Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.15.1 (ACE)
 18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The necessity for a persistent antihypertensive treatment in elderly persons has not been proven until the beginning nineties. An adequate reduction of blood pressure is required also in high age for prevention of cardiovascular accidents. A study is presented which investigates efficacy and tolerance of the ACE-inhibitor fosinopril in an unselected cohort of hypertensive outpatients older than 60 years over 12 weeks. Diastolic hypertension (DBP > or = 96-110 mm Hg) and isolated systolic hypertension (SBP > or = 160-219 mm Hg, DBP 80-94 mm Hg) were analyzed separately. Blood pressure values in both groups were normalized in more than 80% of the patients. In the case of insufficient response an additional dose of 12.5 mg hydrochlorochiazide was somewhat more effective than doubling the dose of the ACE-inhibitor. Efficacy and side effects of the antihypertensive treatment with fosinopril in this study were not dependent on the degree of impaired renal function.
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PMID:[Therapy of hypertension in the elderly: Fosinopril in Old Patients Study (FOPS)]. 944 81

The aim of this study was to compare blood pressure rise after interruption of two angiotensin converting enzyme (ACE) inhibitors in hypertensive patients. After a 2-week placebo run-in period, hypertensive patients were treated with either trandolapril 2 mg once daily or perindopril 4 mg once daily for 4 weeks in a double-blind design. A placebo was then administered for 1 week. Three periods of 1-week home self-measured blood pressure (SMBP) were programmed: end of placebo run-in period, end of treatment period, and final withdrawal placebo period. Every day, three consecutive measurements were requested both in the evening and in the morning. Individual reversion to baseline BP level was studied in the subgroup of patients responding to therapy (evening diastolic SMBP decrease > or =6 mm Hg). The ratio (R) of mean post-drug DBP lowering (residual effect) over evening on-drug DBP lowering (full effect) was used to study reversion to baseline. Patients exhibiting a lower value than the median of this ratio were called Reverters, whereas others were called Nonreverters. One hundred-nineteen patients entered the analysis. During the treatment period, mean SMBP decreased significantly, from 150 +/- 14/97 +/- 7 mm Hg to 139 +/- 15/91 +/- 9 mm Hg (all P < .001). The on-drug BP level was similar in the evening in the two treatment groups. However, both systolic and diastolic morning SMBP levels were significantly lower in the trandolapril group. After drug discontinuation, the mean BP level significantly rose to 144 +/- 14/94 +/- 9 mm Hg (all P = .01) but remained lower than the baseline BP values (P = .003 for SBP and P = .002 for DBP). The post-drug BP level was significantly lower in the trandolapril group than in the perindopril group. Seventy-four patients were responders to therapy. In this subgroup, the median of the R ratio used to analyze reversion to baseline after drug discontinuation was 44%. Nonreverters were characterized by a sustained on-drug BP decrease, compared to Reverters. We therefore conclude that ACE inhibitor treatment withdrawal is accompanied by a rapid rise in BP (within 48 h), followed by a 5-day BP plateau that is lower than the initial level. Reverters to baseline after drug discontinuation were more likely to be insufficiently controlled during therapy, particularly in the morning. The longer duration of action of trandolapril was associated with a lower BP level during both the morning during the active treatment phase and the 1-week posttreatment phase.
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PMID:Short-term effects of withdrawing angiotensin converting enzyme inhibitor therapy on home self-measured blood pressure in hypertensive patients. 952 44

