Fixed-Dose Combination Antihypertensives and Reduction in Target Organ Damage

Hypertension is a multifactorial disorder leading to pathophysiologic changes in target organs over time through diverse mechanisms. In addition, hypertension frequently resists control with monotherapy, necessitating combination therapy with two or more antihypertensive agents. Many currently available fixed-dose antihypertensive combinations combine drugs with different, but complementary, mechanisms of action to improve overall efficacy and tolerability. In addition, it is possible to select drug combinations whereby one drug offsets the negative effects of the other drug. Fixed-dose antihypertensive combinations may provide significant advantages over high-dose monotherapy, such as improved BP-lowering efficacy, reduced adverse event frequency, improved patient compliance, potentially lower treatment costs, and shorter time to BP control. Combination therapy has been recommended as potential first-line therapy in recent consensus guideline statements, especially for higher-risk patients, such as those with stage 2 hypertension. The combination of a renin-angiotensin-aldosterone system-targeting agent, such as an ACE inhibitor or angiotensin II receptor antagonist (ARB), and a diuretic or calcium channel antagonist appears to provide synergy with regard to BP lowering. In addition, ACE inhibitors and ARBs have demonstrated beneficial effects beyond BP reduction, reducing cardiovascular morbidity and mortality, inhibiting development and progression of type 2 diabetes mellitus and the progression of renal disease. Preliminary studies of fixed-dose combinations have shown reductions in left ventricular hypertrophy and improvements in markers of renal function. Additional studies currently underway will compare the effects of available fixed-dose combinations on cardiovascular morbidity and mortality, and markers of renal dysfunction.     

Use of single-pill combination therapy in the evolving paradigm of hypertension management

The use of antihypertensive therapy is an evolving paradigm. Although blood pressure (BP) control rates remain low, there have been improvements that may be attributable in part to a recent shift in clinical guidelines that recognizes that most patients will require multiple drugs to reach BP goals and encourages clinicians to use combination therapy as first-line treatment in selected patients. Single-pill combinations of two complementary antihypertensive medications offer benefits beyond those of separate administration of the individual component agents, providing a simpler medication regimen that is effective and well tolerated while enhancing patient adherence to therapy. In the future, there may be single-pill combinations of three antihypertensive drugs to further enhance BP control rates.     

Combination therapy for hypertension: focus on high-dose olmesartan medoxomil (40 mg) plus hydrochlorothiazide

Importance of the field: Cardiovascular disease is a major cause of premature death and disability worldwide, and effective blood pressure (BP) control is crucial for the reduction of cardiovascular risk in patients with hypertension. Despite this, many will fail to attain recommended BP goals. A reappraisal of European guidelines led to revised recommendations for BP reduction to values within the SBP/DBP range of 130 – 139/80 – 85 mmHg in all patients with hypertension, including higher-risk groups such as those with diabetes.

Areas covered in this review: The majority of hypertensive patients will require the enhanced blood-pressure-lowering effects of at least two antihypertensive drugs with complementary mechanisms of action to achieve these goals.

What the reader will gain: The angiotensin II receptor blocker (ARB) olmesartan medoxomil and the thiazide diuretic hydrochlorothiazide (HCTZ) provide greater antihypertensive efficacy when used in combination than as monotherapy with either component, with a similar tolerability profile. In addition, there is evidence that higher doses of olmesartan may prolong the antihypertensive effect of this ARB, and a number of US ‘treat-to-target’ and European add-on clinical trials have been conducted to assess the efficacy and safety of high-dose olmesartan plus HCTZ in a wide range of patients with mild-to-severe hypertension.

Take home message: Combination therapy with olmesartan, including the high 40-mg dose, plus HCTZ is an effective and safe treatment option for controlling BP in patients with mild-to-severe hypertension, particularly those who fail to achieve recommended BP goals with monotherapy.     

