UMLS:C0020538 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Contrasting information has been reported concerning the course of renal function in NIDDM with hypertension alone or in association with renal damage. The aim of the present study was to elucidate the course of the glomerular filtration rate (GFR) in hypertensive NIDDM patients during antihypertensive therapy. Furthermore, we compared the effects of ACE inhibitors (cilazapril, Inibace, Roche, Milan, Italy) and Ca(2+)-channel blockers (amlodipine, Norvasc, Pfizer, Rome, Italy). Of the hypertensive NIDDM patients attending the outpatient's clinic of the internal medicine departments of the University of Padova and Sassari, 44 participated in the present study. Of these patients, 26 were normoalbuminuric and 18 microalbuminuric. They were randomly treated with either cilazapril or amlodipine. The target of antihypertensive treatment was a value < 140 mmHg for systolic and 85 mmHg for diastolic blood pressure (BP). Microalbuminuria was defined as an albumin excretion rate (AER) between 20 and 200 micrograms/min. GFR was measured by plasma clearance of 51Cr-labeled EDTA at baseline and every 6-12 months during a 3-year follow-up interval. A significant decrease was observed in the values of GFR, AER, and systolic and diastolic BP in normoalbuminuric and microalbuminuric patients during antihypertensive therapy. The GFR fall in the overall population of NIDDM patients was significantly and inversely related to the decrease of mean BP (diastolic + 1/3 pulse pressure) (r = -0.80, P < 0.0001) but not to that of HbA1c, triglycerides, and BMI. The GFR decline (mean +/- SE) per year in the normoalbuminuric patient was 2.03 +/- 0.66 ml.min-1 x 1.73 m-2 (95% CI 0.92-3.17) during cilazapril and 2.01 +/- 0.71 ml.min-1 x 1.73 m-2 (95% CI 0.82-3.11) during amlodipine therapy. The GFR decline per year in the microalbuminuric patient was 2.15 +/- 0.69 ml.min-1 x 1.73 m-2 (95% CI 0.86-3.89) during cilazapril and 2.33 +/- 0.83 ml.min-1 x 1.73 m-2 per year (95% CI 1.03-3.67) during amlodipine therapy. Cilazapril and amlodipine lowered AER to a similar extent in normoalbuminuric and microalbuminuric patients. No significant changes were observed concerning other clinical and biochemical features between the two antihypertensive therapies and particularly HbA1c, BMI, triglycerides, and cholesterol plasma values. These results support the tenet that arterial hypertension plays a pivotal role in contributing to renal damage in NIDDM, even when AER is normal. However, the degree of BP control, with both cilazapril and amlodipine, can successfully delay the slope of GFR decline in hypertensive NIDDM patients with or without incipient nephropathy.
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PMID:Effects of cilazapril and amlodipine on kidney function in hypertensive NIDDM patients. 854 68

As part of the Amlodipine Cardiovascular Community Trial (ACCT), which was a large multicenter study designed to assess the effects of the calcium channel blocker amlodipine besylate (Norvasc) as monotherapy for treatment of mild to moderate hypertension, we sought to determine the effects of amlodipine on regression of left ventricular (LV) hypertrophy (LVH). The study began with a 2-week placebo run-in period (baseline), before which antihypertensive drugs had been discontinued. Amlodipine was then administered at 5-10 mg/day during a 4-week titration/efficacy period. Patients achieving a goal diastolic blood pressure (DBP) of < or = 90 mm Hg or a decrease in DBP of > or = 10 mm Hg entered a 12-week maintenance phase and had the option to continue long-term therapy thereafter. Echocardiograms were obtained in a subset of patients at the end of the baseline period. In patients with LVH at baseline, echocardiograms were repeated at the end of 16 weeks of therapy (week 18), and at 42 weeks in patients continuing long-term therapy. Thirty-seven percent of 124 hypertensive patients screened for LVH at baseline had LVH detected on echocardiograms. Blacks had a higher incidence of LVH (64%) as compared with whites (34%, p < 0.05). Patients with LVH were more likely to have a higher baseline systolic BP (SBP) and DBP. Their sitting SBP and DBP decreased significantly from a mean of 163/102 mm Hg at baseline to 139/86 mm Hg with amlodipine therapy at week 18 (p < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of amlodipine on left ventricular mass in the Amlodipine Cardiovascular Community Trial. 858 90

