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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Platelets are intimately involved in atherosclerosis, and hypertension is a known risk factor for coronary artery disease. The angiotensin-converting enzyme (ACE) inhibitors were demonstrated to reduce hypertension and attenuate atherosclerosis. Because increased platelet aggregation was shown in hypertensive patients, the effect of a new ACE inhibitor, fosinopril, on platelet aggregation was studied. Fosinopril therapy (10 mg/day for 4 weeks) in 18 male hypertensive patients showed > or = 31% reduction in ADP-induced platelet aggregation. In vitro studies showed that fosinopril had similar inhibitory effect on ADP-induced platelet aggregation. No inhibitory effect could be detected with collagen as the aggregating agent. Finally, inhibition of platelet aggregation by fosinopril was less effective in platelets derived from hypertensive patients as compared with platelets derived from normal subjects. We conclude that fosinopril possesses a significant inhibitory activity on ADP-induced platelet aggregation both in vitro and in vivo.
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PMID:Fosinopril reduces ADP-induced platelet aggregation in hypertensive patients. 872 Apr 15

Fosinopril is a phosphinic acid derivative which undergoes rapid hydrolysis after oral administration to the active diacid ACE inhibitor fosinoprilat. Cardiotropic effects have been associated with the drug, and the compensatory dual elimination route of fosinopril via renal and hepatic systems offers an opportunity for ACE inhibitor treatment of hypertension in patients with renal or hepatic impairment. Comparative trials of monotherapy with fosinopril 10 to 40 mg/day have demonstrated antihypertensive efficacy equivalent to that of sustained release nifedipine 40 mg/day, hydrochlorothiazide 25 to 50 mg/day, enalapril 5 to 10 mg/day amlodipine 5 to 10 mg/day and sustained release verapamil 240 to 480 mg/day, and superior to that of isradipine 5 mg/day. The efficacy of combination therapy with fosinopril 10 to 20 mg/day and hydrochlorothiazide 12.5 mg/day was significantly superior to that of hydrochlorothiazide alone, tended to be superior to that of fosinopril 20 mg/day alone and was similar to that of sustained release nifedipine 40 mg/day alone. The combination of fosinopril/chlorthalidone 20 to 40/25 mg/day was as effective as propranolol/chlorthalidone 80 to 160/25 mg/day. The incidence of adverse effects associated with fosinopril is low, and cough may possibly occur less often with this drug than with other ACE inhibitors. Fosinopril thus offers an effective and well tolerated option for the treatment of hypertension in adult and elderly patients, including those with renal or hepatic impairment.
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PMID:Fosinopril: a reappraisal of its pharmacology and therapeutic efficacy in essential hypertension. 886 47

Fosinopril is a phosphorus-containing ester prodrug of an angiotensin-converting enzyme (ACE) inhibitor. It is hydrolysed mainly in the gastrointestinal mucosa and liver to the active diacid, fosinoprilat, which has unique pharmacological properties. The majority of the active moieties of other ACE inhibitors are excreted in the urine. This means that an adjustment in either the dosage and/or the administration interval is needed in patients with moderate to severe renal dysfunction, in order to reduce drug accumulation and the possibility of an excessive decrease in blood pressure or other adverse effects. On the other hand, fosinoprilat is excreted both in urine and bile (as with temocaprilat, zofenoprilat and spiraprilat), and thus an adjustment of dosage and/or administration interval may be unnecessary in patients with moderate to severe renal dysfunction, as impaired renal function influences little of the pharmacokinetics of fosinoprilat. Furthermore, the available evidence suggests that the pharmacokinetic variables of fosinoprilat in patients receiving haemodialysis were similar to those in patients with moderate to severe renal dysfunction. Dosage modifications or supplemental dose administration following dialysis may be unnecessary. The hypotensive effect of the combination of fosinopril and a diuretic is synergistic. Pharmacokinetic interactions with fosinopril are unlikely in patients receiving thiazide or loop diuretics. Fosinopril has beneficial effects for patients with hypertension and left ventricular hypertrophy because it produces an adequate reduction in blood pressure and reversal of left ventricular hypertrophy. There are a large number of studies of the pharmacokinetics of fosinopril. However studies of its pharmacokinetic drug interactions with other drugs are far fewer. Further investigations are needed in several clinical settings.
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PMID:Fosinopril. Clinical pharmacokinetics and clinical potential. 919 16

