Time to achieve blood-pressure goal: influence of dose of valsartan monotherapy and valsartan and hydrochlorothiazide combination therapy

BACKGROUND: Our objective was to assess time to achieve blood-pressure (BP) goal with incremental doses of valsartan alone, and together with hydrochlorothiazide (HCTZ), in patients with uncomplicated hypertension. METHODS: This analysis pooled patient-level data from nine randomized, double-blind, fixed-dose, placebo-controlled trials (N = 4278) of once-daily valsartan 80 mg, 160 mg, and 320 mg, and valsartan/hydrochlorothiazide (HCTZ) 80/12.5 mg, 160/12.5 mg, 160/25 mg, 320/12.5 mg, and 320/25 mg. Kaplan-Meier methods estimated the cumulative proportion of patients achieving BP <140/90 mm Hg over 8 weeks and the median time to BP goal. The HCTZ 12.5-mg and 25-mg doses were pooled for the time-to-goal analysis in patients receiving combinations with valsartan 160 mg or 320 mg. RESULTS: Overall, the median time-to-goal was 8.1 weeks with valsartan 160 mg, 6.1 weeks with valsartan 320 mg, 2.6 weeks with valsartan 160 mg/HCTZ, and 2.1 weeks with valsartan 320 mg/HCTZ. In patients with stage 2 hypertension, the median time-to-goal was 4.3 weeks with valsartan 160 mg/HCTZ and 2.4 weeks with valsartan 320 mg/HCTZ. Goal rates by Week 4 for valsartan/HCTZ exceeded rates by Week 8 with the same doses of valsartan alone. Overall, the proportion that achieved BP goal by Week 8 was 32.6% with valsartan 80 mg, 48.4% with valsartan 160 mg, 54.2% with valsartan 320 mg, 74.6% with valsartan 160 mg/HCTZ, and 84.8% with valsartan 320 mg/HCTZ, versus 24.2% with placebo. With valsartan 320 mg/HCTZ, 75.8% of stage 2 patients and 94% of stage 1 patients reached BP goal by Week 8. Discontinuation rates due to adverse events were generally low across doses. CONCLUSIONS: In both stage 1 and stage 2 hypertension, BP control is achieved more frequently and promptly when patients receive higher doses of valsartan monotherapy or valsartan combination therapy, with a favorable benefit-risk profile.     

复方缬沙坦治疗轻中度原发性高血压患者的疗效观察

目的评价复方缬沙坦（缬沙坦80mg／氢氯噻嗪12．5mg复方制剂）治疗经单用缬沙坦80mg控制不良的轻、中度原发性高血压患者疗效和安全性。方法采用多中心、双盲、双模拟、随机、活性药物对照、平行试验方法。对经2周洗脱期的轻、中度原发性高血压患者[坐位舒张压≥95mmHg（1mmHg=0．133kPa）且〈110mmHg]采用单药缬沙坦80mg／d治疗4周,在单药导入结束后,坐位舒张压仍〉190mmHg的864例患者按1：1随机、双盲分为复方缬沙坦组或缬沙坦80mg／d组,继续治疗8周。在治疗4周和结束时评估药物安全性及有效性。结果在轻、中度原发性高血压患者中复方缬沙坦每日1次比单用缬沙坦80mg／d血压进一步下降、达标率提高。治疗结束时平均坐位收缩压多降低3．5mmHg,平均坐位舒张压多下降2．2mmHg,血压控制〈140／90mmHg的患者在复方缬沙坦组和单用缬沙坦80mg／d组分别为53．9％及40．9％。结论轻、中度原发性高血压患者采用复方缬沙坦治疗组降压有效率及达标率均优于每日1次服用缬沙坦80mg／d组。复方缬沙坦适用于缬沙坦单药控制不良的轻、中度原发性高血压患者。     

Aliskiren, an orally effective renin inhibitor, provides antihypertensive efficacy alone and in combination with valsartan

