Quality of Life Comparison Between Bisoprolol and Nifedipine Retard in Hypertension

Quality of life with the selective beta1-blocker bisoprolol and the calcium channel blocker nifedipine as a retard formulation was compared in patients with essential hypertension. A multicenter randomized, double-blind, two-way, crossover study design was used. After a placebo run-in period (4–6 weeks), during which all antihypertensive therapy was withdrawn, 82 patients were randomized. During the active treatment periods (8 weeks each), patients received either bisoprolol once daily or nifedipine retard twice daily, using the double-dummy technique. A washout period (4–6 weeks) separated the treatment periods. Data at baseline (at randomization) and at the end of each treatment period were compared. Seventy-five patients completed the study. Blood pressure (168 ± 2/103 ± 1 mmHg) decreased (p > 0.001) similarly with bisoprolol (153 ± 2/90 ± 1 mmHg) and nifedipine (154 ± 2/90 ± 1 mmHg). Compared with baseline values, none of the quality of life variables investigated changed during bisoprolol or nifedipine retard use. Neither in the intention-to-treat nor the efficacy analysis were differences between bisoprolol and nifedipine found in quality of life variables, such as the Health Status Index, somatic symptoms, anxiety, depression, total psychiatric morbidity, cognitive symptoms, and hostility score. Only in the efficacy analysis did Health Status Index tend to be better (p = 0.055) during nifedipine intake when compared with bisoprolol. This trend was not present in the intention-to-treat analysis. The number of dropouts during bisoprolol (n = 2) and nifedipine (n = 3) treatment, and the number of patients reporting side effects (21% and 16%, respectively) did not differ (p = 0.64) between both treatments. It can be concluded that at equipotent antihypertensive dosages, an 8-week treatment period with the selective beta1-blocker bisoprolol or the calcium antagonist nifedipine as a retard formulation does not result in any difference in quality of life variables. It is not clear whether the trend of Health Status Index to become better during nifedipine intake, which was only found in the efficacy analysis and not in the intention-to-treat analysis, is of clinical relevance.     

Twenty-four-hour blood pressure monitoring after a single dose of sustained-release verapamil

Summary The antihypertensive effect of a single dose of 240 mg sustained-release (S-R) verapamil was investigated by ambulatory blood pressure (BP) monitoring in 13 patients with mild to moderate essential hypertension. Following a 2-week washout period, 24-hour BP monitoring was carried out with a Spacelabs ICR 5300 device following random administration of a tablet of S-R verapamil or placebo; BP recording was repeated after crossover 3 to 7 days later. Average whole-day systolic and diastolic BPs were significantly lower after verapamil (130.1±2.6/87.1±1.2 mmHg) than after placebo (142.1±3.3/95.8±2.1 mmHg) (p<0.01). Mean waking BP was 146.4±3.6/99.1±2.2 mmHg after placebo and 135.2±3.3/90.5±1.7 mmHg after verapamil (p<0.01); during sleeping hours BP was 133.8±3.1/88.7±2.6 mmHg following placebo and 122.2±2.3/80.9±1.8 mmHg following verapamil (p<0.01). Blood pressure profile was significantly reduced by verapamil up to 20 hours after tablet administration, while from 21 to 24 hours after drug intake BP values were similar to placebo. Response to verapamil was not correlated to the pretreatment BP values and to the patient's age. In summary, this study suggests that acute administration of 240 mg S-R verapamil in hypertensive patients produces a BP reduction during 24-hour, daytime, and nighttime periods. The hypotensive efficacy is preserved for many hours after tablet intake and seems to be due to individual variation in cardiovascular reactivity to the drug.     

Long-term treatment with nifedipine reduces urinary albumin excretion and glomerular filtration rate in normotensive type 1 diabetic patients with microalbuminuria

