Long-term antihypertensive effects and safety of nitrendipine in patients with mild, moderate, and severe hypertension

A study of 31 patients with mild or moderate hypertension and 17 patients with severe hypertension was conducted to evaluate the long-term safety and efficacy of nitrendipine, a new calcium channel blocker with a long duration of action. Nitrendipine (5-40 mg bid) was given as monotherapy or in combination with hydrochlorothiazide and/or propranolol. Seventeen patients (54%) with mild to moderate hypertension were controlled with nitrendipine alone, but all except one patient with severe hypertension required combination therapy. In patients with mild or moderate hypertension, nitrendipine reduced supine blood pressure from a baseline mean 154/100 mm Hg to 136/87 mm Hg after 1 year of treatment (P less than .05). In patients with severe hypertension, supine blood pressure was reduced from 186/124 mm Hg to 148/91 mm Hg by the end of the planned treatment period (P less than .05; mean duration, 10 weeks). During extended observation, antihypertensive effect was sustained for up to 2.5 years and 1.6 years in patients with mild or moderate and severe hypertension, respectively. Nitrendipine was well tolerated; and only one patient, a moderate hypertensive, discontinued treatment because of pedal edema. The results of this long-term study show that nitrendipine alone or in combination with a diuretic and/or a beta blocker is a safe and effective agent for the treatment of patients with all degrees of hypertension.     

Felodipine. A review of the pharmacology and therapeutic use of the extended release formulation in cardiovascular disorders.

Felodipine is a vascular-selective, dihydropyridine calcium antagonist previously investigated as a conventional tablet formulation administered twice daily. More recently considerable experience has been gained with an extended release (ER) formulation which has the convenience of once daily administration. Felodipine ER has been well studied in patients with essential hypertension. As monotherapy in mild to moderate essential hypertension, felodipine ER is at least as effective in reducing blood pressure as other calcium antagonists, beta-blockers, diuretics and ACE inhibitors, with some results favouring felodipine ER at a statistically significant level at the dosages used. It is also effective combined with controlled release metoprolol or enalapril in patients with mild to moderate essential hypertension. In patients with more severe forms of essential hypertension uncontrolled by beta-blocker and/or diuretic therapy, felodipine ER was effective as an 'add-on' therapy in placebo-controlled trials, and, at the dosages used, more effective than either sustained release nifedipine or nitrendipine. Felodipine produces effective control of blood pressure without negative effects on cardiac performance. In addition to its antihypertensive action, results suggest that felodipine therapy is associated with significant regression of left ventricular hypertrophy. Furthermore, it appears suitable for use in patients with concomitant diabetes, renal dysfunction or asthma, and is also being investigated for use in patients with congestive heart failure or angina pectoris. Felodipine ER is an effective drug for the treatment of all grades of essential hypertension, and can be used both as monotherapy and in combination with other antihypertensive agents. Further clinical experience should fully establish the long term tolerability of felodipine ER and consequently its place in therapy relative to other accepted antihypertensive drugs. However, with the convenience of once daily administration, felodipine ER is a worthwhile innovation in the treatment of hypertension.     

An open, parallel, comparative evaluation of amlodipine and nitrendipine in the monotherapeutic treatment of mild and moderate essential hypertension

The efficacy and safety of the dihydropyridine calcium antagonists amlodipine and nitrendipine as single-agent therapy of mild to moderate hypertension were compared in an open, parallel-group study. Interim analysis of data from 74 patients (43 male, 31 female) from an expected final total of 96 patients is reported. Amlodipine normalized blood pressure (< or = 90 mm Hg) in 94.7% of patients with a mean final dose of 8.3 mg/day, compared with normalization of blood pressure in 83.3% of patients treated with nitrendipine with a mean final dose of 28.3 mg/day. Only nitrendipine produced a statistically significant increase in heart rate after 2 and 4 weeks of therapy. Nitrendipine-treated patients reported more adverse events (47.2%) than the amlodipine-treated group (26.3%). Two patients from the nitrendipine group discontinued treatment due to treatment-related adverse events and one patient required a dose reduction. In the amlodipine-treated group, all adverse events were mild to moderate and dose reduction was required in one patient. In conclusion, although amlodipine and nitrendipine have comparable antihypertensive efficacy, in this study amlodipine was associated with fewer adverse effects.     