In 15 centres of the Czech Republic the antihypertensive effect of Amlodipine-Norvasc of Pfizer Co. was tested in 155 patients with mild or medium severe hypertension. The patients were treated by monotherapy, using doses of 5 mg (92%) and 10 mg (8%) per day. In all investigated hypertensive subjects a statistically significant decline of the systolic and diastolic blood pressure occurred in the course of the 12-week investigation (P smaller than 0.01) without affecting the heart rate. The rate of undesirable effects of treatment was very low: only three patients (1.9%) discontinued treatment on account of undesirable effects. The most frequent ones included perimalleolar oedema, the sensation of fullness, headache, cardiac palpitations, vertigo and insomnia. Evaluation of the antihypertensive effectiveness and tolerance of the preparation by the physician and patient is positive, and Amlodipine-Norvasc of Pfizer Co. holds therefore, because of its pharmacokinetic and pharmacodynamic properties, an important place among calcium channel inhibitors of the second generation.
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PMID:[Personal clinical experience in the treatment of arterial hypertension using amlodipine]. 868 1

Amlodipine besylate, a calcium channel blocker, was used to treat (mean +/- standard deviation [SD], 127 +/- 68 days) 12 cats with systemic hypertension. Amlodipine was administered orally at a dosage of 0.625 mg per cat (range, 0.08 to 0.23 mg/kg body weight; mean dose +/- SD, 0.17 +/- 0.04 mg/kg body weight) once daily as a single agent. Average indirect systolic blood pressure measurements in the 12 cases decreased significantly from 198 to 155 mmHg during amlodipine treatment. Significant changes in body weight and serum creatinine and potassium concentrations were not detected. Amlodipine appears to be a safe and effective oral treatment for systemic hypertension in cats when used chronically once daily as a single agent.
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PMID:Treatment of systemic hypertension in cats with amlodipine besylate. 913 33

Issues raised recently concerning the safety of calcium channel blockers (CCBs) prompted an analysis of the occurrence of cardiovascular events and death in the Pfizer Inc. hypertension clinical trial databases for amlodipine (Norvasc) and nifedipine in the gastrointestinal therapeutic system (GITS) formulation (Procardia XL). Prospectively defined analyses of data from comparative and noncomparative trials of amlodipine and nifedipine GITS were conducted. Outcome measures included cardiovascular and noncardiovascular deaths, and adverse cardiovascular events including new/worsened angina, myocardial infarction (MI), serious arrhythmia, stroke, congestive heart failure, and bleeding. Among all amlodipine-treated patients (n = 32,920), the incidence rates for all-cause death, MI, and new/worsened angina were 3.0, 3.3, and 1.6/1,000 patient-years of exposure, respectively. Among those in comparative trials alone (n = 4,126), the all-cause death rate was 4.1/1,000 patient-years, which was comparable to that of other non-CCB agents and significantly less than that of other CCBs (23.8/1,000 patient-years, p = 0.015), although the difference in rates represents only 2 deaths. Among all nifedipine-GITS-treated patients (n = 2,645), the rate of all-cause death was 4.1/1,000 patient-years, of MI 6.5/1,000 patient-years, and of new/ worsened angina 5.7/1,000 patient-years. The incidence rates for MI and other cardiac events were low in these hypertension trials, and did not differ among treatment groups in either the amlodipine or nifedipine GITS comparative analyses. In the clinical trial databases analyzed, there is no signal suggesting excessive risk of death or cardiovascular events for hypertensive patients treated with amlodipine or nifedipine GITS.
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PMID:Safety of long-acting dihydropyridine calcium channel blockers in hypertensive patients. 959 99

Hypertension (HTN) is a significant problem in pediatric renal transplant (TP) recipients, predisposing the individuals to the development of cardiovascular disease and graft dysfunction. Calcium channel blockers (CCB) are considered excellent agents to treat post-TP HTN. We compared the efficacy and adverse effects of the two most commonly prescribed CCBs in our pediatric renal TP population: nifedipine (Procardia, or P) and amlodipine (Norvasc, or N). All patients (n = 24) had been started on a CCB for systolic (SBP) and/or diastolic BP (DBP) > 95%. There were no other changes in adjunctive antihypertensive medications or doses during the cross-over period. Post-TP, pretreatment (pretx) SBP was 137.6 +/- 10.9 mmHg. The post-treatment SBP were (in mmHg): 128.5 +/- 11.9 (all patients, n = 24) (p = 0.009 vs. pretx); 126.4 +/- 10.0 (P alone, n = 15) (p = 0.007 vs. pretx); 132.8 +/- 14.4 (P + other antihypertensive(s), n = 9) (p = 0.331, NS vs. pretx). The post-TP, pretreatment DBP was 88.2 +/- 11.1 mmHg. The post-treatment DBP were (in mmHg): 78.5 +/- 6.9 (all patients, n = 24) (p = 0.03 vs. pretx); 77.2 +/- 7.4 (P alone, n = 15) (p = 0.008 vs. pretx); 80.7 +/- 6.1 (P + other antihypertensive(s), n = 9) (p = 0.063, NS vs. pretx). P and N were equally effective in reducing SBP (p = 0.843, NS) and DBP (p = 0.612, NS). Cyclosporin A (CyA) dose (p = 0.81) and trough levels (p = 0.19) were similar in P- and N-treated patients. Calculated GFR was virtually identical in P- and N-treated patients (p = 0.89). Patients (or parents of) reported a higher incidence of various side-effects while receiving P, including headache, flushing, dizziness and leg cramps. Furthermore, 22/24 (91.7%) reported some degree of gingival hyperplasia during treatment with P, and all these patients reported a stabilization or reduction of hypertrophy after the switch from P to N. We conclude that CCBs (N) are efficacious drugs for the purpose of BP control and renal protection in pediatric renal TP recipients.
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PMID:Use of calcium-channel blockers in pediatric renal transplant recipients. 1056 73

