Metoprolol succinate extended release/hydrochlorothiazide combination tablets

Lowering elevated blood pressure (BP) with drug therapy reduces the risk for catastrophic fatal and nonfatal cardiovascular events such as stroke and myocardial infarction. Given the heterogeneity of hypertension as a disease, the marked variability in an individual patient's BP response, and low response rates with monotherapy, expert groups such as the Joint National Committee (JNC) emphasize the value of combination antihypertensive regimens, noting that combinations, usually of different classes, have additive antihypertensive effects. Metoprolol succinate extended-release tablet is a beta-1 (cardio-selective) adrenoceptor-blocking agent formulated to provide controlled and predictable release of metoprolol. Hydrochlorothiazide (HCT) is a well-established diuretic and antihypertensive agent, which promotes natruresis by acting on the distal renal tubule. The pharmacokinetics, efficacy, and safety/tolerability of the antihypertensive combination tablet, metoprolol extended release hydrochlorothiazide, essentially reflect the well-described independent characteristics of each of the component agents. Not only is the combination product more effective than monotherapy with the individual components but the combination product allows a low-dose multidrug regimen as an alternative to high-dose monotherapy, thereby, minimizing the likelihood of dose-related side-effects.     

Optimal blood pressure level and best measurement procedure in hemodialysis patients

Hypertension occurs frequently among hemodialysis (HD) patients and can be due to many factors, such as salt intake, elevated sympathetic tone, and uremic toxins. It is responsible for the high cardiovascular risk associated with renal disease. Generally, in HD patients, while there is an elevation of systolic blood pressure (BP), diastolic BP seems to decrease, and the resultant effect is high pulse pressure, which can have a deleterious effect on the cardiovascular system. Although controversial, in the HD population the relationship between BP and risk of death seems to be U shaped, probably because of pre-existing cardiac disease in patients with the lowest BP. In chronic kidney disease, BP lower than 130/80 mmHg is recommended, but an appropriate target for BP in the HD population remains to be established. Moreover, there is no consensus regarding which routine peridialysis BP (pre- or post-dialysis BP, or both) can ensure the diagnosis of hypertension in this population. Ambulatory BP monitoring remains the gold standard to quantify the integrated BP load applied to the cardiovascular system. As well, home BP assessment could contribute to improve the definition of an optimal BP in the HD population. An ideal goal for post-dialysis systolic BP seems to be a value higher than 110 mmHg and lower than 150 mmHg. However, HD patients are generally old and often have cardiac complications, so a reasonable pre-dialysis target systolic BP could be 150 mmHg. It is prudent to suggest that an improvement in BP control is necessary in the HD population, first by slow and smooth removal of extracellular volume (dry weight) and thereafter by the use of appropriate antihypertensive medication.     

Olmesartan medoxomil combined with hydrochlorothiazide for the treatment of hypertension

In most patients with hypertension, especially Stage 2 hypertension, adequate control of blood pressure (BP) is only achieved with combination drug therapy. When using combination therapy, antihypertensive agents with complementary mechanisms of action are recommended, for example, an angiotensin receptor blocker (ARB) in combination with hydrochlorothiazide (HCTZ), a beta-blocker + HCTZ, an ACE inhibitor + HCTZ, or a calcium channel blocker + an ACE inhibitor. One such combination is olmesartan medoxomil + HCTZ, which is available as fixed-dose, single-tablet combinations for once-daily administration. In clinical trials, olmesartan medoxomil/HCTZ reduced systolic BP (SBP) and diastolic BP (DBP) to a greater extent than either component as monotherapy. A clinical study in patients with Stage 1 or 2 hypertension showed that olmesartan medoxomil/HCTZ achieved a similar mean reduction in DBP, but a significantly greater mean reduction in SBP and higher rate of BP control (< 140/90 mmHg) than observed with losartan/HCTZ, at US/European-approved starting doses. In a non-inferiority trial, the antihypertensive efficacy of olmesartan medoxomil/HCTZ was comparable to that of atenolol/HCTZ. Furthermore, indirect comparisons have shown that olmesartan medoxomil/HCTZ compares favorably with other antihypertensive combination therapies, including other ARB/HCTZ combinations and amlodipine besylate/ benazepril. Olmesartan medoxomil/HCTZ is generally well tolerated. In conclusion, olmesartan medoxomil/HCTZ is an effective and well-tolerated combination antihypertensive therapy that results in significant BP reductions and BP control in many patients.     

