ESC 2012 Clinical Trial and Registry Updates I
Headline findings and implications for patients and clinicians
Guillaume Pare (Hamilton, CA)
RELY-Genetics: genetic determinants of dabigatran plasma levels and their relation to clinical response.
Headline finding: genome-wide association analysis identified that carriage of a CES1 genetic variant occurred in 32.8% of patients in RELY and was associated with lower dabigatran exposure. The presence of the polymorphism was associated with a 27% lower risk of bleeding.
Implications for patients: our findings could potentially lead to safer and more effective anticoagulation with dabigatran etexilate in patients with atrial fibrillation.
Implications for clinical practice: the magnitude of excess bleeding risk associated with these genetic variants is even greater than that seen when comparing the two doses of dabigatran tested in the RE-LY trial, raising the possibility that routine genotyping may enable clinicians to tailor the dose of dabigatran for individual patients and thereby optimize the balance between efficacy and safety.
Stefan H. Hohnloser
Stefan H. Hohnloser (Frankfurt, DE)
ARISTOTLE: efficacy of apixaban when compared with warfarin in relation to renal function in patients with atrial fibrillation—insights from the ARISTOTLE Trial.
Headline finding: apixaban is more effective than warfarin in reducing stroke/SEE, mortality, and bleeding irrespective of renal function.
Implications for patients: more AF patients with impaired renal function can be considered candidates for stroke prevention by means of anticoagulation.
Implications for clinical practice: our findings suggest that apixaban may be particularly suited to address the unmet need for more effective and safe stroke prevention in patients with AF and renal dysfunction.
Jeff Healey (Hamilton, CA)
RE-LY AF: global variations in the 1-year rates of death and stroke in 15 432 patients presenting to the emergency department with atrial fibrillation in 47 countries: the RE-LY AF Registry.
Headline finding: among patients presenting to an emergency department with atrial fibrillation, the global 1-year mortality rate is >10%, with most deaths resulting from heart failure. The overall rate of stroke within 1 year is 4%; with the CHADS-2 risk factors playing a large role in predicting stroke and the presence of rheumatic heart disease a smaller role. For both mortality and stroke, there is important regional variation in event rates.
Implications for patients: physicians caring for patients with atrial fibrillation in the emergency department may now have a clearer idea of the rate of heart failure, stroke, and death that these patients have within 1 year of presentation. They will also have a better understanding of how to predict these outcomes, so that they may apply the appropriate interventions to improve patient prognosis.
Implications for clinical practice: atrial fibrillation is a global disease; however, much of our understanding of how to treat it is based on studies from Europe and North America. If we are to improve patient outcomes, we must first understand the causes and consequences of atrial fibrillation for each region, so that we may apply available therapies in an ideal fashion.
Carlo Di Mario
Carlo Di Mario (London, UK)
EORP transcatheter valve treatment (TCVT) Sentinel Pilot Registry: the 1-month follow-up of the ESC Sentinel Registry 2010–12 on TCVT.
Headline finding: the Pilot European Transcatheter Valve Registry included 4571 patients undergoing transcatheter aortic valve implantation (TAVI) in 2011–12 in 137 centres of 10 European countries. The average age was 81.4 ± 7.1 years with a Logistic Euroscore of 20.2 ± 13.3. In-hospital mortality was 7.4%, stroke 1.8%, myocardial infarction 0.9%, major vascular complications 3.1% with no difference between balloon expandable SapienXT and self-expandable CoreValve, P = 0.15. Need for pacemaker implantation and the presence of Grade 2–3 paravalvular aortic regurgitation were statistically more frequent in the CoreValve group.
Implications for patients: TAVI is a valid solution for inoperable patients with symptomatic severe aortic valve stenosis and a potential alternative for patients at very high-surgical risk. Overall, the practice of TAVI in Europe focuses on these two categories of patients who were often denied surgery leading to high mortality and poor quality of life.
Implications for clinical practice: the femoral approach is preferred when possible (74.2%), with a growing application of local anaesthesia (39% of transfemoral procedures). In patients with peripheral vascular disease or too small femoral arteries the transapical but also transubclavian and direct aortic approach offer an alternative but with higher mortality (12.8 and 9.7%, respectively).
Martine Gilard (Brest Cedex, FR)
FRANCE 2: French Transcatheter Aortic Valve Intervention Registry: FRANCE 2.
Headline finding: FRANCE 2 Registry is the largest prospective registry and reflects the real-life TAVI experience in high-risk elderly patients in France. The FRANCE 2 registry gives a real-life status of this new therapeutic option. Complication rates seem to be acceptable considering the frequent co-morbidities of this population.
