The expanding role of angiotensin receptor blockers in the management of the elderly hypertensive

The world faces the challenge of an ageing population, and for developed countries, the particular challenge is the increasing number of very old people, over 80 years of age. Hypertension is a condition associated with increasing age, but elderly patients with hypertension are often difficult to manage. Nevertheless, treatment of hypertension is of greatest value in older patients who often have additional risk factors or cardiovascular disease. Older patients have generally tolerated antihypertensive therapy well in randomised, placebo-controlled trials. The tolerability of angiotensin receptor blockers (ARBs) is better than that of many other classes of drugs currently used for the management of hypertension and these drugs have virtually no contraindications. Thus, ARBs have a bright future in the management of hypertension and in the treatment of stroke and cognitive decline in the elderly.     

Drug interactions with angiotensin receptor blockers

Many patients with high blood pressure receive multiple medications for hypertension and other conditions, placing them at risk for adverse drug interactions. Additionally, as the prevalence of hypertension increases with age, factors like greater frailty, comorbidity of the elderly requiring polypharmacy, and reduced hepatic and renal clearance rates for the elimination of drugs increase the likelihood of drug interactions. Angiotensin receptor blockers (ARBs) are the most recent class of agents for the treatment of hypertension. Due to a favourable side effect profile, this class of drugs deserves increased attention. This article reviews drug interactions of ARBs and suggests measures for reducing the risk of adverse events when drugs are co-administered. MEDLINE, EMBASE, Cochrane library, and CINAHL were searched. Reported and likely clinical relevant interactions of ARBs with concomitantly given drugs are summarised in Table 2 and 3. Compared to other classes of antihypertensive agents, the ARBs appear to have a low potential for drug interactions; however, interactions with this class occur and variations within the class have been detected, mainly due to different affinities for cytochrome P450 isoenzymes.     

Current treatment of hypertension in patients with coronary artery disease recommended by different guidelines

Introduction: It is important to know how to treat hypertension in patients with coronary artery disease (CAD). The reason for the review was to update this treatment and to discuss the 2015 American Heart Association/American College of Cardiology/American Society of Hypertension 2015 guidelines of treatment of hypertension in patients with CAD.

Areas covered: Studies between 1968 and 2015 were reviewed on treatment of hypertension in patients with CAD using a Medline search, and studies between 1977 and 2015 were reported. Hypertension should be treated with beta blockers and ACE inhibitors or angiotensin receptor blockers (ARBs). Long-acting nitrates are effective antianginal and anti-ischemic drugs. Calcium-channel blockers (CCBs) may be added if angina persists despite beta blockers and long-acting nitrates. The 2015 guidelines recommend that the blood pressure should be < 140/90 mm Hg in patients aged ≤ 80 years and the systolic blood pressure < 150 mm Hg if they are ≥ 80 years.

Expert opinion: Hypertension in patients with CAD should be treated with beta blockers and ACE inhibitors or ARBs. Long-acting nitrates are effective antianginal and anti-ischemic drugs. CCBs may be added if angina persists despite beta blockers and long-acting nitrates. The blood pressure should be < 140/90 mm Hg in patients aged < 80 years and the systolic blood pressure < 150 mm Hg if they are ≥ 80 years.     

Current problems in hypertension and nephrology

The aim of this issue of Expert Opinion on Pharmacotherapy is to present the most important and controversial problems in hypertension and nephrology. To this end, the most important points of the current (2009) recommendations of the European Society of Hypertension (ESH) are discussed, including aspects related to the treatment of hypertension – the role of beta-blockers, combined therapy with angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) the treatment of hypertension in elderly patients, and role of destiffening therapy. The authors also present current recommendations for the management of dyslipidemia in hypertensive and chronic kidney disease (CKD) patients, and new strategies to prevent cardiovascular risk in CKD patients, the optimal level of blood pressure in patients with hypertensive nephropathy and which hypotensive drugs are the most nephroprotective. The Editors are aware that many other important problems have not been addressed in this issue of the journal; however, they hope the readers find it interesting and useful.     