Trandolapril/verapamil combination in hypertensive diabetic patients

Cardiovascular diseases are directly affected by arterial hypertension. When associated with diabetes mellitus, the potential deleterious effects are well amplified. Both conditions play a central role in the pathogenesis of coronary artery disease, heart failure, stroke, and renal insufficiency. Prevalence of hypertension is much higher among diabetic than non-diabetic patients, and the hypertensive patient is more likely to develop type 2 diabetes. Current international guidelines recommend aggressive reductions in blood pressure (BP) in hypertensive patients with additional risk factors, including cardiovascular risk factors, and emphasize the relevance of intensive reduction in patients with diabetes mellitus; a goal of 130/80 mm Hg is required. To achieve BP target a combination of antihypertensives will be needed, and the use of long-acting drugs that are able to provide 24-hour efficacy with a once-daily dosing confers the noteworthy advantages of compliance improvement and BP variation lessening. Lower dosages of the individual treatments of the combination therapy can be administered for the same antihypertensive efficiency as that attained with high dosages of monotherapy. Angiotensin-converting enzyme inhibitors and calcium-channel blockers as a combination have theoretically compelling advantages for vessel homeostasis. Trandolapril/verapamil sustained release combination has showed beneficial effects on cardiac and renal systems as well as its antihypertensive efficacy, with no metabolic disturbances. This combination can be considered as an effective therapy for the diabetic hypertensive population.     

Risk factors to be considered at the beginning of antihypertensive therapy in diabetes mellitus

The treatment of hypertension in diabetic patients due to its high prevalence rate belongs to the everyday clinical practice of internists, diabetologists and general practitioners. The main points of the initiation on of antihypertensive treatment in diabetic patients are reviewed. In order to decrease the target organ damages the treatment of early recognized cardiovascular risk factors are of great importance. The target value of antihypertensive treatment in diabetic patients is < 130/80 mmHg (in case of proteinuria > 1 g daily: < 125/75 mmHg). The global cardiovascular risk is high or very high in diabetic patients both with grade I-III hypertension and with high normal blood pressure, therefore, treatment with antihypertensive drug (besides life style optimalisation) should be initiated promptly in these cases. In case of micro- or macroalbuminuria antihypertensive drug (mainly with characteristics of blocking the renin-angiotensin-system) should be given to each diabetic subject irrespective of actual blood pressure values. Success of antihypertensive treatment in diabetic patients could be achieved mainly with combination therapy only. It is reasonable to initiate antihypertensive therapy primarily with a low dose combination of two agents in diabetic patients with hypertension.     

The practice guideline 'Hypertension' (third revision) from the Dutch College of General Practitioners; a response from the perspective of general practice

In the revised practice guideline on hypertension from the Dutch College of General Practitioners, some changes have been made in the areas of diagnosis and therapy in comparison to the previous edition. Finding people with hypertension is a major goal for the prevention of cardiovascular disease. A systolic blood pressure > 140 mmHg (> 160 mmHg in patients > 60 years) necessitates non-pharmaceutical advice and antihypertensive therapy with diuretics, beta-blockers, angiotensin-converting-enzyme (ACE) inhibitors or calcium antagonists, either as monotherapy or in combination. In view of the ever-increasing importance of ACE inhibitors in antihypertensive therapy, we expect that the next revision of the practice guideline will soon be necessary.     