The Controlled ONset Verapamil INvestigation of Cardiovascular Endpoints (CONVINCE) Trial is a randomized, prospective, double-blind, parallel-group, two-arm, actively controlled, multicenter, international 5-year clinical trial involving 15,000 patients. CONVINCE will compare the incidence of fatal or nonfatal myocardial infarction (MI), fatal or nonfatal stroke, or cardiovascular-disease-related death in two antihypertensive treatment regimens. One treatment arm begins with controlled onset-extended release (COER)-verapamil, which has its major antihypertensive effect 6-12 hours after administration. The other arm (standard of care (SOC)) begins with either hydrochlorothiazide (HCTZ) or atenolol, one of which is preselected by the investigator for an individual patient prior to randomization. Secondary objectives include comparisons of the regimens for each of the components of the primary endpoint (separately), death or hospitalization related to cardiovascular disease, efficacy in lowering blood pressure to goal, primary events occurring between 6 am and noon, all-cause mortality, withdrawals from blinded therapy, cancer, and hospitalizations due to bleeding. Patients may be enrolled if they are hypertensive and at least 55 years of age and have an established second risk factor for cardiovascular disease. Initial medications include COER-verapamil (180 mg/d), HCTZ (12.5 mg/d), or atenolol (50 mg/d). Initial doses are doubled if blood pressure (BP) does not reach goal (systolic BP < 140 mm and diastolic BP < 90 mm Hg). If BP is not controlled by the higher dose of the initial medication, HCTZ is added to COER-verapamil, or the SOC choice not initially selected is added in the SOC arm. An ACE-inhibitor is recommended (although nearly any open-label medication is allowed) as the third step for patients whose BP is not adequately controlled or who have a contraindication to one of the two SOC medications. Patients take two sets of tablets daily, one in the morning and one in the evening. Although most patients switch from an established antihypertensive medication to randomized treatment, untreated patients with stages I-III hypertension (SBP between 140 and 190 or DBP between 90 and 110 mm Hg) are eligible. Outcomes are monitored by an independent Data and Safety Monitoring Board. Enrollment began during the third quarter of 1996, and follow-up is to be completed in the third quarter of 2002.
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PMID:Rationale and design for the Controlled ONset Verapamil INvestigation of Cardiovascular Endpoints (CONVINCE) Trial. 968 12

The effects of 2 fixed antihypertensive combination drugs on blood pressure and aortic elastic properties were compared in 2 parallel groups. Twenty-six patients for 6 months received a calcium antagonist plus ACE inhibitor (verapamil SR 180 mg/trandolapril 1 mg (Vera/Tran)) and 25 patients a beta-adrenoceptor antagonist plus diuretic (metoprolol 100 mg/hydrochlorothiazide 12.5 mg (Meto/HCTZ)). In addition to blood pressure (SBP, DBP), carotidofemoral pulse wave velocity (PWV) was assessed non-invasively. Total peripheral resistance (TPR) was determined from cardiac output derived by electrical impedance cardiography. Sitting DBP decreased for -14.4 mmHg following Vera/Tran compared with -9.2 mmHg following Meto/HCTZ (p = 0.02 for difference between treatments). Blood pressure was normalized (i.e. DBP < 90 mmHg) in 69% of patients with Vera/Tran and in 52% with Meto/HCTZ. PWV was lowered with Vera/Tran to a higher extent than with Meto/HCTZ (differences between group means -0.46 to -0.98 m/sec, statistically not significant). Vera/Tran induced a decrease in TPR of about 15% of baseline values, whereas Meto/HCTZ showed no influence. Treatment-related adverse events following Meto/HCTZ were bradycardia and associated symptoms; following Vera/Tran these were cough and edema in 1 case each. In the Meto/HCTZ group, there were more withdrawals/drop-outs (9/25) than in the Vera/Tran group (2/26). The somewhat more intense reduction in PWV with Vera/Tran is indicative of an increase in aortic elastic properties associated with the more potent decrease in BP. In the present study, the combination of calcium antagonist plus ACE inhibitor was found to be an effective and well tolerated antihypertensive regimen and in these respects appears to have some advantages compared with a combination of beta-blocker plus diuretic.
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PMID:Blood pressure and aortic elastic properties--verapamil SR/trandolapril compared to a metoprolol/hydrochlorothiazide combination therapy. 972 95

