High-risk Hypertensive Patients Research Articles

Role of Diuretics in the Prevention of Heart Failure

Hypertension is a major cause of heart failure (HF) and is antecedent in 91% of cases. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) stipulated assessment of the relative effect of chlorthalidone, lisinopril, and amlodipine in preventing HF. ALLHAT was a double-blind, randomized, clinical trial in 33,357 high-risk hypertensive patients aged > or =55 years. Hospitalized/fatal HF outcomes were examined with proportional-hazards models. Relative risks (95% confidence intervals; P values) of amlodipine or lisinopril versus chlorthalidone were 1.35 (1.21 to 1.50; <0.001) and 1.11 (0.99 to 1.24; 0.09). The proportional hazards assumption of constant relative risk over time was not valid. A more appropriate model showed relative risks of amlodipine or lisinopril versus chlorthalidone during year 1 were 2.22 (1.69 to 2.91; <0.001) and 2.08 (1.58 to 2.74; <0.001), and after year 1, 1.22 (1.08 to 1.38; P=0.001) and 0.96 (0.85 to 1.10; 0.58). There was no significant interaction between prior medication use and treatment. Baseline blood pressures were equivalent (146/84 mm Hg) and at year 1 were 137/79, 139/79, and 140/80 mm Hg in those given chlorthalidone, amlodipine, and lisinopril. At 1 year, use of added open-label atenolol, diuretics, angiotensin-converting enzyme inhibitors, and calcium channel blockers in the treatment groups was similar. HF risk decreased with chlorthalidone versus amlodipine or lisinopril use during year 1. Subsequently, risk for those individuals taking chlorthalidone versus amlodipine remained decreased but less so, whereas it was equivalent to those given lisinopril. Prior medication use, follow-up blood pressures, and concomitant medications are unlikely to explain most of the HF differences. Diuretics are superior to calcium channel blockers and, at least in the short term, angiotensin-converting enzyme inhibitors in preventing HF in hypertensive individuals.

Combined assessment of left ventricular perfusion and function by gated single-photon emission computed tomography for the risk stratification of high-risk hypertensive patients

This study was aimed at verifying whether combined information on left ventricular perfusion and function by electrocardiogram-gated single-photon emission computed tomography (SPECT) retains its known prognostic value in patients with systemic hypertension. A total of 415 hypertensive patients underwent rest and stress (exercise in 278 and dipyridamole in 137) gated 99mTc-sestamibi SPECT and prospective follow-up for the composite endpoint of death and acute coronary syndrome. Patients undergoing revascularization were censored. The individual effect of clinical and stress imaging data on outcome was evaluated by Cox regression analysis. Model validation was performed using bootstrap methods adjusted by the degree of optimism in estimates. Survival analysis was performed using the product-limit Kaplan-Meier method. During a median follow-up of 24 months, 12 cardiac deaths and 32 acute coronary syndromes occurred. After adjusting for the most significant covariates, age [hazard ratio (HR) 1.62, 95% confidence interval (CI) 1.02-2.57], diabetes (HR 7.51, 95% CI 1.61-35.2), summed stress score (HR 2.06, 95% CI 1.07-4), and peak end-systolic volume (HR 3.62, 95% CI 1.35-9.69) were multivariable predictors of outcome. The normal perfusion pattern was associated with a low event rate independently of peak end-systolic volume. Conversely, in the case of moderate to severe perfusion abnormalities, a peak end-systolic volume greater than 74 ml was able to identify an increased risk of adverse outcome. Moreover, peak end-systolic volume was significantly higher among patients who died of a cardiac cause compared with those with different outcomes. A combined assessment of left ventricular perfusion and function by gated SPECT significantly improves risk stratification in hypertensive patients.