Antihypertensive Potential of Combined Extracts of Olive Leaf,Green Coffee Bean and Beetroot: A Randomized,Double-Blind,Placebo-Controlled Crossover Trial

Extracts of olive leaf, green coffee bean and beetroot may deliver cardiovascular benefits. This study sought to evaluate the effects of regularly consuming a combination of these extracts on blood pressure (BP), arterial compliance, blood lipids, blood glucose and insulin sensitivity. A double-blind randomised placebo-controlled crossover trial was conducted in adults with untreated high normal or borderline elevated BP. They were randomised to take an active supplement, comprising 500 mg olive leaf extract, 100 mg green coffee bean extract and 150 mg beet powder, or a matching placebo twice daily for six weeks, followed by the alternate supplement for a further six weeks. Assessments of 24-h ambulatory BP (ABP), clinic BP arterial compliance (pulse-wave analysis), blood lipids, blood glucose and insulin were obtained at baseline and at the end of each treatment phase. Baseline clinic BP in 37 overweight middle-aged men and women who completed the trial averaged 145/84 mmHg. There was no significant effect of treatment on ABP or any other outcome measure. The failure to confirm prior evidence of the antihypertensive benefits of these extracts emphasises the importance of placebo control and the value of ABP monitoring. Further dose-response evaluation of olive leaf, green coffee bean or beetroot extracts is required to confirm or refute the purported benefits.     

Blood pressure target attainment in the background of guidelines: the very elderly in Swiss primary care

Background There are only a few trials for the very elderly population (>79 years). No consensus, which blood pressure (BP) goals and substances should be applied, has been found yet. This survey was undertaken to investigate how octogenarians are treated and attain BP targets in the Swiss primary care. Methods Data from 4594 hypertensive patients were collected within 7 days. Eight hundred and seventy-seven patients met the requirement to be >79 years. We assessed substances/combinations and investigated pulse pressure and target blood pressure attainment (TBPA) using three different recommendations [Canadian Hypertension Education Program (CHEP), Swiss Society of Hypertension (SSH), European Society of Hypertension-European Society of Cardiology (ESH-ESC)]. Secondarily, we compared TBPA attained by angiotensin-converting enzyme inhibitor (ACEI)/diuretic (D), angiotensin receptor blocker (ARB)/D and calcium channel blocker (CCB)/D with any other dual therapy and investigated whether Ds/beta-blockers (BBs) or Ds/renin angiotensin-converting enzyme inhibitors (RAAS-Is) lead to higher TBPA. Finally, we assessed the impact of drug administration, practical work experience, location and specialization of GPs on TBPA. Results Octogenarians attained target blood pressure (TBP) between 44% (ESH-ESC) and 74% (SSH). Optimal/normal BP was reached in 22.8% of patients. Pulse pressure <65 mmHg was shown in 66.4% of patients. Monotherapy was most commonly applied followed by dual single-pill combination with ARB/D (46.5%) or ACEI/D (36.0%). No benefit in TBPA was found comparing a RAASI/D and CCB/D treatment with any other dual combination. There was also no difference between BB/D and RAAS-I/D combination therapy and between single-pill combination and dual free combinations. Conclusions GPs adhere to the use of substances proven in outcome trials and attain high TBP. No difference in meeting BP goals could be found using different drug classes. There is an unmet need to harmonize recommendations and to add additional information for the treatment of octogenarians.     

Fixed combinations in the management of hypertension: patient perspectives and rationale for development and utility of the olmesartan-amlodipine combination

Although the awareness and control of hypertension has increased, only 37% of hypertensive patients in the US achieve the conservative goal of <140/90 mmHg. Achieving optimal blood pressure (BP) control is the most important single issue in the management of hypertension, and in most hypertensive patients, it is difficult or impossible to control BP with one drug. Blocking two or more BP regulatory systems provides a more effective and more physiologic reduction in BP, and current guidelines have recommended the use of combination therapy as first-line treatment, or early in the management of hypertension. Fixed combination therapy is an efficacious, relatively safe, and may be cost-effective method of decreasing BP in most patients with essential hypertension. Similar to other combinations, fixed-dose combination tablets containing the dihydropyridine calcium channel blocker amlodipine and the angiotensin II receptor blocker olmesartan bring together two distinct and complementary mechanisms of action, resulting in improved BP control and potential for improved target organ protection relative to either class of agent alone.     

