探讨中国、美国及欧洲高血压防治指南中有关药物治疗的问题

高血压治疗,药物的选择是关键,我国临床应用的降压药物种类,包括中西药及各种复方制剂有几百种之多,但我国高血压的治疗率和控制率都很低,高血压防治形势不容乐观。本文对中国、美国及欧洲高血压防治指南中有关药物治疗方面的差异进行比较,并对高血压药物临床选择的原则进行探讨。中、美、欧指南均认为不同类别的降压药物在某些治疗效果或特殊的人群中确实存在差异,因此对特定的强制性适应症应采用特定类别的降压药物。三个指南都强调合并用药的益处,并建议采用能维持24 h的长效药物或制剂。但三个指南在是否推荐一线治疗药物上存在明显分歧,美国指南建议噻嗪类利尿剂可作为大多数无并发症高血压患者的首选药,而欧洲指南和中国指南均未推荐一线药物,认为几个主要类别的降压药均可用于高血压的起始治疗和维持治疗。中医药是我国特有的宝贵资源,各种降压中成药在临床上有广泛的应用,但由于缺乏高质量证据,2004年中国高血压防治指南中缺少中成药部分。临床上降压药物的选择首先取决于药物的疗效和安全性,在疗效与安全性相差不大的情况下,应优先选择相对价廉的药物。对于我国大多数高血压患者,如果没有必需使用其他药物的适应症,低剂量噻嗪类利尿药可以作为治疗的首选方案。2004年中国高血压防治指南的出台,对我国高血压防治工作具有重要的意义,现阶段应加强指南的推广和实施,促进临床高血压药物的合理使用,提高血压控制率。     

Indapamide. A review of its pharmacodynamic properties and therapeutic efficacy in hypertension

Indapamide is an orally active sulphonamide diuretic agent. Although some evidence appears to indicate that the antihypertensive action of indapamide is primarily a result of its diuretic activity, only a limited diuresis occurs with the usual antihypertensive doses of 2.5 mg daily, and in vitro and in vivo data suggest that it may also reduce blood pressure by decreasing vascular reactivity and peripheral vascular resistance. In mild to moderate hypertension it is as effective as thiazide diuretics and beta-adrenergic blocking agents in lowering blood pressure when used as the sole treatment. Indapamide has been successfully combined with beta-adrenergic blocking agents, methyldopa, and other anti-hypertensive agents. While such findings need confirmation, it appears that indapamide shares the potential with other diuretic agents to induce electrolyte and other metabolic abnormalities, although it may do so with less frequency or severity. Thus, indapamide appears to offer a suitable alternative to more established drugs as a 'first-line' treatment in patients with mild to moderate hypertension. Whether it differs significantly from other diuretics when used as antihypertensive therapy, either in its mode of action or its side effect profile, needs further clarification.     

A practical guide to the management of hypertension in renal transplant recipients

Hypertension as well as hypotension can be harmful to a newly transplanted renal allograft. Elevated blood pressure is also a major risk factor for cardiovascular death, which is a frequent occurrence despite successful renal transplantation. Renal artery stenosis, immunosuppressive drugs, chronic rejection, retained native kidneys, and excessive extracellular fluid volume may all contribute to post-transplant hypertension. Antihypertensive agents are widely used in the management of post-transplant hypertension. Careful clinical judgement and knowledge of the pharmacology, pharmacodynamics, pharmacokinetics, adverse drug reaction profiles, potential contraindications, and drug-drug interactions of antihypertensive agents are important when therapy with antihypertensive drugs is initiated in renal transplant recipients. Since blood pressure elevation in any individual is determined by a large number of hormonal and neuronal systems, the effect of antihypertensive agents on the allograft should be considered a critical factor in the management of hypertension in renal transplant recipients. Most renal transplant recipients have other risk factors for premature cardiovascular death such as diabetes mellitus, hypercholesterolemia, insulin resistance, obesity, left ventricular hypertrophy and ischaemic heart disease. Initial antihypertensive therapy should be tailored individually according to the patient's risk factors. A realistic therapeutic goal for blood pressure management in the initial post-operative state is a systolic blood pressure <160 mm Hg and a diastolic blood pressure <90 mm Hg with lower pressure targets becoming applicable late post-transplantation.     

