Showing papers by "Luis M. Ruilope published in 2012"

ESH Position Paper: Renal denervation ^ an interventional therapy of resistant hypertension

Abstract: Experts from the European Society of Hypertension prepared this position paper in order to summarize current evidence, unmet needs and practical recommendations on the application of percutaneous transluminal ablation of renal nerves [renal denervation (RDN)] as a novel therapeutic strategy for the treatment of resistant hypertension. The sympathetic nervous activation to the kidney and the sensory afferent signals to the central nervous system represent the targets of RND. Clinical studies have documented that catheter-based RDN decreases both efferent sympathetic and afferent sensory nerve traffic leading to clinically meaningful systolic and diastolic blood pressure (BP) reductions in patients with resistant hypertension. This position statement intends to facilitate a better understanding of the effectiveness, safety, limitations and issues still to be addressed with RDN.

Mineralocorticoid receptor antagonists for heart failure with reduced ejection fraction: integrating evidence into clinical practice

Abstract: Mineralocorticoid receptor antagonists (MRAs) improve survival and reduce morbidity in patients with heart failure, reduced ejection fraction (HF–REF), and mild-to-severe symptoms, and in patients with left ventricular systolic dysfunction and heart failure after acute myocardial infarction. These clinical benefits are observed in addition to those of angiotensin converting enzyme inhibitors or angiotensin receptor blockers and beta-blockers. The morbidity and mortality benefits of MRAs may be mediated by several proposed actions, including antifibrotic mechanisms that slow heart failure progression, prevent or reverse cardiac remodelling, or reduce arrhythmogenesis. Both eplerenone and spironolactone have demonstrated survival benefits in individual clinical trials. Pharmacologic differences exist between the drugs, which may be relevant for therapeutic decision making in individual patients. Although serious hyperkalaemia events were reported in the major MRA clinical trials, these risks can be mitigated through appropriate patient selection, dose selection, patient education, monitoring, and follow-up. When used appropriately, MRAs significantly improve outcomes across the spectrum of patients with HF–REF.

Clinical differences between resistant hypertensives and patients treated and controlled with three or less drugs.

Abstract: Background and aim:Clinical characteristics of resistant hypertensive patients in comparison to controlled patients have not been fully investigated in large cohorts. The aim of the study was to evaluate clinical differences, target organ damage and ambulatory blood pressure monitoring in resistant

Olmesartan for the Delay or Prevention of Microalbuminuria in Type 2 Diabetes

Abstract: A b s t r ac t Background Microalbuminuria is an early predictor of diabetic nephropathy and premature cardiovascular disease. We investigated whether treatment with an angiotensin-receptor blocker (ARB) would delay or prevent the occurrence of microalbuminuria in patients with type 2 diabetes and normoalbuminuria. Methods In a randomized, double-blind, multicenter, controlled trial, we assigned 4447 patients with type 2 diabetes to receive olmesartan (at a dose of 40 mg once daily) or placebo for a median of 3.2 years. Additional antihypertensive drugs (except angiotensin-converting–enzyme inhibitors or ARBs) were used as needed to lower blood pressure to less than 130/80 mm Hg. The primary outcome was the time to the first onset of microalbuminuria. The times to the onset of renal and cardiovascular events were analyzed as secondary end points. Results The target blood pressure (<130/80 mm Hg) was achieved in nearly 80% of the patients taking olmesartan and 71% taking placebo; blood pressure measured in the clinic was lower by 3.1/1.9 mm Hg in the olmesartan group than in the placebo group. Microalbuminuria developed in 8.2% of the patients in the olmesartan group (178 of 2160 patients who could be evaluated) and 9.8% in the placebo group (210 of 2139); the time to the onset of microalbuminuria was increased by 23% with olmesartan (hazard ratio for onset of microalbuminuria, 0.77; 95% confidence interval, 0.63 to 0.94; P = 0.01). The serum creatinine level doubled in 1% of the patients in each group. Slightly fewer patients in the olmesartan group than in the placebo group had nonfatal cardiovascular events — 81 of 2232 patients (3.6%) as compared with 91 of 2215 patients (4.1%) (P = 0.37) — but a greater number had fatal cardiovascular events — 15 patients (0.7%) as compared with 3 patients (0.1%) (P = 0.01), a difference that was attributable in part to a higher rate of death from cardiovascular causes in the olmesartan group than in the placebo group among patients with preexisting coronary heart disease (11 of 564 patients [2.0%] vs. 1 of 540 [0.2%], P = 0.02). Conclusions Olmesartan was associated with a delayed onset of microalbuminuria, even though blood-pressure control in both groups was excellent according to current standards. The higher rate of fatal cardiovascular events with olmesartan among patients with preexisting coronary heart disease is of concern. (Funded by Daiichi Sankyo; ClinicalTrials.gov number, NCT00185159.)