The aim of the present study was to investigate the renal effects of long-term treatment with the calcium channel blocker nifedipine in normotensive type 1 diabetic patients with microalbuminuria. In a randomized, double-blind trial, 15 type 1 diabetic patients were treated with either nifedipine (n=8; dosage 30 mg/day) or placebo (n=7) for 12 months. At baseline and after 6 and 12 months of therapy, the albumin excretion rate (UAER, radioimmunoassay), glomerular filtration rate (GFR, chromium 51 ethylenediamine tetra-acetic acid clearance) and renal plasma flow (RPF, iodine 125 hippuran clearance) were determined. Nifedipine treatment caused a significant reduction of UAER after 6 and 12 months (median, Q₁/Q₃ in mg/24 h): baseline 84 (65/163); 6 months 35 (23/90),P<0.02; 12 months 39 (15/79),P<0.05. GFR was significantly decreased by nifedipine treatment (baseline 157±15, 6 months 122±8, 12 months 111±47 ml/min;P<0.05, mean ± SEM), whereas RPF remained constant. Nifedipine treatment did not influence systolic (baseline 121±7, 12 months 124±2 mmHg, mean ± SEM) or diastolic (baseline 72±2, 12 months 74±3 mmHg) arterial blood pressure. With placebo treatment no significant alterations of UAER, GFR, RPF and arterial blood pressure were observed. Metabolic control was constant throughout the whole study period. Thus, 1 year's treatment with nifedipine reduces the UAER and GFR in normotensive type 1 diabetic patients without influencing the systemic arterial blood pressure. The data, however, do not present a recommendation for the general use of nifedipine in these patients as the exact intrarenal mechanism of calcium channel blockers in humans remains to be established.     

A controlled trial of a high fibre,low fat and low sodium diet for mild hypertension in type 2 (non-insulin-dependent) diabetic patients

Summary Fifty hypertensive Type 2 (non-insulin-dependent) diabetic patients were allocated, in a controlled trial, to a treatment diet of high fibre, low fat and low sodium composition, or to a control diet by the hospital dietitian. After 3 months treatment, the modified diet-treated group showed a highly significant reduction in mean systolic (180.5±19.0 to 165.0±20.7 mmHg) and diastolic blood pressure (96.6±9.3 to 88.0±10.5 mmHg), accompanied by significant reductions in urinary sodium excretion (183.0±62.1 to 121.7+ 65.8 mmol/day) glycosylated haemoglobin (12.4±3.1 to 10.5±2.9%), weight (74.6s±13.5 to 71.7±12.1 kg) and serum triglyceride levels (p<0.05). The mean values of diastolic pressure (p<0.01), urinary sodium/potassium ratio (p< 0.001), urinary potassium (p<0.01) was significantly reduced at 3 months compared to control. No changes in serum HDL-cholesterol levels were observed. The number of patients with normal blood pressure at 3 months was greater in the modified diet-treated group (ten versus five). Treatment of mild hypertension in diabetic subjects with this form of dietary regimen has a hypotensive response, with improvement in glycaemic control and no side effects. This modified diet may be an attractive alternative to anti-hypertensive drug therapy as a first line treatment.     

Transcapillary escape rate of albumin in hypertensive patients with Type 1 (insulin-dependent) diabetes mellitus

Summary Diabetic patients with elevated urinary albumin excretion rate (incipient or clinical nephropathy) also have an increased transcapillary escape rate of albumin. This study was designed to clarify whether this is caused by a general vascular dysfunction or by elevated systemic blood pressure. The systemic blood pressure and the transcapillary escape rate of albumin were measured in the following groups after 4 weeks without antihypertensive treatment: Group 1 — eleven healthy control subjects. Group 2 — ten Type 1 (insulin-dependent) diabetic patients with incipient nephropathy (urinary albumin excretion rate: 30–300 mg/24 h) and normal blood pressure. Group 3 — eleven non-diabetic patients with essential hypertension. Group 4 — nine Type 1 diabetic patients with hypertension but normal urinary albumin excretion (<30 mg/24 h). Group 5 — eleven Type 1 diabetic patients with nephropathy (urinary albumin excretion rate > 300 mg/24 h) and hypertension. Systolic and diastolic blood pressure were similar in the three hypertensive groups: group 3, 148±8/95±6; group 4, 150±12/94±8 and group 5; 152±12/92±7mmHg, but significantly elevated (p<0.001) compared to control group 1,117±12/74±9 and group 2, 128±7/82±4 mm Hg. The transcapillary escape rate of albumin was similar in the control subjects (5.2±2.7%) and the subjects in the normoalbuminuric groups 3 and 4 (6.2±1.9 and 5.1±1.4 %, respectively) and significantly lower (p<0.001) than in patients with elevated urinary albumin excretion without or with hypertension group 2, 10.1±2.8 and group 5, 11.4±5.7 %. The increased transcapillary escape rate of albumin in patients with elevated urinary albumin excretion is unrelated to moderate systemic hypertension and may therefore be caused by alterations in the properties of the capillary walls.     