Calcium antagonists, particularly the newer, longer-acting agents, are clearly effective in reducing elevated blood pressure with minimal to modest adverse effect profiles, and are therefore used extensively. The goal of antihypertensive therapy, however, is not simply to reduce blood pressure, but also to reduce vascular injury due to hypertension. Prospective controlled clinical trials evaluating cardiovascular morbidity and mortality are needed to test calcium antagonists in patients with hypertension. This review summarises the design and, in some cases, the results of 7 trials (5 of them still ongoing) that have provided insight into the effects of moderate- to long-acting calcium antagonists on mortality and target-organ damage in patients with hypertension. The Systolic Hypertension in Europe (Syst-Eur) trial studied 4695 elderly patients with isolated systolic hypertension, and demonstrated significant reductions in stroke and all fatal and nonfatal cardiac end-points in patients randomised to nitrendipine versus placebo. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) compares the effects of standard diuretic treatment with 3 alternatives (amlodipine, lisinopril, and doxazosin) on the incidence of fatal coronary artery disease and nonfatal myocardial infarction in more than 42,000 hypertensive patients with additional cardiovascular risk factors. The Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) compares the effects of amlodipine +/- perindopril with atenolol +/- bendrofluazide on fatal coronary artery disease and nonfatal myocardial infarction in 18,000 high risk patients. The Controlled ONset Verapamil INvestigation of Cardiovascular End-points (CONVINCE) study is assessing the incidence of fatal or nonfatal myocardial infarction and stroke, and cardiovascular disease-related death in patients on controlled-onset extended-release verapamil compared with a standard regimen of hydrochlorothiazide or atenolol. The Nordic Diltiazem Study (NORDIL) also compares a calcium antagonist (diltiazem) with conventional antihypertensive drug treatment (diuretics or beta-blockers) with add-on therapy as needed, in preventing cardiovascular mortality or morbidity. The Prospective Randomized Evaluation of the Vascular Effects of Norvasc Trial (PREVENT) tests a similar hypothesis, examining the effects of amlodipine on atherosclerotic lesions. The African-American Study of Kidney Disease (AASK) trial is evaluating the effects of amlodipine in hypertensive patients with renal disease. These important clinical trials of different classes of antihypertensive agents are critical for optimising the treatment of hypertensive patients in order to prevent coronary artery disease and other vascular diseases in this new millennium. Importantly, these randomised trials are free of the major problems of observational studies, i.e., confounding by indication, and should fully address the concerns raised by observational studies and small, under-powered, randomised trials that calcium antagonists may have adverse effects on myocardial infarction, bleeding and cancer. To date, these trials in progress have provided no evidence to support these concerns.
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PMID:[Calcium antagonists in cardiovascular disease. Clinical evidence from morbidity and mortality trials]. 1100 56

Calcium antagonists are currently considered first-choice agents for treating hypertension. They are also active antianginal drugs. Their protective effects against ischaemia and their antiatherogenic potential, which have been demonstrated in various experimental models, may contribute to their preventive effect against the early atherosclerotic processes. However, their effects on survival and cardiovascular events have been inconsistent and controversial. Recent studies have suggested that mortality may be increased by short-acting agents. The effects of certain long-acting calcium antagonists may be different. In early clinical trials, nifedipine and nicardipine did not alter the progression of significant coronary artery narrowing, but did reduce the development of new atherosclerotic lesions. Nevertheless, the number of cardiovascular events was not decreased. The Multicenter Isradipine Diuretic Atherosclerosis Study (MIDAS) showed a higher incidence of angina and more frequent cardiovascular events in patients treated with isradipine. In the Prospective Randomized Evaluation of the Vascular Effects of Norvasc Trial (PREVENT), after 3 years' follow-up, progression of significant atherosclerotic lesions and the development of new lesions were not significantly altered by treatment with amlodipine. However, it would appear that quantitative angiography may not be appropriate for monitoring the progression of atherosclerosis. Because of arterial remodelling, angiographic images may not show changes in the arterial lumen, in arteries where intravascular ultrasound may detect important atherosclerotic plaques. High resolution B-mode ultrasonography of the carotid artery may be more informative, since carotid intima media thickness is strongly correlated with cardiovascular risk factors, the prevalence of cardiovascular disease, and the presence of atherosclerotic lesions at other arterial sites. In the PREVENT trial, carotid ultrasonography showed that intima media thickness was stabilised in the amlodipine group, while progression was uninterrupted in the placebo group. The mechanism of amlodipine in slowing the progression of intima media thickness may be related to its antiatherogenic effect, as well as to its effect on cellular growth and hyperplasia of the arterial wall. It is interesting to note that, as a secondary objective of the PREVENT trial, patients treated with amlodipine had fewer ischaemic events than those treated with placebo. The beneficial effects of amlodipine on arterial thickening and on the prevention of ischaemic events suggest that amlodipine may be recommended for the management of all patients with stable angina. A larger trial with a longer follow-up period should be performed in order to confirm the promising results of PREVENT.
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PMID:[Effects of calcium antagonists on atherosclerosis progression and intima media thickness]. 1100 57

