Subject(s)
Hypertension/diagnosis , Humans , Hypertension/physiopathology , Language , Terminology as TopicABSTRACT
Progressive improvements in antihypertensive drug therapy over the past four decades have provided clear benefits in limiting cardiovascular complications. Unfortunately, and largely inexplicably, the inclusion in meta-analyses of defective trials plus the employment of inappropriate diagnostic criteria for adverse coronary events have led to spurious, exaggerated claims for the advantages of such treatment. The consequence has been a devaluation of the very real worth of prophylactic drug therapy for hypertension.
Subject(s)
Antihypertensive Agents , Clinical Trials as Topic/methods , Evidence-Based Medicine , Hypertension , Meta-Analysis as Topic , Aged , Antihypertensive Agents/adverse effects , Antihypertensive Agents/therapeutic use , Clinical Trials as Topic/standards , Female , Humans , Hypertension/complications , Hypertension/drug therapy , Hypertension/mortality , Male , Reproducibility of ResultsSubject(s)
Aldosterone/blood , Angiotensin II/blood , Hyperaldosteronism/blood , Humans , Hypertension/bloodSubject(s)
Renin-Angiotensin System/drug effects , Renin-Angiotensin System/physiology , Adrenocortical Adenoma/drug therapy , Adrenocortical Adenoma/etiology , Adrenocortical Adenoma/physiopathology , Antihypertensive Agents/pharmacology , Antihypertensive Agents/therapeutic use , Cardiovascular Diseases/drug therapy , Cardiovascular Diseases/etiology , Female , Humans , Hypertension, Renal/drug therapy , Hypertension, Renal/etiology , Male , PregnancyABSTRACT
Antihypertensive drug treatment trials and meta-analyses thereof have been reviewed. Disturbing inaccuracies and inconsistencies have been exposed. Some commentators have excluded certain trials from consideration for explicit reasons on one occasion, and then unaccountably relaxed their rigor subsequently. Most problematic and notorious have been the varied evaluations of the large American HDFP study, which compared patients allocated to two quite different health care systems, addressed multiple risk factors additional to hypertension, and employed very questionable definitions of nonfatal coronary events. Data from this large and pervasive study especially have polluted several meta-analyses and treatment guidelines. There have been several exaggerated claims of benefit concerning coronary artery disease and all-cause mortality.
Subject(s)
Antihypertensive Agents , Clinical Trials as Topic/methods , Hypertension/drug therapy , Adult , Antihypertensive Agents/classification , Antihypertensive Agents/therapeutic use , Female , Humans , Hypertension/mortality , Male , Meta-Analysis as Topic , Middle Aged , Risk FactorsABSTRACT
Progress in the treatment of hypertension over the past 50 years is reviewed. While achievements have been considerable, they have sometimes been exaggerated by uncritical analyses and meta-analyses of trials. Data of the large but seriously flawed American HDFP study especially have distorted appreciation of therapeutic benefits.
Subject(s)
Antihypertensive Agents/therapeutic use , Diet, Sodium-Restricted , Hypertension/therapy , Psychotherapy/methods , Clinical Trials as Topic , Humans , Meta-Analysis as Topic , Treatment OutcomeABSTRACT
Nebivolol was compared in a dose of 5 mg once daily with enalapril 10 mg once daily over 7 months in a double-blind randomised trial in essential hypertension. The two drugs had very similar sustained effects in lowering both systolic and diastolic pressures; neither had an orthostatic component. Both drugs were well-tolerated. No haematological, biochemical, or urinary abnormalities were seen.
Subject(s)
Adrenergic beta-Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Antihypertensive Agents/therapeutic use , Benzopyrans/therapeutic use , Enalapril/therapeutic use , Ethanolamines/therapeutic use , Adrenergic beta-Antagonists/administration & dosage , Adult , Aged , Angiotensin-Converting Enzyme Inhibitors/administration & dosage , Antihypertensive Agents/administration & dosage , Benzopyrans/administration & dosage , Blood Pressure/drug effects , Body Weight , Double-Blind Method , Electrocardiography/drug effects , Enalapril/administration & dosage , Ethanolamines/administration & dosage , Female , Heart Rate/drug effects , Humans , Hypertension/drug therapy , Hypotension, Orthostatic/prevention & control , Longitudinal Studies , Male , Middle Aged , Nebivolol , Patient Satisfaction , PlacebosABSTRACT
A double-blind, randomised, parallel-group trial was conducted in patients with essential hypertension in British general practices, of nebivolol 5 mg, atenolol 50 mg, and placebo each given once daily. Both active drugs, in comparison with placebo, caused highly significant and similar reductions in systolic and diastolic pressures without orthostatic effect, and small significant falls in heart rate. Both active drugs were well tolerated, nebivolol marginally more so. Nebivolol, a long-acting, cardioselective, vasodilating beta-blocker which acts partly via the l-arginine/nitric oxide mechanism, appears potentially valuable for the treatment of hypertension.
