Angiotensin receptor blocker added to previous antihypertensive agents on arteries of diabetic hypertensive patients

Lowering elevated blood pressure (BP) in diabetic hypertensive individuals decreases cardiovascular events. We questioned whether remodeling of resistance arteries from hypertensive diabetic patients would improve after 1 year of tight BP control with addition of either the angiotensin receptor blocker (ARB) valsartan or the beta-blocker (BB) atenolol to previous therapy, which included angiotensin-converting enzyme inhibitors (ACEIs) and/or calcium channel blockers. Twenty-eight hypertensive type 2 diabetic patients treated with oral hypoglycemic and antihypertensive agents (not receiving ARBs or BBs) were randomly assigned to double-blind treatment for 1 year with valsartan (80 to 160 mg) or atenolol (50 to 100 mg) daily, added to previous therapy. Resistance arteries dissected from gluteal subcutaneous tissues were assessed on a pressurized myograph. After 1 year of treatment, systolic and diastolic BP and glycemia were equally well controlled in the valsartan and atenolol groups. Endothelium-dependent and independent relaxation did not change in the treated groups. After 1 year of treatment, resistance artery media:lumen ratio decreased in the valsartan group (7.9+/-0.5% after versus 9.8+/-0.6% before; P < 0.05) but not in the atenolol-treated group (9.9+/-0.9% versus 10.6+/-1%; P value not significant). Artery walls from atenolol-treated patients became stiffer, with no change in the valsartan-treated patients. In conclusion, similar intensive BP control for 1 year with valsartan was associated with improved structure of resistance arteries in diabetic hypertensive patients, whereas vessels from atenolol-treated patients exhibited unchanged remodeling and a stiffer wall. The addition of ARBs but not BBs to antihypertensive medications that may include angiotensin-converting enzyme inhibitors and/or calcium channel blockers results in an improvement in resistance artery remodeling in diabetic hypertensive patients.     

Comparison of the effects of aliskiren/valsartan in combination versus valsartan alone in patients with Stage 2 hypertension

The extent to which the combination of a renin inhibitor with an angiotensin receptor blocker (ARB) lowers clinic and ambulatory blood pressure (BP) versus an ARB alone in stage 2 hypertension is not well known. Hence, we performed an 8-week, randomized, double-blind study in 451 patients with stage 2 hypertension to compare the efficacy of the combination of aliskiren/valsartan 300/320 mg versus valsartan 320 mg. The primary endpoint was change in seated systolic BP from baseline to week 8 analyzed on the intent-to-treat (ITT) population using the last-observation-carried-forward (LOCF) approach; patients completing the entire treatment period (per-protocol completers) were similarly analyzed. For the predefined primary analysis, systolic BP reductions for aliskiren/valsartan (n = 230) and valsartan (n = 217) were ?22.1 and ?20.5 mm Hg, respectively (P = .295). In per-protocol completers, aliskiren/valsartan (n = 201) lowered BP significantly greater than valsartan (n = 196); ?23.7 mm Hg versus ?20.3 mm Hg, respectively (P = .028). Although limited by a small sample size (n = 76) using ambulatory BP monitoring, aliskiren/valsartan lowered the 24-hour BP significantly more than valsartan alone (?14.6/?9.0 mm Hg versus ?5.9/?4.2 mm Hg; P < .01). Safety and tolerability were similar for the two treatment groups. These data demonstrate the importance of multiple modalities to assess BP changes in clinical trials of antihypertensive therapies, particularly in stage 2 hypertension.     

Temporal trends in management of hypertension among Israeli adults, 2002–2010: Lesson from the Acute Coronary Syndromes Israeli Survey (ACSIS)

Our aim was to evaluate trends in blood pressure (BP) management and BP levels among patients admitted with acute coronary syndromes (ACS) over the past decade. The study population comprised 7658 ACS patients enrolled in the Acute Coronary Syndromes Israeli Survey (ACSIS) between 2002 and 2010. We compared patients' characteristics, admission systolic BP levels, and antihypertensive therapy between those hospitalized during the early (years: 2002–2004) and late (years: 2008–2010) periods. Among 7658 study participants, 4421 (58%) were hypertensive. Hypertensive patients presenting from 2008 to 2010 tended to exhibit lower BP levels (P < .001). The use of angiotensin converting enzyme inhibitors (ACEi)/angiotensin receptor blockers (ARB) and beta-blockers has increased over the years (P < .001 for both), whereas the use of diuretics and calcium antagonists has remained stable (P = .77 for both). The use of diuretics tended to increase in hypertensive subjects without prior cardiovascular disease (P = .05). In addition, the late period was characterized by a significant increase in the use of two or more antihypertensive agents (combination therapy) compared with the early period (57% vs 50%; P < .001). BP levels decreased among Israeli hypertensive patients presenting with ACS between 2002 and 2010, possibly due to increased use of ACEi/ARB, and combination therapies during this time period.     