Once- and twice-daily nitrendipine in patients with hypertension and noninsulin-dependent diabetes

One hundred and six patients with uncomplicated mild to moderate essential hypertension received nitrendipine 10 mg twice a day or 20 mg once a day in a double-blind, randomized design. At the end of the dosing interval, supine and standing blood pressures were lowered 6/4 and 6/3 mm Hg respectively with the former regimen, and 2/3 mm Hg with the latter. In 10 patients, blood pressure variability through the dosing interval was not increased by nitrendipine 10 mg twice daily, but in another 10, 20 mg daily increased the variability by 28% compared to placebo. Significantly more patients had adverse effects with 20 mg daily than 10 mg twice daily; and both regimens caused more side effects than placebo. In 20 patients, serum glucose levels did not change significantly during treatment with nitrendipine, but in 10 of those with noninsulin-dependent diabetes, the range of maximum plasma insulin in response to a high-carbohydrate meal was 7 times as great during treatment with nitrendipine as it was during treatment with placebo. Nitrendipine lowers blood pressure when given once or twice daily, but twice-daily administration appears to be better tolerated.     

Nisoldipine. A preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in the treatment of angina pectoris, hypertension and related cardiovascular disorders

Nisoldipine is an orally administered calcium entry blocking drug structurally related to nifedipine. In limited clinical trials it has been shown to be effective and relatively well tolerated in the treatment of patients with chronic stable angina pectoris and mild to moderate essential hypertension. As for all dihydropyridine-calcium antagonists, its major properties include potent peripheral and coronary vasodilation and improvement in myocardial oxygen supply relative to demand. These actions occur without depression of cardiac conduction or left ventricular function. Short term clinical trials have shown nisoldipine to produce both symptomatic and objective improvements in patients with chronic angina of effort and have suggested a benefit in vasospastic angina. A small number of comparative trials indicate that nisoldipine is equally as effective as nifedipine. In addition, in combination with beta-adrenoceptor blockade nisoldipine appears to offer additional benefit compared with beta-blockade alone and is well tolerated. In patients with mild to moderate essential hypertension nisoldipine monotherapy, in 1 or 2 daily doses, has maintained blood pressure control and has also been a useful addition to diuretics and beta-adrenoceptor blocking drugs in patients with poorly controlled disease. Side effects appear to be dose related, generally mild and transient, and are primarily those resulting from potent peripheral vasodilation - headache, flushing and pretibial or ankle oedema. Although studies to date are promising, there are no published long term studies (greater than 1 year) of nisoldipine in comparison with other calcium entry blockers and other drugs currently in clinical use for the treatment of angina pectoris or hypertension. Until such studies are completed the exact place of nisoldipine in the treatment of these diseases remains to be established.     

Pinacidil. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in the treatment of hypertension

Pinacidil is an orally administered antihypertensive drug that acts via direct relaxation of vascular smooth muscle to produce peripheral vasodilatation and a reduction in blood pressure without significant direct effects on cardiac electrophysiology. Pinacidil is unrelated to other antihypertensive drugs in clinical use, either in structure or mechanism of action. It belongs to a new class of agents called 'potassium channel openers' which act via potassium efflux to hyperpolarize cell membranes, indirectly causing a net reduction in intracellular calcium that leads to relaxation of vascular smooth muscle. Pinacidil is indicated in the management of essential hypertension. In clinical trials of up to 1 year duration, pinacidil administered twice daily in a controlled release capsule formulation has been shown to achieve adequate blood pressure control both in previously untreated patients and in those with blood pressure inadequately controlled by beta-adrenoceptor blocking drugs or thiazide diuretics. In long term (up to 1 year) comparative studies pinacidil was at least as effective as hydralazine, prazosin or nifedipine in maintaining blood pressure control. Pinacidil may also have a potential use in the treatment of patients with secondary renal hypertension. Clinical trials to date have usually allowed the addition of a thiazide diuretic and/or beta-adrenoceptor blocking drug to enhance the efficacy of pinacidil and/or to reduce the incidence of adverse effects. The main adverse effects of pinacidil treatment, which result from its peripheral vasodilator activity, are headache, oedema, palpitations and tachycardia. Although the overall incidence of adverse effects is quite high, they are usually mild, transient in nature and respond to a reduction in dose. Nevertheless, these effects may occasionally be severe, necessitating withdrawal from therapy. Thus, pinacidil is an effective antihypertensive drug for the treatment of mild to moderate essential hypertension. Despite its novel mechanism of action pinacidil causes adverse effects typical of peripheral vasodilators; during long term use with twice daily administration of the controlled release capsule formulation, the addition of a diuretic is often necessary to attenuate peripheral oedema and maintain adequate control of blood pressure. Further long term controlled trials are needed to determine the precise role of pinacidil relative to that of the angiotensin converting enzyme (ACE) inhibitors and calcium channel blocking drugs.     

