Clinical differences among angiotensin II receptor antagonists.

The six major classes of antihypertensive agents prescribed worldwide are similar in efficacy but dissimilar in tolerability. Recently, the World Health Organization-International Society of Hypertension (WHO-ISH) concluded that agents from all six classes are suitable for the initiation and maintenance of antihypertensive therapy, including the newest class of agents, the angiotensin II receptor antagonists (AIIRAs). The ideal antihypertensive agent should be effective and well tolerated, as well as synergistic in blood pressure-lowering effects when combined with other agents. As monotherapy, AIIRAs have demonstrated efficacy similar to other classes of antihypertensive agents in numerous clinical trials. Several AIIRAs have also demonstrated enhanced efficacy when combined with a low dose of the diuretic hydrochlorothiazide (HCTZ). A well-known feature of this new class of agents is placebo-level tolerability; however, less is known about intra-class differences. Losartan, the first approved AIIRA, has become an important benchmark for within-class comparisons with respect to antihypertensive efficacy. Head-to-head comparisons between losartan and newer AIIRAs have been conducted; their cumulative results indicate that the antihypertensive effect and antagonistic activity of losartan may be the weakest among AIIRAs. In a recent clinical trial, we demonstrated that irbesartan produces statistically superior blood pressure reduction when compared to valsartan. This may have clinical implications for agent selection among the AIIRAs

Preventing new-onset diabetes in thiazide-treated patients

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Incidence of adverse events with telmisartan compared with ACE inhibitors: evidence from a pooled analysis of clinical trials

Telmisartan is indicated for the prevention of cardiovascular events in high-risk patients, based on comparable efficacy to the angiotensin-converting enzyme (ACE) inhibitor, ramipril, in the ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET®) trial. However, tolerability must be considered when selecting treatments. This analysis compared the tolerability of telmisartan and ACE inhibitors using data pooled from 12 comparative, randomized studies involving 2564 telmisartan-treated patients and 2144 receiving ACE inhibitors (enalapril, lisinopril, or ramipril). Incidence rates of adverse events for the combined ACE inhibitor treatments and for telmisartan were similar (42.8% vs 43.9%, respectively) as were the rates of serious adverse events (1.8% vs 1.7% for telmisartan, respectively). Patients receiving ACE inhibitors had more cough (8.6% vs 2.6% with telmisartan, P < 0.0001). Results were similar irrespective of age, gender, or ethnicity. The adverse event of angioedema was observed in four patients (0.2%) receiving ACE inhibitors versus none with telmisartan (P = 0.043). There were small, numerical differences in serious adverse events. A total of 107 patients (5.0%) receiving ACE inhibitors and 93 patients (3.6%) receiving telmisartan discontinued treatment because of adverse events (P = 0.021); of these, 32.7% and 5.4%, respectively, were discontinuations due to cough (relative risk reduction of 88% [P < 0.0001] with telmisartan). Telmisartan and ACE inhibitors produced comparable blood pressure reductions at marketed doses. Telmisartan and ACE inhibitors are suitable for the prevention of cardiovascular events in high-risk patients, but telmisartan is better tolerated, particularly with regard to cough

The new European Society of Hypertension/European Society of Cardiology (ESH/ESC) Guidelines

The 2007 guidelines on hypertension of the European Society of Hypertension (ESH) and the European Society of Cardiology (ESC) [Mancia et al. 2007] differ for several aspects from the previous hypertension guidelines issued by the two Societies in 2003 [Guidelines Committee ESH/ESC, 2003]. In some instances the difference mainly consists in a reinforcement or extension of what was only suggested by the previous guidelines, based on the increased amount of data obtained in the last four years. In other instances, however, it consists in an actual change from what was recommended in 2003 because of the new data provided by trials and other types of studies. In this paper we will report on some of these differences and discuss their rationale

Blood Pressure Non-Dipping and Obstructive Sleep Apnea Syndrome: A Meta-Analysis

AIM: We examined the reduced blood pressure (BP) nocturnal fall in patients with obstructive sleep apnea (OSA) by a meta-analysis including studies that provided data on prevalence rates of non-dipping (ND) pattern during 24-h ambulatory blood pressure monitoring (ABPM). DESIGN: The PubMed, OVID-MEDLINE, and Cochrane CENTRAL literature databases were searched for appropriate articles without temporal restriction up to April 2019 through focused and sensitive search methods. Studies were identified by crossing the search terms as follows: "obstructive sleep apnea", "sleep quality", "non dipping", "reduced nocturnal BP fall", "circadian BP variation", "night-time BP", and "ambulatory blood pressure monitoring". RESULTS: Meta-analysis included 1562 patients with OSA from different clinical settings and 957 non-OSA controls from 14 studies. ND pattern prevalence in patients with OSA widely varied among studies (36.0-90.0%). This was also the case for non-OSA controls (33.0% to 69.0%). Overall, the ND pattern, assessed as an event rate in the pooled OSA population, was 59.1% (confidence interval (CI): 52.0-65.0%). Meta-analysis of the seven studies comparing the prevalence of ND pattern in participants with OSA and controls showed that OSA entails a significantly increased risk of ND (Odds ratio (OR) = 1.47, CI: 1.07-1.89, p < 0.01). After the exclusion of patients with mild OSA, OR increased to 1.67 (CI: 1.21-2.28, p < 0.001). CONCLUSIONS: The present meta-analysis, extending previous information on the relationship between OSA and impaired BP dipping, based on single studies, suggests that this condition increases by approximately 1.5 times the likelihood of ND, which is a pattern associated with a greater cardiovascular risk than normal BP dipping