Is renoprotection by angiotensin receptor blocker dependent on blood pressure?: the Saitama Medical School, Albuminuria Reduction in Diabetics with Valsartan (STAR) study.

To explore the effects of various antihypertensive regimes on microalbuminuria, an angiotensin II receptor blocker (ARB), valsartan, was substituted for or added to treatment with a calcium channel blocker (CCB). After a 6-month CCB baseline period, 28 Japanese hypertensive patients with incipient diabetic nephropathy (defined as a urinary albumin excretion [UAE] of 30-300 mg/g creatinine), were assigned to two groups according to their blood pressure (BP) levels: in patients with a BP of more than 130/85 mmHg (n=17), valsartan was added to the CCB (Group A), while in patients with a BP <130/85 mmHg, valsartan alone was given (Group B: n=11) for 12 months. UAE was determined before and at 3, 6 and 12 months after the initiation of ARB. Although the initial BP was significantly higher in Group A (150/83 mmHg) than Group B (127/77 mmHg), BP was decreased to 141/78 mmHg in Group A and slightly, but not significantly, increased to 130/82 mmHg in Group B. In both groups, UAE was significantly decreased after ARB treatment (to 89% of the basal value in Group A and to 40.5% of the basal value in Group B) and did not differ each other and the amount of decrease did not differ significantly between the two groups. These results suggest that combination therapy with an ARB and CCB is very effective in lowering BP and UAE in cases in which BP is not well controlled, while, even in patients with a sufficient BP control of <130/85 mmHg, the use of ARB singly resulted in a significant decrease in UAE without a further decrease in BP, implying that the ARB had a renoprotective action independent of changes in BP.     

Long-term Antihypertensive Efficacy of Losartan/Hydrochlorothiazide Combination Therapy on Home Blood Pressure Control

Angiotensin receptor blocker (ARB)/hydrochlorothiazide (HCTZ) combination therapy has been shown to produce a prompt reduction in clinic blood pressure (BP) without serious adverse effects; however, long-term antihypertensive efficacy on home BP has not been fully investigated. In this open-label multicenter observational study, a total of 151 hypertensive patients uncontrolled with antihypertensive regimens including standard dose of ARBs were switched to the fixed-dose combination of losartan (50 mg)/HCTZ (12.5 mg) (mean age 66.9 ± 9.5 years, 51% male, 19% with diabetes mellitus, and 57% with dyslipidemia). After 3 months, losartan/HCTZ treatment significantly reduced mean home systolic BP/diastolic BP from a baseline level of 153 ± 11/85 ± 9 mm Hg to 136 ± 12/77 ± 10 mm Hg (P < .001) and mean clinic BP from 158 ± 9/87 ± 9 to 136 ± 12/77 ± 10 (P < .001), which were maintained through the study period of 12 months (132 ± 11/75 ± 9 and 136 ± 12/77 ± 10; home and clinic BP at 12 months, respectively, P < .001). Furthermore, younger patients (<65 years) receiving ARB monotherapy at the start of the study showed a significantly greater reduction in home BP, but not in clinic BP, compared with elderly patients (≥65 years). In conclusion, losartan/HCTZ combination therapy exerted a 1-year long-term efficacy on home BP as well as clinic BP. In patients uncontrolled with ARB monotherapy, the antihypertensive efficacy on home BP is more pronounced in younger patients compared with that in elderly patients.     

