Treatment of arterial hypertension after ischemic cerebral stroke

Lethality associated with secondary cerebral stroke is higher than in primary one. Data on the clinical course of arterial hypertension after stroke are contradictory. In recent years, the risk of a repeated ischemic stroke has been considered to be in a direct correlation with both systolic and diastolic blood pressure (BP), while the optimal BP level differs depending on the type of the stroke. Lowering BP should not exceed the ability of brain flow autoregulation to maintain normal cerebral perfusion. Data on the effectiveness of different groups of antihypertensive drugs in terms of secondary stroke prevention are contradictory. It has been reported that the risk of a secondary cerebral stroke lowered depending on the degree of BP decrease. At the same time, various antihypertensive drug classes were directly compared only in MOSES study. As far as secondary stroke prevention is concerned, differences between these classes suggest the existence of other than hypotensive mechanisms of their action. The presence of carotid atherosclerosis may compromise cerebral perfusion and predispose the patient to a second stroke, when a hypotensive effect is achieved.     

积极降压对脑小血管病防治策略的影响

2017年，美国心脏病学会和美国心脏协会提出将高血压诊断标准降为130/80 mm Hg(1 mm Hg=0.133 kPa)，这与其他指南有所不同。降压治疗的核心目标在于靶器官的保护，近年来降压治疗与脑小血管病预防的相关问题日益受到临床重视。目前研究结果表明, 降压治疗对腔隙性卒中患者的二级预防以及白质病变进展的预防可能有一定积极意义，但确切的降压目标值并未确定。血压与临床结局可能呈现J型关系，血压过低或过高可能均有害，而取得最大获益的降压目标有待进一步探索。     

Preventable stroke and stroke prevention

Stroke is a major cause of death and disability in the world. The main causes of stroke are atherothromboembolism and cardiogenic embolism. The main causal and treatable risk factors for atherothromboembolic ischemic stroke are increasing blood pressure (BP), increasing cholesterol, cigarette smoking and diabetes; and the main risk factors for cardiogenic ischemic stroke are atrial fibrillation (AF) and ischemic heart disease. Strategies to reduce the incidence of stroke include prevention of first-ever and recurrent stroke, and treatment of patients with acute stroke to reduce death and disability. The two main strategies of stroke prevention are the 'population' (or 'mass') approach and the 'high risk' approach. The 'population' approach aims to reduce stroke by lowering the prevalence and mean level of causal risk factors in the community, by means of public education and government legislation. The 'high risk' approach aims to reduce stroke by identifying individuals at high risk of stroke, and lowering their risk by means of optimal medical therapies. Level 1 evidence from randomized controlled trials indicates that effective treatments for high risk patients include control of causal risk factors (lowering BP, lowering blood cholesterol), antithrombotic therapy (antiplatelet therapy with aspirin, clopidogrel, or the combination of aspirin and dipyridamole for patients in sinus rhythm, and anticoagulation with warfarin or ximelagatran for patients in AF) and, where appropriate, carotid revascularization for patients with severe carotid stenosis.     

Hypertension associated with stroke

Antihypertensive treatment for hypertensive patients with stroke differs according to clinical subtypes (hemorrhage or ischemia) and phases (acute phase or chronic phase). In cerebral infarction that is not an indication for thrombolytic therapy, antihypertensive therapy is indicated when systolic pressure is > 220 mmHg or diastolic pressure is > 120 mmHg. In cerebral hemorrhage, a systolic blood pressure > 180 mmHg or a mean blood pressure > 130 mmHg is an indication for antihypertensive therapy. In the chronic phase of stroke, the eventual target of blood pressure control should be < 140/90 mmHg. Antihypertensive drugs recommened in the chronic phase are Ca channel blockers, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), diuretics, etc. In patients with diabetes mellitus or atrial fibrillation, ACE inhibitors and ARBs are recommended.     

