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Dr. Luis Ruilope
The 2007 Hypertension guidelines were necessary and new : assess cardiovascular risk with corresponding therapeutic approach, coexistence of the metabolic syndrome and elevated blood pressure levels as a situation of high added cardiovascular risk, Pharmacological intervention from the early stages of blood pressure elevation, control of lipids and serum glycaemia, and the use of antiplatelet therapy when the global risk is elevated, more combination therapy... However the ADVANCE, ONTARGET and ACCOMPLISH's results call for new guidelines. An annual update of the guidelines in those areas where new data has been published deserves to be considered.
June 2007 : the ESC and the ESH publish the new joint edition of the European Guidelines for the management of arterial hypertension (1,2).
Publication of evidence that must be applied to daily clinical practice must take place incessantly and evidence accumulates in four years.
An annual update of the guidelines in those areas where new data has been published deserves to be considered. Here are three recently published or presented studies that could influence the nature of future guidelines.
The ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation) trial.
It aimed to address two important questions related to the care and well being of those with Type 2 diabetes:
This study has shown that the relative risk of death from cardiovascular disease was reduced by 18% and death from any cause was reduced by 14% in those patients receiving active treatment (4).
Moreover, it is well-known that the use of an angiotensin receptor blocker (ARB) reduces the rate of death or hospitalisation for heart failure in patients with heart failure (5,6), and reduces vascular events in high-risk patients with hypertension and left ventricular hypertrophy (7). However, in other high-risk populations, the role of ARBs as an alternative or in addition to ACE inhibitors to prevent cardiovascular outcomes is not known. The ONTARGET (Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial) study compared the ACE inhibitor ramipril, the ARB telmisartan, and the combination of the two drugs in patients with vascular disease or high-risk diabetes (8). ONTARGET tested two hypotheses :
Given the similarity of the patient population, in terms of medical conditions, to that of the HOPE (Heart Outcomes Prevention Evaluation) study, this is a very interesting comparison.
In March 2008, the results of ONTARGET trial were published, and showed that telmisartan is equivalent to ramipril in patients with vascular disease or high-risk diabetes and is associated with less angioedema. The combination of the two drugs is associated with more adverse events without an increase in benefit (9).
A number of prespecified analyses and substudies in ONTARGET are examining intermediate endpoints, such as albuminuria, left ventricular hypertrophy, arterial stiffness, erectile dysfunction, glucose tolerance and blood markers. These will allow us to observe not only the comparative effects of telmisartan, ramipril and the combination on target organ damage, but also to clarify the relationship between drug effects on these surrogate endpoints and hard clinical outcomes – at least for the population of relatively high-risk patients being studied in ONTARGET.
Furthermore, ACCOMPLISH (Avoiding Cardiovascular events through Combination therapy in Patients Living with Systolic Hypertension) is the first trial designed to compare the effects on major fatal and non-fatal cardiovascular endpoints of two forms of antihypertensive combination therapy in hypertensive patients at high cardiovascular risk (10). :
The study was stopped early because treatment with benazepril plus amlodipine was more effective than treatment with the ACE inhibitor plus diuretic, reducing the risk of morbidity and mortality by 20% compared with the comparative standard combination (11). All these data and other coming soon require the consideration of the Task Forces writing Guidelines without the need to wait several years.
The current version of the guidelines for the management of arterial hypertension contains new evidence corroborating the
The clinical evidences that influence our attitude to treat a patient have been fundamentally obtained in studies aimed at identifying significant differences on the final consequences of the cardiovascular and renal disease (non mortal events, chronic or terminal renal insufficiency and cardiovascular mortality).
Nevertheless, cardiovascular and renal diseases develop progressively throughout many years. This process is accompanied by a parallel progression of atherosclerosis that finally will be translated in atherotrombotic events, which are the fundamental cause of fatal and non-fatal cardiovascular and renal events.
Therefore, the early detection of an elevated cardiovascular risk through the clustering of cardiovascular risk factors and/or the presence of target organ damage must be followed by prompt intervention. Such a strategy would impede the development and progression of cardiovascular and renal damage. For this purpose these guidelines describe a simple and easily applicable list of cardiovascular risk factors and subclinic organ damage that will allow correct risk stratification in order to intervene adequately.
