Once vs twice daily administration of a fixed combination of captopril plus hydrochlorothiazide in essential hypertension: a double-blind crossover study in known responders to a standard combination.

The purpose of this randomized, double-blind, crossover trial was to compare the hypotensive effects of a fixed combination of captopril (C) 50 mg and hydrochlorothiazide (HCTZ) 25 mg (C 50/HCTZ 25) once daily with those of a fixed combination of C 25 mg and HCTZ 12.5 mg (C 25/HCTZ 12.5) twice daily. We studied 199 patients (108 M, 91 F) with mild to moderate essential hypertension whose BP was already controlled by the co-administration of C 25 mg and HCTZ 12.5 mg twice daily. They were randomly assigned to either C 25/HCTZ 12.5 twice daily during the first 6 weeks and C 50/HCTZ 25 once daily during the second 6 weeks or C 50/HCTZ 25 once daily followed by C 25/HCTZ 12.5 twice daily. Both regimens showed comparable efficacy on office diastolic BP (91.6 vs 91.3 mm Hg). Systolic BP was slightly but significantly higher (P = 0.02) with the once daily formulation (141.2 vs 139.1 mm Hg). Fixed combinations once daily and twice daily resulted in identical working ambulatory BP (133.7 +/- 13/83.6 +/- 8 mm Hg vs 132.4 +/- 11/83.3 +/- 7 mm Hg) without affecting heart rate. Adverse events were reported by 16% of patients and cough was the most common occurring in 7%. In conclusion, these results indicate that the fixed combination of C 50/HCTZ 25 given once daily controls office and working BP as well as the fixed combination C 25/HCTZ 12.5 given twice daily in patients with mild to moderate hypertension.     

Enalapril and nifedipine in the treatment of mild to moderate essential hypertension: a 6 month comparison.

1. In a double-blind, randomised, parallel group study, 128 patients with sitting diastolic blood pressure between 95 and 125 mm Hg (Phase V) after 2-4 weeks run-in on placebo, received enalapril 10-40 mg once daily (65 patients) or nifedipine retard 10-40 mg twice daily (63 patients), utilising a double dummy technique. Dual target blood pressures were less than 150 mm Hg systolic and less than 90 mm Hg sitting diastolic. Inadequate responders had hydrochlorothiazide 12.5-50 mg once daily added. 2. The 3 h post-dose sitting blood pressures were lowered by 18/14 mm Hg (enalapril) and 20/14 mm Hg (nifedipine), but nifedipine gave greater standing reductions (16/13 mm Hg enalapril, 22/17 mm Hg nifedipine). The dual target blood pressures were achieved by 45% of those taking enalapril monotherapy and 43% of those taking nifedipine monotherapy. At the end of the hydrochlorothiazide phase the dual target pressures were achieved by 63% of the enalapril group and 56% of the nifedipine group. 3. Overall, 17 patients reported adverse events during the placebo run-in. During the active treatment-periods, 42 patients in the enalapril group experienced adverse events, as did 49 of those on nifedipine. Orthostatic effects were confined to those taking enalapril, whereas flushing/erythema, oedema and palpitations were more common in the nifedipine group. 4. Five patients in the enalapril and 14 in the nifedipine groups were withdrawn because of adverse events. One of those withdrawn on enalapril had angioneurotic oedema.(ABSTRACT TRUNCATED AT 250 WORDS)     

Slow release nifedipine and atenolol as initial treatment in blacks with malignant hypertension.

We have compared the efficacy and safety of slow release nifedipine and atenolol given orally as initial treatment for malignant hypertension. Twenty consecutive black patients with untreated malignant hypertension, whose diastolic pressure remained greater than 120 mm Hg after 3 h bed rest, were randomized to receive either slow release nifedipine 40 mg at 1 and 12 h, or atenolol 100 mg at 0 h only. Patients remained supine throughout the study. Blood pressure was measured using a semi-automatic recorder (Omega 1000) at 15 min intervals from -3 to 24 h. Baseline blood pressure was similar in the nifedipine (233/142 mm Hg) and atenolol (226/141 mm Hg) groups. The rate of fall of pressure was greater after nifedipine whose maximum hypotensive effect occurred 4-5 h after each dose. Blood pressure decreased more slowly and more enduringly after atenolol, although the extent of fall was the same (delta BP 5 h after first dose nifedipine = 67/41 mm Hg; delta BP 16 h after atenolol = 64/40 mm Hg). There were no precipitous falls in pressure. No patient developed focal neurological signs, nor was heart failure precipitated by either form of treatment. These results support recommendations that most patients with malignant hypertension can be managed without recourse to parenteral therapy.     

