Dose-Dependent Antihypertensive Efficacy and Tolerability of Perindopril in a Large, Observational, 12-Week, General Practice-Based Study

Background

Current guidelines recommend the use of full therapeutic dosages of antihypertensive agents, or combination therapy, to improve BP control of hypertensive patients in primary healthcare.

Objective

The aim of this study was to assess the dose-dependent antihypertensive efficacy and safety of perindopril 4 and 8 mg/day in the clinical setting.

Study Design and Setting

The CONFIDENCE study was a prospective, observational, multicenter trial. This was a real-world, clinic-based, outpatient study involving 880 general practitioners/primary-care clinics and 113 specialists in Canada.

Patients

The study included untreated or inadequately managed patients with hypertension (i.e. seated BP≥140/90 mmHg, or ≥130/80 mmHg in the presence of diabetes mellitus, renal disease, or proteinuria) without coronary artery disease (CAD).

Intervention

Treatment consisted of perindopril 4 mg/day, uptitrated to 8 mg/day as required for BP control at visit 2, for 12 weeks. Among the patients already being treated at baseline, perindopril either directly replaced all previous ACE inhibitors or angiotensin II type 1 receptor antagonists (angiotensin receptor blockers [ARBs]), or was added to antihypertensive treatment with calcium channel blockers (CCBs), diuretics, or β-adrenoceptor antagonists (β-blockers).

Main Outcomes Measures

The primary outcomes were the mean changes in BP from baseline following treatment with perindopril 4 and 8 mg/day as well as the proportion of patients achieving BP control (BP <140/90 mmHg, or <130/80 mmHg in diabetic patients) in the intent-to-treat (ITT) population. Secondary analyses included the incidence of adverse events and compliance.

Results

A total of 8298 hypertensive patients entered the study: 56% with newly diagnosed hypertension and 44% with uncontrolled hypertension. Mean SBP/DBP decreased significantly from baseline (152.5 ±10.8/89.5 ±9 mmHg) over 12 weeks (?18.5/?9.7 mmHg; p < 0.001). At visit 2, 23% of patients were uptitrated to perindopril 8 mg/day, which resulted in an additional mean 10.1/5.3 mmHg BP reduction; this reduction was even greater (15.1/5.7 mmHg) among a separate group of severely hypertensive patients (i.e. SBP >170 mmHg or DBP > 109 mmHg at baseline). Target BP was achieved in 54% of the ITT population. Both perindopril 4 mg/day and perindopril 8 mg/day were well tolerated and compliance was high throughout the study.

Conclusion

In the clinical outpatient setting, perindopril was found to be an effective dose-dependent and well tolerated antihypertensive treatment, with good compliance. Uptitration to the full therapeutic dosage of perindopril is an efficient approach for the management of a broad range of hypertensive patients without CAD.     

The Role of Angiotensin Receptor Blocker and Calcium Channel Blocker Combination Therapy in Treating Hypertension

Hypertension remains a significant health problem, affecting approximately 30% of the US population. Of these, only 36.8% have BP controlled to recommended levels of <140/90mmHg for uncomplicated hypertension and <130/80 mmHg for patients with diabetes mellitus or renal disease. For those with uncontrolled hypertension, the risk of diabetes, renal disease, stroke, and cardiovascular disease is increased. Therapeutic options for the treatment of hypertension include several major classes of drugs: diuretics, ß-adrenoceptor antagonists (ß-blockers), ACE inhibitors, angiotensin II type 1 receptor antagonists (angiotensin receptor blockers [ARBs]), renin inhibitors, calcium channel blockers, and central sympatholytics, alone or in combination. Guidelines recommend thiazide diuretics as preferred first-line monotherapy. However, only 50% of patients will respond adequately to this therapy and the rest will require two or more antihypertensive agents to achieve BP goals. Clinical evidence demonstrates that some drugs have advantages when used in combination rather than as monotherapy. Drugs that block the renin-angiotensin-aldosterone system not only provide BP control but may also provide vascular protection and are metabolically neutral. This is a concise review of the safety and efficacy of ARBs in combination with amlodipine for the treatment of hypertension, with focus on the telmisartan-amlodipine combination. A MEDLINE search of the English literature from 2006 to 2009 of amlodipine in combination with ARBs revealed six publications, which are included in this review.     

