR) measurement does obviate unnecessary stenting during a cardiac catheterisation. But why perform CTCA — which cannot diagnose ischaemia — in the first place, only to then perform an expensive invasive catheterisation to compensate for it? Why not diagnose ischaemia with an initial non-invasive stress test (nuclear or echocardiography) and only proceed to catheterisation if revascularisation is warranted, thus also lessening the radiation dose? Modern gamma cameras allow nuclear stress studies with radiation doses as low as 2–3 mSv. Yes, CTCA can (as opposed to does) achieve comparable doses with prospective gating, but without the left-ventricular function analysis that nuclear or echocardiography studies provide. Advocating the elimination of the rebate for nuclear stress studies is thus premature, if not ill informed. Harper and Ko’s algorithm relies on the assumption that medical therapy is appropriate in asymptomatic patients for any degree of coronary atherosclerosis, hence justifying the use of CTCA for its detection. However, there is considerable uncertainty about the benefits of medical therapy for primary prevention in low-risk patients.3 Furthermore, the use of CTCA has not been validated as a determinant of appropriate medical management leading to favourable patient outcomes. This contention remains speculative. Indeed, contrary to the claims of CTCA supporters, the United States Centers for Medicare and Medicaid Services has declared that there is uncertainty regarding any potential health benefits or patient management alterations from including coronary CTA [computed tomography angiography] in the diagnostic workup of patients who may have CAD. No adequately powered study has established that improved health outcomes can be causally attributed to coronary CTA ... the body of evidence is of overall limited quality and limited applicability ... in community practice.4 Consequently, the technology also poses significant potential to unnecessarily increase the population radiation burden.5

Peter Karamoskos

To the Editor: Harper and Ko stress the importance of differentiating the presence of atherosclerosis from ischaemia,1 a concept that has been well understood for years. We agree that identifying myocardial ischaemia is important in the management of atherosclerosis; there are a variety of well validated non-invasive tools for this, including exercise electrocardiography, stress echocardiography, and nuclear myocardial perfusion imaging (MPI). However, we have concerns about some of the sweeping changes suggested by the authors — in particular, replacing nuclear MPI with stress echocardiography. While published studies report similar accuracy for these modalities, it is clear that each has strengths and weaknesses. Stress echocardiography is an excellent tool that will often suffice but it is operator-dependent, while MPI is more accurate for single-vessel ischaemia. It is well known that a diagnostic stress echocardiogram cannot be achieved in some patients, so an alternative modality may be required. This is particularly problematic in Australia, where there is no mechanism in place to fund the use of ultrasound contrast imaging. MPI remains a widely accepted technique globally, with a substantial evidence base to support its diagnostic and prognostic impact. For instance, a negative MPI study is generally associated with a cardiac event rate of < 1% in the following year.2 Further, its role in directing the mode of treatment on the basis of extent of ischaemia and its cost-effectiveness as the “gatekeeper” to cardiac catheterisation have been amply demonstrated.3 The use of radiation in medical procedures is always subject to the ALARA (as low as reasonably achievable) principle, and prescribed doses in Australia are typically lower than those quoted in the American literature cited by Harper and Ko. Recent advances in hardware and software with MPI have achieved additional gains in reducing radiation exposure.4 The cost of MPI is greater than stress echocardiography, but remains less than angiography and fractional flow reserve (FFR) measurement. Further, Harper and Ko’s proposed cost savings will not be realised with their call for an increased use of computed tomography coronary angiography and FFR measurement. The job of a good clinician is to choose the right test for the patient; in some cases this is a stress echocardiogram but it is often an MPI study, as supported by international guidelines.5 Thus, readers should be mindful that Harper and Ko’s views about replacing nuclear stress tests with stress echocardiography and abolishing the Medicare item number for nuclear stress tests are personal and may be contrary to sound evidence.

Nathan Better · Myles B Webb · David L Prior · Steven A Unger · George Larcos

In reply: We thank the authors of these letters for their comments on our article. In response to Kalff and colleagues, we firmly believe stress testing should be reserved for the diagnosis of ischaemia in patients with known coronary artery disease (CAD), and computed tomography coronary angiography (CTCA) is the investigation of choice for anatomical diagnosis of CAD in patients with suspected CAD. In this, we are supported by recent guidelines from the American Heart Association and others.1 Most heart attacks occur as a result of plaque rupture in coronary lesions of insufficient severity to cause ischaemia on stress testing, but that would be detected on CTCA.2 In view of the undoubted benefits of medical therapy in both primary3 and secondary prevention of CAD events, do Kalff et al seriously suggest that coronary atherosclerosis detected on CTCA should not be treated with proven anti-atherosclerotic therapy? Regarding comments made by van Gaal and Allman, and Karamoskos, we believe the upfront use of CTCA in our proposed algorithm would substantially decrease downstream referrals for both stress testing and invasive angiography in patients with suspected CAD. The current practice of referrals for invasive angiography based on clinical assessment and functional tests results in a low yield of obstructive disease.4 Furthermore, we believe the responsible use of CTCA can be promoted by restricting its use to the anatomical diagnosis of CAD as a once-only investigation. Once the diagnosis is established, further functional testing can be pursued if clinically indicated. Multicentre studies designed to determine the optimal role of CTCA are underway and will provide important insights regarding our viewpoint.5 Van Gaal and Allman place considerable emphasis on the 5000-patient study of myocardial perfusion imaging.6 We point out, however, that this was an observational study. In contrast, the FAME study on which we base our views of fractional flow reserve (FFR) was a randomised study.7 In addition, we are bemused by their statement that “The review cited quotes a lower sensitivity and specificity of FFR compared with perfusion scintigraphy, and lists scintigraphy as the ‘clinical gold standard of ischaemia’”. To quote directly from the review article: ... scintigraphy, although considered the clinical gold standard of ischemia, has limitations in identifying the hemodynamic significance of individual lesions in patients with multivessel CAD.8 Regarding comments made by Better and colleagues, we believe both stress echocardiography and nuclear stress testing are overused in clinical practice. In most circumstances, a standard electrocardiographic stress test is sufficient to exclude significant ischaemia and thus to determine who should undergo invasive angiography. In circumstances requiring stress imaging, our preference is to perform stress echocardiography, as its accuracy is comparable to nuclear stress testing, with no additional radiation. Notably, in multilesion CAD, none of the stress testing modalities are sufficiently accurate to determine which lesions require intervention.9,10 Only FFR, a proven cost-effective investigation, can decide this.9,10 Rather than putting the cart before the horse, as suggested by Kalff et al, our algorithm provides a horse with the potential to win the Melbourne Cup.

Richard W Harper · Brian S Ko