A cross-over study comparing the efficacy of a combination of atenolol and nifedipine at different doses in angina pectoris

Summary

Although the combined administration of atenolol and nifedipine has been shown to be effective in the treatment of angina pectoris the optimum dosage level of the combination has not yet been established. A double-blind, randomly assigned three period cross-over study was carried out therefore to investigate the effects of different daily doses of a fixed combination of 50?mg atenolol and 20?mg sustained-release nifedipine per capsule. Twenty-one patients with stable angina pectoris were randomized, after a 2-week run-in period, to receive treatment for 4 weeks with either 1 capsule twice daily (A), 2 capsules in the morning and 1 in the evening (B), or 2 capsules twice daily (C). A treadmill exercise tolerance test was performed together with a clinical evaluation after the run-in and each of the three treatment periods. Analysis of the results from the 19 patients who completed the study revealed there were no significant differences between the three treatment periods with respect to the general exercise test parameters, number of anginal attacks per week or nitrate consumption. Few side-effects were reported and were only mild in nature. On these findings, therefore, there would appear to be little justification for increasing the dose of the combination above the equivalent of treatment A.     

Antihypertensive Effect and Tolerability of Perindopril in Indian Hypertensive and Type 2 Diabetic Patients: 1-Year Randomised, Double-Blind, Parallel Study vs Atenolol

OBJECTIVE: This study compared the antihypertensive effect and acceptability of a perindopril-based group with that of an atenolol-based group in Indian hypertensive type 2 (non-insulin-dependent) diabetic patients. DESIGN AND SETTING: 100 ambulant patients aged between 35 and 69 years were recruited into this monocentric, randomised, double-blind study in two parallel groups for 1 year after a 1-month washout period on placebo. The setting was a tertiary care institution. PATIENTS: All patients had stable, essential hypertension between 95mm Hg and 115mm Hg, type 2 diabetes with glycosylated haemoglobin (HbA(1C)) <12%, and albuminuria between 300mg and 3.5g/24 hours. There were 50 patients per treatment group and two patient population groups were studied, intention-to-treat (ITT) and per-protocol (PP). The former constituted all patients, whilst the latter included those without major protocol deviation and who completed the 12-month study. INTERVENTIONS: The study drugs were perindopril 4 to 8mg once daily or atenolol 50 to 100mg once daily. In each group therapeutic adjustment was planned by doubling the dose and then by the addition of hydrochlorothiazide 25mg daily. Nifedipine 30 to 60mg daily was subsequently added if the desired drop in blood pressure was not obtained. The ITT group was analysed by Student's t-test, and a 2-way analysis of variance was performed for the PP population. MAIN OUTCOME MEASURES: A comparison of the control of hypertension, biochemical abnormalities, blood sugar and adverse effects was performed in the atenolol group versus the perindopril group. RESULTS: On single-dose therapy after 1 month 17 patients (60%) had normal blood pressure [diastolic blood pressure (DBP) 相似文献   

Comparison of quinapril and atenolol as single drugs or in combination with hydrochlorothiazide in moderate to severe hypertensives, using automated ambulatory monitoring.

1. Forty patients with moderate to severe hypertension and daytime ambulatory diastolic blood pressure > or = 90 mm Hg were randomized double-blind to once-daily treatment with either quinapril up to 20 mg (n = 20) or atenolol up to 100 mg (n = 20) as single drugs or in combination with hydrochlorothiazide 25 mg over a period of 12 weeks. 2. Conventional and ambulatory blood pressure, heart rate, side effects and metabolic changes were compared at the end of the run-in period on placebo, after 4 weeks on monotherapy and at the end of the 12-week period of active treatment. 3. Quinapril and atenolol reduced conventional blood pressure equally with substantial additional effect seen on combination therapy. The two regimens induced a significant decrease in ambulatory BP. However, the atenolol treated ambulatory hypertensive group experienced significantly greater decreases in diastolic blood pressure during 24 h, awake and sleep periods than did the quinapril group. 4. Adverse reactions were mild with both drugs except for severe Raynaud phenomenon in one patient in the atenolol group. Triglyceride levels were significantly increased with atenolol alone and in combination with hydrochlorothiazide. 5. Thus, within the limits of the dose ranges tested, quinapril and atenolol as single drugs or in combination with hydrochlorothiazide reduce significantly conventional and ambulatory blood pressure in moderate to severe hypertensives, but atenolol is more effective in reducing ambulatory diastolic blood pressure.     