Besides earlier intervention, updated guidelines recommend a more frequent use of therapeutic combinations using the different classes of antihypertensive drugs, in order to facilitate a better blood pressure control. A good daily compliance and long-term adherence to life-style changes and antihypertensive treatment are the key factors to reducing the fatal consequences of arterial hypertension.
As a leading risk factor for CVD, hypertension represents a major clinical and financial burden in Europe. Currently, hypertension is under treated and the benefits of antihypertensive therapy are undervalued. There is a current shift to an integrated comprehensive risk management strategy that advocates treatment of hypertension according to overall CV risk based on assessment of numerous prognostic factors known to influence the risk of CVD. This approach is likely to improve hypertension management and reduce CVD morbidity and mortality. In consequence, the guidelines renewed by the European Society of Hypertension and the European Society of Cardiology are opportune, introduce new advice and without a doubt they will contribute to a better control of the risk of cardiovascular disease in our patients. All new editions of guidelines must well be received, considering that our clinical practice will be facilitated with its reading and the application of the recommendations included in these guidelines.
The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.
1. Mancia G, De Backer G, Dominiczak A, Cifkova R, Fagard R, Germano G, et al. 2007 Guidelines for the Management of Arterial Hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens 2007; 25:1105–1187.
2. Mancia G, De Backer G, Dominiczak A, Cifkova R, Fagard R, Germano G, et al. 2007 Guidelines for the management of arterial hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur Heart J 2007; 28: 1462-1536. Study rationale and design of ADVANCE: action in diabetes and vascular disease-preterax and diamicron MR controlled evaluation. Diabetologia 2001; 44: 1118-1120.
4. Patel A; ADVANCE Collaborative Group, MacMahon S, Chalmers J, Neal B, Woodward M, Billot L, Harrap S, et al. Effects of a fixed combination of perindopril and indapamide on macrovascular and microvascular outcomes in patients with type 2 diabetes mellitus (the ADVANCE trial): a randomised controlled trial. Lancet 2007; 370(9590): 829-840.
5. Granger CB, McMurray JJ, Yusuf S, et al. Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function intolerant to angiotensin-converting-enzyme inhibitors: the CHARM-Alternative trial. Lancet 2003; 362: 772-776.
6. McMurray JJ, Ostergren J, Swedberg K, et al. Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function taking angiotensin-converting-enzyme inhibitors: the CHARM-Added trial. Lancet 2003; 362: 767-771.
7. Dahlöf B, Devereux RB, Kjeldsen SE, et al. Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet 2002; 359: 995-1003.
8. Teo K, Yusuf S, Sleight P, et al. Rationale, design, and baseline characteristics of 2 large, simple, randomized trials evaluating telmisartan, ramipril, and their combination in high-risk patients: the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial/Telmisartan Randomized Assessment Study in ACE Intolerant Subjects with Cardiovascular Disease (ONTARGET/TRANSCEND) trials. Am Heart J 2004; 148: 52-61.
9. The ONTARGET Investigators. Telmisartan, ramipril or both in patients at high risk for vascular events. N Engl J Med 2008; 358: 1547-1559.
10. Weber MA, Bakris GL, Dahlöf B, Pitt B, Velazquez E, Gupte J, et al. Baseline characteristics in the Avoiding Cardiovascular events through Combination therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) trial: a hypertensive population at high cardiovascular risk. Blood Press 2007; 16: 13-19.
11. Jamerson KA, on behalf of the ACCOMPLISH investigators. Avoiding cardiovascular events in combination therapy in patients living with systolic hypertension. American College of Cardiology Scientific Sessions; March 31, 2008; Chicago, IL.
Dr J. Segura, *Prof. L. M Ruilope Madrid, Spain *Nucleus member of the working group on Cardiovascular Pharmacology and Drug Therapy
Correspondence to: Dr Luis M Ruilope Hypertension Unit. Hospital 12 de Octubre Av. Córdoba s/n 28041 Madrid. Spain Phone: +34 91 3908198 Fax: +34 91 3908035 Email: email@example.com
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