A large scale study of angiotensin II inhibition therapy in an elderly population: the CHANCE study

This 8-week, multicenter study evaluated the efficacy and safety of candesartan cilexetil (CC, 8-16 mg) in elderly (>65 years) hypertensive patients. Patients (n=3013) received CC 8 mg during 8 weeks which eventually doubled to CC 16 mg at week 4 if blood pressure remained uncontrolled (> or = 140/90 mmHg). At week 8, 65.5% of patients were normalized (BP < 140/90 mmHg). Mean changes at week 8 were -25.8, -13.2, and -12.7 mmHg for systolic, diastolic, and pulse pressure, respectively. Age, sex, and diabetic status did not influence the antihypertensive effect of CC. 68% of the patients treated with, but uncontrolled or intolerant of, prior antihypertensive treatment were normalized by CC 8-16 mg. In summary, CC 8-16 mg once daily was effective and well tolerated in the management of arterial hypertension in elderly subjects.     

Fixed combination of zofenopril plus hydrochlorothiazide in the management of hypertension: a review of available data

Angiotensin-converting enzyme (ACE) inhibitors effectively interfere with the renin-angiotensin system and exert various beneficial actions on vascular structure and function beyond their blood pressure-lowering effects. Zofenopril, a potent sulphydryl ACE inhibitor, is characterized by high lipophilicity, sustained cardiac ACE inhibition, and antioxidant and tissue protective activities. Its ancillary properties, such as antioxidant activity and cardiovascular (CV) protection, make this drug potentially suitable for the treatment and prevention of certain CV diseases. The Survival of Myocardial Infarction Long term Evaluation trials have demonstrated that the early administration of zofenopril to patients with acute myocardial infarction is associated with a significant reduction in the 6-week occurrence of major CV events in high-risk patients with anterior non-thrombolyzed myocardial infarction. The fixed combination of zofenopril-hydrochlorothiazide (HCTZ) 30/12.5 mg/day is approved for the management of mild-to-moderate hypertension in different European countries. In clinical trials comparing zofenopril-HCTZ with each agent administered as monotherapy, combination therapy was clearly more effective in normalizing blood pressure (BP). In addition, combination therapy provided sustained and consistent BP control over the entire 24 hour dosing interval. The efficacy and safety profile of zofenopril-HCTZ highlights that this combination is a potentially useful addition to currently available therapy for patients with BP inadequately controlled by monotherapy, as well as for patients who require more rapid and intensive BP control.     

Managing hypertension in diabetic patients--focus on trandolapril/verapamil combination

Hypertensive diabetes individuals are at higher risk for cardiovascular events and progression to end stage renal disease. Several well conducted clinical trials indicate that aggressive treatment of hypertension in individual with diabetes reduces these complications. Combinations of two or more antihypertensive drugs are frequently required to reach the target blood pressure and to improve the cardiovascular and renal outcomes in these patients. There are physiological and clinical rationales for renin-angiotensin system blockade in hypertensive diabetics. Trandolapril/verapamil sustained released (SR) is a fixed-dose combination of trandolapril and a sustained release formulation of verapamil and indicated in treatment of hypertension in patients who require more than one drug to reach target blood pressure. The antihypertensive efficacy of trandolapril/verapamil SR has been evaluated extensively in large trials. In the INVEST trial, a verapamil SR-based treatment strategy that included trandolapril in most patients was effective in reducing the primary outcome in hypertensive patients with coronary artery disease. The new onset of diabetes was also significantly lower in the verapamil SR/trandolapril treatment group in comparison with those on the atenolol/hydroclorothiazide treatment group. The BErgamo NEphrologic Diabetes Complications Trial (BENEDICT) documented that in hypertensive diabetes and normoalbuminuria, trandolapril plus verapamil or trandolapril alone delayed the onset of microalbuminuria independent of their blood pressure-reducing effect. Thus, trandolapril/verapamil is an effective option for treatment of hypertensive diabetes patients requiring more than one agent to achieve target blood pressure.     