Cardiovascular Outcomes in High-Risk Hypertensive Patients Stratified by Baseline Glomerular Filtration Rate

Chronic kidney disease is common in older patients with hypertension. To compare rates of coronary heart disease (CHD) and end-stage renal disease (ESRD) events; to determine whether glomerular filtration rate (GFR) independently predicts risk for CHD; and to report the efficacy of first-step treatment with a calcium-channel blocker (amlodipine) or an angiotensin-converting enzyme inhibitor (lisinopril), each compared with a diuretic (chlorthalidone), in modifying cardiovascular disease (CVD) outcomes in high-risk patients with hypertension stratified by GFR. Post hoc subgroup analysis. Multicenter randomized, double-blind, controlled trial. Persons with hypertension who were 55 years of age or older with 1 or more risk factors for CHD and who were stratified into 3 baseline GFR groups: normal or increased (> or = 90 mL/min per 1.73 m2; n = 8126 patients), mild reduction (60 to 89 mL/min per 1.73 m2; n = 18,109 patients), and moderate or severe reduction (< 60 mL/min per 1.73 m2; n = 5662 patients). Random assignment to chlorthalidone, amlodipine, or lisinopril. Rates of ESRD, CHD, stroke, and combined CVD (CHD, coronary revascularization, angina, stroke, heart failure, and peripheral arterial disease). In participants with a moderate to severe reduction in GFR, 6-year rates were higher for CHD than for ESRD (15.4% vs. 6.0%, respectively). A baseline GFR of less than 53 mL/min per 1.73 m2 (compared with >104 mL/min per 1.73 m2) was independently associated with a 32% higher risk for CHD. Amlodipine was similar to chlorthalidone in reducing CHD (16.0% vs. 15.2%, respectively; hazard ratio, 1.06 [95% CI, 0.89 to 1.27]), stroke, and combined CVD (CHD, coronary revascularization, angina, stroke, heart failure, and peripheral arterial disease), but less effective in preventing heart failure. Lisinopril was similar to chlorthalidone in preventing CHD (15.1% vs. 15.2%, respectively; hazard ratio, 1.00 [CI, 0.84 to 1.20]), but was less effective in reducing stroke, combined CVD events, and heart failure. Proteinuria data were not available, and combination therapies were not tested. Older high-risk patients with hypertension and reduced GFR are more likely to develop CHD than to develop ESRD. A low GFR independently predicts increased risk for CHD. Neither amlodipine nor lisinopril is superior to chlorthalidone in preventing CHD, stroke, or combined CVD, and chlorthalidone is superior to both for preventing heart failure, independent of level of renal function.

New Onset of Type 2 Diabetes Mellitus during Antihypertensive Therapy

Hypertension is a widely diffused clinical condition in the general population and it is often associated with people who are overweight (i.e. have abdominal adiposity) or obese and with metabolic syndrome. Evidence shows that hypertensive patients are at increased risk of developing type 2 diabetes mellitus (T2DM) since angiotensin II is involved in the pathogenesis of hypertension and insulin resistance, which are both the key components of metabolic syndrome. The preventive effect of renin-angiotensin system (RAS) inhibition on the development of T2DM could reflect the closely linked mechanisms of blood pressure and blood glucose homeostasis. Since hyperglycaemia is a consequence of insulin resistance and β-cell dysfunction, preventing T2DM by RAS inhibition may result from an improvement of β-cell function and/or an enhancement of insulin sensitivity, which are secondary to modifications in microcirculation and changes in ionic status. On the basis of this hypothesis, several trials in treating hypertensive patients have shown a positive effect of drugs inhibiting RAS in reducing the number of hypertensive patients that develop T2DM. We analysed the results of the following clinical studies that found a reduction in the incidence of new-onset T2DM in hypertensive patients using angiotensin II type 1 receptor blockers (ARBs): LIFE (Losartan Intervention For Endpoint reduction in hypertension) [losartan]; SCOPE (Study on COgnition and Prognosis in the Elderly) [candesartan]; ALPINE (Antihypertensive treatment and Lipid Profile In a North of Sweden Efficacy evaluation) [candesartan]; CHARM (Candesartan in Heart failure Assessment of Reduction in Mortality and morbidity) [candesartan]; and VALUE (Valsartan Antihypertensive Long-term Use Evaluation) [valsartan]. We analysed the results of the following clinical studies that found a reduction in the incidence of new-onset T2DM in hypertensive patients using angiotensin II type 1 receptor blockers (ARBs): LIFE (Losartan Intervention For Endpoint reduction in hypertension) [losartan]; SCOPE (Study on COgnition and Prognosis in the Elderly) [candesartan]; ALPINE (Antihypertensive treatment and Lipid Profile In a North of Sweden Efficacy evaluation) [candesartan]; CHARM (Candesartan in Heart failure Assessment of Reduction in Mortality and morbidity) [candesartan]; and VALUE (Valsartan Antihypertensive Long-term Use Evaluation) [valsartan]. Evidence shows that blood pressure reduction, when associated with lifestyle modifications (especially in high-risk patients), is more important than the mechanism of action of the antihypertensive drugs, which is to normalise blood pressure and thus reduce the incidence of cardiovascular events. In this regard, the identification of the potential influence of RAS inhibition in preventing new-onset T2DM in hypertensive subjects is a promising topic for the healthcare system. In the future, data from the ongoing trials, where prevention of diabetes is the primary endpoint, may prove to what extent this class of drugs is actually effective. However, in the previously mentioned clinical trials, the superior effectiveness of ARBs in preventing T2DM is associated with a lower efficacy in preventing cardiovascular events, because of their lesser capacity in lowering blood pressure. Evidence so far suggests the use of ARBs preferably in association with other classes of antihypertensive drugs and under a constant control of blood pressure. In this latter regard, in the recently published ASCOT-BPLA (Anglo-Scandinavian Cardiac Outcomes Trial—Blood Pressure Lowering Arm) study, a combination therapy based on a drug inhibiting RAS (perindopril) and a calcium-channel blocker (amlodipine) significantly reduced the incidence of major cardiovascular events and new onset of diabetes in high-risk hypertensive patients, compared with a combination therapy based on thiazide diuretic and a β-blocker.