Cardiovascular diseases are the most common causes of mortality, and hypertension is the most common cardiovascular disease in all ages. The Systolic Hypertension in the Elderly Program (SHEP) trial has shown that the pharmacologic reduction of isolated systolic hypertension can significantly reduce the incidence of cardiovascular complications. The aim of the Italian multicenter study reported here is to compare the efficacy, safety, and tolerability of fosinopril, a novel angiotensin converting enzyme (ACE) inhibitor with a dual route of excretion, with chlorthalidone, the diuretic administered in the SHEP study, in 312 elderly patients with isolated systolic hypertension. Our results show that fosinopril and chlorthalidone produce identical and statistically significant reductions in systolic blood pressure (-23.9 +/- 11.6 mm Hg and -23.7 +/- 10.9 mm Hg, respectively) and, to a lesser extent, in diastolic blood pressure (-7.1 +/- 3.1 mm Hg and -5.2 +/- 2.3 mm Hg, respectively). Only chlorthalidone caused a statistically significant change in uric acid, total cholesterol, blood urea, and serum potassium concentrations. Fosinopril was also somewhat better tolerated than chlorthalidone. In conclusion, the novel ACE inhibitor fosinopril is an effective and well-tolerated antihypertensive agent for use in elderly patients with isolated systolic hypertension and appears to be a suitable alternative for the treatment of isolated systolic hypertension.
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PMID:An effective approach for treating elderly patients with isolated systolic hypertension: results of an Italian multicenter study with fosinopril. 936 78

Data regarding the tolerance of ACE inhibitors in old age are sparse, despite this class of compound being regarded as one of the first-line agents for the treatment of hypertension. In the present trial, the efficacy and tolerance of the ACE inhibitor fosinopril was examined over a period of 12 weeks in an open trial of hypertensive patients aged over 60 years with diastolic hypertension (diastolic blood pressure 95 to 110 mm Hg) and isolated systolic hypertension (ISH; systolic blood pressure 160 to 219 mm Hg, diastolic blood pressure 80 to 94 mm Hg). Fosinopril decreased blood pressure from 174/101 mm Hg to 149/88 mm Hg in patients with diastolic hypertension and from 182/86 mm Hg to 151/80 mm Hg in patients with ISH. Seventy percent of patients did not require any adaptation of the initial fosinopril dose to achieve an adequate therapeutic response. In the patients in whom 20 mg fosinopril did not adequately reduce blood pressure, the addition of 12.5 mg hydrochlorothiazide was found to be slightly more effective than doubling the initial dose of the ACE inhibitor. Fosinopril was well tolerated and the occurrence of drug-dependent side effects was not increased in patients with renal insufficiency. Fosinopril is an excellent therapy for the treatment of hypertension in elderly patients, particularly because, as a consequence of its dual, compensatory excretion, no adaptation of the dose is necessary, even in patients with a physiological reduction in renal function.
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PMID:Treatment of senile hypertension: the Fosinopril in Old Patients Study (FOPS). 936 82

The complementary action of angiotensin converting enzyme inhibitors and diuretics in the treatment of hypertension has been demonstrated in a number of studies of fosinopril and hydrochlorothiazide (HCTZ). The combination provides a clinically significant reduction in blood pressure while minimizing the dose-dependent adverse effects of HCTZ, such as hypotension and its metabolic effects on plasma lipoproteins, by keeping the dose of each agent to the minimum. Fosinopril has a unique dual mechanism of elimination and can therefore be used in patients with renal impairment. The efficacy of the combination of fosinopril and hydrochlorothiazide compared with placebo and other agents is reviewed in this article. Studies have demonstrated that the combination is effective in the elderly and in renally impaired patients, regardless of severity. In addition, in non-insulin dependent diabetes, antihypertensive effect is achieved without further affecting carbohydrate and lipid metabolism, which is often the case when thiazide diuretics alone are used. A matrix study was performed to evaluate the optimum dose combination to produce blood pressure normalization and minimize side effects. This study evaluated 17 different dose combinations and demonstrated that the lowest dose combination to produce a clinically significant effect was fosinopril 10 mg and HCTZ 12.5 mg. However, a dose-related antihypertensive effect can be seen, giving the option for the use of 20 mg fosinopril for moderately hypertensive patients. Both combination therapy and fosinopril were significantly more effective than HCTZ alone or placebo. The fosinopril/HCTZ combination has also been shown to have a comparable effect to sustained-release nifedipine and propanolol + HCTZ. The studies reviewed here demonstrate that fosinopril/HCTZ combination treatment has a number of advantages over either agent used alone, providing blood pressure normalization in a broad range of hypertensive patients, including diabetic patients and the elderly.
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PMID:Management of hypertension: the role of combination therapy. 936 83