Treating hypertension by rational use of diuretics: results of the Russian ARGUS-2 study

ABSTRACT

Objective: Insufficient use of diuretics in combination antihypertensive therapy is a main cause of poor blood pressure (BP) control in Russia. The objective of the ARGUS-2 study was to demonstrate that a rational use of a thiazide-like diuretic, indapamide sustained release (SR), alone or in combination, improves BP control in patients with arterial hypertension difficult to control due to isolated systolic hypertension (ISH), diabetes mellitus (DM), chronic nephropathy, or metabolic syndrome.

Methods: The open-label, non-comparative, 3-month study without preliminary washout included 1438 hypertensive patients (mean age: 57.3?±?10.7 years, mean BP: 158.8?±?14.2/93.4?±?10.0?mmHg), with difficult-to-control arterial hypertension and who had never been treated with diuretics previously. Throughout the study, patients received indapamide SR 1.5?mg OD. BP control was defined as <140/90?mmHg for all patients and <130/80?mmHg for those with diabetes mellitus or chronic nephropathy.

Results: Indapamide SR was given as initiation monotherapy to 13.7% of the patients, as substitutive monotherapy to 6.8% of the patients uncontrolled by a previous monotherapy, as additive therapy to 31.9% of the patients uncontrolled by previous monotherapy, and as additive therapy to 47.6% uncontrolled by previous combination therapy without a diuretic. Among included patients 75.7% received also an ACE inhibitor or an angiotensin II receptors blocker, 43.9% a calcium channel blocker, and 32.8% a beta-blocker. In 3 months after indapamide SR administration, average BP level decreased to 131.8?±?9.7/80.5?±?6.9?mmHg and 84.5% of the study population achieved BP control. BP was controlled in 91.9% of patients with ISH (n?=?477), 74.8% of those with diabetes (n?=?214), 75.6% of those with chronic nephropathy (n?=?82), and 85.1% of patients with metabolic syndrome (n?=?745). No case of hypokalemia was reported.

Conclusion: The study demonstrates the value of including the thiazide-like diuretic indapamide SR in a combined antihypertensive regimen to control BP in hypertensive patients with added cardiovascular risk factors whose hypertension is difficult to treat. Methodological limitations of this study are its open-label design and the possibility of a change in concomitant antihypertensive treatment during the study.     

Olmesartan medoxomil-based therapy for the management of hypertension

Contemporary practice guidelines for hypertension recommend a goal systolic/diastolic blood pressure (BP) of less than 140/90 mmHg for patients with hypertension and less than 130/80 mmHg for patients with diabetes mellitus or chronic kidney disease. Current guidelines recognize that most patients will require combination therapy to achieve these BP goals and recommend that the agents used in such therapy should have complementary mechanisms of action. Olmesartan medoxomil is an angiotensin receptor blocker approved for the treatment of hypertension as monotherapy or in combination with antihypertensive agents. It is also approved in a fixed-dose combination with hydrochlorothiazide or amlodipine. Olmesartan medoxomil-based therapy can manage hypertension across a range of patient types and has demonstrated good BP-lowering efficacy and goal attainment in individuals with stage 1 or stage 2 hypertension. The comparative antihypertensive efficacy and safety of olmesartan medoxomil, as monotherapy and as part of combination therapy, has been established in several large, randomized clinical trials. This review evaluates the chemistry, efficacy and safety of olmesartan medoxomil-based therapy and its expanding role in hypertension management.     

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.     

Efficacy and tolerability of combination therapy with valsartan/hydrochlorothiazide in the initial treatment of severe hypertension

ABSTRACT

Objective: Most patients with severe hypertension are at high risk for cardiovascular events and require prompt blood pressure (BP)-lowering and combination therapy to achieve BP goals. This study evaluated the therapeutic efficacy and tolerability of initial treatment with the combination of valsartan and hydrochlorothiazide (HCTZ) compared with valsartan monotherapy in patients with severe hypertension.

Research design and methods: This was a 6-week, randomized, double-blind, multicenter, forced titration study that compared initial therapy with the combination of valsartan/HCTZ 160/12.5?mg (force titrated to 160/25?mg after 2 weeks and to 320/25?mg after 4 weeks) to monotherapy with valsartan 160?mg (force titrated to 320?mg after 2 weeks and sham-titrated to 320?mg after 4 weeks). Eligible patients were 18–80 years old with severe essential hypertension (mean sitting diastolic BP?≥?110?mmHg and <120?mmHg and mean sitting systolic BP?≥?140?mmHg and <200?mmHg). The Clinical Trial Registry number was NCT00273299.