Beneficial effect of angiotensin II type 1 receptor blocker antihypertensive treatment on arterial stiffness: the role of smoking

The purpose of the present study was to assess angiotensin receptor blocker (ARB) treatment on arterial stiffness in select hypertensive patients and define possible differences between smokers and nonsmokers. The authors evaluated 81 consecutive, nondiabetic patients (mean age, 52 years; 47 men) with uncomplicated essential hypertension with high plasma renin activity who were administered monotherapy with irbesartan, an ARB, at maximal dose. Patients were divided into smokers (n=24) and nonsmokers (n=57). Carotid-radial pulse wave velocity (PWVc-r), carotid-femoral pulse wave velocity (PWVc-f), and augmentation index (AIx) were measured before and 6 months after ARB antihypertensive treatment. All mean values of elastic effect indices were decreased after irbesartan monotherapy (AIx, from 26.3%to 21.2% [P<.01;] PWVc-f, from 7.7 m/s to 7.3 m/s [P<.05], and PWVc-r, from 8.9 m/s to 8.3 m/s [P<.001]). When comparing smokers vs nonsmokers, no difference was noted in AIx and PWVc-f change (P=not significant), while PWVc-r change was greater in smokers compared with nonsmokers (P<.05). Chronic ARB treatment may favorably affect arterial stiffness and wave reflections in hypertensive chronic smokers with elevated plasma renin levels.     

Angiotensin type 2 receptor in resistance arteries of type 2 diabetic hypertensive patients

The role of angiotensin type 2 receptor (AT(2)R) on vascular responses to angiotensin II in humans remains unclear. In this study we explored whether AT(2)R is expressed and functionally active on peripheral resistance arteries of hypertensive diabetic patients treated for 1 year with either the angiotensin receptor blocker valsartan or the beta-blocker atenolol. Twenty-six hypertensive type 2 diabetic patients treated with oral hypoglycemic and antihypertensive agents (not receiving angiotensin receptor blockers or beta-blockers) were randomly assigned to double-blind treatment for 1 year with valsartan or atenolol once daily added to their previous therapy in a clinical trial that we reported recently and compared with 10 normal subjects. Resistance arteries dissected from gluteal subcutaneous tissues were assessed on a pressurized myograph. Vasomotor response curves to angiotensin II (1 nmol/L to 1 micromol/L) were performed on norepinephrine precontracted vessels in the presence of valsartan (10 micromol/L) with or without the AT(2)R inhibitor PD123319 (1 micromol/L). AT(2)R expression was evaluated by confocal microscopy. After 1 year of treatment, systolic and diastolic blood pressure was controlled and comparable in the valsartan and atenolol groups. Angiotensin II evoked a significant vasodilatory response only on resistance arteries from patients treated with valsartan, effect blocked by PD123319. AT(2)R expression was 4-fold higher in small arteries of valsartan-treated patients. In conclusion, AT(2)Rs are upregulated and contribute to angiotensin II-induced vasodilation in resistance arteries of hypertensive diabetic patients treated with angiotensin type 1 receptor blockers and may mediate, in part, vascular actions of these drugs in high cardiovascular risk patients.     

The efficacy and safety of valsartan in obese and non-obese pediatric hypertensive patients

J Clin Hypertens (Greenwich). 2011;13:758–766. ©2011 Wiley Periodicals, Inc. This post hoc analysis assessed the efficacy and tolerability of valsartan for the treatment of hypertension in obese vs non‐obese children and adolescents. After a 1‐week antihypertensive washout period, 142 obese and 119 non‐obese hypertensive children and adolescents aged 6 to 16 years were randomized to 2 weeks of once‐daily treatment with valsartan 10 to 20 mg, 40 to 80 mg, or 80 to 160 mg, followed by re‐randomization to either valsartan or placebo for an additional 2 weeks. Patients could continue to receive valsartan during an optional 52‐week, open‐label extension. Valsartan resulted in statistically significant (P<.05) and clinically relevant reductions in mean sitting blood pressure (BP), ranging from approximately 7/4 mm Hg (valsartan 10–20 mg) to 13/9 mm Hg (valsartan 80–160 mg) in both obese and non‐obese patients. BP control was achieved in 44% of obese and 56% of non‐obese patients. Following re‐randomization, non‐obese patients experienced an increase in BP during placebo treatment, albeit levels remained below baseline, whereas BP reductions were maintained in valsartan recipients (P<.05). The most frequent adverse events during the open‐label phase were headache and fever. Valsartan provides similar antihypertensive efficacy in obese and non‐obese hypertensive children and adolescents, with good tolerability in both patient populations.     