Comparison of antihypertensive effects of an angiotensin-converting enzyme inhibitor, a calcium antagonist and a diuretic in patients with hypertension not controlled by angiotensin receptor blocker monotherapy

OBJECTIVE: To compare the additional antihypertensive effects of an angiotensin-converting enzyme inhibitor (ACEI), a dihydropyridine calcium antagonist and a diuretic in patients whose hypertension is not controlled by full-dose angiotensin receptor blocker (ARB) monotherapy. DESIGN AND METHODS: Individuals with an ambulatory blood pressure (ABP) that was not controlled by valsartan 160 mg once daily were allocated randomly to two groups: those in group A (n = 35) were assigned randomly to treatment with benazepril 20 mg once daily or chlorthalidone 12.5 mg once daily, whereas patients in group B (n = 29) were assigned randomly to benazepril 20 mg once daily or amlodipine 5 mg once daily. All individuals continued to receive background valsartan 160 mg once daily. After 5 weeks, patients crossed over to the alternative valsartan-based combination treatment of each group for a second 5-week period. Twenty-four-hour ABP monitoring was performed before the random allocation to groups and at the end of each randomized combination pharmacotherapy period. RESULTS: Sixty-four individuals completed the study: 32 men and 32 women (mean +/- SD age 48.2 +/- 7.9 years, average 24-h ABP on valsartan monotherapy 143.4 +/- 12.6/87.7 +/- 7.8 mmHg). Significant additional antihypertensive effects on the average 24-h ABP were obtained with benazepril (8.6 +/- 8.8/6.3 +/- 6.7 mmHg), amlodipine (15.2 +/- 12.9/9.9 +/- 6.8 mmHg) and chlorthalidone (13.5 +/- 11.6/9.5 +/- 7.7 mmHg) (P < 0.001 for all additional antihypertensive effects). The additional effects of amlodipine and chlorthalidone added to valsartan were approximately 6/3.5 mmHg (P < 0.05) greater than that of benazepril. CONCLUSIONS: In patients in whom hypertension was not controlled by full-dose ARB monotherapy, a diuretic, a calcium antagonist or an ACE inhibitor provided significant additional antihypertensive effect. The antihypertensive effects of the ARB-diuretic and the ARB-calcium antagonist combinations were superior to that of the ARB-ACE inhibitor combination.     

Prevalence of hypertension in Type 1 (insulin-dependent) diabetes mellitus

Summary The prevalence of hypertension in a representative sample (n=10202) of the Danish general population aged 16–59 years was assessed to 4.4% based on three blood pressure readings. In Type 1 (insulin-dependent) diabetic patients of similar age (n=1703) the prevalence was determined in a similar way to 14.7% (p<0.00001). The excess prevalence in Type 1 diabetic patients was due to hypertension in patients with incipient and clinical nephropathy as the prevalence of hypertension among diabetic patients with normal urinary albumin excretion (essential hypertension) was 3.9%, similar to that observed in the general population. The patients with Type 1 diabetes and essential hypertension had higher systolic (146±19 vs 133±18 mmHg, p<0.00001) and diastolic blood pressure (87±12 vs 79±7mmHg, p<0.00001), but less changes in the eye background than patients with incipient nephropathy (urinary albumin excretion 30–300 mg/24 h) (p<0.03), indicating that the two groups were also different with respect to other microangiopathic lesions. Patients with essential hypertension were defined as having a normal urinary albumin excretion before and during antihypertensive treatment (if any). They were followed-up for a 58 (6–234) month period. We confirmed that hypertension is more common among Type 1 diabetic patients than in the general population and found the prevalence of essential hypertension similar in Type 1 diabetic patients to the non-diabetic population. This supports our hypothesis that hypertension is very unlikely to be the cause of diabetic nephropathy.     

Ambulatory blood pressure variability is associated with restenosis after percutaneous coronary intervention in normotensive patients

Background

Previous studies have showed that BP variability is associated with cardiovascular events. However, no data were available regarding binary restenosis as an end-point after percutenous coronary intervention (PCI).

