Are physicians underestimating the challenges of hypertension management? Results from the Supporting Hypertension Awareness and Research Europe-wide (SHARE) survey.

AIMS: The Supporting Hypertension Awareness and Research Europe-wide (SHARE) survey aimed to qualify the key challenges that physicians face when trying to get patients to recommended blood pressure (BP) goals. METHODS AND RESULTS: The survey was open to physicians involved in the treatment of hypertension, was anonymous, and included 45 questions covering: physicians' demographic information, familiarity with BP treatment guidelines, views on the BP targets recommended by the 2007 European Society of Hypertension and European Society of Cardiology (ESH-ESC) guidelines, and perceptions on the proportion of 'challenging patients' in hypertension management (defined as patients not achieving the BP goal, where the BP goal is at least <140/90 mm Hg, and <130/80 mm Hg for patients with co-morbidities or high CV risk). Physicians significantly underestimated the proportions of their 'challenging patients' with hypertension compared with their perceptions of the proportions achieving 2007 ESH-ESC BP targets (p < 0.0001). The majority of cardiologists (75.5%) and general/family practitioners (GPs) (81.3%) as well as internists (59.3%) (p < 0.05 for cardiologists and GPs vs internists) felt that it was a challenge to get their patients to target BP, stating that only 43.2%, 57.4% and 38.2% of their patients, respectively, achieved these targets in practice (p < 0.05 for GPs vs cardiologists and internists). CONCLUSION: Physicians may underestimate the proportion of 'challenging patients' with hypertension and there is a need to improve their BP control. Increasing physicians' awareness about the risks of uncontrolled BP and improving compliance are two possible ways to improve management of hypertension.

Long-term safety and tolerability of the oral direct renin inhibitor aliskiren with optional add-on hydrochlorothiazide in patients with hypertension: a randomized, open-label, parallel-group, multicentre, dose-escalation study with an extension phase.

BACKGROUND: Most patients with hypertension will require combination therapy with at least two agents from different antihypertensive classes to achieve blood pressure (BP) control. Thiazide diuretics, such as hydrochlorothiazide (HCTZ), are widely used in combination therapy. The volume reduction with these agents stimulates the renin-angiotensin system (RAS), making RAS inhibitors such as the direct renin inhibitor aliskiren a logical choice for combination therapy with HCTZ. OBJECTIVE: The aim of this study was to investigate the long-term safety, tolerability and efficacy of the direct renin inhibitor aliskiren, with or without addition of the diuretic HCTZ. METHODS: In the 12-month core study, patients with hypertension (mean sitting diastolic BP ≥90 mmHg and <110 mmHg) were randomized in a 3 : 2 ratio to once-daily aliskiren 150 mg or 300 mg. At months 2, 3, 4, 6 and 9, treatment was adjusted in patients not achieving a BP goal of <140/90 mmHg. Patients not at goal on aliskiren 150 mg once daily were up-titrated to aliskiren 300 mg once daily. Patients not at goal with aliskiren 300 mg once daily received add-on HCTZ 12.5 mg once daily, which was up-titrated to 25 mg once daily if BP remained inadequately controlled. At month 12, patients who received aliskiren/HCTZ 300 mg/25 mg once daily for at least 8 months in the core study were eligible to enter a 4-month extension study. RESULTS: Overall, 1625/1955 patients completed the core study, and 870/1955 patients received add-on HCTZ; 189/198 patients completed the 4-month extension. Aliskiren, with or without add-on HCTZ, was generally well tolerated; the incidence of adverse events (AEs) during the core study was similar among the four final treatment groups. The most frequently reported AEs in the core and extension studies were mild and transient cases of nasopharyngitis, headache and dizziness. Few patients exhibited laboratory abnormalities. Overall, aliskiren, with or without add-on HCTZ, reduced mean BP by 18.0/12.7 mmHg at core study endpoint, and 61.2% of patients achieved BP control. BP reductions with aliskiren/HCTZ 300 mg/25 mg combination therapy at the core study endpoint were maintained during the extension study. CONCLUSION: In patients with hypertension, long-term treatment with aliskiren, with or without add-on HCTZ, is well tolerated and provides effective BP lowering that is sustained over 12 months.