Achievement of cardiometabolic goals in aware hypertensive patients in Spain: a nationwide population-based study.

Abstract: Despite the importance of achieving cardiometabolic goals beyond blood pressure, in the health of hypertensives, no comprehensive assessment of these characteristics has been performed in whole countries. We studied in 2008–2010 a total of 11 957 individuals representative of the Spanish population aged ≥18 years. Information on cardiometabolic characteristics was collected at the participants’ homes, through structured questionnaires, physical examination, and fasting blood samples. A total of 3983 individuals (33.3%) had hypertension (≥140/90 mm Hg or current antihypertensive drug treatment), 59.4% were aware of their condition, 78.8% treated among those aware, and 48.5% controlled among those aware and treated (22.7% of all hypertensives). Of the aware hypertensives, 13.8% had a body mass index 2 , 38.6% consumed

Ambulatory blood pressure monitoring and development of cardiovascular events in high-risk patients included in the Spanish ABPM registry: the CARDIORISC Event study.

Abstract: Background and aim:Ambulatory blood pressure monitoring (ABPM) is superior to conventional BP measurement in predicting outcome, with baseline 24-h, daytime and night-time absolute values, as well as relative nocturnal decline, as powerful determinants of prognosis. We aimed to evaluate ABPM estimat

Current challenges in the clinical management of hypertension.

Abstract: Elevated blood pressure (BP) is probably the most-important modifiable risk factor for cardiovascular disease (CVD). BP influences the development of CVD, even if levels of BP are well below the usual cut-off point that defines the presence of arterial hypertension. Adequate measurement of BP is the most-important requirement for the diagnosis and treatment of patients with suspected hypertension. The use of methodologies such as ambulatory and home BP monitoring have become powerful tools for defining the 'real' BP of patients, discarding the white-coat effect, and discovering masked hypertension. Early intervention with life-style changes and antihypertensive drugs is required to obtain the best outcome for the patient. In this sense, early use of combination antihypertensive drug therapy is recommended. The treatment of resistant hypertension-the type of elevated BP that is most difficult to control-has clearly improved over the past decade. Further studies are required to define how antihypertensive therapy should be used in the earliest stages of hypertension and for the treatment of patients with a mild-to-moderate increase in global cardiovascular risk.

Microalbuminuria breakthrough under chronic renin-angiotensin-aldosterone system suppression.

Abstract: OBJECTIVES Microalbuminuria has been shown to be a potent predictor for future development of cardiovascular and renal events that can be prevented by the use of angiotensin-converting enzyme inhibitors (ACEis) or angiotensin receptor blockers (ARBs). Both classes of drugs are now-a-days widely used in the treatment of arterial hypertension since the very early stages of the cardiorenal continuum when only cardiovascular risk factors are detected. We describe here the development of de-novo microalbuminuria in patients chronically treated with either an ACEi or an ARB at adequate doses. METHODS We reviewed the evolution of 1433 patients (mean age 60.5 ± 12.4 years, 50.3% men, 6.6% having type 2 diabetes), arriving in our hospital-based Hypertension Unit previously treated for a least 2 years either with an ACEi or an ARB, at adequate doses, alone or in combination with other antihypertensive drugs. RESULTS A total of 184 (16.1%) patients developed new-onset microalbuminuria, whereas macroalbuminuria was detected in 11 (1.0%) patients at the end of follow-up. Albuminuria appeared at any level of blood pressure (BP) from below 130/80 mmHg, albeit the highest percentage was seen when SBP was above 160 mmHg. De-novo microalbuminuria was more frequent in those patients presenting with established cardiovascular disease and predicts the future development of cardiovascular events but was not accompanied by a significant worsening of renal function. CONCLUSION These data indicate that a reappraisal of renin-angiotensin-aldosterone system (RAAS) suppression is required when microalbuminuria appears in patients under chronic RAAS suppression.

Risk stratification in cardiovascular disease primary prevention - scoring systems, novel markers, and imaging techniques.