Methods and results

This multicenter study included 100 consecutive normotensive patients with stable coronary artery disease who were planned for PCI. Before the index procedure, office BP and 24-h ambulatory BP measurements were performed. BP variability indices including systolic and diastolic 24-h average, the day and the night values of standard deviation (SD) and variation coefficient (VC) were measured and calculated. All patients underwent repeat coronary angiography at 6-month. According to angiographic results, 2 groups were formed; a restenosis group (n = 30) with binary restenosis of the stented segment and a control group (n = 70) with a stenosis diameter of <50% in stented segment. Systolic SD and VC values for 24-h average (14.0 ± 2.8 mmHg vs. 9.5 ± 1.6 mmHg, p < 0.001 and 16% ± 3 vs. 11% ± 2, p < 0.001, respectively), the day (15.2 ± 3.9 mmHg vs. 10.6 ± 1.7 mmHg, p < 0.001 and 17% ± 4 vs. 12% ± 2, p < 0.001, respectively), and the night (12.8 ± 4.1 mmHg vs. 8.4 ± 2.4 mmHg, p < 0.001 and 14% ± 5 vs. 11% ± 3, p = 0.004, respectively) values were significantly higher in restenosis group compared to control group. Similarly, diastolic SD and VC values for 24-h average (10.6 ± 2.5 mmHg vs. 8.1 ± 1.5 mmHg, p < 0.001 and 12% ± 3 vs. 9% ± 2, p = 0.001, respectively), the day (11.1 ± 2.9 mmHg vs. 9.0 ± 1.8 mmHg, p = 0.003 and 12% ± 3 vs. 10% ± 2, p = 0.006, respectively), and the night (10.0 ± 3.6 mmHg vs. 7.2 ± 2.0 mmHg, p = 0.001 and 11% ± 5 vs. 9% ± 3, p = 0.059, respectively) values were significantly higher in restenosis group compared to no restenosis group except for diastolic VC night. All systolic and diastolic BP variability indices except diastolic VC night were found to be independent predictors of risk of restenosis in multivariate analysis. In addition, the cut-off values of 11.4 mmHg and 13% for 24-h systolic SD and VC, respectively, were found to be highly sensitive (93% for both) and specific (94% and 91%, respectively) for predicting binary restenosis at 6-month after PCI.

Conclusions

BP variability indices are significantly and independently associated with binary restenosis and higher values can predict restenosis after PCI sensitively and specifically.     

Ambulatory Blood Pressure Monitoring in Patients with Essential Hypertension Treated with a New Calcium Antagonist, Cilnidipine

Cilnidipine (FRC-8653), a new dihydropyridine calcium antagonist, was given to 14 hospitalized patients with essential hypertension, and 24-hour ambulatory blood pressure (BP) monitoring was performed. Once-daily administration of cilnidipine (5–20 mg) for 1–3 weeks decreased the 24-hour average BP significantly from 149 ± 4/88 ± 2 mmHg to 141 ± 3/82 ± 2 mmHg without any change in the pulse rate. The decrease in ambulatory BP by cilnidipine was evident during the daytime (156 ± 4/93 ± 2 mmHg to 143 ± 5/84 ± 2 mmHg, p > 0.01 for systolic BP and p > 0.01 for diastolic BP), while it was mild during nighttime (141 ± 4/80 ± 2 mmHg to 133 ± 4/76 ± 3 mmHg, p > 0.05 for systolic and ns for diastolic BP). The decrease in the ambulatory BP over the whole day and during the nighttime was significantly correlated with the basal ambulatory BP levels. When the subjects were divided into the high ambulatory BP (n = 7) and low ambulatory BP (n = 7) groups, the BP reduction by cilnidipine was evident throughout 24 hours in the high ambulatory BP group, while it was mild and significant only during daytime in the low ambulatory BP group. In summary, once-daily cilnidipine exerts a sufficient and prolonged reduction of BP without an increase in the pulse rate in patients with hypertension. The potency of cilnidipine to decrease ambulatory BP may depend on the basal ambulatory BP level. Cilnidipine is thus a useful antihypertensive drug that may not cause an excessive decrease in BP or a reflex tachycardia.     