Hypertension in the elderly: a Japanese perspective

Elderly individuals with hypertension show specific characteristics as a result of advancing arteriosclerosis, a high frequency of isolated systolic hypertension, increased pulse pressure and orthostatic hypotension. The necessity to treat hypertension in the elderly, including isolated systolic hypertension, has been demonstrated in many large-scale intervention trials. Young-old (65-74 years of age) hypertensive patients should be treated the same as nonelderly hypertensive patients. In old-old (75-84 years of age) patients with mild hypertension (140-159/90-99 mm Hg), the recommended target blood pressure (BP) is <140/90 mm Hg. In old-old (75-84 years of age) and oldest-old (> or =85 years of age) patients with systolic BP > or =160 mm Hg, cautious treatment is required. An intermediate target BP of <150 mm Hg is appropriate, followed by a final target BP of <140 mm Hg, if tolerated. Nonmedical therapy, such as salt restriction, exercise and weight reduction, is useful in the elderly. However, individualised management of nonmedical therapy is necessary to avoid deterioration of quality of life resulting from strict management of the patient's lifestyle. Diuretics, calcium channel antagonists, ACE inhibitors and angiotensin II type 1 receptor antagonists have been established as first-line antihypertensive drugs in the elderly. Use of combination therapy helps to achieve target BPs. The starting dose of each drug should be half the usual dose for nonelderly patients, and may be increased at intervals of >4 weeks, with achievement of the target BP in 3-6 months or longer. In hypertensive patients with co-morbid diseases, the target BP should be determined individually and antihypertensive drugs selected bearing in mind the patient's clinical circumstances. Avoiding hypoperfusion of target organs is very important in elderly hypertensive patients. When treating hypertension in elderly patients, the approach should be to identify individual pathophysiological characteristics and lower the BP cautiously and slowly.     

Management of osteoporosis in the elderly

ABSTRACT

Background: Osteoporosis is predominantly a condition of the elderly, and the median age for hip fracture in women is approximately 83 years. Osteoporotic fracture risk is multifactorial, and often involves the balance between bone strength and propensity for falling.

Objective: To present an overview of the available evidence, located primarily by Medline searches up to April, 2009, for the different management strategies aimed at reducing the risk of falls and osteoporotic fractures in the elderly.

Results: Frailty is an independent predictor of falls, hip fractures, hospitalisation, disability and death in the elderly that is receiving increasing attention. Non-pharmacological strategies to reduce fall risk can prevent osteoporotic fractures. Exercise programmes, especially those involving high doses of exercise and incorporating balance training, have been shown to be effective. Many older people, especially the very elderly and those living in care institutions, have vitamin D inadequacy. In appropriate patients and given in sufficient doses, vitamin D and calcium supplementation is effective in reducing both falls and osteoporotic fractures, including hip fractures. Specific anti-osteoporosis drugs are underused, even in those most at risk of osteoporotic fracture. The evidence base for the efficacy of most such drugs in the elderly is incomplete, particularly with regard to nonvertebral and hip fractures. The evidence base is perhaps most complete for the relatively recently introduced drug, strontium ranelate. Non-adherence to treatment is a substantial problem, and may be exacerbated by the requirements for safe oral administration of bisphosphonates.

Conclusion: Evidence-based strategies are available for reducing osteoporotic fracture risk in the elderly, and include exercise training, vitamin D and calcium supplementation, and use of evidence-based anti-osteoporotic drugs. A positive and determined approach to optimising the use of such strategies could reduce the burden of osteoporotic fractures in this high-risk group.     

Treatment of head and neck cancer in the elderly

Introduction: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide and the majority of patients present with advanced stage disease. Chemotherapy is an important component of head and neck cancer treatment regimens and has shown beneficial effects in locally advanced and recurrent/metastatic stages of disease. Approximately 25% of HNSCC patients are aged 70 and older, often associated with co-morbid medical conditions. Most clinical trials exclude patients of advanced chronological age such that valid information about the efficacy and safety of drugs and treatment regimens in elderly patients is not available.

Areas covered: Surgery, radiotherapy and particularly chemotherapy with the six FDA-approved chemotherapeutic agents for head and neck cancer treatment are discussed with a focus on age, performance status, comorbidities. New targeted therapies and the field of immune checkpoint inhibitors are evaluated in the context of elderly populations.

Expert opinion: Surgery, radiotherapy and administration of cytotoxic chemotherapeutic agents are largely safe and effective in elderly patients. Targeted therapies are mostly well tolerated. Clinical studies should be designed to include elderly patients (>70 years). Immune checkpoint inhibitor therapies may exert age-related effects, since substantial functional changes in T cell responses increase during the aging process.     

Investigational drugs for the treatment of osteoarthritis,an update on recent developments

ABSTRACT

Introduction: Osteoarthritis (OA) is the leading cause of pain, loss of function, and disability among elderly, with the knee the most affected joint. It is a heterogeneous condition characterized by complex and multifactorial etiologies which contribute to the broad variation in symptoms presentation and treatment responses that OA patients present. This poses a challenge for the development of effective treatment on OA.

Areas covered: This review will discuss recent development of agents for the treatment of OA, updating our previous narrative review published in 2015. They include drugs for controlling local and systemic inflammation, regulating articular cartilage, targeting subchondral bone, and relieving pain.