Implications for patients: TAVI appears to be a reasonable option for a selected population of inoperable or high-risk patients with severe symptomatic aortic stenosis.
Implications for clinical practice: surgical aortic valve replacement is the definitive therapy for patients with severe symptomatic aortic stenosis. However, TAVI is the definite therapy for inoperable or high-risk patients. Further progress in patient selection techniques, post-procedural care and choice of optimal access are essential to improve results.
The Egyptian Heart Journal
Dr Mahmoud Hassanein reviews the history and progress of this English language journal in the Middle East
The Egyptian Heart Journal is the official journal of the Egyptian Society of Cardiology. It was founded by the late Prof. Mohamed Ibrahim, who was considered the Godfather of modern cardiology in Egypt. The journal dates back to 1960. At that time, there were few (if any) cardiology periodicals in the Middle East region. The journal did well for the first two decades after its inception. However, it started to face several problems that threatened its prestige as a respected and trusted journal.
Lack of original scientific work that met international standards was a great obstacle. This reflected a setback in scientific and medical research all over the country. The absence of international authors and guest editors resulted in the journal rarely being cited.
In 2010, with a new board of directors at the Egyptian Society of Cardiology, an ambitious project to revive the Egyptian Heart Journal was put forward as a priority. I was assigned that responsibility as a deputy editor and then as an editor-in-chief starting from 28 November 2011. An agreement was reached between the Egyptian Society of Cardiology and the Ministry of Scientific Research whereby, the Journal would be published by Elsevier B.V from 1 January 2011. During the term of this agreement, the Journal would be published electronically four times a year in one (four issues) volume(s), with a maximum of 360 pages/year, according to a production schedule determined by the Ministry in consultation with Elsevier B.V. and with the editor-in-chief (representing the Egyptian Society of Cardiology).
The Egyptian Heart Journal is now an international, English language peer-reviewed journal concerned with Cardiovascular Medicine. It aims to publish the highest quality material, both clinical and scientific, in all areas of cardiovascular medicine. It includes articles related to research findings, technical evaluations, and reviews. In addition, it provides a forum for the exchange of information on all aspects of cardiovascular medicine, including educational issues. The journal is honoured by its large board consisting of 22 editorial board members, 42 Egyptian advisory board members, and 54 international guest editors.
A milestone in collaborative publishing was a series of Almanac 2011 papers, appearing more or less simultaneously in many of the Editors' Network Journals and published by The Egyptian Heart Journal in a supplementary issue in March, 2012. The Editors' Network is a task force of the European Society of Cardiology (ESC); representing the 44 National Society Cardiovascular Journals that are published across 37 countries. The Almanac articles presented, select recent research that had driven clinical advances in six major topic areas of cardiology. The content was educational and clinically relevant. Plans for Almanac 2012 are yet more ambitious and pave the way for a new era of joint educational initiatives driven by the Editors' Network of the ESC.
In the lifetime of a scientific journal, the first milestone is to be recognized and indexed by Pubmed. The second is to obtain an impact factor. The Egyptian Heart Journal chose to wait before applying for an impact factor so that it could benefit from the extra exposure gained after its rebirth in 2011. What we are now doing is selecting research work of high-scientific value for publication in the journal. We are using stringent criteria for selection and have a rejection rate of 50% for submitted articles. We are inviting international authors to write review articles and editorial reviews for the journal. We are also publishing interesting case studies and unique images in cardiovascular medicine.
Finally, I would like to sincerely thank the authors who submit their work to the Journal, my fellow deputy and associate editors and to the many reviewers who gave us their time and effort. On behalf of our team, we look forward to carrying on the work with both authors and reviewers to make The Egyptian Heart Journal a premium journal contributing to the progress of science and medicine in the coming years.
Mahmoud Hassanein MD, Editor-in-Chief, Egyptian Heart Journal
People's corner: American Heart Association 2011 J.B. Herrick Award
Bernard Gersh recognized for his contributions to clinical cardiology by AHA
Prof. Bernard J. Gersh, Mayo Clinic and EHJ deputy editor, was presented with the James B. Herrick Award for Outstanding Achievement in Clinical Cardiology at the AHA meeting in Los Angeles, USA on 3 November 2011. The Herrick Award, consisting of a medallion and citation is conferred annually during the Council on Clinical Cardiology Annual Dinner and Business Meeting, held during the Scientific Sessions of the American Heart Association.
The Herrick Award is presented by the Council on Clinical Cardiology of the American Heart Association. The award honours a physician whose scientific achievements have contributed profoundly to the advancement and practice of clinical cardiology.