Antihypertensive effects of a new sustained-release formulation of nifedipine

The blood pressure response to a new sustained-release formulation of nifedipine was evaluated in an 8-week, double-blind, placebo-controlled study. Twenty-nine patients with mild essential hypertension were randomized to receive placebo (N = 9), 30 mg nifedipine (N = 10), or 60 mg nifedipine (N = 10). During treatment, 30-mg and 60-mg doses of nifedipine administered once daily decreased office blood pressures from 137/98 +/- 8/2 mm Hg and 141/98 +/- 15/2 mm Hg at baseline, respectively, to 126/89 +/- 9/7 mm Hg and 126/86 +/- 6/7 mm Hg (P less than .005). Noninvasive automatic ambulatory blood pressure monitoring demonstrated a marginally significant (P less than .10) reduction in the mean 24-hour blood pressure of 2/6 +/- 8/8 mm Hg and 5/6 +/- 9/9 mm Hg for patients taking 30 mg and 60 mg nifedipine once daily, respectively. Diastolic blood pressure load (the percentage of ambulatory diastolic blood pressure readings greater than 90 mm Hg) during 24 hours was decreased by 41% and 35%, with 30 mg and 60 mg nifedipine administered once daily, respectively. No significant dose response to nifedipine at these dose levels was observed. Although the once-daily formulation of nifedipine achieved effective control of office blood pressure, similar control was not observed in awake and 24-hour periods in all patients.     

Effect of the combination of alinidine and other anti-anginal drugs on heart rate and blood pressure in healthy volunteers.

1. Heart rate and blood pressure changes following the administration of alinidine 30 mg alone and in combination with atenolol 25 mg, nifedipine retard 20 mg and glyceryl trinitrate 500 micrograms were investigated in three groups of six healthy male volunteers. 2. Concomitant administration of alinidine and atenolol reduced (P less than 0.05) supine, standing and exercise heart rate when compared with alinidine alone. The maximum reduction in exercise heart rate was 116 +/- 2.4 beats min-1 for the combination vs 129.0 +/- 3.1 beats min-1 for alinidine alone. 3. Supine (3, 4, 8 h) and standing (2 h) systolic BP were also reduced (P less than 0.05) with the alinidine and atenolol combination compared with alinidine alone. Little change occurred in diastolic blood pressure. 4. Alinidine and nifedipine in combination reduced (P less than 0.05) the nifedipine induced increase in heart rate in the supine (2, 4 h) and standing (4 h) position and following exercise (2, 4 h). No further decreases in systolic and diastolic blood pressure occurred with the combination. 5. Alinidine administered 2 h before a glyceryl trinitrate challenge reduced (P less than 0.05) the glyceryl trinitrate induced increase in standing heart rate at all time intervals (1 to 6 min); the maximum reduction occurred at 3 min (105.0 +/- 4.3 (glyceryl trinitrate) vs 86.8 +/- 6.7 beats min-1 (combination]. Systolic blood pressure was further reduced at all time intervals with glyceryl trinitrate taken in the presence of alinidine.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of the combination of low-dose nifedipine GITS 20 mg and losartan 50 mg in patients with mild to moderate hypertension

Most hypertensive patients require more than one medication to effectively control elevated blood pressure (BP) values. This multicenter, randomized, double-blind study was aimed at testing the efficacy and safety of the combination of low-dose nifedipine GITS 20 mg/ losartan 50 mg compared with either monotherapy in patients with grade 1 to 3 hypertension over an eight-week period. Of 352 patients enrolled in the study, 300 were randomized. All the three treatments lowered elevated BP without clinically relevant changes in heart rate. All the three treatments lowered mean 24-hour diastolic BP: nifedipine GITS/losartan -10.6 mm Hg, losartan -5.4 mm Hg, nifedipine GITS 20 mg -8.0 mm Hg. There was a statistically significant difference of diastolic BP change between patients receiving losartan compared with those receiving combination treatment (P < 0.05). Diastolic BP trough-to-peak ratio and smoothness index were highest in the patient group receiving combination therapy (70%). Nifedipine GITS monotherapy had the highest systolic BP trough-to-peak ratio of all treatment arms (78%) and higher diastolic BP trough-to-peak ratio and smoothness index than losartan monotherapy. All treatments were safe. These data provide evidence that in hypertensive patients combination of nifedipine GITS 20 mg and losartan 50 mg improves control of systolic and diastolic BP compared with either monotherapy.     

