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 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The world faces the challenge of an ageing population, and for developed countries, the particular challenge is the increasing number of very old people, over 80 years of age. Hypertension is a condition associated with increasing age, but elderly patients with hypertension are often difficult to manage. Nevertheless, treatment of hypertension is of greatest value in older patients who often have additional risk factors or cardiovascular disease. Older patients have generally tolerated antihypertensive therapy well in randomised, placebo-controlled trials. The tolerability of angiotensin receptor blockers (ARBs) is better than that of many other classes of drugs currently used for the management of hypertension and these drugs have virtually no contraindications. Thus, ARBs have a bright future in the management of hypertension and in the treatment of stroke and cognitive decline in the elderly.
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PMID:The expanding role of angiotensin receptor blockers in the management of the elderly hypertensive. 1367 87

Over the past decade, national and international guidelines have proposed beta-blockers to be used on an equal footing with diuretics for initial therapy of hypertension. This preferred status was supposedly based on evidence documenting a reduction in morbidity and mortality with beta-blocker therapy in hypertension. We systematically analyzed all available outcome studies and found no evidence that beta-blocker based therapy, despite lowering blood pressure, reduced the risk of heart attacks or strokes. Despite the inefficacy of beta-blockers, the incidence of adverse effects is substantial. In the MRC study, for every heart attack or stroke prevented, three patients withdrew from atenolol because of impotence, and another seven withdrew because of fatigue. Thus the risk/benefit ratio of beta-blockers is characterized by lack of efficacy and multiple adverse effects. Given that many thorough, prospective, randomized trials attest to efficacy and safety of diuretics, calcium antagonists, ACE inhibitors, and angiotensin receptor inhibitors, the time has come to admit that beta-blockers should no longer be considered appropriate for first-line therapy in uncomplicated hypertension.
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PMID:beta-Blockers in hypertension-the emperor has no clothes: an open letter to present and prospective drafters of new guidelines for the treatment of hypertension. 1455 68

It is not possible to review all the recent randomized clinical trials in management of atrial fibrillation. The author has chosen to select a few that illustrate key points. "Immediate" or "early" recurrence of atrial fibrillation after electrical cardioversion is an important part of inefficacy of drug therapy and more insight into the mechanisms of this phenomenon is needed. Two recent trials in which verapamil, a calcium channel blocker, and irbesartan, an angiotensin receptor blocking agent, added to a standard antiarrhythmic attenuated early recurrences of atrial fibrillation are of particular interest. Trials of drugs and pacing for maintenance of sinus rhythm continue to demonstrate only modest efficacy. Amiodarone, the most effective agent, is not markedly better and there are concerns about its adverse effect profile during long-term use. Other nonpharmacologic therapies have not yet been, but will need to be, evaluated in properly designed randomized clinical trials with clinically important end-points. The absence of a simple, highly effective treatment for the maintenance of sinus rhythm with few adverse effects has been part of the foundation for recent trials comparing the rate control strategy to the rhythm control strategy, particularly in the elderly patient. Six such trials have been completed and one is in progress. The data from these trials is quite consistent for the elderly patient with stroke risk factors and predominantly persistent atrial fibrillation: (1) any advantage for the rhythm control strategy remains unproven; (2) the rate control strategy has some clear advantages and should be considered more often as a primary approach in such patients; and (3) anticoagulation should not be discontinued in such high risk patients, even when it is felt that sinus rhythm has been maintained. Anticoagulation is under-utilized in this setting and alternatives to warfarin are badly needed. Trials in progress may be helpful in this regard. Finally, primary prevention of atrial fibrillation needs more attention. Recent randomized trials with trandolapril after myocardial infarction and physiologic pacing have given some insight into how this might be accomplished.
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PMID:Some recent randomized clinical trials in the management of atrial fibrillation. 1457 35

Inhibition of the first and rate-limiting step of the renin-angiotensin system has long been an elusive therapeutic goal. Aliskiren, the first known representative of a new class of completely nonpeptide, orally active, renin inhibitors, has been shown to inhibit the production of angiotensin I and II in healthy volunteers and to reduce blood pressure (BP) in sodium-depleted marmosets. The aim of this randomized, double-blind, active comparator trial study was to assess the BP-lowering efficacy and safety of aliskiren. Two hundred twenty-six patients, 21 to 70 years of age, with mild to moderate hypertension, were randomly assigned to receive 37.5 mg, 75 mg, 150 mg, or 300 mg aliskiren or 100 mg losartan daily for 4 weeks. Dose-dependent reductions in daytime ambulatory systolic pressure (mean change, mm Hg [SD of change]; -0.4 [11.7], -5.3 [11.3], -8.0 [11.0], and -11.0 [11.0], P=0.0002) and in plasma renin activity (median change % [interquartile range]; -55 [-64, -11], -60 [-82, -46], -77 [-86, -72], and -83 [-92, -71], P=0.0008) were observed with 37.5, 75, 150, and 300 mg aliskiren. The change in daytime systolic pressure with 100 mg losartan (-10.9 [13.8]) was not significantly different from the changes seen with 75, 150, and 300 mg aliskiren. Aliskiren was well tolerated at all doses studied. This study demonstrates that aliskiren, through inhibition of renin, is an effective and safe orally active BP-lowering agent. Whether renin inhibition results in protection from heart attack, stroke, and nephropathy, similar to angiotensin-converting enzyme inhibition and angiotensin receptor blockade, needs to be researched.
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PMID:Blood pressure lowering in essential hypertension with an oral renin inhibitor, aliskiren. 1459 41