Treatment of Hypertension in People With Dementia: A Multicenter Prospective Observational Cohort Study

ObjectivesTo describe the treatment of hypertension in people with dementia and collate evidence on adverse health events whilst on treatment.DesignA multicenter prospective observational cohort study.Setting and participantsPeople with documented diagnoses of hypertension and dementia were recruited through memory clinics and general practice from 8 sites in the United Kingdom.MethodsThe cohort was recruited between July 2013 and October 2014. Participants underwent face-to-face, standardized assessment of blood pressure (BP), activities of daily living, cognitive function, and medication use. Follow-up was by monthly telephone interview for 6 months to collate data on adverse health events.Results181 participants were recruited and 177 followed up; 126 (70%) were female, mean age was 82 [standard deviation (SD) 6.3] years, median Mini-Mental State Examination score was 23 [interquartile range (IQR) 18-26] and mean BP was 141/78 (SD 22/12) mmHg. Antihypertensive drugs were prescribed in 157 (87%). Participants were prescribed a median of 1 (IQR 1-2) antihypertensive medication. Angiotensin-converting enzyme inhibitors and/or angiotensin receptor blockers were the most frequently prescribed antihypertensives in 63% of participants. Target BP was achieved in 58% (95% confidence interval 49%-64%). Increasing number of antihypertensives was not associated with lower systolic or diastolic BP, or with a higher proportion of patients attaining target BP. Participants had 214 falls, 3 had a fracture, 3 developed symptomatic heart failure, 4 had cerebrovascular events, and 8 died.Conclusions/ImplicationsIn this population of people with mild dementia, participants were treated with standard antihypertensive medications in a similar proportion to the general population, with a similar proportion achieving target BP. The rate of adverse health events was higher than in randomized controlled trials of antihypertensives and raises reservations about the assumptions underpinning antihypertensive treatment in people with dementia. These findings may help inform clinical decision making.     

Influence of albuminuria and glomerular filtration rate on blood pressure response to antihypertensive drug therapy

Background

Albuminuria and glomerular filtration rate (GFR), two factors linked to kidney and vascular function, may influence longitudinal blood pressure (BP) responses to complex antihypertensive drug regimens.

Methods

We reviewed the clinic records of 459 patients with hypertension in an urban, academic practice.

Results

Mean patient age was 57-years, 89% of patients were African American, and 69% were women. Mean patient systolic/diastolic BP (SBP/DBP) at baseline was 171/98 mmHg while taking an average of 3.3 antihypertensive medications. At baseline, 27% of patients had estimated (e)GFR <60 ml/min/1.73², 28% had micro-albuminuria (30–300 mg/g) and 16% had macro-albuminuria (>300 mg/g). The average longitudinal BP decline over the observation period (mean 7.2 visits) was 25/12 mmHg. In adjusted regression models, macro-albuminuria predicted a 10.3 mmHg lesser longitudinal SBP reduction (p < 0.001) and a 7.9 mmHg lesser longitudinal DBP reduction (p < 0.001); similarly eGFR <60 ml/min/1.73² predicted an 8.4 mmHg lesser longitudinal SBP reduction (p < 0.001) and a 4.5 lesser longitudinal DBP reduction (p < 0.001). Presence of either micro- or macro-albuminuria, or lower eGFR, also significantly delayed the time to attainment of goal BP.

Conclusions

These data suggest that an attenuated decline in BP in drug-treated hypertensives, resulting in higher average BP levels over the long-term, may mediate a portion of the increased risk of cardiovascular-renal disease linked to elevated urinary albumin excretion and reduced eGFR.     

