Antihypertensive Agents In Patients Research Articles

β-Adrenergic Antagonists in Hypertension: A Review of the Evidence

To evaluate the effects of beta-adrenergic antagonist therapy on cardiovascular and cerebrovascular outcomes in the treatment of hypertension. Literature searches were conducted using MEDLINE (1966-August 2009), International Pharmaceutical Abstracts (1970-August 2009), and Cochrane Database of Systematic Reviews (until third quarter 2009) to locate clinical trials and meta-analyses comparing beta-blocker therapy with placebo or other antihypertensive agents in patients with hypertension. Bibliographies from relevant research and review articles were reviewed for additional references. All English-language articles identified from the data sources were reviewed. Articles describing original research with cardiovascular or cerebrovascular outcomes and/or death as either primary or secondary endpoints were included. Articles describing the use of beta-blocker therapy for conditions other than hypertension were not included. Five placebo-controlled studies and 10 active-controlled studies were reviewed. In addition, 11 meta-analyses were evaluated. Placebo-controlled trials of beta-blockers in hypertension provide evidence of reduced risk for stroke, cardiovascular events, and heart failure. Only 2 studies comparing beta-blockers with other antihypertensives found significant benefit with beta-blockers. However, the majority of meta-analyses comparing beta-blockers with other antihypertensive agents show increased risk for stroke with beta-blockers, and some data suggest increased risk for cardiovascular events and all-cause mortality. The majority of data results from studies of atenolol, and many studies employed combination antihypertensive therapies, which often included thiazide diuretics. Overall, data supporting beta-blockers as preferred therapy in hypertension are inadequate. Although most negative cardiovascular and cerebrovascular outcomes of beta-blockers were associated with atenolol therapy, data supporting other beta-blockers in hypertension are lacking.

Aliskiren: The Next Innovation in Renin–Angiotensin–Aldosterone System Blockade

Blockade of the renin–angiotensin–aldosterone system (RAAS) with angiotensin-converting enzyme inhibitors or Ang II-receptor blockers has been demonstrated to lower blood pressure and to be effective in heart failure and postmyocardial infarction. It is also beneficial in renal disease. These RAAS blockers further activate the RAAS, leading to an increase of plasma renin activity and plasma renin concentration. Aliskiren, the first orally active direct renin inhibitor, is an effective and well-tolerated antihypertensive agent when used as monotherapy or in combination with other antihypertensive agents in patients with mild-to-moderate hypertension. In contrast with angiotensin-converting enzyme inhibitors and Ang II-receptor blockers, aliskiren reduces plasma renin activity. A number of clinical trials with aliskiren are ongoing or completed and provide us with objective evidence regarding the clinical importance of direct renin inhibition in the treatment of cardiovascular disease.

Blood pressure lowering treatment for preventing stroke recurrence: a systematic review and meta-analysis

BackgroundWhile hypertension is a leading risk factor for an initial stroke, the role of blood pressure lowering to prevent subsequent stroke is less clear. The results of recent large clinical trials investigating effects of antihypertensive agents in patients with a history of stroke have not shown a significant benefit; findings that are at odds with previous data. Our meta-analysis systematically evaluates the available, relevant trials to examine the role of antihypertensive drugs in preventing recurrent stroke.MethodsMEDLINE, CENTRAL, and ClinicalTrials.gov were systematically searched and bibliographies from key reports were examined. All randomized, placebo-controlled trials that tested blood pressure lowering agents in patients with stroke or transient ischemic attack were identified. The results from these trials were combined and meta-analyses were performed.ResultsTen studies were found to contain relevant endpoints and presented data allowing meta-analysis. Agents that lowered blood pressure reduced recurrent stroke (OR 0.71, 95% CI 0.59-0.86, P = 0.0004) and cardiovascular events (OR 0.69, 95% CI 0.57-0.85, P = 0.0004) in patients with a previous stroke or TIA. These agents did not affect the rate of myocardial infarction (OR 0.86, 95% CI 0.73-1.01, P = 0.07) or all-cause mortality (OR 0.95, 95% CI 0.83-1.07, P = 0.39) in this patient population.ConclusionDespite recent large trials showing no significant effect, in patients that have experienced a TIA or stroke, blood pressure lowering agents reduced the occurrence of subsequent stroke and cardiovascular events. The rate of myocardial infarction and all-cause mortality was unchanged.