Polypharmacy and combination therapy in the management of hypertension in elderly patients with co-morbid diabetes mellitus

The demographic shift towards an older population increases the public health burden. Two conditions, commonly occurring together, that contribute to this burden are hypertension and diabetes mellitus. Effective blood pressure (BP) control is particularly important in this patient population, with a recommended BP goal of <130/80?mmHg. Most of these patients will require treatment with a combination of antihypertensive agents to reach this goal. Polypharmacy can be defined as the use of two or more medications, and it is commonly seen in this patient population. The risks of polypharmacy and the potential for inappropriate therapy must be considered and balanced against the possible benefits of multiple drug therapies. An optimal approach to reducing the risks and maximizing the benefits of polypharmacy should include regular reviews of patients' medication lists, which can be changed to include, where appropriate, combination therapy and the use of single-pill combinations. Combination therapy can achieve greater BP reductions than monotherapy and can also enhance the safety and tolerability of pharmacotherapy. The safety and efficacy of numerous antihypertensive combinations in elderly patients have been demonstrated in a number of clinical trials. Single-pill formulations can simplify the medication regimen, and specific combinations can offer further benefits, such as enhanced reduction of macrovascular and microvascular complications, independent of BP reductions. Rational combination therapy can maximize BP control along with glycaemic control and help maximize the benefits of polypharmacy on outcomes in elderly patients with hypertension and co-morbid diabetes.     

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).     

Single-pill telmisartan and amlodipine: a rational combination for the treatment of hypertension

Despite the well documented benefits conferred by adequate control of hypertension, the majority of hypertensive patients display suboptimal control and few patients achieve blood pressure (BP) levels <140/90?mmHg. As a consequence, combination therapy will be required in the majority of patients to achieve target BP. Fixed-dose combinations of antihypertensives not only simplify treatment regimens, contributing to enhanced patient adherence, they provide superior BP-lowering efficacy and an improved tolerability profile. Fixed-dose combinations have become the strategy of choice in high-risk patients or those with stage 2-3 hypertension. The combination of a renin-angiotensin system inhibitor (RASI) with a calcium channel blocker (CCB) is a first-line combination that, in addition to its antihypertensive efficacy, reduces oedema, the main adverse effect of the dihydropyridine CCB and the main factor limiting their use. In morbidity/mortality studies, this fixed-dose combination has also demonstrated superiority over a RASI combined with a diuretic. The single-pill combination of telmisartan and amlodipine has been shown to produce a dose-dependent BP-lowering effect significantly greater than that of either agent administered as monotherapy. These findings have been confirmed by ambulatory BP monitoring in patients with stage 1 and 2 hypertension, which demonstrated that single-pill telmisartan/amlodipine provides substantial 24-hour BP-lowering efficacy. A higher proportion of patients achieved 24-hour BP goals of <130/80?mm?Hg on combination therapy. The superior efficacy of combination therapy has been demonstrated across a broad range of patients, including those with moderate-to-severe hypertension, diabetes mellitus and obesity. Moreover, combined use of telmisartan and amlodipine reduces the incidence of amlodipine-induced oedema, making it a preferred combination for the treatment of hypertension.     

Olmesartan Medoxomil-Based Antihypertensive Therapy Evaluated by Ambulatory Blood Pressure Monitoring