Long-acting lacidipine versus short-acting nifedipine in the treatment of asymptomatic acute blood pressure increase

We compared antihypertensive efficacy and safety of a single administration of equipotent doses of lacidipine versus nifedipine in the hypertensive urgencies. Twenty-nine asymptomatic essential hypertensive patients (nine men, 20 women) with a mean age of 55.03+/-11.19 years and baseline diastolic blood pressure (DBP) of > or =120 mm Hg after resting 30 min, not taking antihypertensive drugs for the last 24 h, were randomized in a single-blind fashion to receive lacidipine, 4 mg (LCD, 15 patients) or short-acting nifedipine, 20 mg (NFD, 14 patients) in a single dose. Blood pressure (BP) and heart rate (HR) were taken every 30 min during the first 8 h and every 2 h until 24 h of follow-up. Baseline BP values were similar in the two groups (LCD, 222.5+/-32.8/124.6+/-8.4 mm Hg vs. NFD, 215.9+/-20.6/128+/-7.7 mm Hg; p = NS). Both drugs promoted a significant reduction of systolic blood pressure (SBP; 169.6+/-27.8 vs. 170.6+/-25.3 mm Hg) and diastolic blood pressure (DBP; 104.1+/-16 vs. 102.9+/-12.4 mm Hg) after 8 h. However, either SBP (165+/-27.3 vs. 190.6+/-18.2 mm Hg; p = 0.008) and DBP (99.9+/-12.3 vs. 117.2+/-11.4 mm Hg; p = 0.001) were significantly higher in the NFD group after 24-h dosing. Eleven patients in the LCD group had a decrease in BP >25% of the baseline value both 8 and 24 h after the dose. Although 10 patients showed the same response in the NFD group 8 h after the dose, only four patients maintained these values at 24 h. One patient treated with NFD had a transient cerebrovascular ischemic attack. No adverse effects were observed in the LCD group. We conclude that the long-acting calcium antagonist lacidipine was more effective than the short-acting nifedipine in both controlling BP and maintaining this BP reduction over 8 h in essential hypertensive patients with acute asymptomatic BP increase.     

Felodipine vs hydralazine: a controlled trial as third line therapy in hypertension. Cooperative Study Group.

In a placebo-controlled, double-blind, randomized, parallel group study one hundred and one patients with supine diastolic blood pressure greater than or equal to 100 mm Hg phase V, despite treatment with atenolol 100 mg plus chlorthalidone 25 mg once daily also received either felodipine 5-20 mg twice daily or hydralazine 25-100 mg twice daily for 6 weeks. Felodipine achieved a lower supine blood pressure (mean +/- s.d. 177/108 +/- 29/8-138/82 +/- 19/8 mm Hg) than hydralazine (174/109 +/- 25/8-149/92 +/- 26/11 mm Hg), (P less than 0.05/P less than 0.001). Felodipine also lowered supine diastolic blood pressure to less than 90 mm Hg more often than hydralazine (42 vs 22 patients, P less than 0.001). The incidence of unwanted effects was similar in both groups. The felodipine treated patients experienced more ankle swelling and flushing than those in the hydralazine group who experienced more headache and minor gastro-intestinal upset.     

A comparison of bisoprolol and atenolol in the treatment of mild to moderate hypertension.

1. Fourteen patients (mean age 56.0, range 37-61 years; eight females) with mild essential hypertension (DBP greater than 90 mm Hg on placebo) completed a randomised, double-blind placebo controlled crossover study comparing the hypotensive effects of bisoprolol (10-20 mg) and atenolol (50-100 mg) each taken once daily. 2. Bisoprolol had a significantly greater antihypertensive effect than atenolol, reducing sitting blood pressures by 15.9 mm Hg (diastolic) and 21.9 mm Hg (systolic) compared with placebo. Corresponding figures for atenolol were 10.7 and 5.7 mm Hg respectively. Bisoprolol reduced standing blood pressures by 15.9 mm Hg (diastolic) and 22.8 mm Hg (systolic) compared with 7.3 and 8.6 mm Hg respectively for atenolol. 3. Examination of the pharmacokinetic data showed that bisoprolol had a median elimination half-life of 11.2 h during chronic dosing, compared with 6.4 h for atenolol. For bisoprolol, the median clearance fell from 264 ml min-1 after a single dose to 212 ml min-1 during chronic dosing, although clinically significant accumulation would not be expected during chronic administration. 4. Overall, the results suggest that bisoprolol may be a more effective antihypertensive agent than atenolol but larger studies are necessary to confirm these findings.     