Calcium channel blockers and treatment of hypertension

Over the past years, research efforts have been focused on the pathophysiologic role of calcium ions, and the implication for the potential role of calcium channel blockers in the management of essential hypertension. Numerous studies have shown that nifedipine and verapamil are effective antihypertensive agents, initial experience with diltiazem is also encouraging. The magnitude of blood pressure reduction with these drugs is related to the pre-treatment blood pressure. In refractory hypertension, combination with other antihypertensive agents provide additive effect. In the elderly population and in patients with ischemic heart disease, supraventricular arrhythmia, bronchospastic disease, peripheral vascular disease or diabetes mellitus, the calcium channel blockers offer potential advantages over other antihypertensive agents. Experimental studies also suggest that these drugs may reverse ventricular hypertrophy. When long-term safety with these drugs is documented from well-controlled clinical trials, the calcium channel blockers may be our first line of therapy for the management of hypertension.     

The management of hypertension in the overweight and obese patient: is weight reduction sufficient?

The management of hypertension in the overweight and obese patient is a frequently encountered but under investigated clinical problem. The conventional management of such patients involves weight reduction with dietary therapy or a combined approach with dietary and anti-obesity drug therapy. However, long-term weight reduction, which is necessary to sustain blood pressure (BP) control, is not feasible in over 80% of patients. Anti-obesity therapy with orlistat has inconsistent effects on BP and may benefit only patients who have uncontrolled or non-medicated hypertension. Anti-obesity therapy with sibutramine may be associated with a modest worsening of BP control. Consequently, antihypertensive drug therapy is often required to supplement a weight reduction programme, and also in patients with severe hypertension or hypertension-associated end-organ damage. Treatment with a thiazide diuretic should be considered as first-line antihypertensive drug therapy in overweight and obese patients. ACE inhibitors or non-dihydropyridine calcium channel antagonists are reasonable alternatives where clinically indicated, or they can be used in combination with a thiazide diuretic if treatment with the diuretic alone is insufficient. If such treatment is inadequate for BP control, the addition or substitution of an alpha- or beta-adrenoceptor antagonist may be considered, although the latter can be associated with weight gain. Concurrent disease is an important determinant of first-line and supplementary antihypertensive drug therapy. Additional studies are needed to determine the long-term (>1 year) efficacy and safety of antihypertensive and anti-obesity management strategies in the overweight and obese hypertensive patient.     

某三甲医院门诊抗高血压药利用分析

目的调查分析临床抗高血压药的应用状况和合理性。方法利用医院信息系统门诊药房管理子系统,对某综合医院门诊抗高血压药处方进行回顾性分析。以药品说明书、新编药物学（2005版）、2007年欧洲高血压治疗指南为标准,采用世界卫生组织推荐的限定日剂量方法、用药频度法对抗高血压药处方的使用情况进行统计、分析。结果该院门诊抗高血压药使用情况基本合理,但还存在一些问题,如利尿药的应用偏少,存在药物联用不适宜、用药间隔不合理现象。结论临床医师和药师应遵循药物治疗指南,掌握各类降压药的降压机制,进行合理的联合用药,提高合理用药水平。     

Should antihypertensive therapies be given to patients with acute ischemic stroke?

Hypertension is a major risk factor for stroke and many patients with acute stroke have elevated blood pressures. The management of hypertension in the setting of acute ischaemic stroke remains a source of confusion and controversy. Lowering blood pressure in this setting may be hazardous because of impaired cerebral autoregulation. Treatment may be considered in patients who are otherwise candidates for thrombolytic therapy, patients who have severe hypertension or patients who have specific concomitant medical conditions including acute myocardial infarction, aortic dissection, hypertensive encephalopathy, or severe left ventricular failure. In choosing an agent for acute treatment, drugs that can produce a precipitous decline in blood pressure (e.g. sublingual calcium antagonists) should be avoided. Drugs with the capacity to dilate cerebral vessels should be used with caution as they have the potential to increase intracranial pressure. Long term management of hypertension in poststroke patients is often required. The potential for certain classes of drugs (e.g. alpha2-adrenergic receptor agonists and alpha1-adrenergic receptor antagonists) to impair the recovery process should be considered when choosing an antihypertensive for treatment of these patients.     

Atenolol: differences in mode of action compared with other antihypertensives. An opportunity to identify features that influence outcome?