Hypertension affects approximately 26% of the world’s adult population and is a recognized major risk factor for morbidity and mortality associated with cardiovascular, cerebrovascular, and renal diseases. However, despite the availability of a range of effective antihypertensive agents and a growing awareness of the consequences of high blood pressure (BP), the treatment and control of hypertension remains sub-optimal. A number of patient subgroups are categorized as ‘high risk’ and may have hypertension that is more difficult to treat, including obese individuals, patients with stage 2 hypertension, those with type 2 diabetes mellitus (T2DM), patients with coronary artery disease or a history of stroke, and Black patients. As the benefits of lowering BP in patients with hypertension are unequivocal, particularly in high-risk patients, treating high-risk patients with hypertension to BP goals and maintaining 24-hour BP control is important to help reduce cardiovascular risk and improve outcomes. Although the BP goals recommended in current consensus guidelines for the management of patients with hypertension are based on cuff BP measurements, ambulatory BP monitoring (ABPM) provides a valuable diagnostic tool and allows a more accurate assessment of BP levels throughout the 24-hour dosing period. ABPM is a better predictor of prognosis than office BP measurement and is also useful for assessing whether antihypertensive therapy remains effective in the critical last few hours of the dosing period, which usually coincides with the morning BP surge associated with arousal and arising. ABPM has been adopted by new evidence-based guidelines in the United Kingdom to confirm a suspected diagnosis of hypertension, which is an indication of the growing importance of ABPM in the management of hypertension. This review provides an overview of the efficacy and safety of anti-hypertensive therapy based on olmesartan medoxomil ± hydrochlorothiazide and amlodipine/olmesartan medoxomil in high-risk patient populations enrolled in studies that reported ambulatory BP endpoints. The studies identified in this review showed that a titrate-to-BP goal strategy using olmesartan medoxomil- or amlodipine/olmesartan medoxomil-based antihypertensive therapy was an effective and well-tolerated approach for maintaining BP control throughout the full 24-hour dosing period in high-risk patients with difficult-to-treat hypertension.     

Telmisartan/Hydrochlorothiazide: a review of its use as fixed-dose combinations in essential hypertension

Fixed-dose combinations of telmisartan and hydrochlorothiazide (HCTZ) [Micardis Plus((R)), Micardis((R)) HCT, PritorPlus((R))] are available in many countries for the treatment of patients with essential hypertension. Combining the angiotensin II receptor antagonist (angiotensin II receptor blocker [ARB]) telmisartan with the thiazide diuretic HCTZ provides antihypertensive therapy with complementary mechanisms of action. In the US and EU, telmisartan/HCTZ is approved for patients whose hypertension is not adequately controlled with telmisartan monotherapy; US labelling for the fixed-dose combination also includes inadequate control of blood pressure (BP) with HCTZ monotherapy.The antihypertensive efficacy of once-daily telmisartan/HCTZ has been demonstrated in several large, randomized trials in patients with stages 1 and 2 hypertension. The addition of HCTZ to telmisartan achieved significant reductions in BP in nonresponders to telmisartan monotherapy, and the antihypertensive efficacy of telmisartan/HCTZ was similar to or significantly greater than that of various comparator agents. Moreover, in studies that used ambulatory BP monitoring, telmisartan/HCTZ provided consistent 24-hour BP reductions throughout morning, daytime and night-time periods. The BP-lowering efficacy over the entire 24-hour dose administration interval is consistent with the pharmacokinetic profile of telmisartan, which has the longest elimination half-life among currently available ARBs and a unique chemical structure. Adverse events with telmisartan/HCTZ in clinical trials were typically mild and transient, and no unexpected events occurred that had not been previously reported with either telmisartan or HCTZ. Extensive tolerability data are available for telmisartan, in particular from the ONTARGET study, the largest clinical outcomes trial with an ARB. As such, fixed-dose combinations of telmisartan/HCTZ provide an effective, rational and generally well tolerated treatment option for the management of patients with hypertension.     

Zofenopril plus hydrochlorothiazide: Combination therapy for the treatment of mild to moderate hypertension