Age related antihypertensive effect of nitrendipine,a new calcium entry blocking agent

Summary The effect of nitrendipine 20 mg o.d., a new calcium entry blocker similar in structure to nifedipine, on blood pressure has been evaluated in 14 patients (aged 24–62 years) with uncomplicated mild or moderate arterial hypertension. A significant decrease both in systolic (160±12 at baseline vs 141±8 mm Hg, p<0.001) and diastolic (106±8 vs 93±3 mm Hg, p<0.001) blood pressure was observed at the end of 8 weeks of nitrendipine treatment. An inverse correlation was found between age and the reduction in diastolic blood pressure (r=0.772, p<0.001 as absolute reduction; r=0.791, p<0.001 as percentage reduction versus baseline). This peculiar characteristic differentiates the effect of nitrendipine from that of other calcium entry blockers, which appear to be more effective in older patients.     

Atenolol. A reappraisal of its pharmacological properties and therapeutic use in cardiovascular disorders.

Atenolol is a selective beta 1-adrenoceptor antagonist with a duration of activity of at least 24 hours. The scope of therapeutic use of the drug has been expanded and become better defined since it was first reviewed in the Journal in 1979. Atenolol is effective and generally well tolerated in patients with all grades of hypertension. Data from comparative studies show that when administered orally, atenolol reduces blood pressure to a similar extent, and in a similar proportion of patients, as usual therapeutic doses of other beta-adrenoceptor antagonists (such as acebutolol, celiprolol, betaxolol, indenolol, metoprolol, nadolol, pindolol, propranolol, tertatolol), angiotensin converting enzyme (ACE) inhibitors (e.g. captopril, enalapril and lisinopril), calcium antagonists (e.g. amlodipine, diltiazem, felodipine, isradipine, nitrendipine, nifedipine, verapamil), doxazosin, ketanserin and alpha-methyldopa. Atenolol effectively lowers blood pressure in elderly patients with hypertension and in women with hypertension associated with pregnancy, and improves objective and subjective indices in patients with stable angina pectoris. Oral atenolol is used for preventing recurrence of supraventricular arrhythmias once control is achieved by intravenous administration of atenolol. Early intervention with intravenous atenolol followed by oral maintenance therapy reduces infarct recurrence and cardiovascular mortality in patients with known or suspected myocardial infarction. There is also encouraging evidence of reduced mortality from cardiovascular disease during long term therapy with atenolol in patients with hypertension. Atenolol is well tolerated in most patients. Increases in plasma levels of both total triglycerides and very low density lipoprotein (VLDL) triglycerides have accompanied atenolol therapy although the clinical relevance, if any, of longer term metabolic effects has yet to be determined. Its low lipid solubility and limited brain penetration results in a lower incidence of central nervous system effects than that associated with propranolol. After many years of clinical usage atenolol is a well established treatment option in several areas of cardiovascular medicine such as mild to moderate hypertension and stable angina pectoris. Furthermore, it has also shown potential in the treatment of some cardiac arrhythmias and has been associated with reduced cardiovascular mortality in patients with hypertension and in patients with myocardial infarction.     

Comparison of once daily atenolol, nitrendipine and their combination in mild to moderate essential hypertension.