The Effect of Doxazosin Mesilate on Cerebral Blood Flow in Patients with Hypertension and Chronic Cerebral Infarction

alpha(1)-Adrenoceptor antagonists are useful antihypertensive agents for patients with hypertension who have hyperlipidemia, benign prostatic hyperplasia, or pheochromocytoma. The purpose of this study was to evaluate the effect of the alpha(1)-adrenoceptor antagonist, doxazosin mesilate, on cerebral blood flow (CBF) and flow velocity in the common carotid artery in patients with hypertension and chronic cerebral infarction. Doxazosin mesilate (1 mg/day) was orally administered for 4 to 8 weeks to 7 patients with hypertension 4 weeks after the onset of cerebral infarction. We determined blood pressure, heart rate, CBF measured with autoradiography single photon emission computed tomography (SPECT) with N-isopropyl-p-[(123)I] iodoamphetamine ((123)I-IMP) as a tracer, and the maximum, minimum and mean flow velocities in the common carotid arteries measured with duplex carotid ultrasonography before and 4 to 8 weeks after the beginning of treatment. Mean CBF was defined as the mean count of tracer from the 8 regions of interest (ROIs) in the frontal, parietal, occipital, and temporal cortices of the cerebral hemisphere. Values were analyzed with paired t tests. With administration of doxazosin mesilate, systolic pressure significantly decreased from 152 +/- 11 to 137 +/- 7 mmHg (p<0.01), but diastolic pressure and heart rate were unchanged. Mean CBF was improved significantly from 32.0 +/- 4.1 to 34.7 +/- 4.1 mL/100 g brain/min (p<0.01) in the ipsilateral cerebral cortex and from 32.6 +/- 6.2 to 36.2 +/- 5.1 mL/100 g brain/min (p<0.05) in the contralateral cerebral cortex. The maximum, minimum, and mean flow velocities in the bilateral common carotid arteries were not changed significantly. In the present study, the improvement of mean CBF in the ipsilateral and contralateral cerebral cortices was demonstrated in patients with hypertension and chronic cerebral infarction after the treatment with doxazosin mesilate. Doxazosin mesilate might be an effective antihypertensive agent for hypertensive chronic cerebral infarction.

The Renoprotective Effects of RAS Inhibition: Focus on Prevention and Treatment of Chronic Kidney Disease

Chronic kidney disease (CKD) shares major risk factors with cardiovascular disease (CVD), including hypertension and diabetes mellitus. In patients with hypertensive kidney disease and diabetic nephropathy, inhibitors of the renin-angiotensin system (RAS) significantly reduce the risk of renal and cardiovascular endpoints. Whether the renoprotective effects of RAS inhibitors can be fully accounted for by blood pressure reductions or whether other mechanisms are involved has not been clearly established. Because RAS inhibitors reduce albuminuria and slow progression of kidney disease, they are recommended as first-line antihypertensive agents in patients with CKD, who often require aggressive treatment with ≥ 2 drugs to reach the goal blood pressure (< 130/80 mm Hg). Greater RAS inhibition with higher-than-usual doses of a single agent or dual RAS inhibition with an angiotensin-converting enzyme inhibitor and an angiotensin receptor blocker may be necessary for maximum renoprotective effects. Ongoing clinical trials assessing treatment and prevention of CKD may resolve unanswered questions about RAS inhibition in patients with hypertension and/or diabetes.

