Antihypertensive therapy in the elderly

Control of hypertension in the elderly has been shown to reduce cardiovascular morbidity. Although it is not known if this is also true for isolated systolic hypertension, drug treatment should be considered for systolic pressures over 170 mm Hg that cannot be controlled with nondrug therapy. The diuretics, calcium channel blockers, and the ACE inhibitors are very effective and generally well-tolerated therapy for the elderly. It may be necessary to combine two of these agents for some patients. Beta blockers are particularly useful for patients with ischemic heart disease or prior myocardial infarction. Beta blockers are the only agents which have been shown to be cardioprotective. For all antihypertensive agents, the elderly should be started on low doses. The drugs should then be titrated slowly if necessary. It is common for the elderly to respond to lower dosages than younger patients, and they should be monitored carefully for adverse reactions to medications. Antihypertensives should be administered once or twice daily whenever possible. If these principles are considered, most patients can be effectively controlled with a minimum of side effects.     

Treatment of hypertension in type 2 diabetes mellitus--2002 update

Arterial hypertension and diabetes are potent independent risk factors for cardiovascular, cerebral, renal and peripheral (atherosclerotic) vascular disease. The prevalence of hypertension in diabetic individuals is approximately twice that in the non-diabetic population. Diabetic individuals with hypertension have a greater risk of macrovascular and microvascular disease than normotensive diabetic individuals. Hypertension is a major contributor to morbidity and mortality in diabetes, and should be recognized and treated early. Type 2 diabetes and hypertension share certain risk factors such as overweight, visceral obesity, and possibly insulin resistance. Life-style modifications (weight reduction, exercise, limitation of daily alcohol intake, stop smoking) are the foundation of hypertension and diabetes management as the definitive treatment or adjunctive to pharmacological therapy. Additional pharmacological therapy should be initiated when life-style modifications are unsuccessful or hypertension is too severe at the time of diagnosis. All classes of antihypertensive drugs are effective in controlling blood pressure in diabetic patients. For single-agent therapy, ACE-inhibitors, angiotensin receptor blocker, beta-blockers, and diuretics can be recommended. Because of concerns about the lower effectiveness of calcium channel blockers in decreasing coronary events and heart failure and in reducing progression of renal disease in diabetes, it is recommended to use these agents as second-line drugs for patients who cannot tolerate the other preferred classes or who require additional agents to achieve the target blood pressure. The choice depends on the patients specific treatment indications since each of these drugs have potential advantages and disadvantages. In patients with microalbuminuria or clinical nephropathy, both ACE-inhibitors and angiotensin receptor blockers are considered first line therapy for the prevention of and progression of nephropathy. Since treatment is usually life-long, cost effectiveness should be included in treatment evaluation.     

Does use of antihypertensive drugs affect the incidence or progression of dementia? A systematic review

Background: Hypertension appears to contribute to the development of dementia. Antihypertensive drugs may play an important role in altering the incidence or progression of dementia, particularly dementia of the vascular type; however, the neuroprotective effects of these agents in other types of dementia are not well characterized.Objectives: The main aims of this review were to examine the relationship between use of antihypertensive agents and the incidence and progression of Alzheimer's dementia (AD), vascular dementia (VaD), and unspecified dementia, and to consider whether these agents may be neuroprotective.Methods: A search of the English-language literature (January 1996–August 2009) was conducted using PubMed, Ovid MEDLINE, EBSCO MEDLINE, and the Cochrane Database of Systematic Reviews for publications mentioning both antihypertensive drugs and dementia. A combination of searches was performed using the following terms: antihypertensive drugs, dementia, cognitive impairment, Alzheimer's dementia, vascular dementia, progression of cognitive impairment, severity of cognitive impairment, severity of dementia, prevalence, and incidence. Searches were also performed using the names of antihypertensive drug classes. The bibliographies of all retrieved articles were reviewed for additional relevant publications. The focus was on randomized controlled trials, cohort studies, and case—control studies, excluding studies in animals, patients aged <45 years, drugs other than antihypertensive agents, and the role in cognition of hormones, receptors, and enzymes.Results: Sixty–five potentially relevant articles were identified from the 536 publications retrieved by the literature search. After application of the exclusion criteria, 12 original studies were included in the review, all published between 1999 and 2008 and most involving patients with AD or VaD. The most frequently studied antihypertensive agents were calcium channel blockers (7 studies), diuretics (6 studies), and angiotensin-converting enzyme (ACE) inhibitors (6 studies). Overall, these medications appeared to be beneficial in dementia, but only ACE inhibitors and diuretics significantly reduced the risk for and progression of dementia in the majority of studies.Conclusions: Antihypertensive medications—particularly ACE inhibitors and diuretics—may be helpful in reducing the risk for and progression of dementia. Large randomized clinical trials are warranted to further explore the relationship between antihypertensive drugs and dementia.     