Physician attitudes to blood pressure control: findings from the Supporting Hypertension Awareness and Research Europe-wide survey.

OBJECTIVES: The Supporting Hypertension Awareness and Research Europe-wide (SHARE) physician survey aimed to qualify the key challenges that physicians face when trying to get patients to blood pressure (BP) goal. METHODS: The SHARE survey was open to physicians involved in the treatment of patients with hypertension, was anonymous, and was designed to take 15 min to complete. The survey included 45 questions covering physicians' demographic information, views on the BP targets recommended by the European Society of Hypertension-European Society of Cardiology guidelines, opinions on acceptable levels of BP control, and perceptions about the challenges associated with getting patients to BP goal. RESULTS: The survey was conducted between May and December 2009, and 2629 European physicians responded. The mean (± SD) levels of SBP/DBP that physicians were satisfied with, concerned about, or would cause them to take immediate action were 131.6  ±â€Š 9.5 /81.9  ±â€Š 5.6, 148.9  ± 11.3 / 91.6 ±  5.8, and 168.2  ±â€Š17.1 / 100.1  ±â€Š 7.8 mmHg, respectively. Overall, 95.0 and 90.1% of the physicians, respectively, felt that patients SBP/DBP needed to be higher than the guideline recommended goal levels before taking immediate action. CONCLUSION: Clinical hesitation in relation to reducing elevated BP to goal levels is putting patients at increased cardiovascular risk and contributing to the substantial health and economic burden associated with uncontrolled BP. A number of strategies are discussed that have been shown to be effective in countering this problem.

Practical solutions to the challenges of uncontrolled hypertension: a white paper.

This white paper is an urgent call to action from an international group of physicians. The continued failure to control hypertension takes an unacceptable toll on patients, families and society and it must be addressed. Any patient with blood pressure of 140/90 mmHg or greater can be characterized as a 'challenging patient', is at significant risk, and requires persistent optimization of therapy until target blood pressure is achieved. Six key challenges in reaching this goal blood pressure are described: (1) inadequate primary prevention; (2) faulty awareness of risk; (3) lack of simplicity; (4) therapeutic inertia; (5) insufficient patient empowerment; and (6) unsupportive healthcare systems. This white paper identifies straightforward actions that will produce rapid improvements in the management of hypertension, with a simple aim: to treat all challenging patients effectively to goal blood pressure, preventing disability and saving lives.

Impact of resting heart rate on outcomes in hypertensive patients with coronary artery disease: findings from the INternational VErapamil-SR/trandolapril STudy (INVEST).

AIM: To determine the relationship between resting heart rate (RHR) and adverse outcomes in coronary artery disease (CAD) patients treated for hypertension with different RHR-lowering strategies. METHODS AND RESULTS: Time to adverse outcomes (death, non-fatal myocardial infarction, or non-fatal-stroke) and predictive values of baseline and follow-up RHR were assessed in INternational VErapamil-SR/trandolapril STudy (INVEST) patients randomized to either a verapamil-SR (Ve) or atenolol (At)-based strategy. Higher baseline and follow-up RHR were associated with increased adverse outcome risks, with a linear relationship for baseline RHR and J-shaped relationship for follow-up RHR. Although follow-up RHR was independently associated with adverse outcomes, it added less excess risk than baseline conditions such as heart failure and diabetes. The At strategy reduced RHR more than Ve (at 24 months, 69.2 vs. 72.8 beats/min; P < 0.001), yet adverse outcomes were similar [Ve 9.67% (rate 35/1000 patient-years) vs. At 9.88% (rate 36/1000 patient-years, confidence interval 0.90-1.06, P = 0.62)]. For the same RHR, men had a higher risk than women. CONCLUSION: Among CAD patients with hypertension, RHR predicts adverse outcomes, and on-treatment RHR is more predictive than baseline RHR. A Ve strategy is less effective than an At strategy for lowering RHR but has a similar effect on adverse outcomes.

Effect of angiotensin receptor blockade on central haemodynamics in essential hypertension: results of a randomised trial.