Application in the STRATHE trial of a score system to compare the efficacy and the tolerability of different therapeutic strategies in the management of hypertension

A score system integrating the evolution of efficacy and tolerability over time was applied to a subpopulation of the STRATHE trial, a trial performed according to a parallel group design, with a double-blind, random allocation to either a fixed-dose combination strategy (perindopril/indapamide 2 mg/0.625 mg, with the possibility to increase the dose to 3 mg/0.935 mg, and 4 mg/1.250 mg if needed, n = 118), a sequential monotherapy approach (atenolol 50 mg, followed by losartan 50 mg and amlodipine 5 mg if needed, n = 108), or a stepped-care strategy (valsartan 40 mg, followed by valsartan 80 mg and valsartan 80 mg+ hydrochlorothiazide 12.5 mg if needed, n = 103). The aim was to lower blood pressure below 140/90 mmHg within a 9-month period. The treatment could be adjusted after 3 and 6 months. Only patients in whom the study protocol was strictly applied were included in this analysis. At completion of the trial the total score averaged 13.1 +/- 70.5 (mean +/- SD) using the fixed-dose combination strategy, compared with -7.2 +/- 81.0 using the sequential monotherapy approach and -17.5 +/- 76.4 using the stepped-care strategy. In conclusion, the use of a score system allows the comparison of antihypertensive therapeutic strategies, taking into account at the same time efficacy and tolerability. In the STRATHE trial the best results were observed with the fixed-dose combination containing low doses of an angiotensin enzyme converting inhibitor (perindopril) and a diuretic (indapamide).     

饮酒对男性原发性高血压患者降压疗效的影响

目的探讨男性原发性高血压患者ACEI(苯那普利)治疗期间饮用白酒对降压疗效的影响。方法采用前瞻性队列研究方法,用多元线性回归和Logistic回归对资料进行统计分析。结果经过15天ACEI治疗,饮酒组收缩压和舒张压下降幅度明显低于非饮酒组,且和饮酒量呈负相关剂量反应关系。其中,每天饮酒大于50ml饮酒组的收缩压和舒张压下降幅度与非饮酒组相比,分别少下降5.26mmHg(0.70kPa)(P=0.0116)和3.32mmHg(0.44kPa)(P=0.0349)。Logistic回归分析发现,每天饮酒大于50ml饮酒组,其收缩压降压有效率为非饮酒组的45%(P=0.0493),舒张压降压有效率为非饮酒组的76%(P=0.4750),但未达到统计显著性差异。结论男性原发性高血压患者在ACEI治疗期间饮用白酒降低降压疗效。     

Treatment of hypertension in people over 80 years should not be discontinued

The 'Hypertension in the very elderly trial' (HYVET) was designed to answer the question whether antihypertensive treatment reduces strokes (both fatal and non-fatal strokes) without increasing total mortality. A total of 3845 patients were assigned to active treatment or placebo. About 90% had a history of hypertension, 65% of which were being treated. At the start of the study all antihypertensive treatment was stopped and the subjects were randomized to either indapamide 1.5 mg with or without perindopril 2-4 mg or to identical looking placebo. After about 2 years the trial was discontinued for ethical reasons as there was less death from any cause in the intervention group. Blood pressure decreased with 30/13 mmHg in the treatment versus 15/7 mmHg in the placebo group. There was a 30% decrease of all strokes (p = 0.06) but a significant reduction in fatal strokes (p < 0.05). Unexpected was the 21% reduction in all-cause mortality (p < 0.02). The 23% reduction in the rate of cardiovascular death was not significant (p < 0.06). Heart failure and total cardiovascular events decreased (p < 0.001). There were fewer adverse effects in the treatment group (p = 0.001). In our opinion HYVET proves that antihypertensive medication should not be stopped when patients pass the age of 80 years. However, it remains to be established whether treatment should be started in new patients who present themselves with hypertension above the age of 80 years.     