The Role of Angiotensin II Type 1 Receptor Antagonists in Elderly Patients with Hypertension

Hypertension is a major risk factor for stroke and coronary events in elderly people and clinical trials have shown that treatment of hypertension with various drugs can result in a substantial reduction in cerebrovascular and cardiovascular events. The angiotensin II type 1 (AT1) receptor antagonists are the newest class of antihypertensive agents to be used widely in clinical practice. AT1 receptor antagonists can generally be given once-daily. They are also extremely well tolerated with minimal first-dose hypotension and an incidence of adverse effects similar to that seen with placebo. Adverse event rates are significantly lower than with other classes of antihypertensive drugs including ACE inhibitors. These factors result in improved compliance and increased rates of continuance on therapy. AT1 receptor antagonists show similar efficacy in lowering blood pressure to other classes of antihypertensive agents and their antihypertensive effect is potentiated when they are given concomitantly with low-dose thiazide diuretics. AT1 receptor antagonists are eliminated predominantly by the hepatic route but most are not subject to extensive metabolism and interactions with other drugs are uncommon. This is an advantage in the elderly, who are often receiving multiple medications which increases the risk for adverse drug interactions. Dose adjustments are not usually required in the elderly unless there is plasma volume depletion. Although plasma AT1 receptor antagonist concentrations are generally higher in the elderly than in younger subjects, this pharmacokinetic difference may be balanced by decreased activation of the circulating renin-angiotensin-aldosterone system in the elderly. Recent clinical studies in high-risk hypertensive patients with left ventricular hypertrophy or in patients with diabetic nephropathy or heart failure have demonstrated that AT1 receptor antagonists can improve clinical outcomes to a similar or sometimes greater extent than other antihypertensive agents. Many of these studies have included large numbers of older patients and have confirmed the excellent tolerability profile of these drugs. Thus, AT1 receptor antagonists should be considered as a possible first-line treatment or as a component of combination therapy in patients with type 2 diabetes mellitus and microalbuminuria or nephropathy and as an alternative or additional treatment to ACE inhibitors in patients with heart failure or left ventricular dysfunction. AT1 receptor antagonists also appear to reduce the onset of new diabetes compared with some other antihypertensive drugs. The benefits in terms of organ protection have mainly been seen in studies using higher doses of particular AT1 receptor antagonists and it is not certain at present whether these results can be extrapolated to other members of the class. As the elderly are more likely to have developed organ damage related to hypertension or to have heart failure or diabetes as concomitant conditions, AT1 receptor antagonists represent an appropriate option for many elderly patients. The main disadvantage of these drugs is the cost of the medication but this may be offset by their improved tolerability with fewer adverse reactions and thus increased compliance, resulting in better blood pressure control and fewer clinical events. Overall, AT1 receptor antagonists are well tolerated and efficacious for blood pressure-lowering when given as a single daily dose in elderly patients and have many potential benefits in high-risk hypertensive subjects.