Evaluation of recent fixed-dose combination therapies in the management of hypertension

Control of hypertension remains sub-optimal with only half of patients achieving adequate control. The Seventh Report of the Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure guidelines recommend initial use of two antihypertensive agents in patients with stage 2 hypertension. This review discusses the drug combinations that have additive effects and those that do not provide additional benefit while increasing the adverse events. Results from late-breaking trials have shown that combinations of a calcium channel blocker and angiotensin-converting enzyme inhibitor are superior to a diuretic with an angiotensin-converting enzyme inhibitor for reducing cardiovascular events. Additionally, in patients with vascular disease with relatively 'controlled' blood pressure at baseline, the combination of an angiotensin-converting enzyme inhibitor and angiotensin receptor blocker did not reduce cardiovascular endpoints compared with either monotherapy and modestly increased the incidence of adverse effects. Combination therapy of antihypertensive agents (e.g. angiotensin-converting enzyme inhibitor/calcium channel blocker, angiotensin-converting enzyme inhibitor/diuretics, and angiotensin receptor blocker/diuretics) as initial therapy in stage 2 hypertension can lead to markedly improved blood pressure control in patients compared with monotherapeutic regimens.

β-Blockers: No longer an option for uncomplicated hypertension

Traditionally, β-blockers, used as first-line agents to treat uncomplicated hypertension, were recommended by national and international guidelines despite a paucity of evidence regarding their cardiovascular benefit. However, evidence from recent trials and metaanalyses has questioned the use of β-blockers as preferred agents. This article reviews the data available from clinical trials and argues that β-blockers are less efficacious than other currently available antihypertensive agents for patients with uncomplicated hypertension.

Primary aldosteronism and aldosterone-associated hypertension

The field of primary aldosteronism (PA) and aldosterone-related hypertension has undergone rapid evolution. From a relatively rare curiosity PA has become a common problem particularly in selected hypertensive populations. Patients...

Influence of Living Style and Situation on the Compliance of Taking Antihypertensive Agents in Patients with Essential Hypertension

As the reason for insufficient control of blood pressure (BP), poor compliance of taking antihypertensive agents is an important issue. In Japan, no prospective study on the compliance of antihypertensive agents has been done. In this study we prospectively investigated the details of the relationship between the compliance of taking antihypertensive agents and living style and situation in hypertensive patients. We prospectively examined 121 outpatients with essential hypertension treated with antihypertensive agents for 12 months. Using an oral interview based on the questionnaire sheet, the factors about living style and situations which worsen the compliance were assessed. Also we evaluated the relationship of BP control and season, which was compared between patients with poor compliance and those with good compliance. As for the background of the poor compliance, many factors related to the patients' living style and situation were clarified. On average for 12 months the levels of the compliance and BP showed a significant negative correlation and BP was significantly higher in patients with poor compliance than those with good compliance. However, in the summer season BP did not differ between patients with poor and good compliance, Many factors regarding the patients' living style and situation were related to poor compliance. The development of strategy that changes these factors is a future task for improving compliance. This study may also imply that unnecessary antihypertensive agents are prescribed in some patients with poor compliance in the summer season. Determination of the suitable prescription by which to attain optimal individual patients' compliance is important in the treatment of hypertensive patients.

Choice of Antihypertensive Agents for Patients with Metabolic Syndrome: ALLHAT Results

Results from the largest antihypertensive trial to date — ALLHAT — suggested that diuretics should be the preferred initial drug for treating patients with hypertension. However, concern persists about thiazides because of their adverse effects on insulin sensitivity and onset of diabetes, particularly among people with diabetes risk factors. In a post hoc analysis, ALLHAT researchers assessed metabolic and cardiovascular outcomes in nondiabetic patients with or …

β-blockers: No longer an option for uncomplicated hypertension

Traditionally, beta-blockers, used as first-line agents to treat uncomplicated hypertension, were recommended by national and international guidelines despite a paucity of evidence regarding their cardiovascular benefit. However, evidence from recent trials and meta-analyses has questioned the use of beta-blockers as preferred agents. This article reviews the data available from clinical trials and argues that beta-blockers are less efficacious than other currently available antihypertensive agents for patients with uncomplicated hypertension.

