Nifedipine and telmisartan for the treatment of hypertension: the TALENT study

A combination of two drugs as initial treatment in patients with a high or very high cardiovascular risk profile is recommended. Nifedipine extended release (GITS) is a calcium-channel antagonist known to be metabolically neutral, to mildly slow the development of atherosclerosis in hypertensive subjects and to significantly decrease cardiovascular risk in diabetic patients. Telmisartan is highly selective for the angiotensin receptor 1, it gives a greater improvement in glycemic and lipid control compared with irbesartan, and it proved its superiority in improving insulin sensitivity compared with eprosartan. The TALENT study was aimed to determine whether combining low-dose nifedipine GITS at and telmisartan reduced ambulatory and clinic blood pressure more than the two components in monotherapy in hypertensive patients at high cardiovascular risk. The study shows that combination treatment with nifedipine GITS and telmisartan provides a greater and earlier blood pressure reduction than the combination components in monotherapy.     

Nifedipine and telmisartan for the treatment of hypertension: the TALENT study

A combination of two drugs as initial treatment in patients with a high or very high cardiovascular risk profile is recommended. Nifedipine extended release (GITS) is a calcium-channel antagonist known to be metabolically neutral, to mildly slow the development of atherosclerosis in hypertensive subjects and to significantly decrease cardiovascular risk in diabetic patients. Telmisartan is highly selective for the angiotensin receptor 1, it gives a greater improvement in glycemic and lipid control compared with irbesartan, and it proved its superiority in improving insulin sensitivity compared with eprosartan. The TALENT study was aimed to determine whether combining low-dose nifedipine GITS at and telmisartan reduced ambulatory and clinic blood pressure more than the two components in monotherapy in hypertensive patients at high cardiovascular risk. The study shows that combination treatment with nifedipine GITS and telmisartan provides a greater and earlier blood pressure reduction than the combination components in monotherapy.     

A comparison of the effects of two modified release preparations of nifedipine-nifedipine retard 10 mg twice daily and nifedipine GITS 20 mg once daily--in the treatment of mild to moderate hypertension

A multicentre, randomised, double-blind, cross-over comparison of nifedipine GITS 20 mg once daily and nifedipine retard 10 mg twice daily in 49 patients with mild to moderate hypertension was conducted. Both treatments resulted in clinically significant trough blood pressure reductions (nifedipine GITS -10.1/-8.9 mmHg, nifedipine retard -7.5/-8.2 mmHg). The study demonstrated that nifedipine GITS was 'at least equivalent' to nifedipine retard in the reduction of trough diastolic blood pressure (one-sided lower 95% confidence limit, -1.2 mmHg). The overall incidence of adverse events (nifedipine GITS 25.5%, nifedipine retard 34.0%), as well as the incidences of headache (nifedipine GITS 8.5%, nifedipine retard 12.8%) and peripheral oedema (nifedipine GITS 2.1%, nifedipine retard 8.5%), was higher with nifedipine retard compared to nifedipine GITS. Nifedipine GITS 20 mg once daily is 'at least equivalent' to nifedipine retard 10 mg twice daily in patients with mild to moderate hypertension, as well as being better tolerated.     

Use of nifedipine in the treatment of hypertension

Hypertension is an important modifiable risk factor for cardiovascular disease; its prevention and treatment currently represent major health concerns around the world, especially in western countries. Effective, well-tolerated drugs such as dihydropyridine calcium channel blockers, to be used either alone or in combination treatments, play a key role in reducing cardiovascular morbidity and mortality. The extended-release formulation of nifedipine given once daily provides a relatively constant concentration profile and has proved to be effective in reducing blood pressure values. In the International Nifedipine gastrointestinal therapeutic system Study: Intervention as a Goal in Hypertension Treatment (INSIGHT) study, it was demonstrated that nifedipine confers cardiovascular protection as effectively as diuretics in high-risk patients, with a smaller incidence of adverse metabolic consequences. Furthermore, two INSIGHT substudies demonstrated that nifedipine prevents the progression of carotid atherosclerosis and reduces the worsening of coronary calcifications, supporting the use of calcium channel blockers in hypertensive patients--especially those at high cardiovascular risk. This review discusses the existing clinical evidence supporting the use of nifedipine in the treatment of hypertension.     