Angiotensin Receptor Blockers in Hypertension and Cardiovascular Diseases

Angiotensin receptor blockers are the newest class of antihypertensive agents marketed for the treatment of hypertension. There is now an important amount of evidence indicating that this class of drugs exerts beneficial effects in patients with a variety of cardiovascular disorders. Evidence-based medicine includes well controlled studies with mortality and morbidity endpoints in patients with left ventricular dysfunction after a myocardial infarction, congestive heart failure, cerebrovascular disease, type-2 diabetic subjects with renal dysfunction and high-risk hypertensive patients. In addition to these hard endpoints, treatment with angiotensin receptor blockers prevents the development of type-2 diabetes, promotes a more pronounced regression of left ventricular hypertrophy, decreases microalbuminuria and proteinuria in renal patients, ameliorates coronary and peripheral vascular endothelial dysfunction and decreases plasma levels of several markers of vascular inflammation. In summary, angiotensin receptor blockers are antihypertensive drugs with a very good profile in terms of efficacy, tolerability and cardiovascular protection. They represent an important step in the search for the ideal antihypertensive agent.

Renal Outcomes in High-Risk Hypertensive Patients Treated With an Angiotensin-Converting Enzyme Inhibitor or a Calcium Channel Blocker vs a Diuretic: A Report From the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)

Renal Outcomes in High-Risk Hypertensive Patients Treated With an Angiotensin-Converting Enzyme Inhibitor or a Calcium Channel Blocker vs a Diuretic: A Report From the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)

Renal Outcomes in High-Risk Hypertensive Patients Treated With an Angiotensin-Converting Enzyme Inhibitor or a Calcium Channel Blocker vs a Diuretic: A Report From the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)

Renal Outcomes in High-Risk Hypertensive Patients Treated With an Angiotensin-Converting Enzyme Inhibitor or a Calcium Channel Blocker vs a Diuretic: A Report From the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)

Treatment of High-Risk Hypertensive Patients

Cardiovascular disease represents the leading cause of morbidity and mortality in Western countries, and hypertension-related cardiovascular events affect about 37 million people per year, worldwide. In this perspective, hypertension represents a reference paradigm to illustrate strategies aimed at achieving cardiovascular prevention. Hypertensive patients are at increased risk of experiencing a cardiovascular event during their life-time, and treatment of high blood pressure represents one of the most effective strategies to reduce the global cardiovascular risk of these patients. However, owing to its multifactorial pathophysiology and its frequent association with other relevant risk factors and clinical conditions, such as dyslipidaemia, diabetes mellitus, left ventricular dysfunction and renal impairment, hypertension requires an integrated approach to treatment, including life-style measures, antihypertensive drugs and other therapies (mostly lipid-lowering regimens). Yet worldwide, general practitioners continue to focus their attention on the management of a single risk factor, e.g. blood pressure, rather than on the global cardiovascular risk profile. Modern strategies of cardiovascular prevention should assess the global cardiovascular risk threshold to manage hypertensive patients at high risk, rather than to focus on the high level of a single risk factor, for achieving effective control of cardiovascular risk profile and reducing cardiovascular morbidity and mortality in the general population, as well as in the hypertensive population.

High risk hypertensives: pre-hospital management of acute myocardial infarction—results from the French nationwide registry USIC 2000

Objective. – To assess the use of mobile coronary care units (MCU) in hypertensive patients previously treated for cardiovascular diseases in comparison with those with no history of cardiovascular disease and to estimate the influence of the use of MCU on cardiovascular outcome in this population. Patients. – We used a nationwide prospective registry of all patients admitted for AMI in French intensive care units in 2000. Patients without history of hypertension or patients admitted with pulmonary oedema or cardiogenic shock were excluded. Men (N = 514) and women (N = 291) were analysed separately . Results. – The proportion of patients with history of myocardial infarction, peripheral artery disease and stroke was not significantly higher in subjects who used physician-staffed MCU as compared with patients with no history of myocardial infarction, peripheral artery disease or stroke. In each sex, revascularization (pre hospital fibrinolysis, in hospital fibrinolysis or coronary angioplasty) were more frequent in patients who used MCU. Also, one year cardiovascular mortality was lower in men who used MCU. Conclusion. – known high risk hypertensive patients did not use physician-staffed MCU more than subjects free of such condition. Education of hypertensive patients at risk during routine visits is required to increase of the use of physician-staffed MCU in case of symptoms suggestive of AMI.