Expert opinion: Although new OA drugs such as monoclonal antibodies have shown marked effects and favorable tolerance, current treatment options for OA remain limited. The authors believe there is no miracle drug that can be used for all OA patients’; treatment and disease stage is crucial for the effectiveness of drugs. Therefore, early diagnosis, phenotyping OA patients and precise therapy would expedite the development of investigational drugs targeting at symptoms and disease progression of OA.     

Update on the treatment and prevention of ischaemic stroke

SUMMARY

Stroke continues to have a devastating impact on public health. Recent epidemiological studies suggest that stroke is becoming more common, perhaps due to the ageing of the population and increased survival of patients with cardiac disease. There are specific and well-defined risk factors in patients with stroke, the most important being hypertension. Treatment options to reverse the effect of acute ischaemic stroke are limited. The only approved therapy is intravenous tissue plasminogen activator (tPA). The disadvantage of tPA treatment is a rate of symptomatic haemorrhage of about 6%. Newer stroke prevention options are currently being investigated including statins, oestrogen, angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs). The challenge for physicians is to select the most effective intervention, and this depends on our knowledge of the underlying stroke mechanism and the patient's risk factors.     

Treatment of hypertension in the elderly in 2017/2018 - what’s new?

ABSTRACT

Introduction: Hypertension is highly prevalent in the elderly and represents a major risk factor for cardiovascular complications such as coronary heart disease, stroke, and cognitive dysfunction.

Areas covered: The recently published AHA/ACC and ESC/ESH guidelines for the management of hypertension in adult populations modified their approach towards hypertension in the elderly, particularly in those older than 85 years. The new concepts presented in these guidelines are discussed. They recommend a less conservative threshold and lower blood pressures targets; an emphasis on considering the biological rather than chronological age for patients >85 years, and the use of single-pill combinations to simplify treatment algorithms and increase long-term drug adherence.

Expert opinion: Considering the high prevalence of hypertension in the elderly and the negative impact of untreated hypertension, early detection of hypertension in patients over 60 years old is crucial. The screening of hypertension should be reinforced in patient populations using out-of-office BP measurements. The author supports the latest ESC/ESH guidelines, which define a threshold at >140 mmHg for patients aged 65 to 79 years and >160 mmHg for those >85 years and propose a target BP of 130–140 mmHg, while considering patient frailty and the tolerability of the treatment.     

Angiotensin II Receptor Antagonists Alone and Combined with Hydrochlorothiazide

Angiotensin II receptor antagonists (angiotensin receptor blockers; ARBs) and thiazide diuretics have an accepted place in the management of hypertension. Most patients require combination therapy with two or more drugs to adequately control blood pressure to targets recommended by European and international guidelines. ARBs and the thiazide diuretic hydrochlorothiazide have complementary modes of action. Fixed-dose combinations of an ARB and low-dose hydrochlorothiazide provide a convenient and effective treatment option for patients who do not achieve blood pressure targets on monotherapy, without compromising the placebo-like tolerability of ARBs. In Europe, fixed-dose combinations with hydrochlorothiazide currently are available for the ARBs candesartan, eprosartan, irbesartan, losartan, telmisartan, and valsartan. Recently, a number of studies have focused on the use of ARBs in monotherapy and in combination therapy, in conditions including congestive heart failure, post-myocardial infarction management, hypertension with cardiovascular risk factors, and diabetic and non-diabetic nephropathy. Evidence from these studies suggests a beneficial role beyond the antihypertensive effect of these therapies in providing protection against cardiovascular, renovascular, and cerebrovascular events.     

Angiotensin receptor blockers: RAAS blockade and renoprotection

ABSTRACT

Introduction: Chronic kidney disease (CKD) is an increasingly prevalent public health concern and is associated with a high risk of adverse cardiovascular outcomes. Renal impairment is frequently associated with hypertension and there is compelling evidence of the benefits of antihypertensive therapy for reducing progression of kidney disease. The central role of the renin-angiotensin-aldosterone system (RAAS) in hypertension and renal disease has led to interest in the ability of RAAS-blocking agents to provide benefits beyond blood pressure control.

Scope: This review explores the mechanisms involved in CKD development, assesses markers of CKD progression, explores the role of the RAAS in renal disease, and examines RAAS blockade as a therapeutic option for renoprotection. For this purpose, a non-systematic literature review was conducted using the Medline database.

Findings: Studies in patients with diabetic renal disease have shown that RAAS blockade with angiotensin converting enzyme (ACE)-inhibitors or angiotensin receptor blockers (ARBs) reduces progression of renal disease. Similarly, several studies have demonstrated the benefits of ACE inhibitors in non-diabetic renal disease, although few studies have been conducted with ARBs in this setting. At present, there is little evidence to determine the relative merits of ARBs and ACE inhibitors in terms of clinical outcomes, although ARBs appear to have advantages in terms of renal haemodynamics and measures of renal function.