Aliskiren Reduces Morning Blood Pressure in Hypertensive Patients with Diabetic Nephropathy on Hemodialysis

Our previous study indicated that the exchange from an angiotensin receptor blocker (ARB) to aliskiren reduced morning blood pressure and albuminuria in hypertensive patients with diabetic nephropathy. We extended the above study and assessed the effects of exchanging from an ARB to aliskiren on home blood pressure in hypertensive patients with diabetic nephropathy on chronic hemodialysis. The patients who were persistently hypertensive despite antihypertensive therapy, including ARB, were considered as candidates for the exchange from the ARB to aliskiren. Patients’ age and durations of diabetes and hemodialysis were averaged as 62 ± 9 years old, 15 ± 8 and 7 ± 3 years, respectively. Aliskiren decreased morning systolic blood pressure (149 ± 14 to 144 ± 13 mm Hg, n = 30, P < .01) and plasma renin activity (3.5 ± 1.1 to 1.2 ± 0.6 ng/mL/h, P < .01) without changes in serum potassium. Aliskiren also reduced interdialytic weight gain (2.7 ± 0.6 to 2.5 ± 0.5 kg/interval, P < .05) and attenuated the magnitude of intradialytic declines in systolic (?20 ± 11 to ?17 ± 10 mm Hg, P < .05) and diastolic blood pressure (?9 ± 6 to ?5 ± 5 mm Hg, P < .01). The exchange from an ARB to aliskiren is safe and useful to control home blood pressure in hypertensive hemodialysis patients with diabetic nephropathy. Aliskiren reduced both intradialytic blood pressure drops and interdialytic weight gain in patients with DN.     

Effect of amlodipine compared to atenolol on small arteries of previously untreated essential hypertensive patients

In a previous retrospective study, long-term treatment of essential hypertensive patients with a slow-release calcium channel blocker resulted in normal resistance artery structure and endothelial function, which did not occur with a β-blocker. In the present prospective study, 19 previously untreated essential hypertensive patients (aged 47 ± 2 years, 75% male) were treated for 1 year in a double-blind randomized study with the long-acting calcium channel blocker amlodipine or the β-blocker atenolol. Resistance arteries (lumen diameter, 150 to 350 μm) dissected from gluteal subcutaneous biopsies were studied on a pressurized myograph. Blood pressure (BP) control (129 ± 2/85 ± 2 mm Hg) was identical in both groups for the last 6 months of the study. After 1 year of treatment with amlodipine, the media-to-lumen ratio (M/L) of resistance arteries decreased from 7.89% ± 0.40% to 6.81% ± 0.41% (P < .05). Acetylcholine-induced endothelium-dependent relaxation tended to improve from 84.3% ± 5.5% to 90.5% ± 4.8% (P = .06), whereas sodium nitroprusside-induced relaxation was unchanged in the patients treated with amlodipine. In the β-blocker-treated group there was no significant change in M/L or acetylcholine-induced relaxation. In conclusion, treatment with the calcium channel blocker amlodipine corrected altered resistance artery structure and tended to improve endothelial function in essential hypertensive patients, whereas similar good control of BP with the β-blocker atenolol did not. Whether the vascular protective effect of amlodipine will result in improved outcomes in hypertension remains to be demonstrated.     

Maintaining Goal Blood Pressures After Switching From Olmesartan to Other Angiotensin Receptor Blockers

This study assessed blood pressure (BP) goal maintenance in patients controlled with olmesartan monotherapy after switching to another angiotensin type II receptor blocker (ARB). Hypertensive patients prescribed olmesartan monotherapy were identified from GE Healthcare's Centricity electronic medical record between 2007 and 2011. After documentation of BP goal (<140/90 mm Hg) attainment, patients were placed into the continuation cohort if olmesartan monotherapy was maintained or into the switch cohort if they were changed to irbesartan, losartan, or valsartan. Follow‐up assessments were the first BP measurement 28 to 390 days after attaining BP goal (continuation cohort) or after prescribing an alternative ARB (switch cohort). Of 3412 patients included (3027 continuation cohort, 385 switch cohort), 52% were women and mean age was 58.0 years. In the switch cohort, 310 (80.5%) were switched to losartan (n=236), irbesartan (n=58), or valsartan (n=16) monotherapy and 75 (19.5%) were switched to combination antihypertensive therapy. Mean baseline and follow‐up BP were 122.5/75.8 mm Hg and 126.6/77.6 mm Hg, respectively, in the continuation cohort (P<.001) and 123.5/75.4 mm Hg and 129.6/78.5 mm Hg, respectively, in the switch cohort (P<.001). BP goal maintenance was 78.7% and 72.2% in the continuation and switch cohort, respectively (odds ratio, 0.707; 95% confidence interval, 0.555–0.899). Patients who continued on olmesartan monotherapy after attaining BP goal had a higher percentage of BP goal maintenance than patients who switched therapy.     