Efficacy and safety of standard dose triple combination of telmisartan 80 mg/amlodipine 5 mg/chlorthalidone 25 mg in primary hypertension: A randomized,double-blind,active-controlled,multicenter phase 3 trial

The authors evaluated the efficacy, safety, and characteristics of patients who respond well to standard dose triple combination therapy including chlorthalidone 25 mg with telmisartan 80 mg plus amlodipine 5 mg in hypertensive patients. This is a multicenter, double-blind, active-controlled, phase 3, randomized trial. Patients are randomized to triple combination (telmisartan 40 mg/amlodipine 5 mg/chlorthalidone 12.5 mg, TEL/AML/CHTD group) or dual combination (telmisartan 40 mg/amlodipine 5 mg, TEL/AML group) treatment and then dose up titration to TEL 80/AML5/CHTD25mg and TEL80/AML5, respectively. The primary endpoint is the change of mean sitting systolic blood pressure (MSSBP) at week 8. A Target BP achievement rate, a response rate, and the safety endpoints are also evaluated. Total 374 patients (mean age = 60.9 ± 10.7 years, male = 78.3%) were randomized to the study. The baseline MSSBPs/diastolic BPs were 149.9 ± 12.2/88.5 ± 10.4 mm Hg. After 8 weeks treatment, the change of MSSBPs at week 8 are −19.1 ± 14.9 mm Hg (TEL/AML/CHTD) and −11.4 ± 14.7 mm Hg (TEL/AML) (p < .0001). The achievement rates of target BP (53.8% vs. 37.8%, p = .0017) and responder rate (54.8% vs. 35.6%, p = .0001) at week 8 were significantly higher in TEL/AML/CHTD. There are no serious adverse event and no one discontinued medication due to adverse event. Among the TEL 80/AML5/CHTD25mg treatment group, patients of female or age ≥ 65 years old showed higher rate of target BP achievement than relatively young male. (61.4 vs. 46.8%, p = .042) Our study showed standard dose triple combination of telmisartan 80 mg/amlodipine 5 mg/chlorthalidone 25 mg is efficacious and safe in treatment of primary hypertension. Target BP achievement with triple therapy would be facilitated in female or old age.     

Negative association between plasma aldosterone concentration/plasma renin activity and morning blood pressure surge in never-treated hypertensive patients

Morning blood pressure (BP) surge (MS) has been known to be a predictor of cardiovascular events. Currently, few studies have evaluated the underlying mechanism underlying MS, which may include neurohormonal factors and the renin–angiotensin–aldosterone system (RAAS). This study aimed to examine plasma aldosterone concentration (PAC) and plasma renin activity (PRA) and BP parameters with or without MS in never-treated subjects with essential hypertension. This cross-sectional study included a total of 261 patients (mean age: 48.8 years; 60.5% male) with never-treated essential hypertension who were registered in a working group at The Catholic University of Korea. The patients were divided into the MS group, which was defined as having the highest quartile of morning BP increase from sleep (>31?mmHg; n?=?66) and the non-MS group (≤31?mmHg; n?=?195). We collected 24-h ambulatory BP, pulse wave velocity, ankle brachial index, PAC and PRA from all patients. The measured PAC and PRA were lower in the MS group than in the non-MS group (PAC: 9.0?±?5.4?ng/dl versus 12.2?±?8.7?ng/dl, p?p?=?0.002). The MS group had greater variations in daytime, nighttime and 24-h systolic blood pressure (SBPs) than the non-MS group (24-h SBP: 15.6?±?4.4?mm Hg for the non-MS group and 18.9?±?4.9?mmHg for the MS group; p?相似文献   

Nifedipine and acebutolol in combination for the treatment of moderate to severe essential hypertension

In a randomised, crossover study of patients with moderate to severe essential hypertension, the effects of the calcium entry antagonist nifedipine and the beta-receptor blocking drug acebutolol were studied on their own, and in combination. After 4 weeks of nifedipine tablets 20 mg twice daily (Adalat, Bayer), mean supine blood pressure (BP) fell by 20 mmHg and after 4 weeks of acebutolol 200 mg twice a day (Sectral, May & Baker) by 11 mmHg. When nifedipine and acebutolol were given in combination in the above doses for 4 weeks, there was a significantly greater fall in BP than with either agent alone, supine mean arterial pressure falling by 27 mmHg. The above BPs were measured 2 h after the last dose of tablets. Measurements 12 h after the last dose showed smaller falls in BP, with a significantly greater fall with combination treatment than with acebutolol alone. The fall in BP 12 h after the last dose of the combination was greater than with nifedipine alone but this difference was not statistically significant. This randomised, controlled study showed that nifedipine and acebutolol have a marked additive effect on BP which is sustained for at least 12 h after treatment.     