Initial antihypertensive therapy. What are the current drugs of choice?

The goal of antihypertensive treatment, in addition to lowering blood pressure, is to reduce the risk of cardiovascular events. Until recently, however, only conventional treatment with diuretics and beta-blockers had been studied in terms of cardiovascular end points. In this article, Dr Yeun reviews the results of recent trials comparing these agents with other classes of antihypertensive drugs. She examines the confounding elements in the trials, provides an interpretation of study results, and suggests a practical approach to initial treatment of uncomplicated hypertension.     

The use of calcium antagonists in the therapy of hypertension in the elderly

Calcium antagonists (calcium channel blockers) are widely used in the treatment of hypertension and other cardiovascular diseases. The results of a large number of clinical trials have demonstrated that calcium antagonists are as efficacious as other classes of antihypertensive agents in decreasing blood pressure in the elderly patients. Large clinical trials have shown the effectiveness of calcium antagonists (with long duration of action) in reducing cardiovascular and cerebrovascular morbidity and mortality in elderly hypertensive patients. The calcium antagonists are a chemically, pharmacologically and therapeutically heterogeneous group of agents. Among themselves, they differ in vasoselectivity, effect on cardiac conduction, sympathetic activation, adverse effect profile, ability to protect against target organ damage, suitability for patients with co-morbid conditions, and pharmacodynamic characteristics. The calcium antagonists can be used as single agents or in combination with other antihypertensive drugs. These drugs should not be used as first-line drugs in treating high blood pressure in patients with heart failure, since drugs in other classes provide more benefits. The dihydropyridine calcium antagonists should not be used in post-myocardial infarction patients or in patients with unstable angina; however, non-dihydropyridines may be used in such patients. The adverse effects of dihydropyridines include peripheral and ankle edema, flushing and headache. The short-acting preparations of the older calcium antagonists are no longer used, because of the potential for adverse cardiovascular outcome.     

Medical management of stable coronary artery disease

All patients with stable coronary artery disease require medical therapy to prevent disease progression and recurrent cardiovascular events. Three classes of medication are essential to therapy: lipid-lowering, antihypertensive, and antiplatelet agents. Lipid-lowering therapy is necessary to decrease low-density lipoprotein cholesterol to a target level of less than 100 mg per dL, and physicians should consider a goal of less than 70 mg per dL for very high-risk patients. Statins have demonstrated clear benefits in morbidity and mortality in the secondary prevention of coronary artery disease; other medications that can be used in addition to statins to lower cholesterol include ezetimibe, fibrates, and nicotinic acid. Blood pressure therapy for patients with coronary artery disease should start with beta blockers and angiotensin-converting enzyme inhibitors. If these medications are not tolerated, calcium channel blockers or angiotensin receptor blockers are acceptable alternatives. Aspirin is the first-line antiplatelet agent except in patients who have recently had a myocardial infarction or undergone stent placement, in which case clopidogrel is recommended. Anginal symptoms of coronary artery disease can be treated with beta blockers, calcium channel blockers, nitrates, or any combination of these. Familiarity with these medications and with the evidence supporting their use is essential to reducing morbidity and mortality in patients with coronary artery disease.     

Expanded role for ARBs in cardiovascular and renal disease? Recent observations have far-reaching implications

The ARBs are a new class of drugs with broad therapeutic potential in cardiovascular disease. These agents act by selectively inhibiting the AT1 subtype of the angiotensin II receptors. They are effective antihypertensive agents with promise, theoretically, in the prevention and regression of ventricular hypertrophy. They are safe and well tolerated in patients with CHF and might be effective in improving survival and reducing morbidity. ARBs also might have a similar role in improving the clinical outcomes of patients with coronary artery disease and chronic nephropathy. Their precise role in the treatment and prevention of cardiovascular and renal disease should be established by several ongoing clinical trials.     