The Comparative Effects of Valsartan and Amlodipine on vWf Levels and N/L Ratio in Patients with Newly Diagnosed Hypertension

High levels of circulating Von Willebrand factor (vWf) and increased neutrophil to lymphocyte (N/L) ratio may reflect vascular inflammation in hypertensive patients. In present study, we aimed to investigate the effects of valsartan as an angiotensin II receptor antagonist and amlodipine as a calcium channel blocker on the vWf levels and N/L ratio in patients with essential hypertension. Patients were randomized to one of the following intervention protocols: calcium channel blocker (amlodipine, 5–10 mg/day) as group A (n = 20 mean age = 51.85 ± 11.32 y) and angiotensine II receptor blocker (valsartan, 80–320 mg/day) as group B (n = 26 mean age = 49.12 ± 14.12 y). Endothelial dysfunction and vascular inflammation were evaluated with vWf levels and N/L ratio in hypertensive patients before treatment and after treatment in the 12th week. No statistically significant differences were found among the groups in terms of age, sex, and body mass index (BMI). There was a significant decrease in vWf levels (P < .001) and N/L ratio after treatment (P = .04, P < .001, respectively) in both the groups. Von Willebrand factor levels and N/L ratio are very important markers having a role in vascular inflammation and antihypertensive treatment with amlodipine and valsartan may improve cardiovascular outcomes by decreasing these biomarkers.     

Efficacy of various antihypertensive agents as evaluated by indices of vascular stiffness in elderly hypertensive patients.

When observed in elderly hypertensive patients, increased pulse pressure (PP) and arterial stiffness are known to be independent risk factors for cardiovascular diseases. Increased systolic blood pressure (SBP) leads to left ventricular hypertrophy, while decreased diastolic blood pressure (DBP) results in decreased coronary circulation. It is known that increased arterial stiffness is the major cause of increased PP. Thus basic morbid states of cardiac failure or ischemic heart diseases are more likely to develop in elderly hypertensive patients with increased PP and arterial stiffness, and there is need of antihypertensive drugs that decrease these effects in elderly hypertensives. In this study, we compared the effects of an angiotensin-receptor blocker (ARB: valsartan), an angiotensin-converting enzyme inhibitor (ACE-I: temocapril), and long-acting Ca antagonists (L- and N-type Ca channel blocker: cilnidipine; and L-type Ca channel blocker: nifedipine CR) on PP and arterial stiffness measured by pulse wave velocity in elderly hypertensive patients for 3 months. The ARB yielded the largest reductions in PP and brachial-ankle pulse wave velocity (baPWV), followed by the ACE-I and L- and N-type Ca channel blocker, while the L-type Ca channel blocker yielded no improvement. The effects on arterial stiffness and PP thus varied among the drug characteristics. Although ARB achieved the largest reduction in baPWV, this decrease was not associated with any reductions in PP, SBP, DBP, or mean blood pressure, as were the baPWV-decreases achieved by the other drugs, suggesting that ARB may further reduce the risk of arteriosclerosis in elderly hypertensive patients by decreasing arterial stiffness in addition to its antihypertensive effect.     