Felodipine compared to nifedipine as "third-line drug" in resistant hypertension

Felodipine is a new dihydropyridine calcium antagonist, and in hypertension it is a much more effective "third-line" drug than hydralazine. Nifedipine, on the other hand, is the established dihydropyridine calcium antagonist that has been increasingly used to treat hypertension. Information is now needed on the relative merits and demerits of these two drugs. This study appraised, therefore, the therapeutic utility of twelve months' treatment with nifedipine 20-60 mg twice daily in 55 patients with previous drug-resistant hypertension who had been successfully treated for the previous year with felodipine 5-20 mg twice daily, each calcium antagonist being used in combination with atenolol 100 mg daily with or without chlorthalidone 25 mg daily. Initially, nifedipine maintained comparable blood pressure control to that which had been achieved by felodipine, although in the longer term (over eight months) nifedipine proved less effective than felodipine had (p less than 0.02) and more patients became uncontrolled (supine diastolic blood pressure, Phase V, greater than or equal to 90 mmHg) on the maximum tolerated dose of the calcium antagonist (chi 2 = 4.13, p less than 0.05 greater than 0.025). The former degree of blood pressure control was, however, reestablished by increasing the dose of nifedipine or reintroducing the diuretic as necessary, and this control was maintained over the next four months. Minor side effects were less common on nifedipine than they had been during the preceding felodipine treatment phase. Felodipine thus has more pronounced and sustained antihypertensive effects than nifedipine, though its side effect burden may appear to be greater.(ABSTRACT TRUNCATED AT 250 WORDS)     

Combination therapy with nifedipine GITS 60 mg: subanalysis of a prospective, 12-week observational study (AdADOSE)

Background: AdADOSE was a 12-week, international, observational study conducted in the Middle East and Russia where patients received nifedipine gastrointestinal therapeutic system (GITS) at a daily dose of 30, 60, or 90?mg as part of an antihypertensive combination therapy. This subgroup analysis of the AdADOSE study assesses the efficacy and tolerability of nifedipine GITS combination therapy when used specifically at the 60-mg strength. Methods: Patients with hypertension who received a daily nifedipine GITS dose of 60?mg, either at constant dose (n?=?686) or up-titrated from 30?mg (n?=?392), were analyzed. Target blood pressure (BP) was <140/90?mmHg (or <130/80?mmHg for those at high/very high cardiovascular risk). Results: Following nifedipine GITS combination therapy, target BP was achieved by 33.7% patients in the 60?mg group (previously untreated, 42.5%; previously treated, 32.0%) and 32.4% patients in the 30–60?mg group (previously untreated, 45.2%; previously treated, 30.7%). Mean systolic BP/diastolic BP changes were ?40.3/?20.7?mmHg and ?35.6/?18.5?mmHg, respectively, and were similar regardless of previous antihypertensive treatment or the number of concomitant diseases. Incidences of drug-related adverse events (AEs) were low (3.2%, 60?mg; 2.0%, 30–60?mg group), few patients discontinued because of AEs (0.6% and 1.0%, respectively), and there were no serious AEs. Conclusion: Combination therapy with nifedipine GITS 60?mg in a real-life observational setting was effective and well tolerated in hypertensive patients, with low rates of treatment-related AEs.

Trial registration: ClinicalTrials.gov identifier: NCT01118286.     

Renal Protective Effects of Efonidipine in Partially Nephrectomized Spontaneously Hypertensive Rats

We investigated the effects of a calcium antagonist, efonidipine, which was reported to dilate not only afferent arterioles but also efferent arterioles, on progression of renal failure in salt-loaded partially nephrectomized spontaneously hypertensive rats (SHR). Forty-four SHR's with 5 of 6 nephrectomy were divided into four groups: group 1 as control (n=20); group 2, efonidipine-treated (n=8); group 3, enalapril-treated (n=8); and group 4, nifedipine-treated (n=8). The rats were given these drugs and a high-salt diet (5% NaCl) for 8 weeks. During the experiment, systolic blood pressure (SBP) and daily urinary protein excretion were measured eveiy 2 weeks. At the end of the study. seniin creatinine was deteimined, and renal tissues were obtained for light microscopic examination. SBI was markedly reduced by 8-week antihypertensive treatment. (control, 267±7 mmHg: efonidipine, 181 ± 7 mmHg; enalapril, 200±12 mmHg; nifedipine, 184±6 mmHg). Glomerular sclerosis developed markedly in the control group, but was partially prevented in all treated groups. Similarly, urinary protein excretion (UPE) was suppressed by efonidipine (180±16 mg/day) and enalapril (180±16 mg/day vs. 301±28 mg/day for control). In contrast, nifedipine failed to prevent the increase in urinaiy protein excretion (258±22 mg/day). In conclusion, efonidipine attenuates SBP increase and ameliorates glomerular injuty as well as nifedipine and enalapril. Furthermore, beneficial effects of efonidipine, but not nifedipine, on proteinuria suggest that different mechanisms mediate the improvement of proteinuria; one possible mechanism could be efferent arteriolar dilation, not reported in nifedipine.     