Role of insulin-sensitizing property of telmisartan, a commercially available angiotensin II type 1 receptor blocker in preventing the development of atrial fibrillation

Atrial fibrillation (Af) is the most common disorder of cardiac rhythm and is responsible for substantial morbidity and mortality in the general population. A recent community-based observational study revealed that diabetes and hypertension were associated with the development of Af. Since there is no definite evidence to show that type 1 diabetes is at increased risk for the development of Af, insulin resistance rather than hyperglycemia per se could explain the link between diabetes and Af. Several clinical trials suggest that the renin-angiotensin system (RAS) plays a pivotal role in the pathogenesis of insulin resistance. Indeed, interruption of the RAS with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II type 1 receptor blockers (ARBs) has been shown to prevent the onset of diabetes in hypertensive patients. Further, several experimental and clinical studies showed the beneficial role for the inhibition of the RAS in preventing Af as well. However, to what extent the insulin-sensitizing effects of ARBs could account for the prevention of Af remains to be clarified. Recently, telmisartan, an ARB, was found to act as a partial agonist of peroxisome proliferator-activated receptor-gamma (PPAR-gamma). PPAR-gamma influences the gene expression involved in carbohydrate metabolism. In animal study, telmisartan administration caused a significant attenuation of weight gain and reduced glucose, insulin, and triglyceride levels in rats fed a high-fat, high-carbohydrate diet, compared with treatments of losartan, another type of ARB. Furthermore, recently, some clinical papers also reported the insulin-sensitizing effects of telmisartan in hypertensive patients. In this paper, we would like to propose the possible ways of clarifying to what extent the insulin-sensitizing effects of ARBs could account for the prevention of Af. (1) Does telmisartan reduce the development of Af in insulin resistant hypertensive patients? (2) When adjusted for blood pressure, is the effect of telmisartan superior to other ARBs? (3) Does this beneficial effect of telmisartan correlate to its insulin-sensitizing properties? Ongoing clinical trial (ONTARGET) has been designed the efficacy of telmisartan with an ACEI, ramipril, alone or in combination. This randomized, double-blind, multicenter international studies will provide further information whether telmisartan can improve insulin resistance and subsequently reduce the development of Af in high-risk hypertensive patients.

Amlodipine or lisinopril was not better than chlorthalidone in reducing renal outcomes in hypertension and impaired renal function

Source Citation Rahman M, Pressel S, Davis BR, et al. Renal outcomes in high-risk hypertensive patients treated with an angiotensin-converting enzyme inhibitor or a calcium channel blocker vs a diu...

Renal Outcomes in High-Risk Hypertensive Patients Treated With an Angiotensin-Converting Enzyme Inhibitor or a Calcium Channel Blocker vs. a Diuretic. A Report From the Antihypertensive and Lipid-lowering Treatment to Prevent Heart Attack Trial (ALLHAT)