Achieving target blood pressure (BP) levels in clinical practice is one of the main challenges for physicians in the management of patients with hypertension. It is now recognised that the majority of patients will require at least two antihypertensive drugs to achieve optimal BP control; the use of combination therapy as first-line treatment is also increasing as BP goals of antihypertensive therapy become more ambitious. The fixed combination of zofenopril/hydrochlorothiazide (HCTZ) 30/12.5 mg/day is approved in Italy, France, Switzerland and Greece for the management of mild to moderate hypertension. In clinical trials comparing zofenopril/HCTZ with each agent administered as monotherapy, combination therapy was more effective in normalising BP. This effect was particularly evident in one trial in which patients who were nonresponsive to zofenopril monotherapy were studied. In addition, in clinical trials to date, combination therapy provided sustained and consistent BP control over the entire 24-hour dose interval. Despite the greater efficacy of zofenopril/HCTZ 30/12.5 mg/day, when directly compared with each agent administered as monotherapy, there were no significant differences in the nature, severity or incidence of treatment-related adverse events; headache, dizziness, cough and polyuria were most frequently reported. Notably, in one study, fewer patients discontinued treatment with combination therapy than with zofenopril monotherapy due to adverse events. In conclusion, zofenopril/HCTZ 30/12.5 mg/day provides more optimal BP control in a larger proportion of patients than would be achievable with monotherapy, while maintaining the tolerability profile observed with each individual agent, and thereby potentially enhancing patient compliance. The efficacy and safety profiles of this combination shown in clinical trials to date indicate that it will be a useful addition to currently available therapy for patients who have mild to moderate hypertension that is not adequately controlled by monotherapy, as well as for patients who require more rapid, intensive BP control.     

Treating hypertension in women of child-bearing age and during pregnancy.

Hypertension is found among 1 to 6% of young women. Treatment aims to decrease cardiovascular risk, the magnitude of which is less dependent on the absolute level of blood pressure (BP) than on associated cardiovascular risk factors, hypertension-related target organ damage and/or concomitant disease. Lifestyle modifications are recommended for all hypertensive individuals. The threshold of BP at which antihypertensive therapy should be initiated is based on absolute cardiovascular risk. Most young women are at low risk and not in need of antihypertensive therapy. All antihypertensive agents appear to be equally efficacious; choice depends on personal preference, social circumstances and an agent's effect on cardiovascular risk factors, target organ damage and/or concomitant disease. Although most agents are appropriate for, and tolerated well by, young women, another consideration remains that of pregnancy, 50% of which are unplanned. A clinician must be aware of a woman's method of contraception and the potential of an antihypertensive agent to cause birth defects following inadvertent exposure in early pregnancy. Conversely, if an oral contraceptive is effective and well tolerated, but the woman's BP becomes mildly elevated, continuing the contraceptive and initiating antihypertensive treatment may not be contraindicated, especially if the ability to plan pregnancy is important (e.g. in type 1 diabetes mellitus). No commonly used antihypertensive is known to be teratogenic, although ACE inhibitors and angiotensin receptor antagonists should be discontinued, and any antihypertensive drugs should be continued in pregnancy only if anticipated benefits outweigh potential reproductive risk(s). The hypertensive disorders of pregnancy complicate 5 to 10% of pregnancies and are a leading cause of maternal and perinatal mortality and morbidity. Treatment aims to improve pregnancy outcome. There is consensus that severe maternal hypertension (systolic BP > or = 170mm Hg and/or diastolic BP > or = 110mm Hg) should be treated immediately to avoid maternal stroke, death and, possibly, eclampsia. Parenteral hydralazine may be associated with a higher risk of maternal hypotension, and intravenous labetalol with neonatal bradycardia. There is no consensus as to whether mild-to-moderate hypertension in pregnancy should be treated: the risks of transient severe hypertension, antenatal hospitalisation, proteinuria at delivery and neonatal respiratory distress syndrome may be decreased by therapy, but intrauterine fetal growth may also be impaired, particularly by atenolol. Methyldopa and other beta-blockers have been used most extensively. Reporting bias and the uncertainty of outcomes as defined warrant cautious interpretation of these findings and preclude treatment recommendations.     