Main outcome measures: The primary efficacy variable was the rate of BP control (mean sitting BP?<?140/90?mmHg) at Week 4. Tolerability was evaluated by monitoring all adverse events, vital signs, and laboratory tests including hematology and biochemistry.

Results: A total of 608 patients were randomized to either valsartan/HCTZ (n?=?307) or valsartan monotherapy (n?=?301). Significantly more patients achieved overall BP control (<140/90?mmHg) with valsartan/HCTZ compared to monotherapy at Week 4 (primary efficacy variable and timepoint) (39.6% vs. 21.8%; p?<?0.0001) and Week 6 (48.2% vs. 27.2%; p?<?0.0001). Mean reductions in BP at Week 4 were significantly greater for valsartan/HCTZ (30.8/22.7?mmHg vs. 21.7/17.5?mmHg; p?<?0.0001), with further reductions at Week 6. BP control rates were greater with combination therapy as early as Week 2. The overall incidence of adverse events was comparable between the combination therapy (34.9%) and monotherapy (36.7%) treatment groups. A potential limitation of the forced-titration design is that some patients were titrated to higher doses despite having achieved goal BP. This may impact the interpretation of the incidence of dose-dependent adverse events.

Conclusions: Initial therapy with valsartan/HCTZ is effective and well tolerated in patients with severe hypertension.     

Combination Therapy with Olmesartan Medoxomil and Hydrochlorothiazide

Background

The combination of olmesartan medoxomil and hydrochlorothiazide (HCTZ) [olmesartan medoxomil/HCTZ] has previously been shown to produce significantly greater SBP/DBP reductions than monotherapy with either agent alone in a randomized, double-blind, factorial study in patients with stage 2 hypertension. Compared with the evaluation of a single mean BP reduction in a patient population, determining the efficacy of an antihypertensive agent in achieving multiple BP targets provides additional information about the range of BP reductions attainable within this study population.

Objective

To conduct a secondary analysis of this study to evaluate the proportion of patients achieving combined SBP/DBP targets recommended in current hypertension treatment guidelines as well as individual SBP and DBP targets.

Methods

A total of 502 patients with DBP ≥100 and ≤115 mmHg were randomized to 8 weeks of treatment with placebo, HCTZ 12.5 or 25 mg/day, olmesartan medoxomil 10, 20, or 40 mg/day, or olmesartan medoxomil/HCTZ 10/12.5, 10/25, 20/12.5, 20/25, 40/12.5, or 40/25 mg/day. Mean baseline SBP ranged from 151.9 to 156.6 mmHg and mean baseline DBP ranged from 102.6 to 104.4 mmHg across the twelve treatment arms. The chi-squared test was used to compare the proportion of patients achieving each BP goal in each of the 11 active treatment regimens with that in the placebo group.

Results

The proportion of patients achieving an SBP <140 or <130 mmHg, DBP <90, <85, or <80 mmHg and combined SBP/DBP <140/90, <130/85, <130/80, or <120/80 mmHg typically increased with escalating dosages of olmesartan medoxomil and HCTZ when administered alone or in combination, but was always highest in those treated with the combination. As the BP goal became progressively more stringent, the proportion of patients achieving the BP goal decreased in each treatment group, although the trend toward greater reductions in patients treated with combination therapy remained intact. All combined SBP/DBP goals were achieved by a statistically significant proportion of patients (p<0.05) in the olmesartan medoxomil/HCTZ 20/25, 40/12.5, and 40/25 treatment groups.

Conclusions

A majority of patients with uncomplicated stage 2 hypertension can achieve recommended BP goals when treated with the combination of olmesartan medoxomil and HCTZ.     

Combination of Amlodipine plus Angiotensin Receptor Blocker or Diuretics in High-Risk Hypertensive Patients

Background and Objectives

Antihypertensive therapy is effective in reducing the risk of major adverse cardiovascular events. However, blood pressure (BP) control rate remains poor and the optimal combination therapy against hypertension is not established in China. The objective of this study was to evaluate the long-term efficacy and safety of two antihypertensive regimens, amlodipine plus telmisartan and amlodipine plus amiloride/hydrochlorothiazide, in patients with essential hypertension and at least one cardiovascular risk factor.