Race-based therapy for hypertension: possible benefits and potential pitfalls

Hypertension is a leading risk factor for cardiovascular disease, which includes coronary heart disease, heart failure and stroke. This article examines the possible benefits and potential pitfalls of utilizing race-based categories for antihypertensive therapy. Although the use of race and ethnicity to guide antihypertensive treatment is fraught with difficulty and is, to a large extent, inadequate, there may be benefit in recognizing specific aspects of race and ethnicity when approaching patients with hypertension. Evidence from clinical trials, including drug efficacy and safety comparisons and cardiovascular outcomes, has demonstrated some differences based on race/ethnicity. American federal standards strongly encourage capturing data on race/ethnicity, and most of the current data are available for self-described African–Americans. International studies increasingly identify race/ethnicity, although the data are not as robust as in US trials. Current guidelines recommend thiazide diuretics and/or long-acting calcium channel blockers as initial treatment for Blacks, although medications for compelling indications agents should be prescribed, regardless of race/ethnicity.     

50 years of thiazides: should thiazide diuretics be considered third-line hypertension treatment?

The purpose of this report is to review available and emerging antihypertensive treatment options in light of current guidelines and evidence from large clinical trials. The published literature was reviewed for evidence regarding first-line options for antihypertensive agents, including thiazide-type diuretics, as monotherapy or as part of combination therapy. Current guidelines recommend using thiazide-type diuretics as first-line therapy alone or in combination with another agent. Other commonly used antihypertensive agents include calcium channel blockers, β-adrenergic receptor blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and the direct renin inhibitor, aliskiren. These agents are associated with varying degrees of evidence that they may provide protection from cardiovascular or renal disease beyond that associated with blood pressure reduction. Thiazide diuretics are inexpensive and effective but may not be preferable to other classes of antihypertensives that reduce blood pressure to a similar extent with a better safety profile and superior reductions in cardiovascular event rates. However, calcium channel blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and direct renin inhibitors also show promise as initial monotherapy or as part of a combination therapy regimen. In patients requiring additional blood pressure reduction, add-on therapy with a diuretic could provide additional blood pressure-lowering efficacy.     

Characteristics and dosage of antihypertensive medication

Several classes of antihypertensive drugs are currently available. Among them, diuretics, Ca antagonists, ACE inhibitors, ARBs and beta blockers are currently established as a first line drug because of its effectiveness for blood pressure lowering as well as prevention of cardiovascular diseases with a long-term use. Each class of antihypertensive drugs has a unique pharmacological property leading to the advantages and disadvantages in the various clinical settings. Furthermore, individual drug in the same class shows a unique pharmaokinetic and pharmacodynamic profiles. Hence, selection of antihypertensive drugs should be individualized, taking into account various factors including age and comorbid conditions. The characteristics of specific antihypertensive drugs, the setting in which they are most useful and the contraindications to use will be reviewed here. From the viewpoint of the strict blood pressure control throughout 24 hour, practical considerations related to dosing and frequency will also be discussed.     

Hypertension treatment and the prevention of coronary heart disease in the elderly

Both isolated systolic hypertension (>140 mm Hg/<90 mm Hg) and systolic/diastolic hypertension (>140 mm Hg/>90 mm Hg) are major risk factors for cardiovascular disease in the elderly. Specific antihypertensive drug therapy is available if lifestyle interventions fail to reduce blood pressure to a normal level. Diuretics and beta blockers both reduce the occurrence of adverse events related to cerebrovascular disease; however, diuretics are more effective in reducing events related to coronary heart disease. Treated patients are less likely to develop severe hypertension or congestive heart failure. In most instances, low-dose diuretic therapy should be used as initial antihypertensive therapy in the elderly. A long-acting dihydropyridine calcium channel blocker may be used as alternative therapy in elderly patients with isolated systolic hypertension. Trials are being conducted to evaluate the long-term effects of angiotensin converting enzyme inhibitors and angiotensin-II receptor blockers in elderly patients with uncomplicated hypertension.     

Importance of renin in blood pressure regulation and therapeutic potential of renin inhibition

Despite improvements in its detection and treatment, hypertension remains a significant public health problem worldwide. In recent years, many international hypertension societies and organisations have set increasingly rigorous blood pressure (BP) targets, with the aim of reducing cardiovascular complications, and this has in turn necessitated the use of more antihypertensive medications to reach these targets in individual patients. There is therefore an ongoing need to develop antihypertensive drugs with new mechanisms of action. Renin inhibitors represent a novel class of compounds which offer considerable promise as BP-lowering agents. Here, we review the rationale for renin inhibition as a therapeutic target and examine the preclinical and clinical evidence for the antihypertensive effectiveness of the renin inhibitors.     