Background: This study was performed to determine whether, in high-risk hypertensive patients with a reduced glomerular filtration rate (GFR), treatment with a calcium channel blocker or an angiotensin-converting enzyme inhibitor lowers the incidence of renal disease outcomes compared with treatment with a diuretic. Methods: We conducted post hoc analyses of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Hypertensive participants 55 years or older with at least 1 other coronary heart disease risk factor were randomized to receive chlorthalidone, amlodipine, or lisinopril for a mean of 4.9 years. Renal outcomes were incidence of end-stage renal disease (ESRD) and/or a decrement in GFR of 50% or more from baseline. Baseline GFR, estimated by the simplified Modification of Diet in Renal Disease equation, was stratified into normal or increased (90 mL /min per 1.73 m 2 , n=8126), mild reduction (60-89 mL/min per 1.73 m 2 , n=18 109), or moderate-severe reduction (60 mL/min per 1.73 m 2 , n=5662) in GFR. Each stratum was analyzed for effects of the treatments on outcomes. Results: In 448 participants, ESRD developed. Compared with patients taking chlorthalidone, no significant differences occurred in the incidence of ESRD in patients taking amlodipine in the mild (relative risk [RR], 1.47; 95% confidence interval [CI], 0.97-2.23) or moderate-severe (RR,0.92; 95% CI, 0.68-1.24) reduction in GFR groups. Compared with patients taking chlorthalidone, no significant differences occurred in the incidence of ESRD in patients taking lisinopril in the mild (RR, 1.34; 95% CI, 0.87-2.06) or moderate-severe (RR,0.98; 95% CI, 0.73-1.31) reduction in GFR groups. In patients with mild and moderate-severe reduction in GFR, the incidence of ESRD or 50% or greater decrement in GFR was not significantly different in patients treated with chlorthalidone compared with those treated with amlodipine (odds ratios, 0.96 [P = .74] and 0.85 [P=.23], respectively) and lisinopril (odds ratios, 1.13 [P=.31] and 1.00 [P=.98], respectively). No difference in treatment effects occurred for either end point for patients taking amlodipine or lisinopril compared with those taking chlorthalidone across the 3 GFR subgroups, either for the total group or for participants with diabetes at baseline. At 4 years of follow-up, estimated GFR was 3 to 6 mL/min per 1.73 m 2 higher in patients assigned to receive amlodipine compared with chlorthalidone, depending on baseline GFR stratum. Conclusions: In hypertensive patients with reduced GFR, neither amlodipine nor lisinopril was superior to chlorthalidone in reducing the rate of development of ESRD or a 50% or greater decrement in GFR. Participants assigned to receive amlodipine had a higher GFR than those assigned to receive chlorthalidone, but rates of development of ESRD were not different between the groups. Arch Intern Med. 2005;165:936-946

Clinical Pharmacology of Antihypertensive Therapy

Adequate control of blood pressure poses challenges for hypertensive patients and their physicians. Success rates of greater than 80% in reducing blood pressure to target values among high-risk hypertensive patients reported by several recent clinical trials argue that effective medications currently are available. Yet, only 34% of hypertensive patients in the United States are at their goal blood pressure according to the most recent national survey. Rational selection of antihypertensive drugs that target both the patient's blood pressure and comorbid conditions coupled with more frequent use of low-dose drug combinations that have additive efficacy and low adverse-effect profiles could improve significantly US blood pressure control rates and have a positive impact on hypertension-related cardiovascular and renal mortality and morbidity. This article reviews the pharmacokinetic and pharmacodynamic principles that underlie the actions of drugs in each of the classes of antihypertensive agents when used alone and in combination, provides practical pharmacologic information about the drugs most frequently prescribed for treatment of hypertension in the outpatient setting, and summarizes the current data influencing the selection of drugs that might be used most effectively in combination for the majority of hypertensive patients whose blood pressures are not controlled adequately by single-drug therapy.

Morbidity and Mortality After Stroke, Eprosartan Compared With Nitrendipine for Secondary Prevention

In hypertensive stroke patients, for the same level of blood pressure control, eprosartan will be more effective than nitrendipine in reducing cerebrovascular and cardiovascular morbidity and mortality. A total of 1405 well-defined, high-risk hypertensives with cerebral event during the last 24 months (proven by cerebral computed tomography scan or nuclear magnetic resonance) were randomized to eprosartan or nitrendipine (mean follow-up 2.5 years). Primary end point was the composite of total mortality and all cardiovascular and cerebrovascular events, including all recurrent events. Randomization was successful without significant differences in the baseline characteristics. Blood pressure was reduced to a comparable extent without any significant differences between the 2 groups during the whole study period (150.7/84 mm Hg and 152.0/87.2 mm Hg with eprosartan and nitrendipine therapy to 137.5/80.8 mm Hg and 136.0/80.2 mm Hg, respectively, confirmed by ambulatory blood pressure monitoring). Moreover, already after 3 months, normotensive mean values were achieved, and 75.5% reached values <140/90 mm Hg with the eprosartan regimen and 77.7% with the nitrendipine regimen. During follow-up, in total, 461 primary events occurred: 206 eprosartan and 255 nitrendipine (incidence density ratio [IDR], 0.79; 95% CI, 0.66 to 0.96; P=0.014). Cardiovascular events were: 77 eprosartan and 101 nitrendipine (IDR, 0.75; 95% CI, 0.55 to 1.02; P=0.06); cerebrovascular events: 102 eprosartan and134 nitrendipine (IDR, 0.75; 95% CI, 0.58 to 0.97; P=0.03). The Morbidity and Mortality After Stroke, Eprosartan Compared With Nitrendipine for Secondary Prevention (MOSES) study was the first to compare an angiotensin II type 1 receptor antagonist with a calcium antagonist in secondary stroke prevention. In these high-risk hypertensive stroke patients, an early normotensive and comparable blood pressure was achieved. The combined primary end point was significantly lower in the eprosartan group.