1. The aim of the study was to compare the efficacy and the tolerability of treatment with atenolol (50-100 mg once daily), nitrendipine (20-40 mg once daily) and their combination (atenolol 50 mg + nitrendipine 20 mg) once daily in patients with mild to moderate essential hypertension. 2. The study was a randomised, double-blind, placebo controlled parallel groups design: blood pressures were measured at 'trough' effect (i.e. 24 h after dosing) to assess the adequacy of once-daily treatment. 3. Mean blood pressures (mm Hg) recorded on four occasions over 12 weeks of treatment were significantly lower both with atenolol (155/97 sitting: 155/104 standing) and with the combination of atenolol plus nitrendipine (153/96 sitting: 152/104 standing) than with placebo (169/108 sitting: 169/114 standing). Nitrendipine alone had no significant effect on blood pressure 24 h after dosing (165/104 sitting: 165/110 standing). 4. Withdrawals due to adverse effects were more common during treatment with nitrendipine: 7/32 of the patients experienced adverse effects attributable to intense systemic vasodilatation (e.g., flushing, erythema, headache). 2/37 patients taking atenolol were withdrawn: one because he developed a psoriatic rash and the other because of impaired peripheral circulation. Of the 35 patients taking combination treatment, two were withdrawn: one developed headaches and dyspnoea, and the other asthma. 5. The results suggest that once daily dosing with nitrendipine does not control blood pressure throughout the 24 h period in the majority of patients, and is associated with a considerable burden of adverse effects. Combination treatment was better tolerated but appeared to offer no advantages over atenolol alone in terms either of blood pressure control or adverse effects.     

缬沙坦长期治疗原发性高血压病人的安全性和疗效

目的 :评估缬沙坦长期治疗原发性高血压的安全性与疗效。方法 :门诊轻、中度高血压的病人3 2例 (男性 2 3例 ,女性 9例 ,年龄 5 1a±s 9a) ,服用缬沙坦 80mg·d-1,wk 4后血压控制不满意者加量至 1 60mg·d-1,共治疗 2 4wk。结果 :舒张压下降程度在治疗后wk 4,8,1 6,2 4末分别为 :1 .6kPa±0 .9kPa,2 .0kPa± 0 .8kPa,2 .1kPa± 1 .0kPa,1 .8kPa± 0 .8kPa,较治疗前差异均有非常显著意义 (P<0 .0 1 )。wk 4,2 4治疗有效率分别为 78%与 75% (P >0 .0 5 )。未见干咳发生 ,不良反应少 ,耐受性良好。结论 :缬沙坦长期治疗轻、中度原发性高血压安全有效     

Effectiveness of a new calcium antagonist in severe hypertension

Nitrendipine is a new nifedipine-like calcium antagonist antihypertensive agent. In this study, nitrendipine 5-40 mg orally bid was administered for up to three months to 16 patients with severe essential hypertension (untreated supine diastolic blood pressure greater than or equal to 115 mm Hg). Hydrochlorothiazide or propranolol or both were also given to patients who did not achieve goal blood pressure with nitrendipine alone. Five patients achieved goal blood pressure (supine less than or equal to 90 mm Hg) with nitrendipine alone and six more after the addition of a second drug, and only four required triple-drug therapy. One patient was terminated from the study because of headaches, a common nitrendipine side effect. This study demonstrates that nitrendipine is an effective and well-tolerated agent in the treatment of severe hypertension.     

缬沙坦对轻中度高血压患者疗效及左室肥厚的影响

目的探讨缬沙坦治疗轻中度原发性高血压病疗效及对左室肥厚的逆转作用。方法门诊确诊40例轻中度高血压病患者在停服各种心血管活性药物2周后服用缬沙坦（80mg／d）4周。所有患者在用药前及治疗后4周末复查动态血压及心脏超声。结果4周末24h收缩压、舒张压,白昼及夜间收缩压、舒张压,收缩压及舒张压负荷均显著降低,P〈0．05。左室质量指数较治疗前降低,P〈0．05。结论缬沙坦对轻中度高血压病患者有明显降压效果。并且可在短期内逆转左室肥厚。     

西尼地平与尼群地平治疗高血压病的疗效比较

目的:比较西尼地平与尼群地平治疗高血压病的疗效及安全性。方法:86例原发性高血压病患者随机均分为西尼地平组和尼群地平组,西尼地平组给予西尼地平,起始剂量为5mg,qd,根据血压可调整至10mg,qd;尼群地平组给予尼群地平,起始剂量为10mg,qd,根据血压可调整至20mg,bid。比较2组的降压疗效及药品不良反应。结果:西尼地平组与尼群地平组的总有效率分别为90.7%和88.4%,2组比较差异无统计学意义(P>0.05);西尼地平组和尼群地平组收缩压的最大降幅分别为(34.2±3.8)和(29.2±2.2)mmHg,舒张压最大降幅分别为(23.8±2.6)和(19.4±2.3)mmHg,差异有统计学意义(P<0.05)。尼群地平组治疗后心率明显快于治疗前及西尼地平组治疗后(P<0.05),但西尼地平组患者心率治疗前、后无显著变化(P>0.05)。治疗过程中2组均未见明显不良反应发生。结论:西尼地平用于治疗高血压疗效与尼群地平相近,但其对患者的心率影响较小。     