Diuretics: still essential drugs for the management of hypertension

According to most current international guidelines for hypertension, diuretics are indicated for elderly and black patients, unless they have any of a long list of other preferential indications. These recommendations are mostly based on the results of corporate-sponsored and biased trials, which have unsuccessfully tried to demonstrate the existence of pleiotropic effects of newer agents. Metaregression analyses have shown that the benefits of treatments are directly proportional to the difference in blood pressure between trial arms. New analyses of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack (ALLHAT) trial demonstrated the superiority of chlorthalidone over other agents in the prevention of end-stage renal disease in diabetics and of cardiovascular events in newer cases of diabetes. Despite this evidence, patients continue to withdraw from effective therapies in recent trials. The use of diuretics has also been challenged by the results of the Avoiding Cardiovascular Events in Combination Therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) trial, which employed hydrochlorothiazide, a diuretic with lower potency and duration of action than chlorthalidone. Diuretics are still essential drugs for hypertension management, but diuretics with higher potency and duration of action, such as chlorthalidone, should be preferred.     

Diuretics in the management of hypertension

Thiazide diuretics have been in use for over 30 years in the treatment of hypertension. Their action results in a reduction in peripheral resistance without a significant decrease in cardiac output or a major shift in plasma volume. They are as or more effective than any of the other antihypertensive agents when used as monotherapy and can serve as baseline therapy in combination with any of the available adrenergic, converting enzyme-inhibiting agents, or calcium-entry blockers. There is a high degree of patient acceptance; titration to an effective dosage is relatively easy; and cost, relatively low. Although certain undesirable metabolic changes may occur following the use of these agents, most of them are controllable, and there is no evidence to date that they offset the benefits achieved by blood pressure lowering. Asymptomatic elevated uric acids have not been shown to be of great significance. If gout occurs, it can be managed. Alterations in glucose metabolism may occur, and in some patients, it appears that blood glucose levels are elevated over time. This is not a desirable metabolic change, but is one of doubtful prognostic significance. Changes in lipids are generally short-term, and in the major clinical trials, lipid levels have not remained elevated with a continuation of diuretic therapy. Although diuretics produce hypokalemia in a fairly high percentage of patients, this is not generally severe (less than 3.3 mEq per liter) and usually does not produce symptoms. There is no firm evidence that the hypokalemia produced by diuretics predisposes the patient to severe arrhythmias or sudden death, although this point has been emphasized repeatedly in recent publications. Diuretics can usually be given without potassium-maintenance therapy. However, hypokalemia should be prevented in the elderly, in patients with ischemic heart disease, left ventricular hypertrophy and those on digitalis, or with diabetes. We prefer potassium-sparing agents along with a diuretic over supplements to prevent hypokalemia; the number of pills is kept at a reasonable level, and cost is minimized. Physicians should continue to prescribe diuretics as first-step therapy in the majority of patients to maximize therapeutic outcome.     

Considerations for drug therapy in hypertension

Both the Joint National Committee and the British Hypertension Society recommend b-blockers and diuretics as first-line therapy in the treatment of uncomplicated hypertension. As a result, many clinicians will also prescribe these drugs in the treatment of patients with hypertension and coexistent disease (unless they are specifically contraindicated), even though they may not always be the most beneficial choice. This review aims to examine factors that should be taken into consideration when choosing appropriate antihypertensive therapy. Particular attention is given to treatment options in two special patient groups, the elderly and patients with co-morbid diabetes, as these groups have an increased risk of developing cardiovascular complications. In response to the increasing evidence base from large-scale trials, the article concludes that cardiovascular risk factors, coexisting disease, concomitant medication and age should all be taken into account when choosing antihypertensive therapy.     

Calcium channel blockers in the treatment of hypertension and prevention of cardiovascular disease: results from major clinical trials

The ability of antihypertensive agents such as ss-blockers and thiazide and thiazide-like diuretics to reduce the risk of cardiovascular disease is well documented. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) was undertaken to determine whether the newer classes of antihypertensive drugs-namely, calcium channel blockers (CCBs), alpha-1 blockers, and angiotensinconverting enzyme (ACE) inhibitors-were as effective as the older agents in preventing cardiovascular events. The results of ALLHAT showed that the diuretic chlorthalidone, the CCB amlodipine, and the ACE inhibitor lisinopril were equally effective in preventing the primary outcome-fatal coronary heart disease or nonfatal myocardial infarction. However, chlorthalidone and lisinopril were more effective at preventing heart failure, whereas amlodipine and chlorthalidone were more effective than lisinopril at preventing stroke. The ALLHAT findings, as well as those of other large, randomized, controlled antihypertensive trials, confirm the value of lowering blood pressure as an approach to reducing the risk, incidence, and economic burden of cardiovascular disease.     