硝苯地平长效与短效制剂对高血压患者生活质量的作用比较

目的：探讨二氢吡啶类钙通道阻滞剂硝苯地平的长效制剂拜新同（nifedipine GITS,硝苯地平控释片）与短效制剂心痛定（nifedipine,硝苯地平）对轻中度高血压患者治疗作用与生活质量的影响。方法：两周停药“冲洗期”后,120例轻中度高血压病人（舒张压95-140mmHg）被随机分配到拜新同组（口服30mg,每日1次）或心痛定组（口服10mg,每日3次）,疗程共3个月,治疗前后分别记录血压和填写生活质量量表。评价治疗前后治疗3个朋后生活质量的改变。结果：降压疗效两组没有显著差别,血压下降拜新同组为15/13mmHg,心痛定组为16/12mmHg(P＞0.05);两组不良反应也无显著差别;拜新同组生活质量三个分量表得分均有明显改善,心痛定组躯体功能与心理健康得到改善,社会功能分量表质量下降,但无显著差别。结论：拜新同与心痛定降压治疗安全、有效,可改善患者的生活质量,两者比较拜新同优于心痛定,为一种比较理想的降压药物。     

硝苯吡啶控释片对脑卒中伴高血压患者运动功能的影响

目的探讨硝苯吡啶控释片对脑卒中伴高血压患者血压控制及肢体运动功能的作用。方法对80例脑卒中伴高血压患者给予运动治疗、作业治疗及神经营养。随机分为治疗组60例和常规组20例。治疗组每天加服硝苯吡啶控释片30mg。治疗过程中2组每日2次测血压,在治疗前及治疗4周后分别采用简式Fugl-Meyer及Barthel指数评定肢体运动功能及日常生活能力(ADL)。结果治疗组降压显效率高于常规组,且血压波动小;治疗组ADL评定增高较常规组显著(P＜0.05);治疗组肢体运动功能改善,以下肢明显(P＜0.05)。结论硝苯吡啶控释片降压效果平稳可靠,并能促进脑卒中患者运动功能的恢复。     

Calcium antagonists and atherosclerosis protection in hypertension

Calcium antagonists are effective in hypertensive patients of all ethnic groups, irrespective of age, dietary salt intake, salt-sensitivity status or plasma renin activity profile. Some prospective studies show that the calcium antagonists, nifedipine GITS and nitrendipine, reduce cardiovascular morbidity and mortality at least to the same extent as the diuretics. Other prospective studies are in progress to evaluate the effect of calcium antagonists on cardiovascular morbidity and mortality, and the progression of atherosclerosis in hypertensive patients. Calcium antagonists, especially the highly lipophilic amlodipine, lacidipine and nisoldipine, are shown to possess antioxidant properties. These drugs reduce the oxidation of LDL and its influx into the arterial wall, and reduce atherosclerotic lesions in animals. Platelet production of malondialdehyde, a marker of oxygen free radical formation, is suppressed by amlodipine, lacidipine or nifedipine in hypertensive patients. New evidence from long-term clinical trials of calcium antagonists indicates that these drugs can reduce the rate of progression of atherosclerosis in hypertensive and coronary heart disease patients. In the Regression Growth Evaluation Statin Study (REGRESS), co-administration of calcium antagonist, amlodipine or nifedipine with pravasatin caused a significant reduction in the appearance of new angiographic lesions. In the Verapamil in Hypertension and Atherosclerosis Study (VHAS), verapamil was more effective than chlorthalidone in promoting regression of thicker carotid lesions in parallel with a reduction in the incidence of cardiovascular events. In the Prospective Randomized Evaluation of the Vascular Effects of Norvasc Trial (PREVENT), amlodipine slowed the progression of early coronary atherosclerosis in patients with coronary artery disease. In a subprotocol of the Intervention as a Goal in the Hypertension Treatment (INSIGHT) study, nifedipine GITS significantly decreased intima-media thickness as compared to co-amilozide (hydrochlorothiazide + amiloride). Preliminary results of the European Lacidipine Study on Atherosclerosis (ELSA) show that lacidipine reduced the intima-media thickness progression rate as compared to atenolol. Thus, selective calcium antagonists are potential antiatherosclerotic agents.     