The beneficial effect of antihypertensive treatment on the risk of major vascular events is well established. Several trials comparing older and newer drugs in the treatment of primary hypertension suggested that it is the blood pressure achieved, rather than choice of the drug that determines most of the primary outcomes. Beta-blockers have been widely used to treat hypertension and are still recommended as first-line drugs in guidelines. However, recent meta-analyses of trials (either placebo-controlled or using drug comparisons) involving atenolol (a popular beta-blocker), have cast doubt on the suitability of atenolol as a first-line antihypertensive drug. We consider the mechanisms which might be responsible for the inferiority of atenolol in preventing vascular morbidity and mortality in patients with primary hypertension. This knowledge may help design drugs that are not only more effective in achieving blood pressure targets but that also markedly decrease vascular events.     

Monotherapy versus combination therapy as first line treatment of uncomplicated arterial hypertension.

Mild to moderate hypertension still remains poorly controlled. This relates to multiple factors including low antihypertensive efficacy of single drug therapies reluctance of primary care physicians to modify/titrate initially chosen therapy to obtain target blood pressure, and poor compliance with medication. Several guidelines for the treatment of high blood pressure now include combination therapy with low doses of 2 drugs as one of the strategies for the initial management of mild/moderate arterial hypertension. Evidence discussed in this article points to superior control of blood pressure by combinations of low doses of 2 drugs as compared with monotherapy in regular doses. This superior effectiveness of combined therapy relates to a better antihypertensive efficacy and higher response rates in the low range of doses as the result of complementary mechanisms of antihypertensive effects, better tolerance as a result of a lower rate of adverse effects in the low dose range, improved compliance from better tolerance and simple drug regimen, and lower cost. Whether increased use of fixed low dose combination therapies would translate to better control of arterial hypertension in the population and thereby further reduction of cardiovascular/cerebrovascular morbidity and mortality caused by hypertension remains to be assessed.     

Adult hypertension: reducing cardiovascular morbidity and mortality

(1) Since our last review of treatments for arterial hypertension in 1999 (Prescrire International no.41), many new data have been published and new antihypertensive drugs have appeared on the market. (2) The working definition of hypertension is unchanged, namely blood pressure of at least 160/95 mm Hg in the general population, and at least 140/80 mm Hg in patients with diabetes and a history of stroke; these figures must be found on several occasions using a standardised method, with the patient at rest. (3) The goals of antihypertensive therapy are to reduce mortality and cardiovascular events, and not simply to drive blood pressure below a fixed (and often controversial) threshold. (4) Some drug and non drug interventions have a positive risk-benefit balance in the long term. (5) When antihypertensive drug therapy is needed, trials based on clinical endpoints show that it is best to start treatment with a single drug. (6) New data support the use of certain thiazide diuretics (chlortalidone, or hydrochlorothiazide if chlortalidone is not available) as first line treatment for most hypertensive patients, including non diabetic adults, diabetic adults, elderly subjects (over 65 years), and stroke patients. Some betablockers and angiotensin-converting-enzyme inhibitors (ACE inhibitor) are second-line alternatives. (7) Assessment of other antihypertensive drugs has also progressed since 1999, including indapamide (thiazide-like diuretic), amlodipine, diltiazem and verapamil (calcium channel blockers), lisinopril (ACE inhibitor), and losartan and valsartan (angiotensin II antagonists). However, these drugs are not as thoroughly evaluated as thiazide diuretics, betablockers and some ACE inhibitors.     

From hypertension to heart failure -- are there better primary prevention strategies?

Although in the developed world the incidence of and mortality from coronary heart disease (CHD) and stroke have been declining over the last 15 years, heart failure is increasing in incidence, prevalence and overall mortality, despite advances in the diagnosis and management of the condition. Hypertension, alone or in combination with CHD, precedes the development of heart failure in the majority of both men and women. Whilst there have been improvements in the overall management of hypertension, as reflected in rates of diagnosis, awareness, treatment and control of blood pressure (BP), there are still many patients with hypertension who remain undiagnosed or untreated and of those who do receive treatment many fail to achieve current targets for BP control. Placebo-controlled trials in hypertension, largely based on diuretic and beta-blocker-based regimens, have unequivocally demonstrated that the treatment of hypertension can significantly reduce the incidence of heart failure. Newer treatment strategies offer theoretical and proven practical advantages over established antihypertensive therapy. In particular, AT1-receptor blockers appear to provide benefits beyond BP control and are effective in the treatment of both hypertension and heart failure. Thus, the primary prevention of heart failure in hypertensive patients should be based upon strategies that provide tight and sustained BP control necessitating the use of multiple drugs. However, there is now compelling evidence to suggest that this therapy should include an antihypertensive agent that inhibits the reninangiotensin- aldosterone system (RAAS).     