The international, prospective, randomized HOT study was aimed at determining the influence of a targeted BP reduction on cardiovascular morbidity and mortality. Patients were randomly allocated to 3 DBP targets (< 80, < 85, < 90 mmHg). In addition, the impact of a coprescription of aspirin was studied. The BP target had to be reached within 3 months, according to a well-defined strategy : felodipine 5 mg o.d. as a 1st intention drug, 1, 2 or 3 additional drugs, if necessary, on the following steps. BP measurements were made, using an oscillometric automatic device (Hestia). From April 1992 to October 1994, 18,790 patients with an age range 50-80 years, coming from 26 countries, entered the study. The data collected on the 36th month were in agreement with those obtained on the 12th and the 24th months. Baseline DBP was reduced by 21, 23 and 25 mmHg in the 90, 85 and 80 mmHg target groups, respectively. The rate of patients whose DBP reached the target, obviously increased from the 3rd to the 12th month: from 43 to 56%, 60 to 70%, 74 to 83% in the 90, 85 and 80 mmHg, target groups, respectively. From the 2nd to the 3rd year, BP control was further improved, with a slightly higher rate of controlled patients in the elderly (age > 60 y), especially in the 80 mmHg target group. From inclusion to the 3rd month, one-drug treated patients decreased, whereas 2- or 3-drug treated patients increased. Felodipine-treated patients decreased on the 36th month, but remained over 80%. From the 6th to the 36th month, additional prescription of a betablocker or an ACE-inhibitor increased from 36 to 39%, and from 23 to 28%, respectively; moreover, the side-effects rate decreased from 10.5 to 3.6%, with a special decline in ankle edema from 4 to 1%. In conclusion, the BP reduction observed on the 36th month was of the same extent as that observed in the first months. It seems obviously possible to reach a targeted DBP and to maintain it over time, along with a good acceptability of the treatment. Targeted DBP could be more easily achieved in elderly patients, possibly due to a better drug compliance.
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PMID:[The Hypertension Optimal Treatment Study: efficacy and tolerability on the 36th month]. 974 62

31 male and female patients, between the ages of 18 and 65 years, presenting mild-to-moderate hypertension (DBP between 95 and 114 mmHg) and stable chronic renal failure (creatinine clearance between 60 and 25 ml/min) after a preinclusion placebo phase were included in a multicentre open study designed to evaluate the clinical, electrocardiographic and laboratory safety, as well as the antihypertensive efficacy of Diltiazem 300 mg Retard, as monotherapy for 3 months, or combined with a diuretic (furosemide) or angiotensin converting enzyme inhibitor (captopril) for 45 days. After an 8-day placebo run-in period, the study consisted of a 45-day phase of strict monotherapy with Diltiazem 300 mg Retard, followed by a final 45-day phase during which either monotherapy was continued (if safety was satisfactory and supine DBP < or = 90 mmHg), or two-agent combination therapy was instituted (when supine DBP was between 91 and 115 mmHg), 6 clinical evaluations were performed during the 3 months of this trial. Overall, 21 patients (mean age: 50 +/- 14 years) completed the study until the 3rd month: 13 remained on monotherapy, and 8 required two-agent combination therapy. Supine and standing systolic and diastolic blood pressures and heart rate were significantly decreased. The number of responding patients controlled (supine DBP < or = 90 mmHg) progressed between D10 (40%) and D90 (57%). The observed adverse events and reasons for drop-outs from the trial for adverse events were mostly related to the vasodilator effects of Diltiazem. The cardiac safety was good, with no significant variation of the PR interval on the ECG (0.15 +/- 0.03 sec on D-8, 0.17 +/- 0.02 sec on D90). No marked modification of blood and urinary laboratory constants (serum electrolytes, blood glucose, liver function tests) was observed during this trial. Renal function, evaluated by creatinine clearance, was not altered by treatment (40.5 +/- 15.2 ml/min on D0, 41.7 +/- 16.9 ml/min on D90). Overall, this study confirmed the good clinical, laboratory and electrocardiographic safety as well as the antihypertensive efficacy of Diltiazem 300 mg Retard administered as monotherapy for 3 months or possibly in combination for 45 days, in hypertensive patients with chronic renal failure.
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PMID:[Evaluation of the tolerance and effectiveness of Diltiazem LP 300 mg in hypertensive patients with chronic renal insufficiency]. 980 45