Subject(s)
Adrenergic beta-Antagonists/therapeutic use , Atenolol/therapeutic use , Benzopyrans/therapeutic use , Ethanolamines/therapeutic use , Hypertension/drug therapy , Adolescent , Adult , Aged , Atenolol/adverse effects , Benzopyrans/adverse effects , Double-Blind Method , Ethanolamines/adverse effects , Female , Humans , Male , Middle Aged , NebivololABSTRACT
The efficacy and acceptability of 5 mg nebivolol once daily, a long-acting, vasodilating cardioselective beta blocker that additionally facilitates the L-arginine/nitric oxide system, was assessed in a double-blind, randomized trial in comparison with 20 mg nifedipine retard twice daily in patients with essential hypertension. At 2 weeks of treatment, nebivolol was significantly more effective. Thereafter, both drugs effectively and similarly lowered systolic and diastolic pressures without orthostatic effect. Nebivolol had a trough-to-peak antihypertensive effect ratio of 90%. Nifedipine gave the expected side effects of headache, flushing, and edema. Nebivolol was well tolerated. Nebivolol slightly but significantly lowered heart rate. Neither drug adversely affected plasma levels of lipids.
Subject(s)
Adrenergic beta-Antagonists/therapeutic use , Antihypertensive Agents/therapeutic use , Benzopyrans/therapeutic use , Calcium Channel Blockers/therapeutic use , Ethanolamines/therapeutic use , Hypertension/drug therapy , Nifedipine/therapeutic use , Adult , Aged , Blood Pressure/drug effects , Double-Blind Method , Female , Heart Rate/drug effects , Humans , Male , Middle Aged , Nebivolol , Treatment OutcomeABSTRACT
A double-blind placebo-controlled dose-response trial of nebivolol, a cardioselective beta-blocking drug which also induces endothelium-dependent dilatation via nitric oxide, has been performed. Nebivolol reduced blood pressure (BP) in a dose dependent way, and was shown to be effective given once daily, without appreciable differences between peak and trough drug levels. There was no postural component to the BP fall. There was no clear inferiority of efficacy in black patients. A single daily dose of 5 mg was appropriate, with no evident advantage at 10 mg. The drug was well tolerated, even at 10 mg daily. BP control was achieved largely in the absence of typical side effects of beta-blockade. The combination of properties of nebivolol renders it an attractive addition to the antihypertensive repertoire.
Subject(s)
Antihypertensive Agents/administration & dosage , Benzopyrans/administration & dosage , Ethanolamines/administration & dosage , Hypertension/drug therapy , Administration, Oral , Adult , Aged , Dose-Response Relationship, Drug , Female , Humans , Male , Middle Aged , NebivololABSTRACT
BACKGROUND: A wide range of drug classes, frequently including centrally acting agents, has been used in clinical trials in hypertension which have shown benefit. Although therapy has clearly limited the complications of hypertension, further improvement is needed, especially concerning coronary artery disease. PERSPECTIVES: Future interest therefore centres on drugs that do not worsen diabetes mellitus, do not cause dyslipidaemia, or induce potassium loss, while not provoking drowsiness, depression, other troublesome side-effects, or being associated with rebound hypertension when stopped. The centrally acting imidazoline agonists merit detailed study in this regard.
Subject(s)
Antihypertensive Agents/therapeutic use , Hypertension/drug therapy , Antihypertensive Agents/adverse effects , Clinical Trials as Topic , Humans , Imidazoline Receptors , Receptors, Drug/agonists , Risk FactorsABSTRACT
The efficacy and acceptability of nebivolol 5 mg and enalapril 10 mg, each given once daily, were compared in essential hypertension in a multicentre, randomised, double-blind trial over 3 months. For the index pre-declared variable, sitting diastolic pressure at trough drug level, nebivolol achieved greater falls in pressure (-12.3 vs -9.9 mmHg; P = 0.009) and a higher response rate (70% vs 55%; P = 0.002). The trough-to-peak sitting diastolic ratios also favoured nebivolol (84% vs 60%, P = 0.002). Nebivolol, but not enalapril, slightly but significantly lowered heart rate. Both drugs were well-tolerated, although enalapril was accompanied by a significantly higher incidence of coughing.