Methods

In a multicenter open-label clinical trial, eligible patients were randomized to receive treatment with amlodipine 2.5–5 mg plus amiloride/hydrochlorothiazide 1.25–2.5 mg/12.5–25 mg (Group A) or amlodipine 2.5–5 mg plus telmisartan 40–80 mg (Group T). If a target BP was not reached, other antihypertensive agents would be added. The target BP was <130/80mmHg for patients with diabetes mellitus or chronic kidney disease and <140/90mmHg for others. Efficacy variables were changes from baseline in systolic BP and diastolic BP at the endpoint of 96 weeks. Safety evaluations included monitoring of any adverse events (AEs).

Results

Of 13 542 patients randomized, 13 080 (96.6%) completed the study: 6529 in Group A and 6551 in Group T. At endpoint, the BP levels were reduced by 27.4/14.3 mmHg in Group A and 27.1/14.5 mmHg in Group T. The BP control rates were similar for the two therapeutic regimens (87.5% vs 86.1%). Less than 4% of patients in each group discontinued their drugs during follow-up. Peripheral edema was one of the most common AEs, and occurred in only 24 patients in Group A and 19 in Group T.

Conclusions

Long-term combination therapy with amlodipine plus telmisartan or amlodipine plus amiloride/hydrochlorothiazide was not only well tolerated but also efficacious in reducing BP levels with acceptable control rates in the majority of hypertensive patients.

Clinical Trials Registration

ClinicalTrials.gov number NCT01011660.     

Beating the clock: reducing cardiovascular risk by rapid blood pressure reduction with olmesartan

Importance of the field: Hypertension is a major cardiovascular risk factor, and treatment guidelines acknowledge the value not only of reducing elevated blood pressure (BP) to target levels (< 140/90 mmHg and < 130/80 mmHg in patients with diabetes or those at high cardiovascular risk) but also of doing this rapidly.

Areas covered in this review: The importance of rapid BP control has been demonstrated by trials like the Valsartan Antihypertensive Long-term Use Evaluation trial. Combination therapy provides greater efficacy than monotherapy and reduces BP more rapidly. Combining angiotensin receptor blockers (ARBs) with agents from other classes, like calcium channel blockers or diuretics, is an established way to provide effective, rapid and well-tolerated BP reduction.

What the reader will gain: Although ARBs are widely used as mono- and combination therapy, it is not widely appreciated that there are differences between these drugs in efficacy and speed of action. The ARB olmesartan medoxomil provides rapid reductions in BP as monotherapy and combination therapy, with large BP reductions observed within the first few weeks of treatment.

Take home message: In addition to controlling BP, speed of onset of action is an important factor in the management of hypertensive patients and treatments that lower BP rapidly should help to reduce cardiovascular risk.     

Introduction

Systemic hypertension is a long-term risk factor for the development of atherosclerotic vascular disease and when uncontrolled is a short-term trigger of acute vascular events such as acute coronary syndromes and stroke. Thus, rapid reduction in BP is desirable. Patients at high risk for vascular disease, such as those with diabetes mellitus, have aggressive goal BP targets because studies have shown that achieving these targets reduces events. Given the dual goals in high-risk patients of reducing BP quickly and to aggressively low targets, the classic ‘step therapy’ of one drug titrated at a time to reduce BP is inadequate. Combination therapy with at least two potent medications makes more sense, and manufacturers are now increasing their offerings of single-pill combinations for hypertension. Combination pills are popular with patients and increase compliance with therapy. Many believe that renin-angiotensin aldosterone system (RAAS) blockers are the cornerstone of hypertension treatment in patients at high risk for vascular disease. The newer combination pills include a RAAS blocker and diuretics or a long-acting calcium channel antagonist (CCA). Recent studies have shown that a RAAS blocker plus a dihydropyridine CCA is superior to older diuretic-based combinations for preventing cardiovascular events. These considerations support a new approach to the higher risk hypertensive patient: effective doses of RAAS blocker/CCA combination pills to rapidly lower BP to <130/80 mmHg.     