A review of telmisartan in the treatment of hypertension: blood pressure control in the early morning hours

Measurement of blood pressure in the clinic may provide a false impression of blood pressure control. Ambulatory blood pressure monitoring (ABPM) allows the automatic recording of the circadian variation in blood pressure and evaluation of the efficacy of antihypertensive medication throughout the dosing interval. Ambulatory blood pressure provides more effective prediction of cardiovascular risk; blood pressure control at the time of heightened risk in the early morning after waking and before taking the next dose of medication is becoming important in order to improve long-term prognosis. To achieve blood pressure control in the early morning, a long-acting antihypertensive agent is essential. Telmisartan, an angiotensin II receptor blocker, as well as having a terminal elimination half-life of 24 h, has a large volume of distribution due to its high lipophilicity. The efficacy of telmisartan 80 mg monotherapy has been demonstrated using ABPM, with superior reduction in mean values for the last 6 h of the dosing interval compared with ramipril 10 mg and valsartan 80 mg. In addition, telmisartan 80 mg provides superior blood pressure control after a missed dose compared with valsartan 160mg. When combined with hydrochlorothiazide (HCTZ) 12.5 mg, telmisartan 40mg and 80mg is more effective than losartan/HCTZ (50/12.5 mg) at the end of the dosing interval. Furthermore, greater reductions in last 6 h mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) are achieved with telmisartan/HCTZ (80/12.5 mg) than with valsartan/HCTZ (160/12.5 mg) in obese patients with type 2 diabetes and hypertension. Recent data from a large group of patients show that telmisartan 80 mg controls the early morning blood pressure surge more effectively than ramipril 5-10 mg and, thus, may have a greater beneficial effect on long-term cardiovascular risk. This supposition is being tested in the ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET) programme.     

Blood pressure normalization by fixed perindopril/indapamide combination in hypertensive patients with or without associate metabolic syndrome: results of the OPTIMAX 2 study

The aim of the observational pharmaco-epidemiological study Optimax II was to seek whether the pre-existence of a metabolic syndrome (MS) defined by the NCEP-ATP III criteria impacts blood pressure (BP) control in hypertensive patients receiving a fixed perindopril/indapamide combination therapy. The primary objective of the study was to compare in patients with and without MS the rate of BP control defined as a systolic BP < or = 140 mmHg and a diastolic BP < or = 90 mmHg. Patients were prospectively included and the follow-up lasted 6 months. The study population consisted of 24,069 hypertensive patients (56% men; mean age 62 +/- 11 years; 18% diabetics; mean BP at inclusion 162 +/- 13/93 +/- 9 mmHg). MS was found in 30.4% of the patients (n = 7322): 35.2% women and 20.1% men. Three therapeutic subgroups were constituted: Group A, previously untreated, received the combination therapy as initial treatment; Group B, previously treated but with unsatisfactory results and/or treatment intolerance, had its previous treatment switched to perindopril/indapamide; and Group C, previously treated, with good treatment tolerance but uncontrolled BP, received the study treatment in adjunction to the previous one. The normalization rate was 70.3% in group A, 68.4% in Group B, and 64.1% in Group C (p < 0.0001). The pre-existence of MS did not show any significant influence on these rates since BP lowering was -22.7 +/- 13.7 (SBP) and -12.0 +/- 10.0 mmHg (DBP) in patients without MS and 22.6 +/- 13.3 (SBP) and -12.1 +/- 9.7 (DBP) in those with MS. The results of this study show a significant effect of perindopril/indapamide treatment on systolic BP lowering, whatever the treatment status: initiation, switch, or adjunctive therapy, and independently from the presence or not of MS. This effect may be related to the specific vascular effect of the perindopril/indapamide combination, which has recently demonstrated in the ADVANCE trial its ability to reduce mortality, and cardiovascular and renal complications in diabetic patients.