Blood pressure control in patients with mild to moderate essential hypertension switched from nifedipine gastrointestinal therapeutic system (GITS) 30 mg to nifedipine GITS 20 mg

BACKGROUND: Nifedipine gastrointestinal therapeutic system (GITS) is a once-daily formulation of nifedipine that provides sustained plasma nifedipine concentrations throughout the 24-hour dosing interval. OBJECTIVE: This study was undertaken to determine if adult patients with mild to moderate essential hypertension whose blood pressure had been controlled for > or = 3 months with nifedipine GITS 30 mg could be successfully switched to a 20-mg daily dose with continued antihypertensive efficacy. METHODS: This was a randomized, double-blind, parallel-group study. Patients entered a 1-week run-in period during which they continued to receive their usual antihypertensive medication, including nifedipine GITS 30 mg. After baseline assessment, patients entered a 6-week treatment period during which they were randomly assigned to receive nifedipine GITS 30 or 20 mg. Men and women were eligible to participate if they were > or = 55 years of age, had received a diagnosis of mild to moderate essential hypertension (sitting diastolic blood pressure [DBP] 95-114 mm Hg), and had exhibited good blood pressure control (sitting DBP < or = 90 mm Hg) while taking nifedipine GITS 30 mg once daily for > or = 3 months. Systolic blood pressure (SBP), DBP, and heart rate were recorded at baseline and after 1, 3, and 6 weeks of treatment. Adverse events were reported by patients. The responder rate was defined as the percentage of patients whose sitting DBP was < 95 mm Hg at the final study assessment. Results were based on the intent-to-treat analyses, which included data for all patients who received > or = 1 dose and had 1 postbaseline blood pressure assessment. Statistical significance was set at P < 0.05. RESULTS: Seventy-five patients entered the 1-week run-in period; 71 patients (94.7%) were randomized to treatment. Twenty-four patients received nifedipine GITS 30 mg for 43.0 +/- 3.3 days, and 47 patients received nifedipine GITS 20 mg for 42.5 +/- 6.7 days. Both groups exhibited a sustained decrease in blood pressure throughout the study; minor variations were not statistically significant. End-point SBP and DBP for the 30- and 20-mg groups were 135.5 +/- 9.8/81.7 +/- 5.4 mm Hg and 138.6 +/- 11.8/82.9 +/- 7.6 mm Hg, respectively. Changes from baseline in end-point SBP and DBP did not differ significantly between groups. At the end of treatment, goal DBP (< 95 mm Hg) was achieved by 24 of 24 patients (100%) receiving the 30-mg dose and 45 of 47 patients (95.7%) receiving the 20-mg dose. Blood pressure control (sitting DBP < 90 mm Hg) was achieved by 21 of 24 (87.5%) patients in the 30-mg group and 35 of 47 (74.5%) patients in the 20-mg group. The most commonly reported adverse event was headache; 2 patients discontinued the study because of adverse events. Overall, 9 of 24 patients (37.5%) in the 30-mg group and 14 of 47 patients (29.8%) in the 20-mg group experienced > or = 1 treatment-related adverse event. CONCLUSIONS: Patients whose mild to moderate essential hypertension is controlled with nifedipine GITS 30 mg once daily may be able to switch to 20 mg once daily with continued antihypertensive efficacy. In addition to safety and economic advantages, such a switch may be a reasonable alternative in patients with lower body weight or as an adjunct to existing antihypertensive therapy.     

Safety and Efficacy of Once-Daily Captopril Plus Hydrochlorothiazide versus Nifedipine Gastrointestinal Therapeutic System in Black Patients with Mild to Moderate Hypertension

The safety and efficacy of captopril plus hydrochlorothiazide (HCTZ) were compared to nifedipine gastrointestinal therapeutic system (GITS) in 145 randomly assigned black patients with mild to moderate hypertension. Following a 4-week placebo lead-in, patients received captopril plus HCTZ 25/15 mg or nifedipine GITS 30 mg for up to 12 weeks. Upward dose titration was permitted at weeks 3 and 6. Mean seated systolic and diastolic blood pressures decreased 16.1 ± 13.5 mm Hg and 11.5 ± 7.4 mm Hg, respectively, with captopril plus HCTZ. Statistically similar decreases were observed with nifedipine GITS: systolic, 19.3 ± 12.2 mm Hg; diastolic, 13.8 ± 7.2 mm Hg. There were no clinically significant between-group differences in serum chemistries. Edema was reported in 20.3% of nifedipine GITS patients versus 1.4% of captopril plus HCTZ patients (p = 0.001). The two regimens were equally effective in controlling blood pressure in black patients; however, a higher incidence of edema occurred with nifedipine GITS compared to captopril plus HCTZ.     