Therapeutic strategies for hypertension treatment in patients with selected cardiovascular diseases

Patients with hypertension and concomitant cardiovascular (CVD) conditions are at high risk for developing deleterious CVD-related clinical sequelae. The selection of therapeutic strategies for hypertension management in patients with cardiovascular diseases is an important first step in normalizing blood pressure (BP) levels (<140/90 mmHg). The ultimate goal of BP normalization for this high-risk group of hypertensive patients is target-organ protection. This review will discuss the management of hypertension in patients with selected CVD conditions (congestive heart failure, coronary artery disease, renal insufficiency/end-stage renal disease) and will incorporate both nondrug and drug therapies. Nondrug therapy, including weight reduction, physical activity, restriction of dietary sodium and alcohol intake are effective strategies for lowering BP. If these measures are not adequate, then the addition of drug therapy is needed in order to provide gradual BP normalization. Drug regimens may include a single antihypertensive agent with up-titration of the dose, or a combination of antihypertensive agents at a lower dose of each agent. The availability of different classes of antihypertensive agents enables therapeutics strategies to be implemented in the management of hypertension that provide maximum target-organ protection for each entity of CVD. Thus, aggressive hypertension management is crucial for delaying/preventing target organ damage and subsequent CVD clinical events.     

Management of Hypertension with the Fixed Combination of Perindopril and Amlodipine in Daily Clinical Practice

Background

Current clinical guidelines recognize that the use of more than one agent is necessary to achieve target BP in the majority of patients. The ASCOT-BPLA trial demonstrated that the free combination of amlodipine and perindopril effectively controlled BP and was better than a β-adrenoceptor antagonist (β-blocker)/diuretic combination in reducing total mortality and cardiovascular outcomes.

Objective

To evaluate the efficacy and tolerability of a fixed combination of perindopril and amlodipine in the clinical setting.

Study design

The STRONG (SafeTy & efficacy analysis of coveRsyl amlodipine in uncOntrolled and Newly diaGnosed hypertension) study was a prospective, observational, multicenter trial.

Setting

This was a naturalistic, real-world, clinic-based, outpatient study involving 336 general practitioners/ primary care physicians in 65 cities in India.

Patients

Adults aged 40–70 years with newly diagnosed/untreated stage 2 hypertension (BP ≥ 160/100 mmHg), hypertension uncontrolled with monotherapy (BP > 140/90 mmHg), or hypertension inadequately managed with another combination therapy.

Intervention

Fixed combination perindopril 4 mg/amlodipine 5 mg once daily for 60 days.

Main outcomes measure

The primary outcomes were the mean change in BP from baseline and the proportion of patients achieving adequate BP control (≤ 140/90 mmHg, or ≤ 130/80 mmHg in patients with diabetes mellitus) in the intent-to-treat (ITT) population. Secondary analyses included incidence of adverse events (ITT) and treatment adherence rate (completers).

Results

In total, 1250 patients comprised the ITT population: 32.6% with newly diagnosed hypertension; 40.5% with hypertension uncontrolled with monotherapy; and 26.9% with hypertension inadequately managed with another combination therapy. Mean SBP/DBP decreased significantly from baseline (167.4±15.2/101.4±9.1 mmHg) over 60 days (?41.9 ± 34.8/?23.2 ± 21.8 mmHg; p<0.0001). Target BP was achieved in 66.1% of patients in the total population, 68.3% of untreated patients, 68.4% of patients uncontrolled with monotherapy, and 59.9% of patients inadequately managed with combination therapy. In 161 patients with SBP >180 mmHg at baseline (newly diagnosed: n = 50; uncontrolled on monotherapy: n = 53; inadequately managed on combination therapy: n = 58), BP was reduced by 63.2 ± 32.5/29.0 ± 21.9 mmHg (p<0.0001) at day 60. The fixed combination was safe and well tolerated. All 1175 patients completing the 60-day study (94%) adhered to their treatment regimen.

Conclusion

Fixed combination perindopril/amlodipine was found to be an effective and well tolerated antihypertensive treatment, with an excellent rate of treatment adherence in the clinical setting. Fixed combination perindopril/amlodipine is expected to be useful in the management of hypertension in primary healthcare, with a positive impact on treatment adherence.     