Efficacy and Safety of Darusentan in Patients With Resistant Hypertension: Results From a Randomized, Double‐Blind, Placebo‐Controlled Dose‐Ranging Study

In this phase 2, randomized, double-blind, placebo-controlled forced dose-titration study, 115 patients with resistant hypertension, receiving background therapy with >/=3 antihypertensive medications including a diuretic at full doses, were randomized 2:1 to increasing doses of darusentan (10, 50, 100, 150, and 300 mg), a selective endothelin receptor antagonist, or matching placebo once daily for 10 weeks. Darusentan treatment decreased mean systolic and diastolic blood pressure levels in a dose-dependent fashion compared with placebo; the largest reductions were observed at week 10 (300-mg dose) (systolic, -11.5+/-3.1 mm Hg [P=.015;] diastolic, -6.3+/-2.0 mm Hg [P=.002]). Darusentan (300 mg) also decreased mean 24-hour, daytime, and nighttime ambulatory blood pressures from baseline to week 10. Darusentan was generally well tolerated; mild to moderate edema and headache were the most common adverse events. This study demonstrates a clinical benefit from a new class of antihypertensive agent in patients classified as resistant by the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure guidelines.

Antihypertensive Agents in Patients With Diabetes

Management of hypertension in patients with diabetes should address both renal and cardiovascular protection. The use of angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) for control of hypertension in patients with diabetic nephropathy is widely advocated by various international guidelines. Use of any agent that provides tight control of blood pressure is indicated in patients with diabetes but without nephropathy. In this article, the authors present a clinical case scenario and review current clinical evidence supporting the use of ACE inhibitors and ARBs in patients with diabetic nephropathy. In addition, the use of ACE and ARBs in patients with diabetes but without nephropathy will be discussed. Available trial evidence confirms the survival benefits of patients taking ACE inhibitors with diabetic nephropathy. However, the efficacy of ARB inhibitors on survival is unknown. In patients with diabetes without nephropathy, only ACE inhibitors have been found to reduce the risk of onset of microalbuminuria, while all agents affect survival provided a tight control of blood pressure is monitored. Dose of ACE inhibitors should be titrated appropriately to obtain proven benefits. In summary, current evidence supports the use of ACE inhibitors in patients with and without nephropathy because of renal and cardiovascular benefits.

Role of Blood Pressure Targets and Specific Antihypertensive Agents Used to Prevent Diabetic Nephropathy and Delay Its Progression

This study evaluated the comparative effects of antihypertensive agents in patients with diabetes and normoalbuminuria and the evidence supporting equivalent use of angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) in patients with diabetes and micro- or macroalbuminuria. A systematic review was conducted by searching for randomized controlled trials (RCT) of antihypertensive agent versus placebo or another agent in hypertensive or normotensive patients with diabetes and no nephropathy and RCT of ACEi or ARB in patients with diabetic nephropathy. Medline, Embase, the Cochrane Controlled Trials Register, conference proceedings, and contact with investigators were used to identify available evidence. Two investigators independently extracted data and assessed quality of trials. Sixteen RCT (7603 patients) of antihypertensive agents conducted in patients with diabetes and no nephropathy and 43 (7739 patients) of ACEi or ARB in patients with diabetic nephropathy were identified. A significant reduction in the risk for developing microalbuminuria in patients who had diabetes with no nephropathy was demonstrated for ACEi only (six trials, 3840 patients; relative risk [RR] 0.60; 95% confidence interval [CI] 0.43 to 0.84), and in patients with diabetic nephropathy, existing RCT have shown a survival benefit of ACEi (20 trials, 2383 patients; RR 0.79; 95% CI 0.63 to 0.99; P = 0.04) but not ARB (four trials, 3329 patients; RR 0.99; 95% CI 0.85 to 1.17). On the basis of available RCT evidence, ACEi are the only agents with proven renal benefit in patients who have diabetes with no nephropathy and the only agents with proven survival benefit in patients who have diabetes with nephropathy.