Antihypertensive Drugs

For most patients with systemic hypertension, long-term drug treatment is indicated and is beneficial. There is overwhelming evidence to suggest that antihypertensive drugs offer protection against complications of hypertension. Whereas nondrug therapeutic options should be implemented in all patients, a vast majority will require pharmacological treatment to achieve goal blood pressure levels. Fortunately, a number of drugs are available to accomplish successful treatment of hypertensive disorders. While it is conventional to initiate treatment with a single drug, a suitable combination of drugs is often required to control the blood pressure effectively. Although diuretics and β-blockers are effective and well tolerated, other classes of drugs are being increasingly used as the initial choice of therapy for hypertension. Every class of antihypertensive drugs offer advantages and some disadvantage; the physician should weigh the benefits and risks in selecting one drug over another. While the clinical parameters are followed in the management of patients with hypertension, it is also necessary to monitor the patients’ biochemical profile periodically in order to modify and adjust the therapy accordingly. A careful selection of drug therapy along with close follow-up offers the best prospect to reduce the burden of morbidity and mortality in hypertension. This article provides an overview of drugs in the management of patients with hypertension.     

Overcoming barriers to effective blood pressure control in patients with hypertension

BACKGROUND: Patients with hypertension remain at increased risk of micro- and macrovascular complications unless their elevated blood pressure (BP) can be adequately controlled. However, helping patients with hypertension to get to, and stay at, target BP goals can be difficult in everyday clinical practice. SCOPE: The present study describes the magnitude of this problem in various regions and attempts to analyse possible underlying reasons. For this purpose, a non-systematic literature review using Medline database was performed. FINDINGS: Reasons for suboptimal blood pressure control include factors under the control of the physician, such as insufficient education and motivation of the patient, reluctance to initiate lifestyle changes or drug treatment; overlooking the importance of controlling systolic BP (especially in the elderly) and failure to modify and expand therapy when it is indicated (e.g. use of combination therapy if monotherapy is proving inadequate for BP lowering). Patient-related factors that may give rise to inadequate BP control include a lack of awareness of the relevance of hypertension, failure to comply with recommended lifestyle modifications and poor medication compliance (e.g. because of forgetfulness, tolerability problems, or incomplete understanding of the long-term nature of therapy). CONCLUSIONS: These issues can be addressed by ensuring that doctors adhere more closely to national or international guidelines and that patients are well-informed about the need for long-term therapy. Further approaches include simplifying the treatment regimen (e.g. use of well-tolerated, fixed-dose combinations) and using various measures to reduce forgetfulness. With properly directed therapy and consideration of potential physician- and patient-related barriers to poor BP control, more hypertensive patients in everyday clinical practice can achieve target BP goals and thereby realise the proven benefits of antihypertensive therapy for decreasing their cardiovascular risk.     

Fixed-dose combination enalapril/nitrendipine: a review of its use in mild-to-moderate hypertension

The fixed-dose combination of enalapril 10mg with nitrendipine 20mg combines an ACE inhibitor with a calcium channel antagonist (CCA) and is indicated for the treatment of patients with mild-to-moderate hypertension whose blood pressure (BP) is inadequately controlled with enalapril or nitrendipine monotherapy. In randomised, double-blind clinical trials, enalapril/nitrendipine 10/20 mg/day was significantly more effective than its individual components in reducing diastolic BP (DBP) in patients with mild-to-moderate hypertension inadequately controlled with enalapril 10 mg/day or nitrendipine 20 mg/day. The fixed-dose combination was similar in efficacy at reducing DBP to amlodipine 10 mg/day in patients who failed to achieve BP control with amlodipine 5 mg/day, and to losartan/hydrochlorothiazide 50/12.5 mg/day in patients who received the combinations as first-line therapy. Enalapril/nitrendipine 10/20 mg produced a consistent antihypertensive effect that persisted for the entire 24-hour dosage interval as shown by ambulatory BP monitoring. Enalapril/nitrendipine 10/20 mg was well tolerated in clinical trials where it was administered to patients with mild-to-moderate hypertension for up to 12 weeks. The adverse events were those expected of ACE inhibitors and CCAs and included cough, headache and flushing. Evidence from clinical trials, including a pooled analysis, suggests that the incidence of oedema may be significantly lower with the fixed-dose combination than with CCA monotherapy.In conclusion, enalapril/nitrendipine 10/20 mg is a well tolerated fixed-dose combination of two established antihypertensive agents administered once daily that effectively lowers BP throughout the 24-hour dosage interval. Importantly, the fixed-dose combination may have a lower incidence of oedema than CCA monotherapy. Enalapril/nitrendipine 10/20 mg provides an additional treatment option for patients with mild-to-moderate hypertension for whom combination therapy is appropriate.     