Persistence of the antihypertensive efficacy of amlodipine and nifedipine GITS after two 'missed doses': a randomised,double-blind comparative trial in Asian patients

Suboptimal management of hypertension is often a result of poor patient compliance in the form of missed doses of their antihypertensive medication. This multicentre, randomised, double-blind, parallel-group trial was designed to compare the persistence of the antihypertensive efficacy of the amlodipine and nifedipine gastrointestinal therapeutic system (GITS) after two 'missed doses', and also to compare the drugs' overall efficacy and safety in Asian patients with mild-to-moderate essential hypertension. Following a 2-week placebo run-in period, 222 patients were randomised to receive either amlodipine (5 mg daily, increased after 6 weeks if necessary to 10 mg daily, n=109) or nifedipine GITS (30 mg daily, increased after 6 weeks if necessary to 60 mg daily; n=113) for 12 weeks. A placebo was then substituted for further 2 days with continuous ambulatory blood pressure (BP) monitoring. The increases in the last 9 h of mean ambulatory BP on day 2 after treatment withdrawal were significantly less with amlodipine than with nifedipine GITS: 4.4+/-7.0 vs 11.2+/-11.3 mmHg for systolic BP (P相似文献   

A randomized controlled trial on the blood pressure–lowering effect of amlodipine and nifedipine‐GITS in sustained hypertension

In a multicenter, randomized trial, we investigated whether the long half‐time dihydropyridine calcium channel blocker amlodipine was more efficacious than the gastrointestinal therapeutic system (GITS) formulation of nifedipine in lowering ambulatory blood pressure (BP) in sustained hypertension (clinic systolic/diastolic BP 140‐179/90‐109 mm Hg and 24‐hour systolic/diastolic BP ≥ 130/80 mm Hg). Eligible patients were randomly assigned to amlodipine 5‐10 mg/day or nifedipine‐GITS 30‐60 mg/day. Ambulatory BP monitoring was performed for 24 hours at baseline and 4‐week treatment and for 48 hours at 8‐week treatment with a dose of medication missed on the second day. After 8‐week treatment, BP was similarly reduced in the amlodipine (n = 257) and nifedipine‐GITS groups (n = 248) for both clinic and ambulatory (24‐hour systolic/diastolic BP 10.3/6.5 vs 10.9/6.3 mm Hg, P ≥ 0.24) measurements. However, after missing a dose of medication, ambulatory BP reductions were greater in the amlodipine than nifedipine‐GITS group, with a significant (P ≤ 0.04) between‐group difference in 24‐hour (–1.2 mm Hg) and daytime diastolic BP (–1.5 mm Hg). In conclusion, amlodipine and nifedipine‐GITS were efficacious in reducing 24‐hour BP. When a dose of medication was missed, amlodipine became more efficacious than nifedipine‐GITS.     

Efficacy of once-daily lisinopril monotherapy in systemic hypertension

Lisinopril is a new, long-acting angiotensin-converting enzyme inhibitor formulated for once-daily treatment of hypertension. This study assessed the 24-h efficacy and tolerability of lisinopril in Chinese patients with mild to moderate hypertension of World Health Organization Stages I to II. A total of 30 patients aged 30 to 60 years (mean 47 ± 9) entered a 2-week washout period. All patients had ambulatory diastolic blood pressure (BP) > 90 mmHg and were given active treatment with lisinopril for 4 to 7 weeks. The dose of lisinopril was titrated from 10 to 40 mg daily (at 8-9 A. M.). In each patient, 24-h ambulatory blood pressure (BP) monitoring (SpaceLabs 90202) was performed twice, once before and once following treatment. Mean 24-hour systolic/diastolic BPs after lisinopril were significantly decreased compared with baseline values (132 ± 12/86 ± 7 vs. 150 ± 11/98 ± 7 mmHg; p < 0.0005/ 0.0005). The average dose of lisinopril was 14.5 ± 5 mg daily after a titration period of 5 weeks of treatment. Mean daytime (6 A. M. to 6 P. M.) BP decreased from 152 ± 11/100 ± 8 to 134 ± 12/87 ± 8 mmHg (p < 0.0005/0.0005) and nighttime (6 P.M. to 6 A. M.) BP from 147 ± 14/95 ± 9 to 128 ± 14/83 ± 8 mmHg ( p < 0.0005/0.0005). BP reduction was more pronounced during the night. Before treatment, the circadian variation showed a peak BP at 11 A. M. and nadir at 3 P. M. After treatment, significant BP reduction (p < 0.0005/0.0005) was seen throughout the 24-h period. The circadian rhythm of BP was preserved as indicated by similar BP standard deviations (14 ± 3/11 ± 2 vs. 13 ± 3/10 ± 2 mmHg). Mean heart rate increased from 76 to 80 beats/min (p < 0.05). Four patients reported having a nonproductive cough. Thus, lisinopril administered as once-daily monotherapy provided effective BP control over a 24-h period with preserved circadian rhythm.     