二甲双胍联用抗高血压药物长期治疗对高血压患者胰岛素抵抗和代谢的影响

目的研究二甲双胍联合尼群地平和阿替洛尔长期治疗对高血压患者胰岛素抵抗(IR)和代谢的影响.方法111例轻中度高血压病人,随机分为2组,分别用尼群地平和阿替洛尔联合治疗(A组,n=51)和二甲双胍联合尼群地平和阿替洛尔治疗(B组,n=60),疗程14个月.结果降压总有效率,A组较B组低,但无显著性差异(P＞0.05).A组病人治疗后较治疗前体重增加(P＜0.05),胰岛素敏感指数(ISI)无显著变化(P＞0.05),空腹血糖显著升高(P＜0.001),低密度脂蛋白显著升高,高密度脂蛋白/低密度脂蛋白比显著下降.B组病人治疗后较治疗前,体重无显著变化,ISI显著升高(P＜0.05),血糖、高密度脂蛋白/低密度脂蛋白比和血肌酐显著下降(P＜0.05).二甲双胍联合尼群地平和阿替洛尔治疗能更有效地控制血压,预防体重增加,降低IR,改善血糖代谢和肾功能.结论二甲双胍和抗高血压药物联合应用可能是一组好的药物配伍.     

Efficacy and tolerability of amlodipine in patients with mild-to-moderate hypertension.

Twenty-one subjects with mild or moderate systemic hypertension were treated for 12 weeks with amlodipine, a new calcium antagonist of the dihydropyridine group. Initial amlodipine dose was 5 mg once daily, but the dose could be increased after four or eight weeks to 10 mg once daily if diastolic blood pressure was not less than or equal to 90 mmHg (12.0 kPa). At the end of the study, a substantial reduction of systolic blood pressure (20 mmHg-2.7 kPa-from baseline) and diastolic blood pressure (14 mmHg-1.9 kPa-from baseline) was observed. Statistically significant changes in systolic and diastolic blood pressure were produced after four weeks of treatment. There were no statistically significant changes in heart rate throughout the study. Six patients with mild and five patients with moderate hypertension became normotensive after amlodipine treatment (64%). Two with mild hypertension finished the trial without change in hypertensive status, and four with initially moderate hypertension changed to mild at the end of the study. Only one patient dropped out due to an adverse reaction, two adverse events were rated severe, but did not require discontinuation. Overall impressions of efficacy were excellent or good in two-thirds of cases and poor in 10%; overall impressions of toleration were excellent or good in 71% of cases and poor in 10%. It is concluded that amlodipine is useful and well tolerated in patients with mild or moderate hypertension.     

Long-term effect of tiapamil in essential hypertension

To evaluate the long-term effect of tiapamil, a new calcium antagonist, in hypertension, 20 adult patients suffering from mild to moderate hypertension were entered into a 58-week open study. In 10 patients, blood pressure returned to normal within 1-6 weeks with a daily dose of 600-900 mg tiapamil. In the remaining 10 patients, the blood pressure became normal after 8-28 weeks with a daily dose of 900-1,200 mg tiapamil. The more severe the hypertension, the higher the dose needed and the longer the time required for the blood pressure to return to normal. The overall results at the end of the 58-week treatment showed a significant decrease of the blood pressure to 142 (+/- 9)/88 (+/- 4) mmHg from a before treatment average of 166 (+/- 16)/105 (+/- 7) (p less than 0.001). There was no marked difference in the blood pressure between supine and sitting positions before or after treatment. Side effects were mild and self-limiting, with no patient being dropped from the study. Electrocardiogram (ECG) and laboratory values were not affected during the treatment with the exception of a moderate decrease in the blood glucose. Neither plasma renin activity, nor aldosterone concentration, nor serum cholesterol or triglyceride levels were altered during tiapamil administration. Tiapamil appears to be an effective and well-tolerated drug for use in mild to moderately severe hypertension.     