The antihypertensive drug classes that have reduced cardiovascular events safely either in large placebo-controlled trials or in comparison with other effective antihypertensive drugs in large morbidity trials are diuretics, beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and calcium channel blockers (CCBs). Although control of blood pressure (BP) is a primary goal of therapy, evidence from several clinical trials suggests that certain antihypertensive agents provide clinical benefits independent of their effect on BP. In the recently reported Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), an ACE inhibitor, a CCB, and an alpha-blocker reduced coronary events and mortality to a similar extent as a thiazide-type diuretic, but the diuretic reduced one or more major cardiovascular events, especially heart failure, more than the other agents. In the Losartan Intervention For Endpoint reduction in hypertension (LIFE) trial, the ARB losartan reduced cardiovascular morbidity (primarily stroke) more than the beta-blocker atenolol. Although an ARB has not yet been compared with a diuretic in a morbidity trial, as most patients require more than one drug to control BP, and a diuretic plus an ARB is a very effective and well-tolerated combination, this uncertainty applies to a minority of patients. A primary goal in treating hypertension should be to reach a patient's goal BP, but initial selection of drugs based on hypertension morbidity study results and other compelling indications should be given priority.
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PMID:Are there benefits to specific antihypertensive drug therapy? 1462 58

High blood pressure is common in the western world and is a major risk factor for the development of stroke. Lowering blood pressure reduces the risk of first and recurrent stroke. High blood pressure is also common in acute stroke and is independently associated with a poor prognosis, in part due to promoting early recurrence and the development of fatal cerebral oedema in patients with ischaemic stroke and, possibly, re-bleeding in those with haemorrhagic stroke. However, the management of blood pressure remains an enigma--its lowering could improve outcome by reducing recurrence or worsen outcome by reducing regional perfusion in the face of dysfunctional cerebral autoregulation. Conversely, raising blood pressure might improve outcome by raising regional perfusion or worsen it by inducing cerebral oedema and early recurrence. Administration of some vaso-active drugs (beta-receptor antagonists and calcium channel blockers) can worsen outcome and reduce cerebral blood flow. In contrast, other drug classes--angiotensin- converting enzyme inhibitors, angiotensin receptor antagonists and nitrates--appear to lower blood pressure without reducing measures of cerebral perfusion. In the absence of definitive trial data, which is urgently needed, blood pressure should not be routinely lowered unless it is extreme (systolic blood pressure >220 mm Hg) or associated with arterial dissection or cardiac ischaemia or failure, in which case cautious lowering (<15%), perhaps with an angiotensin-converting enzyme inhibitor, angiotensin receptor antagonist or nitrate, is appropriate.
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PMID:High blood pressure as risk factor and prognostic predictor in acute ischaemic stroke: when and how to treat it? 1469 80

Calcium channel antagonists are widely used antihypertensive agents. Their popularity among primary care physicians is not only due to their blood pressure-lowering effects, but also because they appear to be effective regardless of the age or ethnic background of the patients. The first available calcium channel antagonists utilized immediate-release formulations which, although effective in patients with angina pectoris, were not approved by the US FDA for use in hypertension. When long-acting once-daily formulations were approved in this indication, the short-acting preparations--which had by then become generic and inexpensive--retained some residual unapproved use for hypertension. An observational case-controlled trial, based on such usage, noted that these agents were associated with a greater risk of myocardial infarctions than conventional agents such as diuretics and beta-adrenoceptor antagonists. Further case-controlled trials showed, in fact, that the dangers of calcium channel antagonists were confined to the short-acting agents and that approved long-acting agents were at least as well tolerated and effective as other antihypertensive drugs. Cardiovascular outcomes during treatment with calcium channel antagonists have been examined in randomized, controlled trials. Compared with placebo, the calcium channel antagonists clearly prevented strokes and other cardiovascular events and reduced mortality. The effects of these agents on survival and clinical outcomes were similar to those with other antihypertensive drugs. There is a slight tendency for the calcium channel antagonists to be more effective than other drug types in preventing stroke, but slightly less effective in preventing coronary events. These observations extend to high-risk patients with hypertension including those with diabetes mellitus. Even so, patients with evidence of nephropathy should not receive monotherapy with calcium channel antagonists. Such patients are optimally treated with angiotensin receptor antagonists or ACE inhibitors, although addition of other drugs, including calcium channel antagonists, is often required to achieve the tight blood pressure control necessary to provide adequate renal protection. Calcium channel antagonists have a highly acceptable tolerability profile and careful reviews of available data have shown that their use is not associated with increased bleeding or promotion of tumor formation. It is now recognized that reduction of blood pressure in patients with hypertension to levels often <130/85 mm Hg should be undertaken in presence of other cardiovascular risk factors or evidence of end organ damage. Because of this important concept, calcium channel antagonists, like the other antihypertensive drug classes, are progressively being prescribed less often as monotherapy, but more typically as part of combination regimens.
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PMID:Calcium channel antagonists in the treatment of hypertension. 1472 56