Metabolic syndrome and multiple organ damage in essential hypertension

Aim. We investigated the prevalence of the metabolic syndrome (MS) in hypertensive patients categorized according to the number of markers of organ damage (OD) in order to assess the value of a systematic search for cardiac and extra-cardiac OD in the MS setting. Methods. A total of 3119 untreated and treated essential hypertensives included in the Evaluation of Target Organ Damage in Hypertension (ETODH), an observational registry of hypertension-related OD, were considered for this analysis. All patients underwent extensive investigation for left ventricular hypertrophy (LVH) or LV concentric remodeling (cardiac OD), carotid plaques and/or intima-media thickening (vascular OD) and microalbuminuria (MA) and/or increased serum creatinine (renal OD). Subjects were classified as: positive for none (group 0), one (group I), two (group II) or three markers (group III) of OD. Results. MS prevalence rates progressively rose across the groups stratified according to the OD score, reaching a 2.3-fold increase in group III compared with their MS counterparts in group 0. The distribution of subjects with and without the MS across the groups was 15% vs 29% (group 0), 32% vs 38% (group I), 39% vs 26% (group II) and 14% vs 7% (group III), respectively. Thus, subjects having two or three markers of OD were 53% among those with MS and 33% (p<0.01) among those without it. Conclusion. Our findings indicate a strong association between the MS and OD by showing that a clustering of two or three markers of OD is the prevalent cardiovascular phenotype in MS hypertensives referred to a specialist center and call for a systematic evaluation of cardiac and extracardiac OD in this setting

Angiotensin II receptor blockers and myocardial infarction: deeds and misdeeds

BACKGROUND: A recent editorial published by Verma and Strauss, entitled 'Angiotensin receptor blockers and myocardial infarction', examined, through a partial analysis of individual trials, the use of angiotensin receptor blockers (ARBs) in a variety of clinical settings. This editorial was reported widely in the lay press and media, and generated disappointment and concern among physicians in many countries, probably because of its provocative subtitle in the British Medical Journal: 'These drugs may increase myocardial infarction and patients may need to be told'. OBJECTIVE AND METHODS: In order to explore the influence of ARBs on myocardial infarction, we performed a more comprehensive and updated meta-analysis, taking into account all major international, randomized trials using ARBs compared with another active drug or conventional therapy (placebo), and reporting information on rates of myocardial infarction. RESULTS: We found no significant differences in fatal and non-fatal myocardial infarction between treatment with ARBs, placebo or active treatment, and the same result was obtained when considering only trials in which ARBs were compared with angiotensin-converting enzyme inhibitors (ACEIs), or when pooling all trials together. The pooled analysis of these trials shows that the relative risk of myocardial infarction lies substantially on the indifference line. CONCLUSION: Our analysis demonstrates that, at this time, there is no evidence of increased risk of myocardial infarction in patients treated with ARBs

The new concept of total cardiovascular risk management

Introduction: Cardiovascular risk factors, such as hypertension, hypercholesterolemia, and diabetes mellitus, often cluster together and can also be seen with other pathophysiological conditions that greatly increase an individual's risk for cardiovascular morbidity and death. Aim of the study: This article emphasizes the importance of assessing and managing the total cardiovascular risk in an individual patient. Materials and methods: Suggestions and recommendations from the most current hypertension management guidelines have been integrated with results from the major clinical trials published in the last decade. Results: Based on a review of the epidemiological data on cardiovascular disease, this paper expands the concept of stratification of hypertensive patients according to the approximate added risk of major cardiovascular events in the next 10 years and stresses the importance of subclinical target-organ damage. Conclusions: Although common in clinical practice, high-risk patients are often undiagnosed. Intensive hypertensive therapy is recommended for high-risk patients, and this treatment strategy will require combination therapy to control or reverse subclinical organ damage and prevent the progression of cardiovascular risk in subjects at low risk or medium risk

The Prognostic Effect of Circadian Blood Pressure Pattern on Long-Term Cardiovascular Outcome is Independent of Left Ventricular Remodeling

We aimed to investigate the predictive value of 24 h blood pressure (BP) patterns on adverse cardiovascular (CV) outcome in the initially untreated hypertensive patients during long-term follow-up. This study included 533 initially untreated hypertensive patients who were involved in this study in the period between 2007 and 2012. All participants underwent laboratory analysis, 24 h BP monitoring, and echocardiographic examination at baseline. The patients were followed for a median period of nine years. The adverse outcome was defined as the hospitalization due to CV events (atrial fibrillation, myocardial infarction, myocardial revascularization, heart failure, stroke, or CV death). During the nine-year follow-up period, adverse CV events occurred in 85 hypertensive patients. Nighttime SBP, non-dipping BP pattern, LV hypertrophy (LVH), left atrial enlargement (LAE), and LV diastolic dysfunction (LV DD) were risk factors for occurrence of CV events. However, nighttime SBP, non-dipping BP pattern, LVH, and LV DD were the only independent predictors of CV events. When all four BP pattern were included in the model, non-dipping and reverse dipping BP patterns were associated with CV events, but only reverse-dipping BP pattern was independent predictor of CV events. The current study showed that reverse-dipping BP pattern was predictor of adverse CV events independently of nighttime SBP and LV remodeling during long-term follow-up. The assessment of BP patterns has very important role in the long-time prediction in hypertensive population