Prevalence and treatment of chest pain syndromes, hypertension and high LDL-cholesterol in primary care

The purpose of this study was to define the prevalence and medical management of chest pain, angina pectoris, chronic angina, and pre-infarction angina/intermediate coronary syndrome (ICS) among hypertensive patients in primary care. The Hypertension Initiative database (N=72,508 records) was analyzed to characterize prevalence and management of chest pain syndromes (CPS) and control of blood pressure (<140/90 mm/Hg) and LDL-cholesterol (<100 mg/dL). Patients with more than one CPS were categorized by the most severe diagnosis. Eleven percent of patients had a CPS diagnosis. Of these, 66% (5,284) were diagnosed with chest pain only, 15% (1204) with angina, and 19% (1508) with ICS. More men than women were diagnosed with angina (18% vs. 4%) and ICS (21% vs. 10%). More women than men were diagnosed with chest pain only (86% vs. 61%). African Americans had more chest pain diagnoses (71% vs. 62%), similar angina diagnoses (14% vs. 16%), and fewer ICS diagnoses (15% vs. 22%) than Caucasians. Women and African-Americans received strikingly fewer medications than men and Caucasians in each diagnostic category. Prescription rates also differed more by gender than by racial group for angiotensin converting enzyme inhibitors, diuretics, aspirin, statins, and nitrates. (Table 1) Hypertensives with CPS received more medications and achieved better risk factor control (blood pressure <140/90 mm/Hg and LDL-cholesterol <100 mg/dL) than hypertensives without CPS but the majority in both groups were above target levels. Primary care physicians treat these high-risk hypertensive patients relatively aggressively. However, large numbers do not reach BP or LDL-c goals and substantial differences between gender and racial groups represent opportunities to reduce disparities. See Table 1. Percent of patients receiving prescription medications of interest by diagnostic category and gender Percent of patients receiving prescription medications of interest by diagnostic category and gender

Management of high-risk hypertensive patients in Spain. The Tarvest study

Management of high-risk hypertensive patients in Spain. The Tarvest study

Renal Outcomes in High-Risk Hypertensive Patients Treated With an Angiotensin-Converting Enzyme Inhibitor or a Calcium Channel Blocker vs a Diuretic

This study was performed to determine whether, in high-risk hypertensive patients with a reduced glomerular filtration rate (GFR), treatment with a calcium channel blocker or an angiotensin-converting enzyme inhibitor lowers the incidence of renal disease outcomes compared with treatment with a diuretic. We conducted post hoc analyses of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Hypertensive participants 55 years or older with at least 1 other coronary heart disease risk factor were randomized to receive chlorthalidone, amlodipine, or lisinopril for a mean of 4.9 years. Renal outcomes were incidence of end-stage renal disease (ESRD) and/or a decrement in GFR of 50% or more from baseline. Baseline GFR, estimated by the simplified Modification of Diet in Renal Disease equation, was stratified into normal or increased (> or =90 mL /min per 1.73 m(2), n = 8126), mild reduction (60-89 mL /min per 1.73 m(2), n = 18 109), or moderate-severe reduction (<60 mL /min per 1.73 m(2), n = 5662) in GFR. Each stratum was analyzed for effects of the treatments on outcomes. In 448 participants, ESRD developed. Compared with patients taking chlorthalidone, no significant differences occurred in the incidence of ESRD in patients taking amlodipine in the mild (relative risk [RR], 1.47; 95% confidence interval [CI], 0.97-2.23) or moderate-severe (RR, 0.92; 95% CI, 0.68-1.24) reduction in GFR groups. Compared with patients taking chlorthalidone, no significant differences occurred in the incidence of ESRD in patients taking lisinopril in the mild (RR, 1.34; 95% CI, 0.87-2.06) or moderate-severe (RR, 0.98; 95% CI, 0.73-1.31) reduction in GFR groups. In patients with mild and moderate-severe reduction in GFR, the incidence of ESRD or 50% or greater decrement in GFR was not significantly different in patients treated with chlorthalidone compared with those treated with amlodipine (odds ratios, 0.96 [P = .74] and 0.85 [P = .23], respectively) and lisinopril (odds ratios, 1.13 [P = .31] and 1.00 [P = .98], respectively). No difference in treatment effects occurred for either end point for patients taking amlodipine or lisinopril compared with those taking chlorthalidone across the 3 GFR subgroups, either for the total group or for participants with diabetes at baseline. At 4 years of follow-up, estimated GFR was 3 to 6 mL /min per 1.73 m(2) higher in patients assigned to receive amlodipine compared with chlorthalidone, depending on baseline GFR stratum. In hypertensive patients with reduced GFR, neither amlodipine nor lisinopril was superior to chlorthalidone in reducing the rate of development of ESRD or a 50% or greater decrement in GFR. Participants assigned to receive amlodipine had a higher GFR than those assigned to receive chlorthalidone, but rates of development of ESRD were not different between the groups.