Slow release nifedipine plus atenolol in chronic stable angina pectoris.

1. The effects of adding slow release nifedipine in doses of 20 mg and 40 mg twice daily to atenolol therapy (50 mg twice daily) were assessed in 18 patients with chronic stable angina. 2. The addition of the lower dose of nifedipine to atenolol did not significantly alter the weekly consumption of glyceryl trinitrate or the mean number of anginal attacks as assessed by diary cards. However, 2 h after dosing there was a significant prolongation during stress testing in the time to onset of both 1 mm ST depression on the ECG (by 28%) and to angina (by 37%) compared with atenolol alone, but no benefit was apparent by 12 h after dosing. 3. At a dose of 40 mg twice daily, nifedipine significantly reduced glyceryl trinitrate consumption by 25% and the number of anginal attacks by 36%. The times to onset of ST depression and angina were increased by 37% and 55% respectively at 2 h and by 24% and 26% respectively 12 h after dosing. 4. Analysis of the frequency distribution of anginal attacks showed decreasing efficacy with time after administration of nifedipine. The overall results also suggest a relationship between efficacy and the plasma nifedipine concentration, with a mean 20% improvement in time to development of angina occurring at a nifedipine plasma concentration of approximately 30-40 ng ml-1. 5. In conclusion, the reduction of effort-related angina by nifedipine is related to its plasma concentration and the effective duration of action of the 20 mg slow release formulation is less than 12 h.     

Atenolol and chlorthalidone in combination for hypertension.

1 The hypotensive effect of single daily dosing with atenolol 100 mg and chlorthalidone 25 mg given alone or in combination has been assessed in a double-blind, crossover, placebo controlled trial in fifteen hypertensive patients. 2 Average lying blood pressures were: Placebo 155.4/103.9 mm Hg, atenolol 134.6/85.8 mm Hg, chlorthalidone 139.5/90.1 mm Hg, combination 127.7/82.5 mm Hg. 3 The effect of the combination therapy in reducing lying diastolic pressure compared with placebo (a fall of 21.4 mm Hg) was significantly less than the 31.9 mm Hg fall predicted from the sum of the individual effects (P = 0.01). 4 Observations on blood pressure at rest and under mental, isometric and bicycle ergometer stress were made pre-dose and post-dose for a 12 h period at the end of the last treatment period. 5 Lying blood pressure declined from the zero hour (pre-dose) reading on all treatments to a low at 15.00--18.00 h and then rose again. 6 The rise in systolic blood pressure after isometric exercise and mental stress was of a similar magnitude with all four treatment regimes. 7 Atenolol, alone and in combination with chlorthalidone, reduced the blood pressure and the pulse rate increase on exercise 2 h post-dose when compared with readings 24 h post-dose. 8 Once daily dosing with a combination of atenolol and chlorthalidone produced a fall in supine blood pressure over a 24 h period but the effect on exercise induced changes was not uniform over this period.     