The safety of antihypertensives for treatment of pregnancy hypertension

This review addresses the maternal and perinatal benefits and risks of antihypertensive therapy in pregnancy. It covers the diagnosis of hypertension in pregnancy (with a brief discussion of ambulatory blood pressure measurement) followed by both the general principles of management of pregnancy hypertension and the specifics of individual antihypertensive drugs and drug classes. Discussion is focused on quantitative overviews of randomised, controlled trials, although observational literature is also discussed, particularly in reference to the potential teratogenicity of agents and the safety of their administration to nursing mothers. The treatment of severe hypertension is addressed separately from the treatment of mild-to-moderate hypertension, for which the maternal and fetal risks are substantially different.     

Hypertension management and control in primary care: a study of 20 practices in 14 states

STUDY OBJECTIVE: To describe the management and control of hypertension in primary care practice. DESIGN: Retrospective medical record review. SETTING: Twenty primary care practices in 14 states. PATIENTS: Thirteen thousand forty-seven patients with hypertension. MEASUREMENTS AND MAIN RESULTS: Diagnoses, drugs prescribed, and blood pressure readings were extracted from the electronic medical record at each practice in the study. For patients with hypertension and comorbid diagnoses, the most recent blood pressure and antihypertensive drugs prescribed were determined. Analyses assessed the blood pressure control rates and the association between control and demographic variables, frequency of visits to the practice site, and pharmacologic treatment patterns. Among the 20 practices in the study, 13,047 patients had received a diagnosis of hypertension and their blood pressures had been measured within the previous 12 months. One third of the patients had comorbid coronary heart disease, diabetes mellitus, heart failure, and/or renal insufficiency. The most recent blood pressure reading was below 140/90 in half the patients. Control was associated with age 60 years or younger, female sex, more than one visit to the practice, more than one comorbidity, and type of practice (p<0.01, logistic regression). Wide variability was noted among practices in the use of multiagent antihypertensive therapy, and in antihypertensive therapy by drug class. Among patients without comorbidity treated with one drug, systolic blood pressure did not differ significantly by drug class. Diastolic blood pressure was slightly lower in patients prescribed thiazide diuretics than in those prescribed angiotensin receptor blockers (p=0.03, analysis of covariance). CONCLUSION: Blood pressure control in primary care practice can be much better than reports usually indicate. Good control in this study was not due to specific drug choice, but instead may have been due to regular monitoring of blood pressure and motivation of the practice to improve patient care.     

Arterial hypertension: second-line treatment. Try other single-agent treatments

(1) Reliable evidence supports the use of thiazide diuretics (chlortalidone or hydrochlorothiazide) as first-line treatment for uncomplicated arterial hypertension. (2) When patients fail to reach blood pressure targets with well-conducted treatment with thiazide diuretics, or this treatment is poorly tolerated, what are the best second-line options? To answer this question, we reviewed the available evidence, based on our standard in-house methodology. (3) We found no published trials specifically designed to evaluate second-line antihypertensive treatments in cardiovascular prevention. There were no available trials of dual- versus single-agent therapy after failure of a thiazide diuretic. (4) When the blood pressure target is not reached, inadequate drug efficacy is only one of several possible causes. Various other factors affecting blood pressure should also be investigated. (5) Dual-agent therapy carries an increased risk of adverse effects and drug interactions compared to monotherapy. (6) There is no consensus among clinical practice guidelines on second-line antihypertensive therapy. However, to minimise the risk of adverse effects, it is clearly better to select single-agent therapy with a drug that has been shown to prevent cardiovascular events in first-line treatment of otherwise healthy hypertensive patients. Possible options include: angiotensin-converting-enzyme inhibitors, angiotensin II antagonists, calcium channel blockers or betablockers. In patients over the age of 60, betablockers seem less effective that the other drugs in preventing strokes. (7) There is too little evidence to choose a specific third-line combination rather than another. However, any adverse effects that the patient experienced during prior treatments should be taken into account.     