Comparison of the effects of telmisartan and nifedipine gastrointestinal therapeutic system on blood pressure control, glucose metabolism, and the lipid profile in patients with type 2 diabetes mellitus and mild hypertension: a 12-month, randomized, double-blind study

BACKGROUND: Angiotensin receptor blockers (ARBs) provide effective blood pressure control. Whereas none of the ARBs appear to affect glucose homeostasis, some ARBs have been associated with a decrease in cholesterolemia. OBJECTIVE: This study was conducted to evaluate blood pressure control glucose homeostasis, and the plasma lipid profile in patients with type 2 diabetes mellitus and mild hypertension during 12 months of treatment with the ARB telmisartan or nifedipine gastrointestinal therapeutic system (GITS). METHODS: In this double-blind trial, patients taking oral hypoglycemic agents were randomized to receive telmisartan 40 mg or nifedipine GITS 20 mg once daily for 12 months. At the time of enrollment, patients were given advice on diet (1400-1600 kcal/d) and exercise (stationary bicycle for > or =30 min, 4 d/wk). Assessments of systolic blood pressure (SBP), diastolic blood pressure, body mass index (BMI), fasting plasma glucose concentrations, glycosylated hemoglobin, fasting plasma insulin concentrations, the homeostasis model assessment of insulin resistance, and the lipid profile were performed at baseline and after 6 and 12 months of treatment. RESULTS: One hundred sixteen patients were divided into 2 age- and sex-matched treatment groups (58 men, 58 women; mean [SD] age, 52.5 [5] years). All patients were in good general health at baseline; had achieved adequate glycemic control with diet and oral hypoglycemic agents; were taking antihypercholesterolemic drugs; and had no evidence of macroangiopathy, microalbuminuria, or neuropathy. There were significant reductions from baseline in seated trough SBP after 12 months of treatment with both telmisartan and nifedipine GITS (from 139 [4] to 132 [4] mm Hg and from 140 [4] to 130 [4] mm Hg, respectively; both, P < 0.01). No change in BMI or glucose metabolism was observed with either treatment. After 12 months, there were significant improvements in concentrations of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) with telmisartan (-9% and -11.5%, respectively; both, P < 0.01) compared with nifedipine GITS (-2% and -1.5%). CONCLUSIONS: In this selected sample of patients with type 2 diabetes and mild hypertension, both telmisartan and nifedipine GITS produced significant reductions in blood pressure. Telmisartan was associated with a slight but statistically significant improvement in plasma TC and LDL-C concentrations compared with nifedipine GITS.     

Unique dual mechanism of action of eprosartan: effects on systolic blood pressure, pulse pressure, risk of stroke and cognitive decline

Hypertension is a common condition associated with considerable morbidity and mortality. Antihypertensive drugs reduce the risk of cardiovascular and cerebrovascular events, and may also be associated with reductions in cognitive decline. Eprosartan is an angiotensin II type 1 receptor antagonist with a unique dual mechanism of action that is approved for the treatment of essential hypertension. In clinical trials, eprosartan has been shown to significantly reduce systolic blood pressure and to be associated with significant reductions in pulse pressure in elderly patients with isolated systolic hypertension. Data suggest that blood pressure reductions achieved with eprosartan in elderly hypertensive patients are also associated with improvements in cognitive function. Eprosartan compares favorably with other classes of antihypertensive agents in terms of reductions in mortality, cardiovascular and cerebrovascular events, and stroke recurrence. Evidence suggests that eprosartan may represent a useful addition to combination drug strategies for the management of hypertensive patients with elevated cardiovascular and cerebrovascular risk.     