Perindopril for control of blood pressure in patients with hypertension and other cardiovascular risk factors: an open-label, observational, multicentre, general practice-based study

BACKGROUND AND OBJECTIVES: Hypertension, one of the major treatable cardiovascular (CV) risk factors, usually occurs in association with other major risk factors. As well as providing rapid blood pressure (BP) goal attainment, antihypertensive therapy should also provide reductions in CV events and mortality in a wide range of patients. For this, higher dosages and combinations of antihypertensive agents are often required. ACE inhibitors are recommended as first-line agents for control of hypertension in patients with additional CV risk factors. The PEACH (Perindopril's Effect At Controlling Hypertension) study was a community-based study performed to evaluate the effectiveness and safety of high-dose perindopril in patients with mild-to-moderate hypertension and additional risk factors for CV disease. METHODS: This was an open-label, multicentre observational study conducted in Canadian general practice clinics. The study assessed the efficacy and tolerability of perindopril given once daily for 10 weeks uptitrated to the maximal recommended dose of perindopril as required for BP control in newly diagnosed or previously treated patients with uncontrolled mild to moderate hypertension and >or=1 additional risk factor. Patients not achieving target BP after 2 weeks of therapy were uptitrated from perindopril 4 mg to perindopril 8 mg once daily. Efficacy endpoints included reduction in systolic (SBP) and diastolic (DBP) BP and BP control. Tolerability assessments included adverse effects and physicians' assessment of tolerability. The number of missed doses was also recorded. RESULTS: Overall, 2220 patients with hypertension and >or=1 other risk factor were prescribed perindopril at 291 centres; 51.9% were male, 78.3% Caucasian, 12.8% Asian, 36.2%>or=65 years of age and 34.5% had uncontrolled BP despite previous antihypertensive treatment. Compared with previously treated patients, treatment-naive patients had fewer risk factors, and a higher proportion were Asian (p<0.05 for all comparisons). Most patients (76%) had 1-2 risk factors. Perindopril produced significant SBP/DBP reductions at 2 and 10 weeks (-15.8/-8.0 and -21.1/-11.0 mmHg, respectively). Overall, at week 10, BP control rate was 53.6%, better than at week 2 in the overall cohort and in all subgroups. Uptitration to high-dose perindopril to achieve BP control was required in 46% of patients with one additional risk factor compared with 64% of patients with >or=4 additional risk factors. These results demonstrate that the more risk factors the patient has, the greater the need for high-dose perindopril to achieve BP control. Perindopril was well tolerated as indicated by the high proportion of physicians (95.9%) reporting 'good' to 'excellent' tolerability at week 10. CONCLUSION: In this community-based clinical practice trial, up to 10 weeks' perindopril therapy, uptitrated to the maximal recommended dose as required for BP control, significantly reduced SBP/DBP in patients with mild-to-moderate hypertension and additional CV risk factors. Patients with more risk factors were more likely to require high-dose perindopril.     

Patterns of antihypertensive medication use in hemodialysis patients.