A double-blind randomized cross-over study of the efficacy and tolerability of nifedipine and nitrendipine in the treatment of mild to moderate hypertension.

1. In order to examine whether nitrendipine was superior to slow release nifedipine as monotherapy in the treatment of mild to moderate essential hypertension, the two agents were administered to 22 patients in a double-blind randomized cross-over study, incorporating low and titrated dose regimes. 2. Six patients failed to complete the study because of vasodilator side-effects such as headache, flushing and ankle swelling. Three were taking nitrendipine and three took nifedipine and all withdrawals occurred at the introduction of the drug. 3. Both agents reduced blood pressure in the 16 patients who completed the study, and neither agent was superior to the other; mean blood pressure after the placebo phase was 177 +/- 5.5/100 +/- 2.6 mm Hg supine and 175 +/- 5.3/113 +/- 2.4 mm Hg standing. At the end of therapy with nifedipine pressures were 160 +/- 4.0/91 +/- 3.0 mm Hg supine and 158 +/- 4.6/103 +/- 2.7 mm Hg standing. After 8 weeks treatment with nitrendipine blood pressures were 162 +/- 4.4/90 +/- 2.9 mm Hg supine and 161 +/- 6.2/104 +/- 2.7 mm Hg standing. Comparisons of these attained blood pressures on both agents showed no statistically significant differences. 4. Nitrendipine did not appear to be effective on a once daily basis.     

Manidipine: a review of its use in hypertension.

Manidipine is a dihydropyridine calcium antagonist, which causes systemic vasodilation by inhibiting the voltage-dependent calcium inward currents in smooth muscle cells. The resulting reduction in blood pressure (BP) in patients with hypertension is maintained over 24 hours. Manidipine 10 to 40 mg once daily for 4 weeks significantly lowered office BP from baseline and compared with placebo, and significantly reduced 24-hour BP compared with placebo in patients with essential hypertension in a well controlled trial. The decline in BP was maintained over 24 hours (trough to peak BP ratios were >50%) without disturbing the circadian BP pattern. BP reductions with therapeutic dosages of manidipine were maintained for up to 1 year in noncomparative trials. The BP-lowering capacity of manidipine 5 to 20 mg/day appears to be similar to that of other calcium antagonists with which it has been compared in randomised double-blind and nonblind trial. In a well controlled short term trial, manidipine 10 mg daily significantly decreased trough sitting BP compared with placebo in elderly patients with mild to moderate essential hypertension. Decreases in BP were maintained for up to 3 years of treatment. The drug (10 or 20 mglday) also significantly lowered sitting BP from baseline in patients with hypertension and type 2 diabetes mellitus in randomised, long term comparative trials. In general, the observed reduction in BP with manidipine was similar to that observed with amlodipine, enalapril or delapril. The effects of manidipine on urinary albumin excretion (UAE) have not been clearly demonstrated in clinical trials in this patient group. BP was also reduced with manidipine in patients with impaired glucose tolerance. Manidipine was well tolerated in clinical trials, with most adverse effects related to vasodilation. Commonly reported events included ankle oedema, headache. palpitation. flushing, dizziness, rash and fatigue. Manidipine appears to have less potential for pedal oedema than amlodipine. CONCLUSIONS: Manidipine has shown antihypertensive efficacy and appears to be well tolerated in adult and elderly patients with mild or moderate essential hypertension. The BP-lowering effects of the drug in patients with hypertension and type 2 diabetes mellitus or impaired glucose tolerance were not associated with any adverse metabolic effects. The effects of manidipine on UAE in this patient group remain unclear. Manidipine provides an additional treatment option for patients for whom dihydropyridine calcium antagonists are appropriate. Manidipine is a dihydropyridine calcium antagonist, which causes systemic vasodilation by inhibiting the voltage-dependent calcium inward currents in smooth muscle cells. The resulting reduction in blood pressure (BP) in patients with hypertension is maintained over 24 hours. Manidipine 10 to 40mg once daily for 4 weeks significantly lowered office BP from baseline and compared with placebo, and significantly reduced 24-hour BP compared with placebo in patients with essential hypertension in a well controlled trial. The decline in BP was maintained over 24 hours (trough to peak BP ratios were >50%) without disturbing the circadian BP pattern. BP reductions with therapeutic dosages of manidipine were maintained for up to 1 year in non-comparative trials. The BP-lowering capacity of manidipine 5 to 20 mg/day appears to be similar to that of other calcium antagonists with which it has been compared in randomised double-blind and nonblind trial. In a well controlled short term trial, manidipine 10 mg daily significantly decreased trough sitting BP compared with placebo in elderly patients with mild to moderate essential hypertension. Decreases in BP were maintained for up to 3 years of treatment. The drug (10 or 20 mg/day) also significantly lowered sitting BP from baseline in patients with hypertension and type 2 diabetes mellitus in randomised, long term comparative trials. In general, the observed reduction in BP with manidipine was similar to that observed with amlodipine, enalapril or delapril. The effects of manidipine on urinary albumin excretion (UAE) have not been clearly demonstrated in clinical trials in this patient group. BP was also reduced with manidipine in patients with impaired glucose tolerance. Manidipine was well tolerated in clinical trials, with most adverse effects related to vasodilation. Commonly reported events included ankle oedema, headache. palpitation. flushing, dizziness, rash and fatigue. Manidipine appears to have less potential for pedal oedema than amlodipine. CONCLUSIONS: Manidipine has shown antihypertensive efficacy and appears to be well tolerated in adult and elderly patients with mild or mo     