Candesartan cilexetil in the management of blood pressure for acute and recurrent stroke in Japan: the Challenge-Stroke study

The Challenge-Stroke study was conducted in Japanese patients initiated on candesartan cilexetil therapy within 3 months of suffering a stroke to investigate the clinical use of candesartan and its efficacy/safety in this therapeutic setting. A total of 869 patients formed the safety analysis set. In total, 79.6% of patients with brain hemorrhage (BH) and 60.2% with brain infarction (BI) began candesartan before post-stroke day 3 and 7, respectively. Baseline average blood pressure (BP) was 152.0/83.2 mmHg in the BH group and 165.2/89.8 mmHg in the BI group; this was reduced to 125.8/75.4 mmHg and 136.3/78.1 mmHg, respectively, at 1 year. The incidence of adverse drug reactions was 6.7 and 8.0%, respectively. There were 12 recurrent strokes in the BH group and 11 in the BI group after 1 year. The risk of recurrent stroke was significantly higher for BH patients with a final systolic BP ≥150 mmHg than for those with a final systolic BP <130 mmHg (hazard ratio: 6.807; p = 0.004). Aggressive antihypertensive therapy is currently employed in Japanese patients with acute stroke. Candesartan was safe and effective for BP control in acute stroke patients. Strict BP management may be useful for secondary prevention of stroke after BH.     

A review of stroke in patients with hypertension and coronary artery disease: Focus on calcium channel blockers

Stroke is a major cause of morbidity and mortality worldwide. Hypertension is one of the most important risk factors for stroke - increasing the risk significantly. The presence and severity of coronary artery disease (CAD), which often coexists with hypertension, also predicts an increased risk of stroke. Lowering blood pressure (BP) to target in patients with hypertension can significantly reduce the incidence of fatal and non-fatal stroke. Effective BP control is even more important in CAD patients who are at greater risk of stroke. Data regarding the effects of antihypertensive therapy on stroke in patients with angina or CAD are limited and have been variable. To date, BP management strategies in patients with CAD have relied on small subsets of data based on high-risk hypertensive patients. Results with calcium channel blockers (CCBs) have been more positive than those with other classes of antihypertensive agents. Findings from the ACTION trial have provided a significant insight into the benefits of CCBs in patients with CAD and hypertension. Nifedipine gastrointestinal therapeutic system (GITS), in addition to best practice therapy for stable angina pectoris, contributes to a significant reduction in the risk of stroke in patients with CAD and hypertension who are at high risk and require effective BP control. Moreover, the incidence of stroke is significantly related to baseline BP, which may be an important factor to consider when deciding on treatment strategies in high-risk patients with CAD.     

Current approaches to the treatment of hypertension in older persons

Hypertension is a major risk factor for cardiovascular disease and is present in 69% of patients with a first myocardial infarction, in 77% of patients with a first stroke, in 74% of patients with chronic heart failure, and in 60% of patients with peripheral arterial disease. Double-blind, randomized, placebo-controlled trials have demonstrated that antihypertensive drug therapy reduces cardiovascular events in patients aged 65 to 79 years. In the Hypertension in the Very Elderly Trial, patients aged ≥ 80 years who were treated with antihypertensive drug therapy had, at 1.8-year follow-up, a 30% reduction in fatal or nonfatal stroke (P = 0.06), a 39% reduction in fatal stroke (P = 0.05), a 21% reduction in all-cause mortality (P = 0.02), a 23% reduction in cardiovascular death (P = 0.06), and a 64% reduction in heart failure (P < 0.001). Although the optimal blood pressure (BP) treatment goal in the elderly has not been determined, existing epidemiologic and clinical trial data suggest that a reasonable therapeutic BP goal should be < 140/90 mm Hg in persons aged < 80 years and a systolic BP of 140 to 145 mm Hg if tolerated in persons aged ≥ 80 years. Nonpharmacologic lifestyle measures should be encouraged both to prevent development of hypertension and as adjunctive therapy in persons with hypertension. Diuretics, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, β-blockers, and calcium channel blockers have all shown benefit in reducing cardiovascular events in randomized trials. The choice of specific drugs depends on efficacy, tolerability, presence of specific comorbidities, and cost. Adverse effects from treatment, such as electrolyte disturbances, renal dysfunction, and excessive orthostatic BP reduction, should be avoided.     