A single-center, prospective double-blind randomized trial was conducted to compare the efficacy and safety of the calcium channel blocker nisoldipine in a sustained release coat-core formulation (CC), titrated from 10 mg to 40 mg daily, with the angiotensin converting enzyme inhibitor enalapril, titrated from 10 to 40 mg daily, in the treatment of black South African patients with severe hypertension (sitting diastolic blood pressure [DBP] between 115 and 140 mm Hg, confirmed by 24-h ambulatory blood pressure monitoring). Treatment target was a sitting DBP < 95 mm Hg by the 9th week of treatment. This was followed by a 4-month open phase using nisoldipine CC 10 to 60 mg daily. Ninety-six patients had complete data at baseline, and at the end of the double-blind and open phases, and were included in this analysis. In both groups, all patients required titration up to the maximal dose of double-blind medication. Monotherapy with nisoldipine CC, but not enalapril, significantly reduced both sitting and 24-h ambulatory blood pressure (BP). Twenty-four-hour BP in the nisoldipine CC group decreased from 179+/-14 / 118+/-7 to 144+/-16 / 94+/-10 mm Hg (P < .0001) versus 181+/-13 / 117+/-5 to 171+/-17 / 110+/-11 mm Hg in the enalapril group (P = ns). The profound decrease in blood pressure achieved with nisoldipine CC was accompanied by a significant reduction in left ventricular [LV] mass index, observed after only 2 months of treatment (from 146+/-40 to 129+/-35 g/m2, P = .05). In contrast, enalapril had no effect on LV mass (from 139+/-36 to 142+/-50 g/m2, P = NS). The antihypertensive effect of nisoldipine CC was further demonstrated in the open phase, during which 24-h BP decreased from 180+/-14 / 118+/-6 mm Hg (at baseline) to 142+/-16 / 92+/-10 mm Hg at the end of the 16-week open phase (P < .0001). This effect was sustained with trough-to-peak ratio of 74% for systolic and 67% for diastolic BP, with further regression in LV mass. Reduction in 24-h systolic BP to < 135 mm Hg was associated with a greater degree of regression of LV mass index in patients treated with nisoldipine CC. The incidence of adverse events in both groups was low and both nisoldipine CC and enalapril were well tolerated. The incidence of significant ventricular arrhythmia was also low and did not change with treatment. In conclusion, our findings suggest that nisoldipine CC administered once daily could be considered as a suitable first-line antihypertensive agent in black patients with severe hypertension, based on its profound and sustained blood-pressure-lowering effect, associated with significant regression of left ventricular mass and its low side effect profile.
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PMID:Antihypertensive monotherapy with nisoldipine CC is superior to enalapril in black patients with severe hypertension. 1009 Mar 48

A disproportionate increase in SBP over DBP has been recognized for many years as a frequent accompaniment of aging. Initially this was considered to be benign, risk free and potentially dangerous to treat. Study over the years has shown that it is not benign and that antihypertensive therapy can reduce the risks of stroke, myocardial infarction, congestive heart failure and cardiovascular death. Currently, the drugs most widely recommended for this purpose are the thiazide diuretics, long acting dihydropiridine calcium channel antagonists, ACE inhibitors, and beta blocking agents. There may be a special place for nitrates, since these agents are very effective in increasing arterial distensibility--a primary abnormality of the disorder--but a formal study of their effectiveness has not been done. Concern about diastolic hypotension during therapy suggests that treatment to lower the blood pressure in this disorder should be carried out gradually with the aim of reducing the SBP toward normal while avoiding diastolic hypotension.
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PMID:Clinical studies and therapeutic trials in systolic hypertension. 1052 66