Abstract: The aim of this paper is to review and discuss current methods of risk stratification for cardiovascular disease (CVD) prevention, emerging biomarkers, and imaging techniques, and their relative merits and limitations. This report is based on discussions that took place among experts in the area during a special CardioVascular Clinical Trialists workshop organized by the European Society of Cardiology Working Group on Cardiovascular Pharmacology and Drug Therapy in September 2009. Classical risk factors such as blood pressure and low-density lipoprotein cholesterol levels remain the cornerstone of risk estimation in primary prevention but their use as a guide to management is limited by several factors: (i) thresholds for drug treatment vary with the available evidence for cost-effectiveness and benefit-to-risk ratios; (ii) assessment may be imprecise; (iii) residual risk may remain, even with effective control of dyslipidemia and hypertension. Novel measures include C-reactive protein, lipoprotein-associated phospholipase A2, genetic markers, and markers of subclinical organ damage, for which there are varying levels of evidence. High-resolution ultrasound and magnetic resonance imaging to assess carotid atherosclerotic lesions have potential but require further validation, standardization, and proof of clinical usefulness in the general population. In conclusion, classical risk scoring systems are available and inexpensive but have a number of limitations. Novel risk markers and imaging techniques may have a place in drug development and clinical trial design. However, their additional value above and beyond classical risk factors has yet to be determined for risk-guided therapy in CVD prevention.

Prevention of microalbuminuria in patients with type 2 diabetes and hypertension.

Abstract: BACKGROUND We have previously demonstrated in the Randomized Olmesartan and Diabetes Microalbuminuria Prevention study that the angiotensin receptor blocker (ARB) olmesartan delays the onset of microalbuminuria in patients with type 2 diabetes. Now, we investigated the effect in the subpopulation with hypertension. METHODS Overall, 4020 patients with type 2 diabetes and hypertension at baseline (defined by a SBP/DBP ≥130/80 mmHg or use of antihypertensive medication) received either 40 mg olmesartan once daily or placebo for a median of 3.2 years in a randomized, double-blind, multicenter, controlled trial. Additional antihypertensive drugs (except angiotensin-converting enzyme inhibitors or ARBs) were used as needed to lower blood pressure (BP) to less than 130/80 mmHg. RESULTS The average BP was 126.3/74.7 and 129.5/76.6 mmHg, respectively (P < 0.001). Olmesartan delayed the time to onset of microalbuminuria by 25% (hazard ratio = 0.75; 95% confidence interval = 0.61-0.92, P = 0.007). Patients with a baseline SBP above the median of 136.7 mmHg and a SBP reduction above the median of 17.45 mmHg had a lower incidence of microalbuminuria than patients with a SBP reduction of less than 17.45 (8.1 vs. 11.2%, P < 0.0001). Independent from the baseline BP and the degree of BP reduction a 15-39% increase in the time to onset of microalbuminuria was detectable by olmesartan treatment. Cardiovascular events were comparable and occurred in 93 (4.6%) patients taking olmesartan and 86 (4.4%) taking placebo. CONCLUSION Patients with a better BP reduction are less likely to develop microalbuminuria. Treatment with olmesartan delayed the onset of microalbuminuria independent of the baseline BP and the degree of BP reduction.

Prevention of cardiovascular disease guided by total risk estimations - challenges and opportunities for practical implementation: highlights of a CardioVascular Clinical Trialists (CVCT) Workshop of the ESC Working Group on CardioVascular Pharmacology and Drug Therapy.

Abstract: This paper presents a summary of the potential practical and economic barriers to implementation of primary prevention of cardiovascular disease guided by total cardiovascular risk estimations in the general population. It also reviews various possible solutions to overcome these barriers. The report is based on discussion among experts in the area at a special CardioVascular Clinical Trialists workshop organized by the European Society of Cardiology Working Group on Cardiovascular Pharmacology and Drug Therapy that took place in September 2009. It includes a review of the evidence in favour of the "treat-to-target" paradigm, as well as potential difficulties with this approach, including the multiple pathological processes present in high-risk patients that may not be adequately addressed by this strategy. The risk-guided therapy approach requires careful definitions of cardiovascular risk and consideration of clinical endpoints as well as the differences between trial and "real-world" populations. Cost-effectiveness presents another issue in scenarios of finite healthcare resources, as does the difficulty of documenting guideline uptake and effectiveness in the primary care setting, where early modification of risk factors may be more beneficial than later attempts to manage established disease. The key to guideline implementation is to improve the quality of risk assessment and demonstrate the association between risk factors, intervention, and reduced event rates. In the future, this may be made possible by means of automated data entry and various other measures. In conclusion, opportunities exist to increase guideline implementation in the primary care setting, with potential benefits for both the general population and healthcare resources.