The future of antihypertensive treatment

Despite progress in recent years in the prevention, detection, and treatment of high blood pressure (BP), hypertension remains an important public health challenge. Hypertension affects approximately 1 billion individuals worldwide. High BP is associated with an increased risk of mortality and morbidity from stroke, coronary heart disease, congestive heart failure, and end-stage renal disease; it also has a negative impact on the quality of life. Hypertension cannot be eliminated because there are no vaccines to prevent the development of hypertension, but, its incidence can be decreased by reducing the risk factors for its development, which include obesity, high dietary intake of fat and sodium and low intake of potassium, physical inactivity, smoking, and excessive alcohol intake. For established hypertension, efforts are to be directed to control BP by lifestyle modification (LSM). However, if BP cannot be adequately controlled with LSM, then pharmacotherapy can be instituted along with LSM. Normalization of BP reduces cardiovascular risk (for cardiovascular death, myocardial infarction, and cardiac arrest), provides renoprotection (prevention of the onset or slowing of proteinuria and progression of renal dysfunction to end-stage renal disease in patients with hypertension, diabetes mellitus types 1 and 2, and chronic renal disease), and decreases the risk of cerebrovascular events (stroke and cognition impairment), as has been amply demonstrated by a large number of randomized clinical trials. In spite of the availability of more than 75 antihypertensive agents in 9 classes, BP control in the general population is at best inadequate. Therefore, antihypertensive therapy in the future or near future should be directed toward improving BP control in treated hypertensive patients with the available drugs by using the right combinations at optimum doses, individually tailored gene-polymorphism directed therapy, or development of new modalities such as gene therapy and vaccines.Several studies have shown that BP can be reduced by lifestyle/behavior modification. Although, the reductions appear to be trivial, even small reductions in systolic BP (for example, 3-5 mm Hg) produce dramatic reduction in adverse cardiac events and stroke. On the basis of the results of clinical and clinical/observational studies, it has been recommended that more emphasis be placed on lifestyle/behavior modification (obesity, high dietary intake of fat and sodium, physical inactivity, smoking, excessive alcohol intake, low dietary potassium intake) to control BP and also to improve the efficacy of pharmacologic treatment of high BP. New classes of antihypertensive drugs and new compounds in the established drug classes are likely to widen the armamentarium available to combat hypertension. These include the aldosterone receptor blockers, vasodilator beta-blockers, renin inhibitors, endothelin receptor antagonists, and dual endopeptidase inhibitors. The use of fixed-dose combination drug therapy is likely to increase.There is a conceptual possibility that gene therapy may yield long-lasting antihypertensive effects by influencing the genes associated with hypertension. But, the treatment of human essential hypertension requires sustained over-expression of genes. Some of the challenging tasks for successful gene therapy that need to be mastered include identification of target genes, ideal gene transfer vector, precise delivery of genes into the required site (target), efficient transfer of genes into the cells of the target, and prompt assessment of gene expression over time. Targeting the RAS by antisense gene therapy appears to be a viable strategy for the long-term control of hypertension. Several problems that are encountered in the delivery of gene therapy include 1) low efficiency for gene transfer into vascular cells; 2) a lack of selectivity; 3) problem in determining how to prolong and control transgene expression or antisense inhibition; and 4) difficulty in minimizing the adverse effects of viral or nonviral vectors. In spite of the hurdles that face gene therapy administration in humans, studies in animals indicate that gene therapy may be feasible in treating human hypertension, albeit not in the near future. DNA testing for genetic polymorphism and determining the genotype of a patient may predict response to a certain class of antihypertensive agent and thus optimize therapy in individual patients. In this regard, there are some studies that report the effectiveness of antihypertensive therapy based upon the genotype of selected patients. Treatment of human hypertension with vaccines is feasible but is not likely to be available in the near future.     

不同高血压人群的降压目标值

高血压是冠心病、脑卒中和肾功能衰竭发展的一个主要独立危险因素。降压治疗的直接目的是达标,终极目的是降低患者的心血管事件风险。然而,降压治疗的目标值确定却缺乏足够的循证医学证据支持。因此,对于高血压患者,什么是合理的降压目标值,那些因素决定降压目标值成为临床实践中关注的焦点。本文将依据近年高血压指南对高血压不同人群的降压目标值做一综述。     

降压治疗对脑卒中二级预防的临床证据

目的综合分析与脑卒中有关的降压治疗大样本随机对照试验,为脑卒中二级预防提供临床证据.方法计算机检索Medline(1966～2003年6月),对已公开发表的大样本随机对照降压治疗预防脑卒中再发的临床试验进行综合分析.分析指标为脑卒中事件、冠心病事件及总死亡率等.结果共纳入脑卒中后抗高血压治疗的随机对照试验(PATS)、多中心培哚普利降压治疗脑卒中/一过性脑缺血发作的随机对照临床试验(PROGRESS)和心脏结局预防评估研究(HOPE)3个试验进行综合分析.结果显示:降压治疗组较安慰剂对照组降低脑卒中再发危险率28%,降低冠心病危险率15%,降低总死亡率11%;降压治疗不仅能降低脑血管病或心血管病高危者伴高血压的脑卒中再发危险,而且对未伴高血压者也能降低其脑卒中危险.结论降压治疗对脑卒中二级预防是有益的.     