Recent trials in hypertensive patients with type 2 diabetes reveal important differences in the risk for major cardiovascular events when individual agents are compared. In the Fosinopril Amlodipine Cardiovascular Events Trial (FACET), 380 patients with hypertension and type 2 diabetes were randomized to fosinopril or amlodipine and followed for up to 3.5 years to assess effects on serum lipids. Although both agents effectively controlled blood pressure, amlodipine caused a significantly greater decrease in systolic pressure. At the end of the trial, serum cholesterol, high-density lipoprotein cholesterol, triglycerides, HbA1c, serum glucose, plasma insulin, serum creatinine, and microalbuminuria were similar in both groups. The patients randomized to fosinopril were significantly less likely to experience the prospectively defined combined outcome of acute myocardial infarction (MI), hospitalized angina, or stroke compared to those randomized to amlodipine (RR 0.49; 95% CI 0.26-0.95). In the Appropriate Blood pressure Control in Diabetes (ABCD) trial, 470 patients with hypertension and type 2 diabetes who were randomized to long-acting nisoldipine had an adjusted sevenfold increased risk for acute MI compared to those randomized to enalapril (RR 7.0; 95% CI 2.3-21.4). In the Multicenter Isradipine Diuretic Atherosclerosis Study (MIDAS) trial, the patients with hypertension and above the median of HbA1c (> or =6.7%) randomized to isradipine had a threefold increased risk for major cardiovascular events compared to those randomized to hydrochlorothiazide (RR 2.81; 95% CI 1.09-7.26). These findings are supported by several observational studies. Therefore, evidence is emerging that angiotensin-converting enzyme inhibitors and low-dose diuretics may be more effective than calcium antagonists for prevention of cardiovascular events in hypertensive patients with diabetes or impaired glucose control.
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PMID:New evidence on the prevention of cardiovascular events in hypertensive patients with type 2 diabetes. 973 37

Macrovascular disease is the major cause of mortality in persons with type 2 diabetes mellitus, and hypertension is an important factor contributing to this high prevalence. High blood pressure is about twice as common in persons with diabetes mellitus as in those without. Up to 75% of diabetes-related cardiovascular complications are attributed to hypertension. These observations are part of the rationale for recommendations for more aggressive lowering of blood pressure (to < 130/85 mm Hg) in persons with coexistent diabetes and hypertension. This may require therapy with a combination of antihypertensive agents. The Fosinopril versus Amlodipine Cardiovascular Events Trial (FACET), discussed herein, supports the case for combination therapy with an angiotensin-converting enzyme (ACE) inhibitor and a calcium antagonist in diabetic patients with hypertension.
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PMID:Comorbidity of hypertension and diabetes: the fosinopril versus amlodipine cardiovascular events trial (FACET) 1008 Apr 55

The results of 2 recently published studies have been interpreted as suggesting that calcium antagonists are unsafe for the management of hypertension in patients with diabetes. These 2 studies, the Fosinopril versus Amlodipine Cardiovascular Events Randomized Trial (FACET) and Appropriate Blood Pressure Control in Diabetes (ABCD), showed that angiotensin-converting enzyme (ACE) inhibitors may be preferable to calcium antagonists for managing hypertension in diabetic patients; they do not, however, show any harm attributable to calcium antagonists. Indeed, results of the FACET study suggest that the combination of an ACE inhibitor and a calcium antagonist is effective antihypertensive therapy. This suggestion is supported by findings in the Systolic Hypertension in Europe (Syst-Eur) Study, which revealed outstanding benefits of either a calcium antagonist alone or a calcium antagonist combined with an ACE inhibitor among diabetic patients with hypertension. The premature termination of the hypertensive arm of the ABCD study was puzzling because, although 2 of 13 subgroups of 1 of the 5 possible secondary endpoints in this part of the trial were apparently favorably affected by the use of the ACE inhibitor rather than the calcium antagonist, such a finding was compatible with chance alone. If the results of the FACET and ABCD studies are considered in the context of the best available data arising from large randomized controlled trials, one may conclude that calcium antagonists are not harmful or contraindicated in hypertensive patients with diabetes and that the combination of an ACE inhibitor and a calcium antagonist is effective for the management of hypertension in diabetic patients.
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PMID:Calcium antagonists and the diabetic patient: a response to recent controversies. 982 44

Recent trials have linked calcium antagonists with adverse cardiovascular events in hypertensive patients with diabetes. A closer examination of these trials (in particular the Appropriate Blood Pressure Control in Diabetes [ABCD] trial and the Fosinopril Versus Amlodipine Cardiovascular Events Trial [FACET]) reveals a lack of data from which to draw conclusions of harm. In fact, based on the results of these trials and the recent Hypertension Optimal Treatment (HOT) Trial, one may conclude that the combination of a calcium antagonist with an ACE inhibitor is a rational therapeutic choice in patients with coexisting hypertension and diabetes.
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PMID:Calcium antagonists and cardiovascular risk in diabetes. 982 45


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