老年高血压特点及治疗

目的观察60岁以上老年人高血压降压用药情况,探讨老年高血压病的治疗,以达到有效地控制血压,减少并发症的目的。方法回顾性分析240例采用药物和非药物治疗的老年住院高血压患者完整的病历资料。结果通过对老年高血压患者进行非药物治疗和药物治疗,药物以联合用药治疗为主,两联最多。240例患者经过3～6个月治疗,血压降至正常或接近正常,无脑卒中及心肌梗死发生。结论联合用药,可以达到有效控制血压,降低心脑血管疾病的作用。     

Drug interactions with angiotensin receptor blockers: a comparison with other antihypertensives.

The ever-increasing introduction of new therapeutic agents means that the potential for drug interactions is likely to escalate. Numerous different classes of drugs are currently used to treat hypertension. The angiotensin receptor blockers offer one of the newest approaches to the management of patients with high blood pressure. Compared with other classes of antihypertensive agents, the angiotensin receptor blockers appear overall to have a low potential for drug interactions, but variations within the class have been detected. Losartan and irbesartan have a greater affinity for cytochrome p450 (CYP) isoenzymes and, thus, are more likely to be implicated in drug interactions. There is pharmacokinetic evidence to suggest that such interactions could have a clinical impact. Candesartan cilexetil, valsartan and eprosartan have variable but generally modest affinity and telmisartan has no affinity for any of the CYP isoenzymes. In vitro studies and pharmacokinetic/pharmacodynamic evaluation can provide evidence for some interactions, but only a relatively small number of drug combinations are usually studied in this way. The absence of any pharmacokinetic evidence of drug interaction, however, should not lead to complacency. Patients should be made aware of possible interactions, especially involving the concurrent use of over-the-counter products, and it may be prudent for all patients receiving antihypertensive treatment to be monitored for possible drug interactions at their regular check-ups. The physician can help by prescribing agents with a low potential for interaction, such as angiotensin receptor blockers.     

两种降压联合用药方案对高血压合并糖尿病患者血压变异性影响的比较

目的比较两种降压联合用药方案对高血压合并糖尿病患者血压变异性影响。方法 68例高血压合并2型糖尿病患者分为2组,分别使用缬沙坦胶囊联合吲达帕胺片及依那普利胶囊联合硝苯地平缓释片降压治疗,治疗前及治疗3个月后分别进行24h动态血压监测,观察血压控制情况,比较两组降压联合用药方案治疗前后血压变异性指标。结果使用两种降压联合用药方案均显著降低血压,均可降低血压变异性,但服用缬沙坦胶囊联合吲达帕胺片治疗的患者血压变异性指标优于服用依那普利胶囊联合硝苯地平缓释片的患者。结论两种降压联合用药方案对高血压合并2型糖尿病患者均能有效降压,但考虑降低血压变异性,缬沙坦胶囊联合吲达帕胺片优于依那普利胶囊联合硝苯地平缓释片。     

Combination therapy in hypertension: an Asia-Pacific consensus viewpoint

Hypertension incurs a significant healthcare burden in Asia-Pacific countries, which have suboptimal rates of blood pressure (BP) treatment and control. A consensus meeting of hypertension experts from the Asia-Pacific region convened in Hanoi, Vietnam, in April 2013. The principal objectives were to discuss the growing problem of hypertension in the Asia-Pacific region, and to develop consensus recommendations to promote standards of care across the region. A particular focus was recommendations for combination therapy, since it is known that most patients with hypertension will require two or more antihypertensive drugs to achieve BP control, and also that combinations of drugs with complementary mechanisms of action achieve BP targets more effectively than monotherapy. The expert panel reviewed guidelines for hypertension management from the USA and Europe, as well as individual Asia-Pacific countries, and devised a treatment matrix/guide, in which they propose the preferred combination therapy regimens for patients with hypertension, both with and without compelling indications. This report summarizes key recommendations from the group, including recommended antihypertensive combinations for specific patient populations. These strategies generally entail initiating therapy with free drug combinations, starting with the lowest available dosage, followed by treatment with single-pill combinations once the BP target has been achieved. A single reference for the whole Asia-Pacific region may contribute to increased consistency of treatment and greater proportions of patients achieving BP control, and hence reducing hypertension-related morbidity and mortality.