OBJECTIVE: Angiotensin-converting enzyme (ACE) inhibitors have been shown to lower central augmentation index (cAI), an index of arterial wave reflection, more than beta-blockers. We tested whether this is also true for long-term treatment with an angiotensin receptor blocker (ARB). METHODS: One-hundred and fifty-six subjects with essential hypertension were randomised to treatment with either irbesartan or atenolol. cAI and central blood pressure (BP) were determined by pulse wave analysis from the radial and the carotid artery after six and after 18 months treatment. RESULTS: Peripheral and central systolic and diastolic BP were reduced to a similar extent in the two groups. cAI was reduced with irbesartan, but increased with atenolol (derived from the carotid artery: -6+/-10 vs. -4+/-12% after six months, p<0.001; -4+/-12 vs. +1+/-11% after 18 months; p=0.011). Furthermore, central to peripheral pulse pressure (PP) amplification was unaffected by treatment with irbesartan, but decreased with atenolol. CONCLUSIONS: Although treatment with irbesartan and atenolol similarly decreased peripheral and central BP, only treatment with irbesartan had beneficial effects on arterial wave reflection and preserved PP amplification. These haemodynamic effects may at least partly explain the reported differential effects of ARB versus beta-blocker treatment on cardiovascular mortality in patients with essential hypertension.

Dogma disputed: can aggressively lowering blood pressure in hypertensive patients with coronary artery disease be dangerous?

BACKGROUND: Because coronary perfusion occurs mainly during diastole, patients with coronary artery disease (CAD) could be at increased risk for coronary events if diastolic pressure falls below critical levels. OBJECTIVE: To determine whether low blood pressure could be associated with excess mortality and morbidity in this population. DESIGN: A secondary analysis of data from the International Verapamil-Trandolapril Study (INVEST), which was conducted from September 1997 to February 2003. SETTING: 862 sites in 14 countries. PATIENTS: 22 576 patients with hypertension and CAD. INTERVENTIONS: Patients from INVEST were randomly assigned to a verapamil sustained-release- or atenolol-based strategy; blood pressure control and outcomes were equivalent. MEASUREMENTS: An unadjusted quadratic proportional hazards model was used to evaluate the relationship between average on-treatment blood pressure and risk for the primary outcome (all-cause death, nonfatal stroke, and nonfatal myocardial infarction [MI]), all-cause death, total MI, and total stroke. A second model adjusted for differences in baseline covariates. RESULTS: The relationship between blood pressure and the primary outcome, all-cause death, and total MI was J-shaped, particularly for diastolic pressure, with a nadir at 119/84 mm Hg. After adjustment, the J-shaped relationship persisted between diastolic pressure and primary outcome. The MI-stroke ratio remained constant over a wide blood pressure range, but at a lower diastolic blood pressure, there were substantially more MIs than strokes. An interaction between decreased diastolic pressure and history of revascularization was observed; low diastolic pressure was associated with a relatively lower risk for the primary outcome in patients with revascularization than in those without revascularization. LIMITATIONS: This is a post hoc analysis of hypertensive patients with CAD. CONCLUSIONS: The risk for the primary outcome, all-cause death, and MI, but not stroke, progressively increased with low diastolic blood pressure. Excessive reduction in diastolic pressure should be avoided in patients with CAD who are being treated for hypertension.

Predictors of adverse outcome among patients with hypertension and coronary artery disease.

OBJECTIVES: We sought to determine predictors for adverse outcomes in hypertensive patients with coronary artery disease (CAD). BACKGROUND: Factors leading to adverse outcomes in hypertensive patients with CAD are poorly understood. The INternational VErapamil-trandolapril STudy (INVEST) compared outcomes in hypertensive patients with CAD that were assigned randomly to either a verapamil sustained-release (SR)- or an atenolol-based strategy for blood pressure (BP) control. Trandolapril and hydrochlorothiazide were used as added agents. During follow-up (61,835 patient-years), BP control and the primary outcome (death, nonfatal myocardial infarction, and nonfatal stroke) were not different between strategies. METHODS: We investigated risk for adverse outcome associated with baseline factors, follow-up BP, and drug treatments using Cox modeling. RESULTS: Previous heart failure (adjusted hazard ratio [HR] 1.96), as well as diabetes (HR 1.77), increased age (HR 1.63), U.S. residency (HR 1.61), renal impairment (HR 1.50), stroke/transient ischemic attack (HR 1.43), smoking (HR 1.41), myocardial infarction (HR 1.34), peripheral vascular disease (HR 1.27), and revascularization (HR 1.15) predicted increased risk. Follow-up systolic BP <140 mm Hg or diastolic BP <90 mm Hg (HRs 0.82 or 0.70, respectively) and trandolapril with verapamil SR (HRs 0.78 and 0.79) were associated with reduced risk. CONCLUSIONS: In hypertensive patients with CAD, increased risk for adverse outcomes was associated with conditions related to the severity of CAD and diminished left ventricular function. Lower follow-up BP and addition of trandolapril to verapamil SR each were associated with reduced risk.