Nitrendipine and enalapril combination therapy in mild to moderate hypertension: assessment of dose-response relationship by a clinical trial of factorial design.

Hypertension is an important cardiovascular risk factor and the goal of its pharmacologic treatment is to reduce morbidity and mortality. Treatment is usually initiated with a low dose of a single agent and titrated to a higher dose as required. As many as 50% of patients require the addition of a second agent to achieve satisfactory blood pressure control. The aim of this study was to assess the dose-response relationship of nitrendipine and enalapril alone or in fixed combination in the treatment of mild to moderate hypertension. A total of 496 patients were enrolled in a multicenter, randomized, double-blind, factorial-design, parallel-group clinical trial comparing placebo, nitrendipine (5, 10, and 20 mg) and enalapril (5, 10, and 20 mg) alone or in combination. After a single-blind, 2-week placebo run-in period, 414 patients whose diastolic blood pressure ranged between 90-109 mm Hg were randomly assigned to a treatment group. The combination of nitrendipine and enalapril, particularly regimens including nitrendipine 20 mg and enalapril 5 or 10 mg, were significantly superior to both monotherapies; mean diastolic blood pressure reductions from baseline to last visit were -12.5 and -14.3 mm Hg, respectively. Response surface analysis provided further evidence that these combinations were optimal in terms of anti-hypertensive efficacy. All treatments were well tolerated and the incidence of adverse events did not differ significantly between groups. In summary, the anti-hypertensive efficacy of the combination was found to be superior to both monotherapies at any doses. The dose combination achieving the greatest blood pressure reduction was nitrendipine 20 mg and enalapril 10 mg.     

Felodipine. A review of the pharmacology and therapeutic use of the extended release formulation in older patients.

Felodipine is a dihydropyridine calcium antagonist which may be administered once daily in an extended release (ER) formulation. As monotherapy in older patients with mild to moderate essential hypertension, felodipine ER once daily provides effective control of blood pressure (BP). The drug has also been effective, either as monotherapy or in combination with other antihypertensive medications, in comparisons with other antihypertensive agents, and does not adversely affect lipid profiles or, in patients with diabetes mellitus, glycaemic control. Results in patients with angina pectoris and congestive heart failure indicate a potential role for felodipine ER in these indications and data also suggest the drug reduces left ventricular hypertrophy. In addition, felodipine ER appears suitable for use in patients with concomitant respiratory disease, renal or hepatic dysfunction, cerebrovascular or peripheral ischaemic disease, or gout, making it particularly useful in the elderly who often have more than one significant clinical condition. Felodipine ER has generally been well tolerated by older patients in clinical trials, although further confirmation in the long term is desirable. Thus, felodipine ER effectively lowers BP in older patients with essential hypertension with the added convenience of once daily administration. It may be used as monotherapy or in combination with other antihypertensive agents and is a practical advance in the treatment of hypertension in the elderly.