Chronotherapy in hypertensive patients: administration-time dependent effects of treatment on blood pressure regulation

Ambulatory blood pressure measurements (ABPM) correlate more closely with target organ damage and cardiovascular events than clinical cuff measurements. ABPM reveals the significant circadian variation in BP, which in most individuals presents a morning increase, small post-prandial decline, and more extensive lowering during nocturnal rest. However, under certain pathophysiological conditions, the nocturnal BP decline may be reduced (nondipper pattern) or even reversed (riser pattern). This is clinically relevant since the nondipper and riser circadian BP patterns constitute a risk factor for left ventricular hypertrophy, microalbuminuria, cerebrovascular disease, congestive heart failure, vascular dementia and myocardial infarction. Hence, there is growing interest in how to best tailor and individualize the treatment of hypertension according to the circadian BP pattern of each patient. Significant administration-time differences in the kinetics and in the beneficial and adverse effects of antihypertensive medications are well known. Thus, bedtime dosing with nifedipine gastrointestinal therapeutic system (GITS) is more effective than morning dosing, while also significantly reducing adverse effects. The therapeutic coverage and efficacy of doxazosin GITS are dependent on the circadian time of drug administration. Moreover, valsartan administration at bedtime, as opposed to upon wakening, results in an improved diurnal/nocturnal BP ratio, increased percentage of controlled patients, and significant reduction in urinary albumin excretion in hypertensive patients. Chronotherapy provides a means of individualizing the treatment of hypertension according to the circadian BP profile of each patient, and constitutes a new option to optimize BP control and reduce the risk of cardiovascular disease.     

Therapeutic strategy for the treatment with hypertensive renal injury

Hypertension constitutes a pivotal determinant of the progression of renal disease, which would raise the risk for cardiovascular events. From the standpoint of renal micro-circulation, correction of glomerular hypertension could retard the development of renal injury, which is attainable by the reduction in renal efferent arteriolar resistance as well as systemic blood pressure. Although both ACE inhibitors and angiotensin receptor blockers are established as a tool for improving glomerular hypertension, whether calcium antagonists ameliorate this abnormality remains unclear. However, recent clinical trials including ALLHAT and INSIGHT demonstrate a beneficial action of amlodipine and nifedipine on the development of renal injury. Therefore, calcium antagonists can be used not only as a first line drug, but also as add-on therapy that could potentiate the hypotensive action of underlying medication.     

Management of hypertension. Useful nonpharmacologic measures

Hypertension is a chronic problem commonly seen by primary care physicians. Inadequate treatment may result in significant morbidity and even death. Therefore, all patients with hypertension or at risk for hypertension should be educated about nonpharmacologic measures to control blood pressure. Weight reduction and sodium restriction are cornerstones of nonpharmacologic management of hypertension. Although studies of the effects of aerobic exercise on blood pressure are not well designed, data confirm the value of such exercise. Relaxation therapy has been shown to lower blood pressure, but effects may be transient. Potassium and calcium supplementation has lowered blood pressure, but because study results are contradictory, the exact clinical criteria for use of such supplements have not been determined. Vegetarians have lower blood pressure than nonvegetarians, but no specific dietary components (eg, fiber, fat) have been documented as the beneficial factors. Because of its significant pressor effect, alcohol should be avoided by hypertensives. A low-fat diet is recommended to decrease cardiovascular risk and assist in weight control.     

How important is optimal blood pressure control?

Background: Evidence for the cardiovascular benefits of antihypertensive treatment is among the strongest in medicine. Randomized, prospective, unconfounded studies in thousands of people have shown that even small reductions in blood pressure for short periods substantially improve cardiovascular outcomes. Recent evidence has emphasized the importance of optimal blood pressure control, particularly in patients with high cardiovascular risk, such as those with type 2 diabetes mellitus.Objective: This article discusses optimal target blood pressure goals, reviews the effects of antihypertensive treatment in high-risk patients, presents current guidelines for blood pressure control, discusses the failure worldwide to achieve such control, and suggests approaches to improved treatment.Conclusions: In high-risk patients, small improvements in blood pressure control are associated with large reductions in cardiovascular risk. National and international guidelines for the management of hypertension therefore now recommend rigorous blood pressure targets. Despite extensive clinical evidence, the delivery of care for hypertension remains unsatisfactory. Hypertension is underdiagnosed and undertreated, and recommended target blood pressures are rarely achieved. Physicians appear reluctant to make changes to treatment, which would lead to more effective use of antihypertensive drugs. Overwhelming evidence supports the benefit of optimal blood pressure control in patients with hypertension. Several studies have shown that such control can be achieved, but most likely requires combination treatment. Combination treatment is likely to be successful only if drugs are well tolerated and patients are compliant. The angiotensin II receptor antagonists (sartans) have the therapeutic advantage of efficacy, excellent tolerability, and a good record of compliance. Blood pressure control can be more easily accomplished by using sartans early in treatment and by recognizing the benefits of even small reductions in blood pressure.     