PURPOSE: Patterns of antihypertensive drug use in patients undergoing long-term hemodialysis therapy were studied. METHODS: Patients attending seven outpatient hemodialysis units in Ohio were eligible for the study if they had been receiving the treatment for at least three months. Demographic and clinical data were obtained from patient interviews and computerized databases, and blood pressure (BP) measurements were obtained before dialysis. Labeled names and dosages of antihypertensive drugs were recorded from containers the patients brought with them. Patients were asked to describe their adherence to the medications, their ability to afford the drugs, and their knowledge and beliefs about hypertension. Physical impairments in taking medication were also evaluated. RESULTS: The frequency of hypertension was 89% in the 270 participants. Antihypertensive drugs were prescribed for 76% of the patients; 25% required three or more drugs. Hypertensive patients who were not receiving antihypertensive drugs (14%) had significantly higher BP than patients who were. Calcium-channel blockers were prescribed for 60% of patients, angiotensin-converting-enzyme inhibitors for 33%, and beta-blockers for 34%. Eighty-three percent said the cost of drugs was never a problem, and 23% said they sometimes forgot to take their medication. Almost all patients said they would not stop taking antihypertensive drugs if they were feeling better and agreed that monitoring BP was important. Twenty-two percent could not read the warning on a standard tablet container, and 12% could not remove one tablet from the container. CONCLUSION: Multidrug antihypertensive therapy was common among hemodialysis patients and was associated with significantly lower BP; calcium-channel blockers were the most frequently prescribed agents. Most patients said they could afford drugs and reported good adherence to antihypertensive drug therapy.     

How do Compliance, Convenience, and Tolerability Affect Blood Pressure Goal Rates?

Uncontrolled hypertension imposes a substantial global health burden, and poor patient compliance with prescribed antihypertensive medication makes a major contribution to the development of suboptimal blood pressure (BP) control. The asymptomatic nature of hypertension, side effects of medication, treatment complexity, and high pill burdens all have a negative impact on patient compliance. It is important to address the issue of poor patient compliance as studies have shown that good compliance is associated with improvement of BP control and positive health outcomes. As the majority of hypertensive patients require treatment with two or more agents to achieve goal BP, treatment guidelines have acknowledged the value of simplifying treatment through the use of fixed-dose combination (FDC) therapy. Triple FDC therapy comprising an angiotensin II type 1 receptor antagonist (angiotensin receptor blocker), calcium channel blocker, and thiazide diuretic is a novel treatment strategy for the improvement of BP control in hard-to-treat patients.     

Use of Calcium Channel Blockers in Cardiovascular Risk Reduction

Cardiovascular disease (CVD) is a continuum that begins with the presence of several risk factors for CVD, including smoking, hypertension, obesity, diabetes mellitus, and high levels of cholesterol, and if unaddressed can result in premature death, ischemic heart disease, stroke, congestive heart failure, and end-stage renal disease. Hypertension is associated with a significant increase in cardiovascular (CV) morbidity and mortality, raising the risk of stroke, myocardial infarction, heart failure, kidney disease, and peripheral arterial disease. In Latin America, the prevalence of hypertension and other CV risk factors has become similar to that seen in more developed countries, increasing the proportion of the population at high risk for CVD and congestive heart failure; however, it is hypertension that is a key driving force behind CV risk in Latin America. Despite the existence of a wide range of antihypertensive agents, BP control and reductions in CV risk remain poor in Latin America and in Hispanics living in the US. Ethnic differences in treatment rates and disease awareness have been well documented. Studies have shown that calcium channel blockers (CCBs; calcium channel antagonists) are at least as effective in reducing BP and improving the CV risk profile as other classes of antihypertensive agents when administered as monotherapy. CCBs have also been shown to be effective when administered as part of combination therapy in both low- and high-risk hypertensive patients, suggesting that CCBs can easily be combined with other antihypertensive classes in order to achieve BP control and CV risk reduction. In patients with hypertension, coronary artery disease, and high cholesterol, CCBs have been associated with beneficial effects on a range of other aspects of the CV continuum, including the vasculature, coronary calcification, and progression of atherosclerosis. CCBs have also been shown to preserve renal function. Unlike diuretics and β-adrenoreceptor antagonists, CCBs are metabolically neutral, inducing minimal changes in serum lipids and decreasing the incidence of new-onset diabetes compared with other antihypertensive agents. CCBs are well tolerated when administered as monotherapy or combination therapy, with long-acting formulations minimizing adverse events even further compared with short-acting formulations. These characteristics make CCBs an attractive option for the treatment of hypertension and CV risk in Latin America, which remain significant health issues in this region.     

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.