Effect of irbesartan versus atenolol on left ventricular mass and voltage: results of the CardioVascular Irbesartan Project.

Regression of hypertensive left ventricular hypertrophy (LVH) is associated with improved prognosis. The aim of this trial was to compare the effects of irbesartan versus atenolol on LVH in subjects with essential hypertension. Because electrocardiographic and echocardiographic parameters of LVH carry disparate prognostic information, both methods were applied in this trial. In the randomized, double-blind, multicenter trial CardioVascular Irbesartan Project, 240 patients with essential hypertension were treated with irbesartan or atenolol for 18 months. Voltage criteria used for LVH were Sokolow index, Cornell index, Cornell voltage x QRS duration product and Lewis index. In parallel, left ventricular mass (LVM) was determined by 2-dimensional guided M-mode echocardiography. After 6 and 18 months, reductions of LVM and voltage criteria for LVH were only found in subjects treated with irbesartan. However, a reduction of LVM was only detectable in subjects within the highest quartile of baseline LVM but not overall. In contrast, reductions of voltage criteria for LVH were detectable after 6 and 18 months even within commonly used normal limits. In conclusion, treatment of hypertension with irbesartan resulted in a significant reduction in the voltage criteria for LVH, although an effect on LVM was only seen in subjects with high baseline LVM. In contrast, atenolol did not lead to reductions in electrocardiographic or echocardiographic parameters of LVH. Because voltage criteria for LVH have been shown to predict cardiovascular outcome independently from LVM, we suggest that both methods should be used to accurately assess the benefits of antihypertensive treatment.

[Compliance problems in therapy resistant hypertension]. / Complianceprobleme bei therapierefraktärer Hypertonie.

DEFINITION AND FREQUENCY: Hypertension may be termed refractory, when a therapeutic plan that has included nonpharmacologic treatment and the prescription of a triple drug combination in adequate doses including a diuretic, has failed to lower the blood pressure < 140/90 mmHg. True resistance can only be found in 2-5% of all hypertensive patients. CAUSES AND DIAGNOSIS: Pseudoresistance to antihypertensive therapy is common and often due to a suboptimal drug regime, interactions with other drugs or a secondary form of hypertension. It is estimated that in more than two thirds of patients with hypertension, poor compliance is at least part of the problem. Poor compliance is not easily detected by the physicians, and studies showed that they could not predict compliance with any more accuracy than if they were guessing. Factors for a poor compliance are lack of patient information about hypertension and its treatment, side effects of prescribed drugs, lack of teaching in the self-measurement of blood pressure and patient's dissatisfaction with the disease. Improvement of compliance can be achieved by selecting long-acting drugs or drug combinations. Structured teaching programs, as they become part of the Disease Management Programs (DMPs) in Germany can improve compliance as well. THERAPY: If noncompliance can be excluded, the dosage of antihypertensive drugs should be increased to a maximum if tolerated, or combinations of four or more drugs can be used, including drugs like minoxidil.

Efficacy of eplerenone versus enalapril as monotherapy in systemic hypertension.