Comparative efficacy of aliskiren/valsartan vs valsartan in nocturnal dipper and nondipper hypertensive patients: a pooled analysis

This pooled analysis of ambulatory blood pressure (BP) monitoring data from two 8-week randomized controlled trials compared the antihypertensive efficacy and safety of combination aliskiren/valsartan vs valsartan alone in hypertensive patients (nocturnal dippers or nondippers). At study end, patients were taking aliskiren/valsartan 300/320 mg or valsartan 320 mg. In dippers (n=138) and nondippers (n=132), aliskiren/valsartan provided significantly (P<.05) greater reductions from baseline to week 8 than valsartan in 24-hour, daytime, and last-4-hour mean ambulatory systolic BP (maSBP). Treatment differences were more pronounced in nondippers. Nighttime maSBP reductions with aliskiren/valsartan were significantly greater vs valsartan in nondippers (-17.0 mm Hg vs -8.9 mm Hg; P<.05) but not dippers (-7.6 mm Hg vs -4.5 mm Hg; P=.16). In all time periods, combination therapy was generally associated with BP reductions that were greater in nondippers than dippers. Conversion from nondipper to dipper status was 32% vs 22% for aliskiren/valsartan vs valsartan (P=.48). Both treatments were similarly well tolerated. Although the addition of aliskiren to valsartan did not significantly alter dipper status, our data suggest an increased contribution of the renin-angiotensin-aldosterone system to the nondipper status of hypertensive patients.     

Reversal of vascular hypertrophy in hypertensive patients through blockade of angiotensin II receptors

Angiotensin II (Ang II) has been linked to vascular dysfunction and target-organ damage. Blockade of the angiotensin II type 1 receptor (AT₁) with an angiotensin receptor blocker may reverse vascular pathology independent of blood pressure (BP) lowering. Stage I hypertensive, nondiabetic patients (61% male; age 38 to 67 years) were randomized after a 4-week washout period to olmesartan medoxomil 20 to 40 mg or atenolol 50 to 100 mg plus additional agents (hydrochlorothiazide, amlodipine, or hydralazine) as needed for a goal BP <140/90 mm Hg. At baseline and after 1 year of treatment, subcutaneous gluteal resistance arteries were examined on a pressurized myograph to evaluate remodeling. Biopsies were available from 22 atenolol recipients, 27 olmesartan medoxomil recipients, and 11 normal volunteer controls. BP was reduced to a comparable degree by olmesartan medoxomil (from 149 ± 11/92 ± 8 mm Hg to 120 ± 9/77 ± 6 mm Hg; P < .05 [mean ± standard deviation]) and atenolol (from 147 ± 10/90 ± 6 mm Hg to 125 ± 12/78 ± 7 mm Hg; P < .05 [mean ± standard deviation]) from baseline for each arm (P = .08 for the 40-week treatment mean between arms). After one year's treatment, the wall-to-lumen ratio in arteries from patients treated with olmesartan medoxomil was significantly reduced (from 14.9% to 11.1%; P < .01), whereas no significant change was observed in arteries from atenolol-treated patients (from 16.0% to 15.5%; P = NS); the wall-to-lumen ratio in controls was 11.0%. Blockade of AT₁ receptors showed a superior corrective effect on the altered structure of resistance arteries in essential hypertension that was independent of the magnitude of BP reduction, and resulted in values similar to those in normotensive controls.     

The differential effects of angiotensin II type 1 receptor blockers on microalbuminuria in relation to low-grade inflammation in metabolic hypertensive patients

BACKGROUND: A dual angiotensin type 1 receptor blocker (ARB)/peroxisome proliferator-activated receptor-gamma (PPARgamma) agonist telmisartan may be more useful for microalbuminuria reduction than ARBs with no PPARgamma agonistic action. We investigated whether there is a difference between the effects of telmisartan and valsartan with respect to microalbuminuria reduction, and the association with improvement of metabolic features or suppression of the inflammatory state. METHODS: Fifty-three patients who had metabolic syndrome and had been taking valsartan were recruited. All of these patients were randomly assigned to replace valsartan by telmisartan (telmisartan group; n = 30) or to keep taking valsartan (control group; n = 21). Various parameters were measured at baseline and 12 weeks after randomization. RESULTS: There were no significant changes in blood pressure (BP), glucose, and lipid parameters between baseline and 12 weeks after randomization in either group. There was a significant increase in high molecular weight adiponectin in the telmisartan group (4.6 v 5.0 microg/mL, P = .024), whereas there was no significant change in the control group. The reductions of microalbuminuria and high-sensitivity C-reactive protein (hs-CRP) were significant in the telmisartan group (28.1 v 18.9 mg/g.Cr and 0.77 v 0.60 mg/L, respectively, P = .001 and P = .022), whereas there was no significant change in the control group. The reductions of microalbuminuria and hs-CRP were significantly correlated with each other (gamma = 0.413, P = .003). CONCLUSIONS: The dual ARB/PPARgamma agonist telmisartan achieved more microalbuminuria reduction than an ARB with no PPARgamma agonistic action, possibly through suppression of the inflammatory state in metabolic hypertensive patients.     