Based on the Medical Research Council study, Brown and Brown hypothesized in 1986 that angiotensin II could protect against strokes by causing vasoconstriction of the proximal cerebral arteries, thereby preventing Charcot-Bouchard aneurysms from rupturing. In light of this hypothesis, we evaluated the cerebroprotective effects of various drug classes in recent double-blinded, prospective, randomized trials, such as SHEP, PATS, CAPPP, HOPE, PROGRESS, INSIGHT, NORDIL, LIFE, SCOPE, ANBP2, and ALLHAT. Drugs that activate the AT2 receptors, such as diuretics, calcium antagonists, and angiotensin receptor blockers (ARBs), were consistently more beneficial for stroke reduction than drugs devoid of such activation, such as beta-blockers and angiotensin-converting enzyme (ACE) inhibitors, despite an equal fall in arterial pressure (at least in patients with a low incidence of cardiac complications). These clinical and epidemiologic observations are supported by experimental data documenting greater cerebroprotection with ARBs (which increase angiotensin II levels and stimulate the AT2 receptors) than with ACE inhibitors. Stroke is the most devastating consequence of hypertensive cardiovascular disease, and our hypothesis of cerebroprotection by AT2 receptor activation should be tested by a head-to-head comparison of an ARB with an ACE inhibitor.
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PMID:Cerebroprotection mediated by angiotensin II: a hypothesis supported by recent randomized clinical trials. 1554 7

The Annual Scientific Sessions of the American Heart Association is the leading scientific conference in the cardiovascular field, both for basic and clinical research in cardiology and related disclipines. This report covers the outcome of major clinical trials that were presented in the 'late-breaking' clinical trial sessions. The Valsartan in Acute Myocardial Infarction Trial (VALIANT) investigated the angiotensin receptor blocker valsartan, the angiotensin-converting enzyme inhibitor captopril, and their combination in 14,703 survivors of an acute myocardial infarction with a reduced left ventricular ejection fraction on clinical outcome. The study demonstrated that valsartan and captopril where equally effective, whereas the combination was associated with an increased risk of side effects without further benefit. VALIANT is a landmark trial because it was the first large study that compared the combination of an angiotensin receptor blocker with an angiotensin-converting enzyme inhibitor in the setting of acute myocardial infarction. Other trials that will be summarised in this report are the Na + /H + Exchange Inhibition to Prevent Coronary Events in Acute Cardiac Conditions Trial (EXPEDITION; cariporide in coronary artery bypass graft surgery), the Reversal of Atherosclerosis with Aggressive Lipid Lowering Trial (REVERSAL; atorvastatin and pravastatin for atherosclerosis reversal), the Stroke Prevention Using an Oral Thrombin Inhibitor in Atrial Fibrillation V (SPORTIF V; ximelagatran and warfarin for stroke prevention in atrial fibrillation), the Prophylactic Amiodarone for the Prevention of Arrhythmias that Begin Early After Revascularisation (PAPABEAR; amiodarone for the prevention of postoperative atrial fibrillation), the Acute and Chronic Therapeutic Impact of a Vasopressin 2 Antagonist in Congestive Heart Failure (ACTIV in CHF; vasopressin 2 antagonist tolvaptan in congestive heart failure) and Prevention of Renal and Vascular Endstage Disease Intervention Trial (PREVEND IT; fosinopril and pravastatin in microalbuminuric subjects without hypertension or hypercholesterolemia).
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PMID:American Heart Association scientific sessions. 1510 93

In the international and the Hungarian guidelines, the diuretics in the first line of the treatment of hypertension. Their sometimes false judgment is based on the side effects, because of the over dosage of the applied medication. According to finished studies, efficiency of thiazides is usually the same as that of their competitors in influencing of the cardiovascular morbidity and mortality. Thiazides have to be given in the first line an antihypertensive treatment to the patients, especially if they are old, or have a great risk for a cardiovascular complication (stroke, coronary heart disease, heart failure, left ventricular hypertrophy). In the case of natrium-retention (diabetes, obesity, nephropathy), the treatment without diuretics is not effective. Thiazides make stronger the effects especially of ACE-inhibitors, angiotensin receptor blockers, and beta receptor blockers. The newer diuretics--with fewer side effects--have very likely extrarenal way of effects, so their long time application seems very favourable.
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PMID:[Revival of antihypertensive therapy: use of thiazide diuretics]. 1512 17


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