The role of combination antihypertensive therapy in the prevention and treatment of chronic kidney disease

The failure to achieve blood pressure (BP) control in the general population makes a substantial contribution to the development of chronic kidney disease (CKD) and subsequent renal failure. Each year, in the United States, more than 94,000 people develop end-stage renal disease; about 65% of these cases are directly attributable to hypertension and diabetes. Like hypertension, CKD does not produce symptoms for many years, and therefore its detection, prevention, and treatment are largely dependent on the vigilance of physicians and other health care providers. Current therapeutic advances make it possible to slow the progression of CKD and to improve clinical outcomes for these patients. Large, randomized, clinical hypertension trials have shown that tighter BP control, compared with less tight BP control, can reduce progression of renal disease by 30% to 50% and cardiovascular disease by 40% to 70%. Achieving BP levels of <130/80 mm Hg, as currently recommended for patients with diabetes or CKD, will often require three or more antihypertensive medications. Furthermore, reduction of BP should be accompanied by reductions in albuminuria and proteinuria to maximize potential benefits to the kidney. Evidence from numerous randomized controlled trials mandate that agents that block the renin-angiotensin system should always be included in the antihypertensive regimens of patients with CKD, particularly with the excellent safety data with serum creatinine levels <3 to 4 mg/dL. Fixed-dose combination agents are useful in bringing high-risk hypertensive patients to appropriate BP goals, primarily by simplifying the complex medical regimens in these patients.

The Avoiding Cardiovascular events through COMbination therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) trial: a comparison of first-line combination therapies

Although multidrug therapy is required in order to achieve good blood pressure control in many hypertensives, there are no studies directly comparing fixed-dose combinations as initial therapy. The Avoiding Cardiovascular events through COMbination therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) trial compares regimens of benazepril plus amlodipine versus benazepril plus hydrochlorothiazide, force-titrated to 40/10 and 40/25mg, respectively. A total of 12,600 high-risk hypertensives have been randomised and will be followed for 3 – 5years, during which cardiovascular events will be monitored. The investigators hypothesise that the benazepril plus amlodipine regimen will decrease cardiovascular events by 15% compared with benazepril plus hydrochlorothiazide. Recruitment began in 2003, and the trial is expected to end in 2008. The ACCOMPLISH trial shares important limitations with many other recent trials that will make it difficult to apply the results in clinical practice. These include the focus on high-risk hypertensive patients, in whom significant reductions in relative risk will translate into meaningful reductions in absolute risk: in lower-risk hypertensives with a low absolute risk, similar relative risk reductions may not be of great impact on the population disease burden. In ACCOMPLISH, as in most industry-sponsored clinical trials, the main goal appears to be market-driven: doses of drugs tested are not those available for clinical practice. The question asked, whether the combination of benazepril with either diuretic or dihydropyridine calcium channel blocker is more efficacious, is not a clinically compelling one. Finally, the univariate subgroup analyses proposed are unlikely to lead to an understanding of whether either combination has specific advantages for patients encountered clinically, most of whom have multiple risk factors. Thus, it appears that ACCOMPLISH, as with many recent pharmacological trials, will not greatly impact the treatment of hypertension.