Lercanidipine : a review of its efficacy in the management of hypertension

Lercanidipine (Zanidip) is a vasoselective dihydropyridine calcium channel antagonist that causes systemic vasodilation by blocking the influx of calcium ions through L-type calcium channels in cell membranes. It is a highly lipophilic drug that exhibits a slower onset and longer duration of action than other calcium channel antagonists. Furthermore, lercanidipine may have antiatherogenic activity unrelated to its antihypertensive effect.In two large, nonblind, noncomparative studies involving approximately 16 000 patients with mild-to-moderate hypertension, systolic blood pressure (BP) [SBP] and diastolic BP (DBP) were significantly reduced after 12 weeks' treatment with lercanidipine 10-20 mg/day. Furthermore, in the largest study, 64% of patients were responders (DBP <90 mm Hg) after 12 weeks of treatment and an additional 32% had their BP normalised (BP <140/90 mm Hg). In comparative trials, lercanidipine 10-20 mg/day was as effective as nifedipine slow release (SR) 20-40 mg twice daily, amlodipine 10 mg/day, felodipine 10-20 mg/day, nifedipine gastrointestinal therapeutic system (GITS) 30-60 mg once daily or verapamil SR 240 mg/day at reducing SBP and DBP in patients with mild-to-moderate hypertension after 2-16 weeks of therapy. In addition, 4 weeks of lercanidipine therapy (10 mg/day) was as effective as captopril 25mg twice daily, atenolol 50 mg/day or hydrochlorothiazide 12.5 mg/day.Lercanidipine 5-30 mg/day effectively decreased BP in elderly patients (aged >60 years) with mild-to-moderate hypertension or isolated systolic hypertension to the same extent as amlodipine 5-10 mg/day, nifedipine GITS 30-60 mg/day or lacidipine 2-4 mg/day after 24-26 weeks of therapy. In addition, a limited number of studies suggest that lercanidipine may have antihypertensive efficacy in patients with severe or resistant hypertension, in hypertensive patients with type 2 diabetes mellitus and in postmenopausal women with mild-to-moderate essential hypertension. Lercanidipine is well tolerated, with most treatment-emergent events related to vasodilation. Common adverse events included headache, flushing and peripheral oedema. Importantly, the incidence of vasodilatory oedema was significantly lower in patients receiving lercanidipine than in those receiving some other calcium channel antagonists. CONCLUSION: Once-daily lercanidipine is an effective and well tolerated antihypertensive agent in patients with mild-to-moderate hypertension.     

The efficacy and tolerability of atenolol,nifedipine, and their combination in the management of hypertension

Summary In this randomized, double-blind, crossover study we investigated the haemodynamic effects of a beta-blocker (atenolol 50 mg) and a calcium antagonist (nifedipine SR 20 mg) given either separately or in combination in three groups of hypertensive patients. Each treatment was administered twice daily.The fixed combination given twice daily for four weeks produced reductions in blood pressure which lasted for at least 12 h after administration of the last dose. The control of blood pressure by the combination was superior to that achieved by its individual components.Adverse effects normally associated with nifedipine were less frequent when it was given with atenolol. Compliance with treatment was good, but best when the drugs were given together rather than separately.A fixed combination of atenolol and nifedipine may prove useful in treating hypertensive patients inadequately controlled on beta-blocker therapy alone.     

Serotonergic blockade compared with beta-adrenergic blockade in systemic hypertension: a double-blind comparison of ketanserin with propranolol

The safety and efficacy of ketanserin, a competitive serotonin blocking agent, and propranolol were compared in 33 patients with mild to moderate hypertension (sitting diastolic blood pressure [DBP] 95-115 mm Hg) using a placebo run-in, randomized, double-blind parallel study design. All patients received placebo for 4 weeks, then were randomized to receive increasing doses of either ketanserin (20, 40 mg twice daily) or propranolol (40, 80 mg twice daily) to achieve a goal sitting DBP less than 90 mm Hg. Patients not achieving the goal blood pressure with either drug as monotherapy, received the other drug in combination. At the end of the active monotherapy phase (week 10 of the study), propranolol demonstrated a greater decrease in DBP from baseline, as compared to ketanserin (-7.9 +/- 10.9 mm Hg with propranolol, P less than 0.05; -1.0 +/- 7.2 mm Hg with ketanserin, P = NS). Four out of 16 patients achieved goal response on propranolol, compared to 3/17 for ketanserin. With combination treatment, 9/18 patients reached the goal response; the addition of propranolol to ketanserin in non-responders resulted in further reduction of sitting DBP of -10.3 +/- 6.3 compared to monotherapy (P less than 0.001), while the addition of ketanserin to non-responders produced no significant response in sitting DBP. Propranolol showed a consistent effect in slowing heart rate. Ketanserin displayed less frequent side effects than propranolol. Propranolol used twice daily appears to be more effective than twice daily ketanserin use in patients with mild to moderate hypertension.     