Dual RAAS suppression: recent developments and implications in light of the ALTITUDE study.

Abstract: Rudolf A de Boer,1 Michel Azizi,2 AH Jan Danser,3 Genevieve Nguyen,4 Jurg Nussberger,5 Luis M Ruilope,6 Roland E Schmieder7 and Massimo Volpe8 1University Medical Center Groningen, Department of Cardiology, University of Groningen, the Netherlands 2Universite Paris-Descartes, Assistance Publique des Hopitaux de Paris, Departement d’Hypertension Arterielle, France 3Division of Pharmacology and Vascular Medicine, Department of Internal Medicine, Erasmus MC, the Netherlands 4Centre for Interdisciplinary Research in Biology (CIRB), France 5Division of Angiology and Hypertension, Centre Hospitalier Universitaire Vaudois, Switzerland 6Hypertension Unit, Hospital 12 de Octubre and Department of Public Health and Preventive Medicine, Universidad Autonoma, Spain 7University Hospital Erlangen, Nephrology and Hypertension, Germany 8Division of Cardiology, Department of Clinical and Molecular Medicine, University of Rome “Sapienza”and IRCCS Neuromed, Italy Email: r.a.de.boer@umcg.nl RAAS Working Group Update

Inhibition of the renin-angiotensin-aldosterone system: is there room for dual blockade in the cardiorenal continuum?

Abstract: Antagonism of renin-angiotensin-aldosterone system is exerted through angiotensin-converting enzyme inhibitors, angiotensin receptor antagonists, renin inhibitors and mineralocorticoid receptor antagonists. These drugs have been successfully tested in numerous trials and in different clinical settings. The original indications of renin-angiotensin-aldosterone system blockers have progressively expanded from the advanced stages to the earlier stages of cardiorenal continuum. To optimize the degree of blockade of renin-angiotensin-aldosterone system, dose uptitrations of angiotensin-converting enzyme inhibitors and angiotensin receptor antagonists or the use of a dual blockade, initially identified with the combination of angiotensin-converting enzyme inhibitors and angiotensin receptor antagonists, have been proposed. The data from the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET) study do not support this specific dual blockade approach. However, the dual blockade of angiotensin-converting enzyme inhibitors/angiotensin receptor antagonists with direct renin inhibitors is currently under investigation while that based on an aldosterone blocker with any of the previous three drugs requires more evidence beyond heart failure. In this review, we revisited potential advantages of dual blockade of renin-angiotensin-aldosterone system in arterial hypertension and diabetes.

Cardiorenal disease development under chronic renin-angiotensin-aldosterone system suppression.

Abstract: Drugs suppressing the renin-angiotensin-aldosterone system (RAAS) are now widely used to treat patients all along the cardiorenal continuum. It supposes that many patients, in particular those with arterial hypertension are treated with converting-enzyme inhibitors and angiotensin receptor blockers for years during which the development and prograssion of cardiorenal disease can be observed. The meaning of this progression in the presence of RAAS suppression requires to be clarified and to be treated in order to diminish the velocity of progression of cardiorenal disease.

Medida de la presión arterial en consulta y automatizada (BPTru®) para evaluar el efecto de bata blanca

Abstract: Resumen Fundamento y objetivo El efecto de bata blanca (EBB) es uno de los principales sesgos que pueden modificar la medida de la presion arterial (PA) en consulta, por lo que se debe considerar para evitar errores diagnostico-terapeuticos en los pacientes hipertensos. La utilizacion de aparatos automatizados en consulta podria disminuir dicho efecto. Metodo Se disenaron 2 estudios con el objetivo de evaluar las diferencias entre la medida rutinaria en consulta y la obtenida por el aparato automatizado de medida de PA en consulta, BPTru ® , asi como su influencia en el EBB. El primero de los estudios, TRUE-ESP, incluyo pacientes normotensos e hipertensos atendidos en consultas especializadas de Cardiologia, Nefrologia, Medicina Interna, Endocrinologia y Medicina Familiar. El segundo, TRUE-HTA, incluyo pacientes hipertensos atendidos en una Unidad de HTA, protocolizada, con personal entrenado. Resultados El estudio TRUE-ESP incluyo 300 pacientes, 76% hipertensos. Se observo una diferencia significativa entre la medida clinica y la medida BPTru ® (media [DE] de PA sistolica/PA diastolica [PAS/PAD] de 9,8 [6,11]/3,4 [7,9] mmHg, p ® (media [DE] de PAS/PAD de 5,7 [3,9]/2,1 [3,5] mmHg, p Conclusiones El empleo de aparatos automatizados de medida de PA en consulta, como el BPTru ® , puede colaborar a disminuir el EBB y mejorar la precision de la medida de la PA en consulta.