BACKGROUND: By blocking the renin-angiotensin-aldosterone system (RAAS) at its rate-limiting step, renin inhibition may provide improved RAAS suppression. We investigated the blood pressure (BP)-lowering effects of the oral direct renin inhibitor aliskiren, alone or in combination with the angiotensin receptor blocker valsartan. METHODS: In this multicenter, randomized, placebo-controlled, 8-week trial, 1123 patients with mild-to-moderate hypertension underwent a 3 to 4 week single-blind placebo run-in and were then randomized in a modified factorial study design to receive once-daily, double-blind oral treatment with placebo, aliskiren monotherapy (75, 150, or 300 mg), valsartan monotherapy (80, 160, or 320 mg), aliskiren and valsartan in combination, or valsartan/hydrochlorothiazide (160/12.5 mg). The primary efficacy variable was the change from baseline in mean sitting diastolic BP (DBP) at endpoint. RESULTS: Once-daily oral treatment with aliskiren 300 mg significantly (P < .0001) lowered mean sitting DBP and systolic BP (SBP) compared with placebo; aliskiren monotherapy demonstrated a safety and tolerability profile comparable to placebo. Changes in DBP and SBP were fitted to a first-order dose-response surface (lack-of-fit test, P = .65), which showed that aliskiren and valsartan alone and in combination produced dose-related reductions in DBP and SBP. Coadministration of aliskiren and valsartan produced a greater antihypertensive effect than either drug alone, comparable in magnitude to the effect of valsartan/hydrochlorothiazide, with similar tolerability to the component monotherapies and to placebo. CONCLUSIONS: Aliskiren monotherapy provides antihypertensive efficacy and placebo-like tolerability in patients with hypertension. Aliskiren and valsartan in combination may provide additive BP-lowering effects with maintained tolerability.     

Additivity of nebivolol/valsartan single‐pill combinations versus other single‐pill combinations for hypertension

The single‐pill combination (SPC) comprising nebivolol (5 mg), a vasodilatory β₁‐selective antagonist/β₃‐agonist, and valsartan (80 mg), a renin‐angiotensin‐aldosterone system inhibitor, is the only Food and Drug Administration–approved β‐blocker/renin‐angiotensin‐aldosterone system inhibitor SPC for hypertension. Additive effects of four nebivolol/valsartan SPC doses (5 mg/80 mg, 5/160 mg, 10/160 mg, 10/320 mg nebivolol/valsartan) were compared with five Food and Drug Administration–approved non–β‐blocker/renin‐angiotensin‐aldosterone system inhibitor SPCs (aliskiren/hydrochlorothiazide, aliskiren/amlodipine, valsartan/amlodipine, aliskiren/valsartan, and telmisartan/amlodipine). Additivity is the ratio of placebo‐adjusted SPC blood pressure (BP) reduction to the placebo‐adjusted monotherapy component BP reduction sums. A weighted average of comparator scores was calculated and compared vs nebivolol/valsartan. Additivity ratio scores for nebivolol/valsartan SPCs (diastolic BP range: 0.735–0.866; systolic BP range: 0.717–0.822) were similar to the comparator weighted average (diastolic BP: 0.837; systolic BP: 0.825). Among the nebivolol/valsartan SPCs, 5/80 mg had the greatest additivity (diastolic BP: 0.866; systolic BP: 0.822). BP reduction contributions with monotherapy were similar for nebivolol/valsartan 5/80 mg SPC. Additivity scores for nebivolol/valsartan and select non–β‐blocker/renin‐angiotensin‐aldosterone system inhibitor SPCs were comparable.     

Effects of the angiotensin II receptor blockers telmisartan versus valsartan in combination with hydrochlorothiazide: a large, confirmatory trial