Metabolic effects of combined antihypertensive treatment in patients with essential hypertension

Single-drug treatment of essential hypertension (HT) is often insufficient to normalize blood pressure (BP), and high doses of antihypertensive agents can have adverse effects on glucose tolerance (GT) and insulin sensitivity. This study tested whether aggressive BP lowering with combination treatment had any influence on GT or insulin action. In all, 29 nonobese (body mass index [BMI], <30 kg/m ), normolipidemic patients with established HT (159 +/- 3/99 +/- 1 mm Hg) but normal GT were recruited. Eleven normotensive (125 +/- 3/85 +/- 1 mm Hg) subjects were matched to the patients for both anthropometric and metabolic variables. Following baseline studies (serum lipid profile, oral GT, insulin release, and insulin sensitivity assessed by the insulin clamp technique), patients were randomized in a double-blind fashion to two combination regimens (verapamil 180 mg/day + trandolapril 2 mg/day or atenolol 50 mg/day + nifedipine 20 mg/day) and restudied 3 months later. Blood pressure was normalized in both groups (with decrements of 25 +/- 5/17 +/- 2 and 29 +/- 3/15 +/- 2 mm Hg, respectively). Lipid profile, GT, insulin release, and insulin sensitivity of both glucose uptake and lipolysis were unchanged following both treatments. The authors conclude that in nonobese, normolipidemic, glucose-tolerant hypertensive patients, BP normalization with combination therapy is feasible at no cost in terms of undesired effects on glucose and lipid metabolism and insulin sensitivity.     

Combination of lisinopril and nifedipine GITS increases blood pressure control compared with single drugs in essential hypertensive patients

The present study was designed to evaluate the effect of combination therapy using the angiotensin-converting enzyme-inhibitor lisinopril and the dihydropyridine calcium antagonist nifedipine GITS on the degree and homogeneity of 24-hour blood pressure reduction in essential hypertensive patients. After a 4-week placebo run-in period, 51 patients (mean age, 54.4 +/- 9.4 years) with essential hypertension and clinic diastolic blood pressure between 105 and 115 mm Hg were randomized to 4-week treatment with lisinopril (20 mg), nifedipine GITS (30 mg), or their combination according to a multicenter, randomized, double-blind, crossover study. Trough clinic blood pressure and 24-hour ambulatory blood pressure were measured at the end of the run-in period and after 4 weeks of treatment. In addition to clinic and 24-hour average blood pressure reduction, the trough-to-peak ratio and the smoothness index, a new measure for the homogeneity of blood pressure reduction, were also calculated. Although both lisinopril and nifedipine GITS produced a significant reduction in clinic and 24-hour average blood pressure values, the reduction obtained with the combination was significantly (P < 0.001) greater. Moreover, the combination therapy increased (P < 0.01) the smoothness index as compared with each single drug for both systolic (lisinopril, 1.02; nifedipine GITS, 1.1; combination, 1.76) and diastolic (lisinopril, 0.98; nifedipine GITS, 0.87; combination, 1.54) blood pressure values, whereas trough-to-peak ratio values (expressed as median) for systolic (lisinopril, 0.41; nifedipine GITS, 0.52; combination, 0.55) and diastolic (lisinopril, 0.35; nifedipine GITS, 0.40; combination, 0.49) blood pressure values were not significantly increased by the combination therapy. Thus, antihypertensive treatment with the combination of lisinopril and nifedipine GITS is more effective and balanced over the 24 hours than the combination components administered alone, confirming that the smoothness index is superior to the trough-to-peak ratio in assessing homogeneity of pharmacologic blood pressure reduction.     

The effect of ageing on the disposition of nifedipine and atenolol.

1. Healthy young and elderly volunteers received 20 mg nifedipine (slow release) orally for 2 weeks with concomitant dosing of atenolol 50 mg orally during the second week. 2. Drug kinetics and dynamics were compared between the groups after a single dose of nifedipine (day 1), after chronic dosing for 1 week (day 8), and following concomitant daily dosing of atenolol (day 15). 3. Plasma profiles of nifedipine were similar within each group on each of the 3 sampling days. The elderly group had higher plasma concentrations from about 6 h but there was no difference in the maximum concentrations achieved. The half-life in the elderly was significantly longer (8.8 +/- 0.9 h) compared with that in the young (5.8 +/- 1.1 h) (P less than 0.01). 4. Blood concentrations of atenolol were higher in the elderly at 12 and 24 h post-dose (P less than 0.001) and the AUC was greater than in the young (P less than 0.001). 5. Systolic blood pressure was reduced by nifedipine in both groups but to a greater extent in the elderly (P less than 0.01); differences in diastolic blood pressure were not significant. Blood pressure was reduced further by the addition of atenolol. Atenolol reduced the heart rate in all subjects.