Rationale for combination therapy in hypertension management: focus on angiotensin receptor blockers and thiazide diuretics

Despite recognition that hypertension is a major risk factor for cardiovascular events and mortality, blood pressure control rates remain low in the US population. Reflecting clinical trial results, hypertension management guidelines assert the clinical benefit of achieving current blood pressure goals and indicate that most patients will require 2 or more drugs to reach goal. Well-designed drug combinations counter hypertension via complementary mechanisms that increase antihypertensive efficacy, potentially with lower rates of adverse events than higher dose monotherapy regimens. Lower adverse event rates, in turn, may contribute to greater adherence with treatment. The combination of a low-dose diuretic with agents that block the effects of the renin-angiotensin system (RAS), such as angiotensin receptor blockers, has been found in numerous clinical trials to be highly effective for lowering blood pressure in patients with uncomplicated as well as high-risk hypertension, with a comparable favorable side effect profile compared with monotherapy. Moreover, agents that block the RAS are associated with a lower risk of new-onset diabetes mellitus than other antihypertensive classes. Complementary combinations of antihypertensive agents provide an efficient and effective approach to hypertension management.     

Incidence of adverse reactions in blood donors taking antihypertensive medications

A study was performed to determine whether donors taking antihypertensive medications other than "beta blocking agents" have an increased incidence of vasovagal reactions to blood donation. A total of 546 reactions were observed in 16,424 blood donors over a period of 3 months. First-time donors had a significantly higher frequency of reactions than repeat donors. Eighty-five percent of all donors were experienced donors and 96 percent of those taking antihypertensive medication were experienced donors. The reaction rate in repeat donors was not significantly different for those taking antihypertensive medication as compared with those not taking medication. Over 97% of all reactions were mild. The deferral of donors taking antihypertensive medication is not indicated when blood pressure is normal, symptoms are absent, and diuretics or similar agents are the only drugs used.     

Clinical role of direct renin inhibition in hypertension

Treatment strategies to improve blood pressure control, reduce end-organ damage, and improve cardiovascular outcomes are more important today than ever before. Most patients will require combination therapy to achieve target blood pressure; early initiation of combination therapy may help patients achieve blood pressure control more rapidly. Low-dose combinations may be more effective with fewer adverse effects than higher doses of single agents. Dysregulation of the renin-angiotensin-aldosterone system (RAAS) is an important contributor in the pathogenesis of hypertension and its sequelae. Treatment with a direct renin inhibitor blocks the rate-limiting step in the RAAS, resulting in decreased angiotensin I and II production and decreased urinary aldosterone excretion. Like the angiotensin converting enzyme inhibitors and angiotensin II receptor blockers, treatment with a direct renin inhibitor increases plasma renin concentration, but unlike the other RAAS inhibitors, treatment with a direct renin inhibitor decreases plasma renin activity. This unique combination of effects on the RAAS make a direct renin inhibitor an attractive option to combine with other antihypertensive agents for the management of hypertension and its comorbidities. Clinical studies have shown that combining the direct renin inhibitor, aliskiren, with drugs representing each of the major classes of antihypertensive agents (thiazide diuretics, beta blockers, angiotensin converting enzyme inhibitors, angiotensin II receptor blockers, and calcium-channel blockers) reduces blood pressure, improves markers for cardiovascular outcomes, or does both. Results of several ongoing randomized clinical trials should provide additional insights into the potential of therapeutic combinations that include aliskiren to improve cardiovascular morbidity and mortality in patients with hypertension and related comorbidities.     

Hypertension and ambulatory blood pressure monitoring

Advancing technology will develop lighter, less expensive, more compatible, and more reliable ambulatory blood pressure recording devices, which will result in an increased use of the procedure in clinical practice. Future longitudinal prospective studies of normotensive and hypertensive subjects may authenticate the relationship between ambulatory blood pressure values and cardiovascular morbidity and mortality, thus enabling clinicians to generate guidelines for the diagnosis and treatment of hypertension. Until that happens, ambulatory blood pressure monitoring can provide meaningful supplemental information that overcomes the limitations of office blood pressure. In addition, various cardiovascular disorders may only be evaluated by using ambulatory blood pressure monitoring. Finally, ambulatory blood pressure monitoring is valuable in determining the efficacy of antihypertensive medications and improving the research trials of these drugs.