老年高血压病患者停服降压药物的原因分析

目的为了调查老年高血压病患者停服降压药物的原因,以提高老年高血压患者的治疗效果.方法采用面谈和查阅患者病历的方法,调查115例高血压病患者停服降压药物的原因及其动态血压检测结果,然后进行数据统计和分析.结果 115例停服降压药物的原因分别为多次测量血压偏低、对高血压病了解不够、对降压药物了解不够、服药方案过于复杂、老年患者记忆力较差、一时配不到同种药物,其中因血压偏低而停药患者(血压控制率为77.35%)与因其他原因而停药患者(血压控制率为33.87%)比较,差异有统计学意义(P＜0.001).结论对患者加强健康教育,定期检测血压,以提高血压控制率.     

Blood pressure treatment target in patients with diabetes mellitus--current evidence

Hypertension is a very common cardiovascular disease (CVD) risk factor in diabetes, affecting more than half of diabetic patients. Major guidelines on the management of hypertension recommend to start antihypertensive drugs in all diabetic patients with a systolic blood pressure (SBP) 140 mmHg or more and/or a diastolic blood pressure (DBP) 90 mmHg or more, and to adjust the treatment strategy in order to lower their BP below these values. The present body of evidence suggests that in patients with type 2 diabetes mellitus/impaired fasting glucose/impaired glucose tolerance, a SBP treatment goal of 130 to 135 mmHg is acceptable. Aiming at SBP levels of 130 mmHg decreases stroke risk, but the risk of serious adverse events may increase with very low BP levels. The results regarding the attained DBP level is somewhat complex, since middle-aged people with diastolic hypertension and pre-existing CVD may have increased CVD mortality if their DBP is lowered drastically to a very low level. With the currently available very limited trial data on low attained BP level, it is not possible to set a specific treatment target regarding BP levels for diabetic hypertensive patients, but it is important to use a personalized approach in their antihypertensive treatment.     

Blood pressure lowering therapy for mild hypertensive patients with a history of stroke

Hypertension is the primary and one of the major risk factors for stroke. Many hypertensive patients with a history of stroke might have mild to moderate hypertension at the same time. In order to prevent recurrence of cardiovascular diseases including stroke, we should lower their blood pressure levels, carefully and slowly below less than 140/90 mmHg or much lower. Additionally, the patients having any occlusion or stenoses in their carotid and/or intracranial arteries, or even in old-old patients with atherosclerosis, might need further consideration for the cerebral blood flow insufficiency in the course of blood pressure lowering therapy. Although the advantages of inhibitors of renin-angiotensin system are lionized these days (advertisement based medicine: ABM), we should never forget to select more favorable antihypertensive drugs for each patient in case by case (individual based medicine: IBM), to get the definite blood pressure lowering effects without worsening any complications. We also need further gathering of many evidences in a net-work-meta-analysis way, on blood pressure lowering therapy in those hypertensive patients with a history of stroke (evidence based medicine: EBM).     

Untoward effects of blood transfusion

Abstract

Hypertension affects approximately 73 million individuals in the United States. Clinical studies have shown that antihypertensive therapy can reduce blood pressure (BP) and the risk of cardiovascular events. However, the majority of patients with hypertension do not achieve the recommended BP goal of < 140/90 mm Hg (or < 130/80 mm Hg for patients with diabetes) with antihypertensive monotherapy, and require therapy with 2 or more antihypertensive agents. Combination therapy utilizes antihypertensive agents from different drug classes, which act via distinct pharmacologic mechanisms to improve overall efficacy and tolerability. Although combination therapy is superior to monotherapy in achieving BP goals across the entire spectrum of hypertension, the proportion of patients achieving the recommended BP goal can be further improved by the use of new antihypertensive drug combinations. The beneficial antihypertensive characteristics of both angiotensin receptor blockers and calcium channel blockers suggest that combining these classes may result in a highly efficacious antihypertensive therapy with regard to both activity and safety when used as a fixed-dose combination. In particular, a fixed-dose combination of olmesartan medoxomil plus amlodipine besylate has been demonstrated to be an efficacious antihypertensive combination due in part to the benefits associated with each of these agents within their respective drug classes.     