An Olmesartan Medoxomil-Based Treatment Algorithm is Effective in Achieving 24-Hour BP Control in Patients with Type 2 Diabetes Mellitus, Regardless of Age, Race, Sex, or Severity of Hypertension

Background

Hypertension often occurs concomitantly with diabetes mellitus, such that >50% of adults with type 2 diabetes have hypertension. These individuals are at a greater risk of developing renal and cardiovascular disease. The currently recommended BP goal of <130/80 mmHg for patients with type 2 diabetes is achieved in only 37.5% of treated patients with diabetes and hypertension.

Methods

The antihypertensive efficacy of olmesartan medoxomil (OM) ± hydrochlorothiazide (HCTZ) was investigated in prespecified subgroups (age <65/≥65 years, Blacks/non-Blacks, males/females, or stage 1/ stage 2 hypertension) of patients with hypertension and type 2 diabetes enrolled in an open-label, single-arm study (n= 192). Patients started treatment with OM 20 mg/day and were uptitrated at 3-week intervals to OM 40, OM/HCTZ 40/12.5, and OM/HCTZ 40/25 mg/day if BP was ≥120/70 mmHg. The primary endpoint was the change in mean 24-hour ambulatory SBP from baseline to week 12, assessed by mean 24-hour ambulatory BP monitoring. Secondary endpoints included changes in mean 24-hour ambulatory DBP, mean daytime ambulatory BP, mean nighttime ambulatory BP, and mean office seated BP, and the proportions of patients achieving prespecified ambulatory BP targets.

Setting

This was a multicenter study (24 sites) that took place between November 2006 and November 2007 in the US.

Results

BP reductions were significant (p<0.0001) and similar among subgroups of patients with type 2 diabetes. Following dose titration to OM/HCTZ 40/25 mg/day, similar proportions of patients in the age, race, and sex subgroups (approximately 60–64% across these subgroups) achieved an ambulatory BP target of <130/80 mmHg. A larger proportion of patients with type 2 diabetes and stage 1 hypertension achieved this same goal compared with patients with stage 2 hypertension (75% vs 46.3%). The combination of OM/HCTZ was well tolerated in all patient subgroups irrespective of age, race, sex, or hypertension severity.

Conclusions

In this open-label study, OM/HCTZ combination therapy was efficacious and well tolerated in subgroups of patients with diabetes and hypertension.     

Efficacy and tolerability of the perindopril/indapamide combination therapy for hypertension: the PRIMUS study*

ABSTRACT

Background: Tight blood pressure (BP) control is required to reduce cardiovascular morbidity and mortality.

Objective: To evaluate the efficacy and tolerability of the first line combination perindopril/indapamide in hypertension in daily practice.

Design and methods: In this prospective, open-label, observational trial, 1892 general practitioners in Germany recruited patients with hypertension (?n = 8023; mean age 59.6 years, 48.1% males, body mass index 27.6?kg/m², systolic BP ≥ 140?mmHg and/or diastolic BP ≥ 90?mmHg) between October 2002 and December 2004. Patients received perindopril 2?mg/indapamide 0.625?mg for 12 weeks. BP measured in the general practice setting, safety, and tolerability were evaluated after 4 and 12 weeks.

Results: At baseline, most patients had moderate to severe hypertension (78%); initial BP was 164.6/95.8?mmHg. At inclusion, 38% of the patients were newly diagnosed hypertensives (mean BP 166.1/97.2?mmHg) and 58% of patients had uncontrolled BP despite preexisting antihypertensive treatment (163.5/94.9?mmHg). Previous treatment consisted of β‐blockers (49.5%), ACE inhibitors (36.4%), calcium-antagonists (29.3%), diuretics (28.8%), AT‐I receptor antagonists (7.1%), and other treatments (8.1%). In the entire study cohort, treatment with perindopril/indapamide significantly decreased systolic BP (27.9?mmHg), diastolic BP (13.7?mmHg), and pulse pressure (14.2?mmHg), compared with baseline (?p < 0.0001); 96% of patients responded to treatment and in 50% of patients BP was normalized (< 140/90?mmHg). Treatment dose was doubled in 9.5% of patients. Similar results were found in various subgroup analyses (newly diagnosed patients, the elderly, and patients with isolated systolic hypertension, additional cardiovascular risk factors, associated diseases, or target organ damage). The most frequent adverse events (< 1% of patients) were dry cough and nausea.