Benefits of nifedipine GITS in stable coronary artery disease: Further analysis of the “ACTION” database

Introduction  

Retrospective analyses of specific subgroups of patients from the database of the ACTION study have evaluated the effectiveness of a nifedipine gastrointestinal therapeutic system (GITS) on clinical outcomes. These subgroups included those patients receiving: 1) full “optimal” therapy at baseline; 2) full “optimal” therapy at baseline but excluding renin angiotensin system (RAS)-blocking drugs; 3) treatment with nifedipine GITS who were not treated with RAS blockers versus those treated with RAS blockers but not nifedipine GITS.     

The case for blood pressure control in risk groups

Hypertension rarely occurs in isolation, and many hypertensives have additional risk factors for cardiovascular disease in addition to elevated blood pressure. Each patient's cardiovascular disease risk profile should be determined individually, and the treatment approach tailored to each case. Cardiovascular disease risk factors and high blood pressure are closely linked, suggesting that the ideal treatment should not only lower blood pressure, but also effectively lower overall risk. This is likely to require more than one drug, and one of the most effective and safe combinations is that of an angiotensin receptor blocker with a diuretic. The completion of one of the most important trials undertaken to explore risk factors and anti-hypertensive treatment, the Valsartan long-term evaluation trial (VALUE), will certainly enhance understanding for the role of combination treatment in high-risk patients, as well as contribute to the design of rational treatments for blood pressure control.     

厄贝沙坦、硝苯地平及美托洛尔逆转高血压病左心室肥厚的效果观察

目的比较厄贝沙坦、硝苯地平及美托洛尔治疗原发性高血压逆转左心室肥厚的作用。方法选择150例原发性高血压伴左心室肥厚患者,随机分为厄贝沙坦组(A组)、硝苯地平控释片(B组)及美托洛尔组(C组)各50例。全组患者未曾接受降压治疗(或仅用过利尿剂)或已停用降压药物3周以上。A组服用厄贝沙坦150~300 mg,1次/d,B组服用硝苯地平控释片30~60 mg,1次/d,C组服用美托洛尔25~50 mg,2次/d;疗程均为24周。观察治疗前后血压及超声心动图变化。结果各组患者治疗后血压均显著降低(P<0.01),组间降压幅度无明显统计学差异(P>0.05)。各组患者治疗后舒张期左室后壁厚度、舒张期室间隔厚度、左室舒张末期内径及左室重量指数均有显著改善(P<0.05,0.01)。而且A组左室重量指数下降优于B、C组(P<0.05)。结论三种药物在有效降压的同时均可逆转左心室肥厚,厄贝沙坦对左心室肥厚的逆转作用相对更强。     

Epidemiology of postmenopausal hypertension

Hypertension is more common in younger men than women but this trend is inverted at approximately 60 years of age--thereafter hypertension is more common in women. Menopause's contribution to this phenomenon is complex. Oestrogen deficiency after menopause precipitates a number of factors and these have established the 'menopausal metabolic syndrome' as a concept in postmenopausal women. However, studies have indicated that changes in the prevalence of hypertension, and overall cardiovascular risk profiles in postmenopausal women, might be due to ageing and not oestrogen deficiency. Undoubtedly, there is a strong multicolinearity between the two phenomena. Furthermore, hormone replacement therapy (HRT) may reduce age-induced blood pressure increases, thus decreasing cardiovascular risks. However, recent results have questioned HRT's role in cardiovascular disease (CVD) prevention in postmenopausal women and trials have unequivocally shown that CVD risk in postmenopausal women with hypertension can be effectively reduced by common antihypertensive drugs.