The importance of early antihypertensive efficacy: the role of angiotensin II receptor blocker therapy

Desirable features of antihypertensive agents include efficacy, tolerability, prolonged duration of action and rapid achievement of target blood pressure (BP). Recent studies have examined the relationship between the onset of antihypertensive effect and cardiovascular events. Data from the Valsartan Antihypertensive Long-term Use Evaluation (VALUE), the Study on Cognition and Prognosis in the Elderly (SCOPE), and the Systolic Hypertension in Europe (Syst-Eur) trials support the hypothesis that the time it takes to reach target BP influences cardiovascular outcomes. VALUE, which compared BP-lowering and clinical event rates between patients treated with the angiotensin II receptor blocker (ARB) valsartan or the calcium channel blocker (CCB) amlodipine as well as between those who achieved immediate or delayed BP control, provides the strongest evidence of this to date. Additional data from SCOPE and Syst-Eur suggest that delays of 3 months to 2 years in starting antihypertensive therapy can increase the risk of certain cardiovascular end points, especially stroke. These data suggest that it may be beneficial to examine the efficacy of antihypertensive agents, not only long term, but also at earlier times to assess the onset and impact of early antihypertensive effect. The ARB olmesartan medoxomil (olmesartan) and the CCB amlodipine were compared in a randomized, double-blind, placebo-controlled clinical trial, which demonstrated that the onset of antihypertensive effect of olmesartan is comparable with that of amlodipine. Another study demonstrated that more patients treated with olmesartan achieved target BPs within 2 weeks of treatment compared with the ARBs losartan, valsartan and irbesartan.     

Valsartan alone or with a diuretic or ACE inhibitor as treatment for African American hypertensives: relation to salt intake

Previous clinical trials have demonstrated the important influence of ethnicity and dietary salt on the antihypertensive efficacy of drugs that block the renin angiotensin system. Angiotensin II receptor blockers are a new therapeutic entity that have not been widely studied in African American hypertensives, either alone, or in combination with other therapies such as diuretics or angiotensin converting enzyme inhibitors. We performed a pilot, prospective, open label, randomized design clinical trial to evaluate the effects of the angiotensin II receptor blocker valsartan (160 mg once a day) on systolic and diastolic blood pressure in hypertensive African Americans (n = 88) on a low salt (100 mEq Na⁺/day) for 2 weeks and the same diet supplemented by 100 mEq Na⁺ for 4 weeks. After this evaluation, while continuing the Na⁺ supplementation, patients were randomized to valsartan 320 mg/day (n = 28), or the addition of hydrochlorothiazide (HCTZ) 12.5 mg/day (n = 30), or benazepril 20 mg/day to the valsartan 160 mg/day for an additional 6 weeks.Valsartan (160 mg/day) lowered blood pressure significantly in African American patients on both low salt (−6.4/−4.8 mm Hg: P < .001) and a high salt diet (−4.9/−3.8 mm Hg: P = .01). The high salt diet attenuated the antihypertensive effect slightly (1.6/1.3 mm Hg, P = not significant). When comparing the efficacy of the three randomized therapeutic regimens while on the Na⁺ supplement, the valsartan 160 mg/HCTZ 12.5 mg was the most effective therapy with an incremental reduction in blood pressure of −10.5/−6.9 mm Hg (P < .01), compared to valsartan 160 mg/day alone. Doubling the dose of valsartan to 320 mg incrementally lowered blood pressure by −3.8/−3.3 mm Hg (P = not significant). The least effective approach was adding benazepril 20 mg/day to valsartan 160 mg/day with no incremental reduction in systolic blood pressure and diastolic blood pressure reduction of only 1.7 mm Hg (P = not significant).We conclude that in our open label pilot study, the antihypertensive activity of valsartan is not significantly attenuated by supplemented salt diet in hypertensive African Americans. Moreover, adding a low dose of HCTZ appears to be the most effective strategy in enhancing the antihypertensive activity of this angiotensin II receptor blocker in contrast to either doubling the dose or adding an angiotensin converting enzyme inhibitor.     