This study compared the efficacy and tolerability of eplerenone and enalapril in 499 patients with stage 1 or 2 hypertension who were randomized to receive eplerenone or enalapril for 6 months in a 3-step titration-to-effect study. After 6 months, patients whose diastolic blood pressure (BP) was <90 mm Hg had their dosages down-titrated were followed for an additional 6 months. Diastolic BP was the primary end point. Eplerenone was as effective as enalapril in reducing both systolic BP (eplerenone, -14.5 mm Hg; enalapril, -12.7 mm Hg; p = 0.199) and diastolic BP (eplerenone, -11.2 mm Hg; enalapril, -11.3 mm Hg; p = 0.910) at 6 months. BP reductions at 12 months were also similar between groups (-16.5/-13.3 mm Hg for eplerenone, -14.8/-14.1 mm Hg for enalapril; p = 0.251 and 0.331, respectively). Withdrawal rates for adverse events (eplerenone 7.9%, enalapril 9.3% at 6 months) and treatment failures (eplerenone 23.3%, enalapril 22.8% at 6 months) were also equivalent. Approximately 2/3 of each group had normal BP with monotherapy treatment at 6 months. BP response was independent of renin levels in the eplerenone group, but not in the enalapril group. Both agents reduced albuminuria in patients who had an elevated value at baseline, with significantly greater improvement in patients treated with eplerenone versus enalapril (-61.5% vs -25.7%; p = 0.01). Both agents were similarly well tolerated, and there was no increased incidence of any sexual adverse events in the eplerenone group. Patients taking enalapril had a higher rate of cough. Both agents increased serum potassium levels, but <1% in each group reported adverse events from hyperkalemia. Eplerenone was as effective as enalapril as monotherapy in patients with stage 1 or 2 hypertension, was more effective in reducing albuminuria, and was well tolerated for 12 months.

[Systolic hypertension-treat or not to treat?]. / Systolische Hypertonie-Treat or Not to Treat?

UNLABELLED: HEMODYNAMICS: Elevated diastolic as well as elevated systolic blood pressure substantially contribute to the increase of cardiovascular risk. Conclusive results have proven that lowering diastolic and/or systolic blood pressure can reduce cardiovascular risk. There is evidence that not only the absolute values for diastolic and systolic blood pressure alone but also the pulse pressure as an additional indicator of cardiovascular risk have to be considered. The prevalence of isolated systolic hypertension increases with age. Remodeling of the arterial wall with increase of collagen and decrease of elastic fibers are leading to an impaired arterial compliance. Decreased compliance and acceleration of the pulse wave velocity can elevate systolic and lower diastolic blood pressure. In consequence cardiac stress and pulse pressure will rise. CONCLUSION: There is a strong correlation in elderly patients between cardiovascular mortality and morbidity and systolic blood pressure. Antihypertensive therapy is able to lower cardiovascular event rate in elderly patients with isolated systolic hypertension with a predominant risk reduction for stroke.

Design of the Omapatrilat in Persons with Enhanced Risk of Atherosclerotic events (OPERA) trial.

The Omapatrilat in Persons with Enhanced Risk of Atherosclerotic events (OPERA) trial is a large clinical trial of omapatrilat, a vasopeptidase inhibitor, in patients with stage 1 isolated systolic hypertension (ISH). OPERA is the first study to examine whether effective antihypertensive treatment can provide survival and clinical end point benefits in older persons with this common condition. This 5-year multinational, randomized, double-blind, parallel-group, placebo-controlled, forced-titration study will be conducted in approximately 12,600 subjects randomized by approximately 1100 study centers worldwide over a recruitment period of approximately 2 years. The primary objective of OPERA is to determine whether treatment with once-daily omapatrilat (target dose 40 mg) will reduce cardiovascular (CV) morbidity and mortality in older (> or = 65 years) men and women with enhanced risk for atherosclerotic events due to stage 1 ISH plus other risk factors for which currently there is no evidence-based requirement for treatment. Blood pressure inclusion criteria are systolic blood pressure (SBP) 140 to 159 mm Hg (SBP 125 to 139 mm Hg in diabetic individuals) and diastolic blood pressure (DBP) <90 mm Hg. The primary end point is defined as the composite of fatal/nonfatal stroke, fatal/nonfatal myocardial infarction, fatal/nonfatal heart failure, and other CV mortality. Secondary end points include the individual components of the primary end point, CV mortality, and major cardiovascular end points, as well as effects on cognitive function and initiation of treatment for diabetes. Additional analyses will be conducted in men and women, in diabetic patients, in different risk classes and according to prior evidence of vascular disease.