Selection of antihypertensive agents in patients at risk for diabetes

Type 2 diabetes mellitus (DM2) has increased 41% in the United States, with an estimated one third undiagnosed and another 41 million with prediabetes. Hypertension affects 20% to 60% of all diabetics, contributing to up to 75% of deaths due to cardiovascular disease. These staggering statistics make it imperative that hypertensive patients who are at risk for DM2 are identified and treated early. Numerous studies have been done involving choice of antihypertensive in established diabetics, and a slowing or halting of the progression in the development of diabetes in these patients has been noticed. However, to date, nothing is conclusive. For now, following the JNC 7 guidelines of using a diuretic as monotherapy or in combination with an angiotensin-converting enzyme inhibitor (ACEI), angiotensin II-receptor blocker (ARB), beta-blocker, or calcium channel blocker may be prudent. Two current studies, the DREAM trial and the ONTARGET trial, may shed more light as to whether ACEIs or ARBs have a preferred niche in initial treatment of the hypertensive patient who is at risk for diabetes.

Amlodipine preserves the glomerular number in spontaneously hypertensive rats

The calcium channel blockers have individual pharmacological and therapeutic properties that may vary, but as a group, they are effective antihypertensive agents in patients with renal disease. Their effects on the kidney may extend beyond BP reduction alone. Fifteen one-year-old male spontaneously hypertensive rats (SHR) were separated in three groups: Initial control group (IC), Final control group (FC, SHR received standard rat chow and fresh water ad libitum during 15 weeks), Amlodipine group (Aml, SHR) received 0.2 mg/kg/day of amlodipine in addition to food and water during 15 weeks. The glomerular number was estimated using the disector method. In the Control group, the BP level increased almost 20 per cent in the first six weeks (from 186 +/- 11 to 223 +/- 16 mmHg, p<0.01) and then BP level increased almost 15 percent until week 15 (from 223 +/- 16 to 258 +/- 20 mmHg, p<0.01). In the same period, the Aml group showed a progressively low BP, reaching a level almost 50 per cent lower in the week 15 than in the week 1 (from 190 +/- 15 to 101+/-8 mmHg, p<0.01). Amlodipine treatment significantly decreased the serum creatinine, more than 12 per cent lower than the FC group (from 70.4 +/- 6.2 to 61.4 +/- 5.2 micromol/L, p<0.05). However, proteinuria was not different when groups were compared. The FC group reached a glomerular number almost 20 percent smaller than the IC and Aml groups (from 35 x 10(3) +/- 7 x 10(3) in IC group, 34 x 10(3) +/- 4 x 10(3) in Aml group to 27 x 10(3) +/- 3 x 10(3) in FC group, p<0.05). A possible protective effect of amlodipine against the loss of glomeruli in SHR is a major additional action of amlodipine in the treatment of hypertension mainly when the renal lesion already exists.