In establishing the James B. Herrick Award, the Council on Clinical Cardiology of the American Heart Association pays homage to a great clinician. Dr James Bryan Herrick (1861–1954) was a pioneer among cardiologists. One of his most significant contributions was his classic paper on ‘Clinical Features of Sudden Obstruction of the Coronary Arteries’ published in 1912. Besides giving the medical world a definitive description of coronary thrombosis, his studies emphasized the important observation that sudden obstruction of a coronary artery is not necessarily fatal. Dr Herrick lived to see his investigations confirmed and recognized. He served as President of the American Heart Association in 1927–28, and received its Gold Heart Award in 1951.
Dr Gersh joins past recipients of the award, which include: Eugene Braunwald 198, Valentin Fuster 2001, Bertram Pitt 2005, Patrick Serruys 2006.
The European Heart Journal is proud to have Dr Gersh a deputy editor.
Bernard Gersh receiving Award from Kristin Newby Duke University and Chair Council of Clinical Cardiology
Bernard Gersh with Award and Mayo Clinic Fellows
NICE Guideline on hypertension
Helen Jaques outlines the 2011 update of the UK's National Institute for Health and Clinical Excellence guideline on diagnosis and treatment of hypertension
The National Institute for Health and Clinical Excellence (NICE) guideline on hypertension (CG127), first published in 2004 and updated five times since, provides guidance for UK clinicians on how to diagnose and treat hypertension (HTN) in adults.1,2 The 2011 version of the guidance—which comprises 65 recommendations, 36 of which are new—recommends among other things that primary care doctors should use 24 h ambulatory blood pressure monitoring (ABPM) instead of clinic blood pressure (BP) to diagnose HTN and that thiazides should no longer be used as first line drugs to treat HTN.
One of the main points of the 2011 guideline is that doctors should use 24 h ABPM to confirm a diagnosis of HTN in individuals who have a BP of 140/90 mmHg or higher when measured in clinic. This approach will help to avoid the ‘white coat effect’ experienced by around a quarter of patients, whereby the patient's BP in clinic is increased artificially as a result of anxiety associated with the clinic visit.2 The main basis for this recommendation is that ABPM is a more accurate and more cost-effective way of diagnosing HTN than either clinic or home monitoring,3,4 says Bryan Williams, Professor of Medicine in the Institute of Cardiovascular Sciences at University/Leicester College London and chairman of the guideline development group for the 2011 update. ‘We've known for years that ABPM is a much better way of predicting cardiovascular outcomes and also likelihood of damage because it gives you a much more accurate appreciation of the patient's true blood pressure’, he says.
NICE's own cost-effectiveness analysis suggested that switching to ABPM could save the NHS around £10 million (€12.6 million) after 5 years by reducing the number of consultations patients attend, a problem inherent in clinic monitoring, and making sure that only those patients who genuinely require treatment receive it. The health service will have experienced an initial cost in adopting this approach, as many primary care practices would have needed to purchase ABPM equipment at a cost of around £1016 (€1280) and invest around £380 (€479) a year per device for upkeep.4 However, these initial cost anxieties have not necessarily played out, says Prof. Williams. ‘The immediate reaction of everybody was that this would be too expensive but in reality when you take account of all other factors involved in the current method of diagnosis, the cost effectiveness actually works out very much in favour of this approach’, he says.
The 2007 European Society of Cardiology (ESC) Guidelines for the management of arterial HTN recommend that doctors should first use office or clinic BP monitoring to establish a diagnosis of HTN, ABPM is then used in patients with considerable variability in their BP measurements.5 This recommendation was made because the evidence on ABPM is really quite ‘scattered’ and inconclusive, says Prof. Giuseppe Mancia, Director of Clinical Medicine, Department of Clinical Medicine, University of Milan—Bicocca and Co-Chairperson of the 2007 ESC HTN Guideline Task Force. ‘I've been working on ABPM for 40 years now and I think there's a lot more work to do before this can be an established procedure in clinical practice’, he says. ‘The most important thing we need to know is how much predictive ability we gain by doing ABPM when added to clinic BP’.
The NICE guideline makes several interesting recommendations with respect to how each stage of HTN and patients of particular ages should be treated. Those patients with severe HTN—that is, a clinic BP of 180/110 mmHg or higher—should receive treatment for HTN straight away without the doctor waiting for the results of BP monitoring. People aged under 80 years with ‘stage one’ HTN—that is, a clinic BP of 140/90 mmHg or higher and a subsequent ABPM daytime average or a home BP monitoring (HBPM) average of 135/85 mmHg or higher—who have one or more of target organ damage, established cardiovascular disease, renal disease, diabetes, or a 10-year cardiovascular risk equivalent to 20% or greater, should receive antihypertensive drug treatment, as should individuals with a clinic BP of 160/100 mmHg or higher and an ABPM or HBPM average of 150/95 mmHg or higher—stage 2 HTN.