Reducing cardiovascular events and end-organ damage in patients with hypertension: new considerations

Hypertension treatment should focus on achieving blood pressure (BP) of < 140/90 mm Hg in most patients and < 130/80 mm Hg in patients with diabetes. Lifestyle modifications play a central role in therapy and should be the first line of treatment in all patients. However, long-term lifestyle changes are rarely achieved and pharmacotherapy is required. The selection of an optimal regimen for each patient will depend on comorbid conditions. Most patients will require combination therapy with ≥ 2 antihypertensive agents to control their BP. The most useful combinations employ drugs from different classes with complementary mechanisms of action, producing additive or synergistic BP reduction with minimal adverse events.     

Blood pressure variation and cardiovascular risk in hypertension

Disruption of circadian rhythm of blood pressure (BP) is associated with advanced target organ damage and poor cardiovascular prognosis. We studied silent cerebrovascular disease and stroke events in older Japanese patients with different nocturnal BP dipping. There was a J-shaped relationship of nocturnal dipping status with silent cerebral infarcts detected by brain MRI at baseline, and with stroke incidence during the follow-up period. The extreme-dippers (with marked nocturnal BP dipping) and risers (with higher nocturnal BP than awake BP) had a higher prevalence of silent cerebral infarcts and poorer stroke prognosis than those with appropriate nocturnal BP dipping (dippers). Extreme-dippers tended to have predominant systolic hypertension and increased BP variability. Several factors are affecting the diurnal BP variation pattern. The non-dipping pattern is associated with autonomic nervous dysfunction and poor sleep quality due to nocturnal behavior and sleep apnea. Extreme-dippers might have increased arterial stiffness with reduced circulating blood volume in addition to an excessive morning surge due to alpha-adrenergic hyperactivity. Morning BP surge, which is partly associated with nocturnal BP dipping status, was a predictor of stroke event independently for ambulatory BP level and silent cerebral infarcts. Antihypertensive medication that normalize the disrupted circadian BP variation might improve cardiovascular prognosis in high-risk hypertensive patients.     

INVEST revisited: review of findings from the International Verapamil SR–Trandolapril Study

The International Verapamil SR–Trandolapril Study (INVEST), a randomized trial of 22,576 predominantly elderly patients with an average 2.7-year follow-up, compared a calcium antagonist-led strategy (verapamil SR plus trandolapril) with a β-blocker-led strategy (atenolol plus hydrochlorothiazide) for hypertension treatment and prevention of cardiovascular outcomes in coronary artery disease patients. Patients received individualized dose and drug titration following a flexible, multi-drug, guideline-based treatment algorithm, with the objective of achieving optimal blood pressure (BP) control individualized for comorbidities (e.g., diabetes). The primary outcome (PO) was first occurrence of death (all-cause), nonfatal myocardial infarction or nonfatal stroke. The strategies resulted in significant and very similar BP reduction, with approximately 70% of patients in both strategies achieving BP control (<140/90 mmHg). Increasing number of office visits with BP in control was associated with reduced risk of the PO. Overall, there was no difference in the PO comparing the strategies; however, new-onset diabetes occurred more frequently in those assigned the atenolol strategy. This report summarizes findings from INVEST and puts them in perspective with our current state of knowledge derived from other large hypertension treatment trials. INVEST findings support that BP reduction is important for prevention of adverse cardiovascular morbidity and mortality, and selection of antihypertensive agents should be based on patient comorbidities and other risk factors (e.g., risk for diabetes) and not necessarily that any one drug be given to all.     