Antihypertensive Agents for Primary Prevention of Diabetic Nephropathy

The objective of this study was to evaluate the comparative effects of antihypertensive agents in patients with diabetes and normoalbuminuria. Randomized, controlled trials that compared any antihypertensive agent with placebo or another agent in hypertensive or normotensive patients with diabetes and normoalbuminuria (albumin excretion rate <30 mg/d) were identified on Medline, in Embase, on the Cochrane Controlled Trials Register, in conference proceedings, and by contacting investigators. Two authors independently extracted data on renal outcomes and other patient-relevant outcomes (e.g., mortality, serious cardiovascular events) and assessed quality of trials. Analysis was by a random-effects model, and results were expressed as relative risk (RR) and 95% confidence intervals (CI). Sixteen trials (7603 patients) were identified, six of angiotensin-converting enzyme inhibitors (ACEi) versus placebo, six of ACEi versus calcium antagonists, one of ACEi versus calcium antagonists or combined ACEi and calcium antagonist, and three of ACEi versus other agents. Compared with placebo, ACEi significantly reduced the development of microalbuminuria (six trials, 3840 patients; RR 0.60; 95% CI 0.43 to 0.84) but not doubling of creatinine (three trials, 2683 patients; RR 0.81; 95% CI 0.24 to 2.71) or all-cause mortality (four trials, 3284 patients; RR 0.81; 95% CI 0.64 to 1.03). Compared with calcium antagonists, ACEi significantly reduced progression to microalbuminuria (four trials, 1210 patients; RR 0.58; 95% CI 0.40 to 0.84). A significant reduction in the risk for developing microalbuminuria in normoalbuminuric patients with diabetes has been demonstrated for ACEi only. It seems that the effect of ACEi is independent of baseline BP, renal function, and type of diabetes, but data are too sparse to be confident that these are not important effect modifiers, and an individual patient data meta-analysis is required.

The role of calcium antagonists in patients with chronic renal failure

The objective of antihypertensive treatment in patients with chronic renal failure, many of whom have elevated blood pressure levels, is to reduce cardiovascular events and to slow down the progression of kidney function impairment. Calcium antagonists have been shown to be effective and safe antihypertensive drugs in patients from different age groups, including children. On the basis of numerous studies, one may conclude that the main benefit of antihypertensive therapy is because of the blood pressure lowering effect per se and that calcium antagonists do not differ from other antihypertensive drugs in the ability to prevent cardiovascular complications of hypertension. In particular, calcium antagonists are not inferior to other groups of antihypertensive agents in the prevention of coronary artery disease. There is, however, now evidence from controlled clinical trials that drugs interfering with the renin-angiotensin system are more beneficial than other antihypertensive agents in patients with chronic renal failure. Thus, several studies have demonstrated that ACE-inhibitors and, in patients with type-2 diabetic nephropathy, AT 1-antagonists are superior to other classes of antihypertensive drugs, including calcium antagonists, in delaying the progression of renal insufficiency. Therefore, in hypertensive patients with chronic renal failure antihypertensive treatment should be initiated with a drug that inhibits the renin-angiotensin system.

Orthostatic Hypotension and Supine Hypertension in Primary Autonomic Failure

To the Editor: We read with interest the article of Shibao et al dealing with the treatment options when neurogenic orthostatic hypotension is complicated by supine hypertension.1 When orthostatic hypotension is caused by central and peripheral nervous system disorders such as primary autonomic failure, the patients report several syncope episodes, and treatment of hypertension is a “dilemma.” In the “management of supine hypertension” section, the authors propose a stepwise approach to treat hypertension, including the use of antihypertensive agents in patients with pure autonomic failure (PAF) and multiple system atrophy. Because it is more important to avoid daytime hypotension than hypertension, we suggest caution in the use of antihypertensive agents. The physician in charge should remember that the decision of starting antihypertensive drugs should not be based on the blood pressure values measured while the patient is lying in bed in the hospital. In case of supine hypertension, laboratory investigation, resting electrocardiography, echocardiography, and ultrasound carotid examination should be performed according to recent guidelines for the management of arterial hypertension.2 Moreover, a 24-hour noninvasive ambulatory blood pressure measurement (ABPM) should be included in the clinical assessment because it correlates strictly with target organ damage,2–3⇓ and it can show the real blood pressure pattern during everyday life. The documentation of …

Analysis of Recent Papers in Hypertension Jan Basile, MD, Senior Editor

Analysis of Recent Papers in Hypertension Jan Basile, MD, Senior Editor