Conclusions: The open-label, observational study PRIMUS, extends the existing evidence that the first line combination treatment of hypertension with perindopril/indapamide is effective, safe, and well tolerated in a representative cross-section of patients with newly diagnosed or pretreated but uncontrolled hypertension in daily practice.     

Antihypertensive efficacy and safety of benidipine and its effects on cardiac structure and function in elderly Chinese patients with mild to moderate hypertension: an open-label, long-term study

Benidipine (CAS 91599-74-5) has been reported as an effective antihypertensive treatment and its cardioprotective effects have been shown in several basic and clinical studies. However, the long-term efficacy and safety of benidipine remain unknown in elderly Chinese patient with hypertension. In this prospective, multicenter, open-label clinical trial, 152 eligible patients aged 60 to 75 years with mild to moderate essential hypertension (sitting systolic blood pressure (BP) > or = 140 mmHg and/or sitting diastolic BP > or = 90 mmHg) entered a 52-week study. All patients initially received benidipine 2-4 mg once a day, followed by titration to benidipine 8 mg/day to achieve the target BP (< 140/90 mmHg in non-diabetics and <130/80 mmHg in diabetics). Add-on hydrochlorothiazide (CAS 58-93-5) and/or metoprolol tartaric acid (CAS 3750-58-6) were permitted during the study. Overall, 132 patients completed the 52-week treatment with benidipine as monotherapy or combination therapy. It showed that the regimen based on benidipine provided an obvious mean trough BP reduction of 13.8 +/- 12.4/8.3 +/- 9.2 mmHg (p < 0.001), and 62.5% of patients reached the target BP. In patients with left ventricular hypertrophy, the left ventricular mass index significantly decreased from 147.1 +/- 27.6 g/m2 at baseline to 136.0 +/- 17.5 g/m2 at 52 weeks (p = 0.036). Clinical adverse events (AEs) were found in 15.1% of all patients, and six patients discontinued the treatment due to drug-related AEs during the entire trial. Patients' compliance was an average of 98.7%. Benidipine, with a favorable tolerability profile, provides a long-term antihypertensive effect and potential benefit for the heart in elderly patients with mild to moderate hypertensive, suggesting that it is suitable for elderly patients with hypertension.     

Effect of three months’ treatment with irbesartan on blood and pulse pressure of hypertensive type 2 diabetic patients: open,observational study in 31 793 patients

ABSTRACT

Objectives: In hypertensive diabetics the cardiovascular risk is substantially increased. Therefore, an effective reduction of both blood pressure and pulse pressure is of particular importance for these patients. The aim of the prospective observational study in hypertensive type 2 diabetics was to assess the effect of a switch from the previous antihypertensive therapy to the angiotensin-II-receptor antagonist irbesartan (alone or in combination with HCTZ) on the reduction of blood pressure and pulse pressure, the reduction of diabetic nephropathy (microalbuminuria), and tolerability.

Methods: 8714 general practitioners included 31?793 type 2 diabetics aged at least 18 years in an open observational study. After inclusion in to the study the patients received irbesartan 300?mg as monotherapy or in combination with hydrochlorothiazide 12.5?mg (HCTZ). Main outcome measures for efficacy were the reduction of systolic (SBP) and diastolic (DBP) blood pressures, reduction of pulse pressure, and blood pressure responder (reduction in DBP ≥ 10 mmHg or diastolic < 90 mmHg), diastolic normalization (DBP < 90 mmHg) and overall normalization rates (SBP < 140 mmHg and DBP < 90 mmHg) after 3 months. Further outcome measures included the reduction of microalbuminuria or proteinuria, and adverse events (AEs) as a measure of tolerability.

Results: Thirty-eight per cent of patients received irbesartan 300?mg and 61% irbesartan in combination with HCTZ. Mean systolic blood pressure was reduced by 22.5?mmHg, diastolic blood pressure by 10.7?mmHg (baseline values: 160.2 and 93.2?mmHg). Pulse pressure fell on average by 11.6?mmHg. 83.4% of the patients were responders, with an overall normalization rate of 42.7% (SBP < 140?mmHg and DBP < 90?mmHg), respectively 73.8% (DBP < 90?mmHg). The antihypertensive benefit was achieved irrespective of the previous medication. Mean albuminuria decreased by about 27.7?mg/L. Only 0.3% of patients experienced adverse events.