Advantages of blood pressure optimization

Lowering blood pressure (BP) reduces cardiovascular events, but aggressive BP management may not be advantageous. Optimal BP control (target: < 120/ 80 mm Hg) and conventional BP control (target: < 140/90 mm Hg) were compared in patients with hypertension in terms of target-organ damage and tolerability. A total of 23 patients with hypertension were randomly assigned to optimal versus conventional therapy for 6 months. Therapy was initiated with lercanidipine 10 mg/day. For BP control, the dose could be doubled or other drugs added. Three indices of target-organ damage were studied: left ventricular mass (LVM) index, flow-mediated dilatation (FMD) of the brachial artery, and 24-hour urinary albumin excretion. The BP decreased markedly by 21.3±3.4/13.2±1.7 mm Hg in the conventional therapy group and by 26.6±3.6/17.9±1.5 mm Hg in the optimal therapy group. Diastolic BP was significantly lower, by 4.7±2.3 mm Hg, in the optimal therapy group (P < .05). Ambulatory BP was also decreased in both groups. There was no significant change in LVM or FMD in either group. Baseline LVM index and FMD values were correlated with systolic BP (r=0.51, P=.02; r=0.54, P=.009). In the optimal therapy group, urinary albumin excretion increased significantly (P=.04). Plasma levels of B-type natriuretic peptide (BNP) decreased with antihypertensive therapy (P=.03). Treatment was well tolerated, and none of the patients withdrew from the study. There was no significant difference in adverse events between the 2 groups. Optimization of BP is feasible, safe, and well tolerated; however, a larger study of longer duration may be needed to demonstrate improvements in LVM and endothelial function with conventional versus optimal therapy.     

Clinical experience with perindopril in patients nonresponsive to previous antihypertensive therapy: a large US community trial

A subgroup analysis of a large US community trial was conducted to evaluate the antihypertensive efficacy and safety of perindopril, an angiotensin-converting enzyme inhibitor (ACEI), in 3159 patients who lacked blood pressure (BP) control at entry with previous antihypertensive therapy. Patients received 4 mg perindopril daily for 6 weeks. Based on physicians' assessment of BP response, the patients were then either maintained on 4 mg daily (group 1) or the dose was increased to 8 mg daily (group 2) for an additional 6 weeks. The mean baseline sitting BP was 158.2/92.9 mm Hg. Perindopril monotherapy produced a significant BP decrease from baseline of 11.6/6.5 mm Hg and 14.9/8.4 mm Hg at weeks 6 and 12, respectively. In group 1 patients, the majority of BP decrease occurred at week 6 (17.3/9.5 mm Hg) and was maintained until the end of week 12 (18.2/10.1 mm Hg). In group 2 patients, the BP decrease on the 4-mg dose was modest at week 6 by 5.2/3.1 mm Hg. However, further dose up-titration of perindopril to 8 mg resulted in a clinically significant BP decrease of 11.9/6.8 mm Hg from baseline to week 12. Significant antihypertensive effects of perindopril were also demonstrated in the special patient populations of elderly (>or=65 years), black, isolated systolic hypertension, patients with concomitant cardiovascular diseases, and patients nonresponsive to other ACEI therapy. Overall, BP control (<140/<90 mm Hg) was achieved in 40.0% of patients at week 12. Perindopril was well tolerated with cough and angioedema reported in 8.5% and 0.4% patients, respectively. Physicians assessed therapeutic response to perindopril as satisfactory in 73.8% patients who were nonresponsive to previous antihypertensive therapy. These results suggest that, in a community-based practice, perindopril monotherapy (4-8 mg/d) is an effective and safe therapeutic option in patients nonresponsive to previous antihypertensive therapy.     

Treating hypertension with cardioprotective therapies: the role of ACE inhibitors, ARBs, and beta-blockers

Hypertension is both a disease and risk factor for cardiovascular disease (CVD) and each 20/10 mm Hg rise in blood pressure (BP) doubles the risk for CVD. Although BP reduction through lifestyle modification and/or antihypertensive therapy has been shown to dramatically reduce the risk for CVD, recent evidence has shown that many patients with hypertension do not have adequate BP control. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) provides comprehensive guidelines on the diagnosis, classification, and management of hypertension and related CV conditions. The JNC 7 guidelines recommend that most patients receive first-line therapy with thiazide diuretics, but the majority of patients will require 2 or more antihypertensive agents to achieve adequate BP control. The selection of additional antihypertensive therapies should be based on the presence of concomitant CV and metabolic conditions as well as patient-specific factors such as race. An important role exists for angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and beta-blockers, particularly in patients with comorbid CV or metabolic conditions. Clinical evidence suggests that these agents may offer benefits beyond simple BP lowering. Furthermore, synergies among antihypertensive classes may improve BP control and combination therapy may also permit the use of smaller doses of each medication and reduce the risk of dose-related adverse effects.