Évaluation par l’automesure au domicile de l’efficacité de monothérapies antihypertensives chez des hypertendus traités en France

ObjectiveTo evaluate the blood pressure (BP) control and the efficacy of antihypertensive monotherapy using home BP self-measurement in a French population of treated hypertensive subjects in 2007 2009 and 2010.MethodsThe French League Against Hypertension Surveys (FLAHS) are conducted among a representative sample of individuals aged 35 years and older living in France. For the 2007, 2009 and 2010 surveys, a sample of 1467 subjects who owned a BP self-measurement device and performed three consecutive morning BP measurements were included. Among the 60% of subjects who reported taking at least one antihypertensive drug, we analyzed subjects treated with one of the following antihypertensive monotherapy, i.e., beta-blocker (BB), ACE inhibitors, calcium channel blocker (CCB) and angiotensin receptor blockers (ARB).ResultsAmong treated hypertensive subjects (n = 886), 66% (n = 586) had home BP below the 140/90 mmHg threshold and 50% (n = 449) below 135/85 mmHg. Three hundred two subjects were treated with a single antihypertensive drug, 33% had ARB, 25% BB, 19% CCB and 13% ACE inhibitors. Age (years) for each treatment group is different (P < 0.01) CCB (72.1 ± 9.3), BB (65.6 ± 9.8), ARB (68.6 ± 8.9) and ACEI (67.3 ± 10.2). The mean systolic/diastolic BP (mmHg) is not comparable between monotherapy 130.7/76.1 (ARB), 130.7/78.7 (BB), 134.0/75.2 (CCB) and 139.1/80.3 (ACEI) for ARB, BB, CCB and ACE inhibitors respectively. Compared to ACE inhibitors, BP was significantly lower with ARB (P < 0.01). The proportion of subjects with a BP below 140/90 mmHg was 73% for ARB, 52% for BB, 68% for CCB and 47% for ACE with a statistical significance (P = 0.03) for ARB vs. ACEI and CCB vs. ACEI.ConclusionAmong subjects treated for hypertension who owned a BP self-measurement device, 50 to 66% had a controlled BP (depending on the threshold used). It is observed differences between antihypertensive efficacy of monotherapy with a larger number of patients controlled with ARB or CCB.     

Aldosterone breakthrough during angiotensin II receptor blockade in hypertensive patients with diabetes mellitus

BACKGROUND: Aldosterone is an important pathogenetic factor, independent of the renin-angiotensin system in cardiovascular and renal disease. Aldosterone breakthrough during angiotensin-converting enzyme (ACE) inhibitor therapy was reported in hypertension, diabetes mellitus, and chronic renal disease. It is unclear whether the angiotensin II receptor blocker (ARB) causes aldosterone breakthrough in patients with hypertension and diabetes mellitus, and whether aldosterone breakthrough contributes to renal injury in these patients. METHODS: We prospectively studied 95 hypertensive patients with diabetes mellitus. Patients were treated with candesartan (8 mg/day, n = 47) or valsartan (80 mg/day, n = 48) for 15 months. Blood pressure (BP), urinary albumin excretion (UAE), biochemical markers, plasma aldosterone concentration (PAC), and plasma renin activity (PRA) were measured before and at 3, 6, 12, and 15 months of treatment. Nine patients who exhibited aldosterone breakthrough after treatment with ARB were placed on spironolactone (25 mg/day) for 3 months, and BP, UAE, and biochemical markers were measured after treatment. RESULTS: Although the overall PAC was significantly decreased (P < .05) in each group, it eventually increased in 21 (candesartan, 11 patients; valsartan, 10 patients) of 95 patients (22%; aldosterone breakthrough). Blood pressure, PRA, and biomedical markers did not differ between the two groups during treatment. Although UAE was significantly decreased in patients with or without aldosterone breakthrough at 6 months, it was increased again at 15 months of treatment in patients with aldosterone breakthrough. Treatment with spironolactone markedly reduced UAE in these patients. CONCLUSIONS: Aldosterone breakthrough was seen to be equal in hypertensive patients with diabetes mellitus treated with candesartan or valsartan. Aldosterone blockade therapy may be effective in preventing renal injury in hypertensive patients with aldosterone breakthrough.