Conclusions: In type 2 diabetics with hypertension and either uncontrolled or no previous antihypertensive therapy a change to treatment with irbesartan or irbesartan/HCTZ for 3 months resulted in a distinct reduction of systolic and diastolic blood pressures, with concomitant effective reductions of pulse pressure and microalbuminuria.     

Efficacy and tolerability of the perindopril/indapamide combination therapy for hypertension: the PRIMUS study

BACKGROUND: Tight blood pressure (BP) control is required to reduce cardiovascular morbidity and mortality. OBJECTIVE: To evaluate the efficacy and tolerability of the first line combination perindopril/indapamide in hypertension in daily practice. DESIGN AND METHODS: In this prospective, open-label, observational trial, 1892 general practitioners in Germany recruited patients with hypertension (n = 8023; mean age 59.6 years, 48.1% males, body mass index 27.6 kg/m2, systolic BP >or= 140 mmHg and/or diastolic BP >or= 90 mmHg) between October 2002 and December 2004. Patients received perindopril 2 mg/indapamide 0.625 mg for 12 weeks. BP measured in the general practice setting, safety, and tolerability were evaluated after 4 and 12 weeks. RESULTS: At baseline, most patients had moderate to severe hypertension (78%); initial BP was 164.6/95.8 mmHg. At inclusion, 38% of the patients were newly diagnosed hypertensives (mean BP 166.1/97.2 mmHg) and 58% of patients had uncontrolled BP despite preexisting antihypertensive treatment (163.5/94.9 mmHg). Previous treatment consisted of beta-blockers (49.5%), ACE inhibitors (36.4%), calcium-antagonists (29.3%), diuretics (28.8%), AT-I receptor antagonists (7.1%), and other treatments (8.1%). In the entire study cohort, treatment with perindopril/indapamide significantly decreased systolic BP (27.9 mmHg), diastolic BP (13.7 mmHg), and pulse pressure (14.2 mmHg), compared with baseline (p < 0.0001); 96% of patients responded to treatment and in 50% of patients BP was normalized (< 140/90 mmHg). Treatment dose was doubled in 9.5% of patients. Similar results were found in various subgroup analyses (newly diagnosed patients, the elderly, and patients with isolated systolic hypertension, additional cardiovascular risk factors, associated diseases, or target organ damage). The most frequent adverse events (< 1% of patients) were dry cough and nausea. CONCLUSIONS: The open-label, observational study PRIMUS, extends the existing evidence that the first line combination treatment of hypertension with perindopril/indapamide is effective, safe, and well tolerated in a representative cross-section of patients with newly diagnosed or pretreated but uncontrolled hypertension in daily practice.     

Evaluation of long-term efficacy and acceptability of indapamide SR in elderly hypertensive patients

OBJECTIVE: To assess the long-term antihypertensive efficacy and acceptability of indapamide SR 1.5 mg in elderly hypertensive patients (> or = 65 years). STUDY DESIGN: Open, 12-month, follow-up study of 444 patients, treated with indapamide SR, who were responders and/or achieved target BP levels following a 3-month, randomised, controlled, double-blind short-term comparison of indapamide SR versus hydrochlorothiazide 25 mg and amlodipine 5 mg. RESULTS: The long-term decrease in systolic blood pressure (SBP)/diastolic blood pressure (DBP) after 12 months follow-up with indapamide SR was -24.0/-13.1 mmHg from baseline (M0). The percentage of patients that achieved target BP levels (DBP < 95 mmHg, SBP < or = 160 mmHg) was 80.1% [84.3% for isolated systolic hypertension (ISH) subgroup], and the response rate (BP < 140/90 mmHg or decrease in supine diastolic BP > or = 10 mmHg or in supine systolic BP > or = 20 mmHg) 81.5%. Blood pressure (BP) remained stable throughout the 12 months follow-up period (M3-M15), whatever the previous treatment received during the 3-month, doubleblind period (M0-M3). Clinical and biological acceptability was good. A low occurrence of withdrawals (7.2%), was reported. CONCLUSION: Over the course of the long-term, 12-month follow-up study, indapamide SR was shown to be an effective and well tolerated antihypertensive therapy, even after a switch from amlodipine or hydrochlorothiazide, in patients aged 65 years-80 years with systolo-diastolic hypertension (SDH) or ISH.