Antihypertensives in people with gout or asymptomatic hyperuricaemia

Abstract: Losartan and calcium channel blockers are most effective owing to their uricosuric properties

Are there new threshold and goals in the treatment of arterial hypertension

Abstract: Eur J Clin Invest 2012 Abstract Background About half of the global burden of cardiovascular disease has been attributed to high blood pressure (BP). Worldwide, 7·6 million premature deaths (about 13·5% of the global total), 54% of strokes, and 47% of cases of ischemic heart disease were caused by high BP in 2001. Methods and results All guidelines agree that pharmacological treatment of patients with hypertension should be initiated as soon as BP rises >140/90 mmHg. Available data support the reduction of BP to values to <140/90 mmHg, but do not favor a reduction to <130/80 mmHg in patients with diabetes or a history of cardiovascular disease because of the absence of evidence obtained in prospective studies. Conclusions This review updates the controversies and challenges involved in the treatment of patients with established arterial hypertension, such as the progression of high-normal BP to overt hypertension, the choice of appropriate threshold and goal BP levels, the adequate number of drugs to be used since the early stages of hypertension, and which type of combination therapy offers most advantages to the patient.

Telmisartan 80 mg/hydrochlorothiazide 25 mg single-pill combination in the treatment of hypertension.

Abstract: Introduction: International guidelines emphasize the importance of blood pressure (BP) control to reduce cardiovascular risk. Telmisartan, an angiotensin II receptor blocker, provides large BP reductions and also prevents cardiovascular events in patients at high risk. The thiazide diuretic, hydrochlorothiazide (HCTZ), has a complementary mode of action, and combination with telmisartan is an established and rational treatment option for patients uncontrolled on monotherapy. A single-pill combination (SPC) of telmisartan 80 mg with high-strength HCTZ 25 mg (T80/H25) is widely available. Area covered: Clinical data on T80/H25 SPC for the management of hypertension was identified via MEDLINE searches. T80/H25 SPC provides greater BP reductions and higher goal achievement rates in patients who cannot achieve BP goal with T80/HCTZ 12.5 mg SPC, and also as initial therapy compared with T80 monotherapy. T80/H25 also reduced BP significantly more than valsartan 160 mg/H25 combination, and demonstrated favorable ...

Current status of renal denervation in resistant hypertension

Abstract: Resistant hypertension is a frequent form of arterial hypertension that, with the exception of malignant hypertension, constitutes the most dangerous stage of arterial hypertension. Recently we have improved the detection, diagnosis, and therapy of resistant hypertensives. The technique of renal denervation with a catheter has improved the control of blood pressure in such patients. The technique is simple, safe, and available data indicates that it is effective. More data and longer follow-up of patients are required to promote wide acceptance of this new technique.

Combination Therapy in Hypertension

Abstract: Arterial hypertension is the most important modifiable cardiovascular risk factor leading to death in general population Optimal treatment strategies are continuously being debated and both the initiation and maintenance of a pharmacologic approach have been evaluated in the latest clinical trials Although monotherapy is widely used as the initial therapy in most of the hypertensives, blood pressure-lowering drug combinations have offered some benefits in high-cardiovascular risk patients It is part of common clinical experience that the vast majority of patients with stage 2 hypertension require 2 or more pharmacologic agents to obtain a satisfying control Moreover, antihypertensive combinations should be considered in a number of clinical situations depending on the cardio-renal risk

Diabetes: Glycemic and blood-pressure control--lower is not better.

Abstract: The combined effect of intensive glycemic and blood-pressure control on microvascular complications has been examined in an analysis of the ACCORD study. The investigators hypothesized that simultaneous intensive management would have an additive effect on outcomes; however, the results provide no evidence to support the combined intensive control of glycemia and blood pressure.