For the first time, NICE recommends that patients over the age of 80 years should receive the same treatment for HTN as patients aged 55–80 years, with the goal of lowering BP to <150/90 mmHg, slightly less ambitious than the target of <140/90 mmHg in people under 80. The recommendation to treat patients aged >80 years is an ‘important addition’, says Prof. Williams. ‘Up until this point guidelines around the world have been very cautious as to what to recommend in the so called very elderly’, he says. ‘There was genuine anxiety that there might be benefit in terms of reducing the risk of stroke in particular, but actually that's offset by harm from side effects’. However, the HYVET trial clearly demonstrates that treating HTN in this age group is safe and effective,6 he says. ‘The dilemma for doctors is whether this recommendation applies to everyone over the age of 80, and the answer is almost certainly not’, he adds. ‘There needs to be an element of clinical judgment about whether the patient is likely to get net benefit from treatment’.
The drugs that NICE recommends for treating HTN are also stratified on the basis of age. People younger than 55 years of age should be offered an angiotensin-converting enzyme (ACE) inhibitor or a low-cost angiotensin-II receptor blocker (ARB) (but not these two classes in combination), whereas those aged 55 or older and black people of African or Caribbean decent of any age, should instead, be treated with a calcium channel blocker (CCB). For patients whose HTN is not controlled by this first approach NICE then suggests ‘step two’ treatment with a CCB in combination with an ACE inhibitor or an ARB, followed by step three treatment with an ACE inhibitor or an ARB, a CCB, and a thiazide-like diuretic all in combination. Those individuals whose BP remains >140/90 mmHg despite this combination treatment should be viewed as experiencing resistant HTN and should receive further diuretic therapy with either low-dose spironolactone or higher dose thiazide-like diuretic treatment on the top of step three treatment.
The NICE guidance suggests steering clear of conventional thiazide diuretics such as bendroflumethiazide in favour of a thiazide-like diuretic such as chlorthalidone. This particular ruling could prove tricky given that bendroflumethiazide is widely used in the UK and the most commonly prescribed antihypertensive drug in Scotland.7 However, the drug is not used much in other countries and there is not a convincing evidence base for low doses (i.e. 2.5 mg/day), says Prof. Williams, hence it is removed from the 2011 NICE guideline. NICE states that CCBs are the most cost-effective intervention for treating HTN, with an incremental cost-effectiveness ratio of under £2000 per quality adjusted life year gained for both men and women.
The ESC Guidelines on the other hand do not make any specific recommendations as to which drugs should be used to treat HTN, instead simply recommending the five major classes of antihypertensive agents—thiazide diuretics, CCBs, ACE inhibitors, ARBs, and beta-blockers—alone or in combination. ‘There is evidence that there is no difference in cardiovascular risk between these five classes, so there is no reason to prefer one class over another’, says Prof. Mancia. ‘The evidence suggests that it is BP lowering per se no matter how it is obtained, that produces the benefit, so because of this the European guidelines were quite liberal’. It should be up to the physician to decide which treatment to use, he adds, although there are some situations where one class of drug might be preferable to another, for example in individuals at risk of developing diabetes or individuals with subclinical organ damage.
Although the lifestyle advice elements of the NICE HTN guideline were not considered in the 2011 update, the 2004 recommendations are still included and are still very relevant to patients with HTN. NICE recommends that doctors should find out the diet, exercise, alcohol, and smoking habits of patients with HTN and suggest a healthy diet, regular exercise, and giving up smoking. Doctors should discourage excessive consumption of coffee and other caffeine-rich products and encourage people to reduce their dietary sodium intake, both of which can reduce BP. The ESC Guideline also specifically recommends that patients with HTN should increase their fruit and vegetable intake and decrease the amount of saturated and total fat they consume. Lifestyle modifications are not only recommended for patients who are already being treated but are also ‘absolutely recommended’ for people who are not yet being treated but look like they are going to develop HTN, says Prof. Williams.
The main message from the guideline is that for patients with HTN the important things are getting the diagnosis right—that is, only treating patients who need treatment and not treating those who do not—and getting BP controlled once you start treatment, says Prof. Williams. ‘All of the other stuff – what drugs to use, the thresholds and so on – are important in terms of providing a framework to do that, but the reality is, that the key outcome measurement is the quality of blood pressure control because that's the thing that drives the benefit’, he says.