Afterload reduction by nifedipine--the acute haemodynamic response to exercise in hypertensive subjects

In 16 people with essential hypertension, heart rate (HR), bloodpressure (BP) and relative cardiac volumes were measured atrest and during submaximal upright exercise before and after10 mg of sublingual nifedipine using radionuclide ventriculography. In 10 patients who had had no previous therapy (BP 152/103±5/3mmHg) nifedipine produced a fall in BP of 6/12±3/3 mmHg(SEM) and a rise in HR of 15±5 bpm (P<0.001). Thiswas associated with a rise in LVEF of 0.07±0.02 (P<0.005)and in cardiac output of 44±9%, presumably as a resultof ventricular offloading. The cardiac response to exercisegiven the different starting values, was unchanged by nifedipine.Thus the HR was 101±6 bpm at rest after nifedipine andon exercise rose to 124±6 bpm (P<0.001): stroke volumewas +22±8% at rest after nifedipine and rose to +43±12%on exercise. Thus cardiac output which had increased by 44±9%after nifedipine increased by 100±10% from the initialvalue. In 6 patients pre-treated with atenolol (100 mg) and with similarresting BP (158/101±5/4 mmHg) there was a fall in BPof 32/15±3/2 mmHg after nifedipine which was greaterthan in the previously untreated group (P<0.01). In thisgroup HR increased by 8±3 bpm (P<0.05). Followingnifedipine the exercise response was similar given the differentstarting values. The combination of nifedipine and a beta adrenoceptor antagonistcan depress myocardial function and the difference between pressure–volumeratios in the two groups supports this view but there was noimportant depressant effect. We conclude that the combinationof beta blocker and nifedipine therapy is effective and safein hypertensive subjects without significant myocardial dysfunction.     

Effects of daily walking on office,home and 24-h blood pressure in hypertensive patients

Abstract

Aerobic exercise has been recommended in the management of hypertension. However, few studies have examined the effect of walking on ambulatory blood pressure (BP), and no studies have employed home BP monitoring. We investigated the effects of daily walking on office, home, and 24-h ambulatory BP in hypertensive patients. Sixty-five treated or untreated patients with essential hypertension (39 women and 26 men, 60?±?9 years) were examined in a randomized cross-over design. The patients were asked to take a daily walk of 30–60?min to achieve 10?000 steps/d for 4 weeks, and to maintain usual activities for another 4 weeks. The number of steps taken and home BP were recorded everyday. Measurement of office and ambulatory BP, and sampling of blood and urine were performed at the end of each period. The average number of steps were 5349?±?2267/d and 10?049?±?3403/d in the control and walking period, respectively. Body weight and urinary sodium excretion did not change. Office, home, and 24-h BP in the walking period were lower compared to the control period by 2.6?±?9.4/1.3?±?4.9?mmHg (p?<?0.05), 1.6?±?6.8/1.5?±?3.7?mmHg (p?<?0.01), and 2.4?±?7.6/1.8?±?5.3?mmHg (p?<?0.01), respectively. Average 24-h heart rate and serum triglyceride also decreased significantly. The changes in 24-h BP with walking significantly correlated with the average 24-h BP in the control period. In conclusion, daily walking lowered office, home, and 24-h BP, and improved 24-h heart rate and lipid metabolism in hypertensive patients. However, the small changes in BP may limit the value of walking as a non-pharmacologic therapy for hypertension.