Conclusions: The beneficial effects of ARBs, which result from a combination of antihypertensive, haemodynamic, antiproteinuric and pleiotropic mechanisms, provide a strong rationale for considering the use of these agents in the treatment of high-risk patients.     

Safety concerns with current treatments for psoriasis in the elderly

ABSTRACT

Introduction: The approach to manage psoriasis in the elderly (ages ≥65 years) patients can be challenging. They often suffer from multiple comorbidities and polypharmacy with possible adverse effects and undergo a progressive functional impairment of the immune system that increases susceptibility to infections as well as to auto-reactivity. Despite the increasing aging of the general population and although several therapies are currently available for psoriasis treatment, data regarding their use and tolerability in the elderly are quite limited.

Areas covered: This review focuses on topical and systemic therapies that have been investigated in elderly patients in order to provide their safety profile in this population.

Expert opinion: Conventional systemic therapies in elderly patients should be carefully dispensed and the correct dosage individually determined, taking into account the metabolism changes, organ impairment, comorbidities, concomitant medications, and contraindications. Apremilast, due to its satisfactory safety profile and low risk of drug interactions, results as an appropriate treatment option for elderly patients. Biologics (TNF-α, IL-12/23, IL-17, and IL-23 inhibitors) come out as safe and long-term options for the management of these patients resulting not associated with a higher risk of adverse events.     

Antihypertensive agents acting on the renin–angiotensin system and the risk of sepsis

AimsIn response to safety concerns from two large randomized controlled trials, we investigated whether the use of telmisartan, an angiotensin receptor blocker (ARB), ARBs as a class and angiotensin-converting enzyme inhibitors (ACEIs) increase the risk of sepsis, sepsis-associated mortality and renal failure in hypertensive patients.MethodsWe performed a nested case–control study from a retrospective cohort of adults with hypertension from the UK General Practice Research Database diagnosed between 1 January 2000 and 30 June 2009. All subjects hospitalized with sepsis during follow-up were matched for age, sex, practice and duration of follow-up with 10 control subjects. Exposure was defined as current use of antihypertensive drugs.ResultsFrom the cohort of 550 436 hypertensive patients, 1965 were hospitalized with sepsis during follow-up (rate 6.9 per 10 000 per year), of whom 824 died and 346 developed acute renal failure within 30 days. Compared with use of β-blockers, calcium-channel blockers or diuretics, use of ARBs, including telmisartan, was not associated with an elevated risk of sepsis (relative risk 1.09; 95% confidence interval 0.83–1.43); but use ACEIs was (relative risk 1.65; 95% confidence interval 1.42–1.93). Users of ARBs, β-blockers, calcium-channel blockers or diuretics, but not users of ACEIs, had lower rates of hospitalization for sepsis compared with untreated hypertensive patients. Findings were similar for sepsis-related 30 day mortality and renal failure.ConclusionsHypertensive patients treated with ARBs, including telmisartan, do not appear to be at increased risk of sepsis or sepsis-related 30 day mortality or renal failure. On the contrary, users of ACEIs may have an increased risk.     

Drug treatment of hypertension in older patients with diabetes mellitus

Introduction: Hypertension is more prevalent in the elderly (age>65 years) diabetic population than in the general population and shows an increasing prevalence with advancing age. Both diabetes mellitus (DM) and hypertension are independent risk factors for cardiovascular (CV) related morbidity and mortality. Optimal BP targets were not identified in elderly patients with DM and hypertension.

Areas covered: In this review article, the authors briefly discuss the pathophysiology of hypertension in elderly diabetics, present evidence with various antihypertensive drug classes supporting the treatment of hypertension to reduce CV events in older diabetics, and then discuss the optimal target BP goals in these patients.

Expert opinion: Clinicians should have a BP goal of less than 130/80 mm in all elderly patients with hypertension and DM, especially in those with high CV-risk. When medications are required for optimal BP control in addition to lifestyle measures, either thiazide diuretics, angiotensin-converting-enzyme inhibitors, angiotensin receptor blockers, or calcium channel blockers should be considered as initial therapy. Combinations of medications are usually required in these patients because BP control is more difficult to achieve in diabetics than those without DM.     

Multi-centre study of acebutolol in hypertensive subjects: results for patients from the 50 to 64-years' old and over 65 years' old age groups

Summary

The results of a multi-centre general practice study on acebutolol in the treatment of hypertension were examined for two age groups of patients, namely those aged from 50 to 64 years and those aged 65 years and over. A total of 1501 patients was studied and followed-up over a period of 3 months. There was a marked reduction in systolic and diastolic blood pressure with treatment and the results, in terms of efficacy and tolerance, were comparable in both age groups. These findings indicate that acebutolol is warranted in the treatment of elderly patients with hypertension.