Atherosclerosis is a systemic disease that can ultimately lead to ischaemia and infarction in the heart, brain and peripheral vasculature. According to the "response to injury" hypothesis, endothelial dysfunction is the early event that allows penetration of lipids and inflammatory cells into the arterial wall, contributing to the development of the atherosclerotic lesion. Endothelial dysfunction is causally related to a variety of risk factors for atherosclerosis, including hyperlipidaemia and hypertension. Agents that restore endothelial function and NO bioavailability have beneficial anti-atherogenic activities and can improve cardiovascular outcomes; this has been observed with angiotensin-converting enzyme (ACE) inhibitors, statins and certain dihydropyridine-type calcium channel blockers (CCBs). In the Prospective Randomised Evaluation of the Vascular Effects of Norvasc Trial (PREVENT), the CCB amlodipine provided significant clinical benefits compared with placebo, including a marked reduction in cardiovascular morbidity and a reduction in the progression of carotid atherosclerosis. As these beneficial effects of amlodipine have not been observed with other dihydropyridine-type CCBs, it has been proposed that this agent has distinct anti-atherosclerotic properties related to its strong lipophilicity and membrane location. Experimental support for this hypothesis has been obtained from various in vitro and in vivo models of atherosclerosis. These findings support a broader therapeutic role for third-generation dihydropyridine-type CCBs in the treatment of atherosclerosis.
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PMID:Atheroprotective effects of long-acting dihydropyridine-type calcium channel blockers: evidence from clinical trials and basic scientific research. 1274 May 51

Calcium antagonists are effective in hypertensive patients of all ethnic groups, irrespective of age, dietary salt intake, salt-sensitivity status or plasma renin activity profile. Some prospective studies show that the calcium antagonists, nifedipine GITS and nitrendipine, reduce cardiovascular morbidity and mortality at least to the same extent as the diuretics. Other prospective studies are in progress to evaluate the effect of calcium antagonists on cardiovascular morbidity and mortality, and the progression of atherosclerosis in hypertensive patients. Calcium antagonists, especially the highly lipophilic amlodipine, lacidipine and nisoldipine, are shown to possess antioxidant properties. These drugs reduce the oxidation of LDL and its influx into the arterial wall, and reduce atherosclerotic lesions in animals. Platelet production of malondialdehyde, a marker of oxygen free radical formation, is suppressed by amlodipine, lacidipine or nifedipine in hypertensive patients. New evidence from long-term clinical trials of calcium antagonists indicates that these drugs can reduce the rate of progression of atherosclerosis in hypertensive and coronary heart disease patients. In the Regression Growth Evaluation Statin Study (REGRESS), co-administration of calcium antagonist, amlodipine or nifedipine with pravasatin caused a significant reduction in the appearance of new angiographic lesions. In the Verapamil in Hypertension and Atherosclerosis Study (VHAS), verapamil was more effective than chlorthalidone in promoting regression of thicker carotid lesions in parallel with a reduction in the incidence of cardiovascular events. In the Prospective Randomized Evaluation of the Vascular Effects of Norvasc Trial (PREVENT), amlodipine slowed the progression of early coronary atherosclerosis in patients with coronary artery disease. In a subprotocol of the Intervention as a Goal in the Hypertension Treatment (INSIGHT) study, nifedipine GITS significantly decreased intima-media thickness as compared to co-amilozide (hydrochlorothiazide + amiloride). Preliminary results of the European Lacidipine Study on Atherosclerosis (ELSA) show that lacidipine reduced the intima-media thickness progression rate as compared to atenolol. Thus, selective calcium antagonists are potential antiatherosclerotic agents.
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PMID:Calcium antagonists and atherosclerosis protection in hypertension. 1462 78

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