The objective of the present study was to analyze the influence of the I/D polymorphism of the ACE gene on the outcome of microalbuminuria in essential hypertensive patients who were receiving antihypertensive treatment. One hundred thirty-six essential hypertensive patients who were <50 years old and had never previously received treatment with antihypertensive drugs were included in the study. During a 3-year period, patients received nonpharmacological treatment consisting of moderate salt restriction and a low-calorie diet they were obese, with or without a regimen of antihypertensive drugs based on beta-blockers or ACE inhibitors. Hydrochlorothiazide was added when necessary to maintain the blood pressure goal of <135/85 mm Hg. At the beginning of the study and at yearly intervals, systolic and diastolic blood pressures (SBP and DBP, respectively), 24-hour urinary albumin excretion (UAE), renal function, and biochemical profile measurements were made. The insertion/deletion (I/D) polymorphism of the ACE gene was determined through the use of polymerase chain reaction. The variables used in the statistical analysis were the measurements at the start of the study and the increase or decrease detected during the follow-up, estimated as individual specific regression line slope values. At baseline, no differences in blood pressure or UAE values were observed among genotypes. Likewise, the genotype or allele frequency was not significantly different between normoalbuminurics and microalbuminurics. After the 3 treatment years, significant reductions in SBP, DBP, and UAE were found (SBP 151.6+/-17.3 reduced to 137.2+/-14.3 mm Hg, P<0.001; DBP 96.6+/-8.9 reduced to 84.5+/-9.8 mm Hg, P<0.001; UAE 36.7+/-71.5 reduced to 28.3+/-78.6 mg/24 h, P<0. 05). The slopes of these parameters over time did not differ significantly among genotypes. The slope of SBP was the main factor related to the slope of logUAE (P<0.003). A significant positive correlation coefficient between the SBP and logUAE slopes was observed for the DD patients (r=0.57, P<0.0001) but was absent in patients carrying the I allele (II r=-0.03, P=NS; I/D r=0.01, P=NS). Follow-up studies should be used to achieve a better understanding of the impact of candidate gene polymorphisms on the development of hypertension-induced organ damage. Assessment of the I/D polymorphism of the ACE gene may identify subjects who require a greatly lowered blood pressure to prevent organ damage and to reduce hypertension-associated complications and death.
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PMID:Influence of the I/D polymorphism of the angiotensin-converting enzyme gene on the outcome of microalbuminuria in essential hypertension. 1064 47

In this study, using 24-hour ambulatory blood pressure (BP) monitoring, the authors assessed the potential for BP control using hydrochlorothiazide (HCTZ, 12.5 mg daily), given as a monotherapy over 12 months to 49 black South African patients with mild to moderate hypertension (mean day diastolic blood pressure [DBP] > or = 90 and < 115 mmHg). Uncontrolled patients received fixed combination of quinapril/HCTZ 10/12.5, 20/12.5, and 20/25 mg, with dose titration at 3 monthly intervals if BP control was not achieved (day DBP < 90 mmHg). Overall, profound and sustained BP reduction was observed at the end of the study. The 24-hour BP decreased from 151 +/- 14/98 +/- 7 to 136 +/- 15/87 +/- 9 mmHg (p < 0.0001 at end of study vs. baseline); the mean day BP decreased from 155 +/- 14/104 +/- 7 to 140 +/- 15/91 +/- 10 mmHg (p < 0.0001 at end of study vs. baseline). The overall control (mean day DBP < 90 mmHg) and response (decrease in day DBP > or = 10 mmHg) rates were 49% and 61%, respectively. At the end of the study, only 2 patients (4%) remained on treatment with HCTZ. Out of the initial 12 patients controlled on HCTZ at 3 months (12/49, 24%), 5 patients remained controlled at 6 months and only 1 patient at 12 months. In contrast, quinapril/HCTZ combinations maintained their antihypertensive effect up to 9 months, with a significant number of patients (22/49, 45%) requiring the highest dose of the combination (20/25 mg daily). In conclusion, low-dose HCTZ should not be recommended as monotherapy in black patients with mild to moderate hypertension due to the fact that the BP-lowering effect is attenuated already at 6 months of treatment, with most patients requiring the addition of the ACE inhibitor.
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PMID:Antihypertensive effect of low-dose hydrochlorothiazide alone or in combination with quinapril in black patients with mild to moderate hypertension. 1088 12


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