In 2004-2005, the antihypertensive effects of telmisartan 80 mg versus valsartan 160 mg combined with hydrochlorothiazide 25 mg were assessed in a large placebo-controlled trial in patients with stages 1 and 2 hypertension and demonstrated that both agents were highly effective in lowering blood pressure (BP) compared with placebo and that telmisartan lowered BP significantly greater than valsartan. To confirm this finding according to Food and Drug Administration guidelines, we performed a second large trial using the same design in an entirely separate patient population. The trial was double-blind with a 4 : 4 : 1 randomization scheme to compare once daily telmisartan 80 mg plus hydrochlorothiazide 25 mg versus once daily valsartan 160 mg plus hydrochlorothiazide 25 mg versus once daily placebo on reductions in seated clinic BP in patients with stages 1 and 2 hypertension. The primary endpoints were the changes from baseline in seated diastolic and systolic BP at the end of the 8-week treatment period. Safety endpoints included adverse events, changes in laboratory parameters and pulse rate. In total, 1185 patients were randomized (of which 1181 were treated and included in the primary analysis: 528 in the telmisartan-hydrochlorothiazide group, 523 in the valsartan-hydrochlorothiazide group, and 130 in the placebo group), changes from baseline in BP following telmisartan-hydrochlorothiazide (-24.6/-18.2 mmHg) were significantly greater than both placebo (-4.1/-6.1 mmHg) and valsartan-hydrochlorothiazide (-22.5/-17.0 mmHg) (versus placebo, P<0.0001 for systolic and diastolic BP; versus valsartan-hydrochlorothiazide, P=0.017 for systolic BP and P=0.025 for diastolic BP). The total number of patients with at least one adverse event reported was similar among the three treatment groups (placebo, 42%, telmisartan-hydrochlorothiazide, 36%, and valsartan-hydrochlorothiazide, 37%). Thus, this large, second trial confirms that telmisartan-hydrochlorothiazide at doses of 80/25 mg lowered both systolic and diastolic BP to a greater extent than valsartan-hydrochlorothiazide at doses of 160/25 mg in stages 1-2 hypertension. Although these are not the highest doses of these agents at present, at the time that the studies were conducted, they were the maximally approved dosages. Both studies support the strategy of using angiotensin receptor blockers with a higher dose of a thazide diuretic (25 mg) for enhancing the control of hypertension.     

Antihypertensive effects of valsartan/hydrochlorothiazide combination in essential hypertension.

Fixed-dose combination therapy has received increased interest since publication of JNC-VI report and WHO/ISH guidelines 1999. We compared in a randomized, double-blind study the efficacy and tolerability of valsartan 80 mg combined with hydrochlorothiazide (HCTZ) 12.5 mg to monotherapy with either HCTZ 12.5 mg or 25 mg in patients with essential hypertension inadequately controlled by previous HCTZ 12.5 mg monotherapy. Two hundred and seventeen patients whose blood pressure (BP) control remained poor (95 mmHg < or = sitting diastolic BP < 115 mmHg) after a 4-week single-blind period with HCTZ 12.5 mg were randomized to receive either combination therapy with valsartan 80 mg plus HCTZ 12.5 mg (V/HCTZ) or monotherapy with HCTZ 12.5 mg or HCTZ 25 mg for 8 weeks. Reduction of sitting trough diastolic BP between baseline and week 8 as well as tolerability was evaluated. Reduction in trough diastolic BP was most pronounced in the V/HCTZ group (-11.3 mmHg) and significantly greater than in the HCTZ 12.5 mg group (-2.9 mmHg, p < 0.001) and the HCTZ 25 mg group (-5.7 mmHg, p < 0.001). Tolerability of study medication was comparable between all three groups. In conclusion, switching to V/HCTZ combination therapy provides an additional lowering of BP compared to dosage increase of the thiazide in patients with BP insufficiently controlled by HCTZ 12.5 mg monotherapy.     

24-hour ambulatory blood-pressure effects of valsartan and hydrochlorothiazide combinations compared with amlodipine in hypertensive patients at increased cardiovascular risk: a VAST sub-study

BACKGROUND: There is a lack of data on the effects of angiotensin-receptor blocker and diuretic combinations on ambulatory blood pressure (ABP) in hypertensive patients with additional cardiovascular risk factors. METHODS: In a randomized, double-blind trial, the effects on 24-h ABP of the combination valsartan 160 mg od and hydrochlorothiazide 25 or 12.5 mg during 24 weeks of therapy were compared with the effects of amlodipine 10 mg monotherapy (group A10) in 474 stage-II hypertensive patients with additional cardiovascular risk factors. After a two-week single-blind placebo run-in period, patients were randomized to receive valsartan 160 mg od or amlodipine 5 mg od. At week 4, HCTZ 12.5 mg (group V160/HCTZ12.5) and 25 mg (group V160/HCTZ25) were added to the valsartan groups and in the A10 patients the amlodipine dose was force-titrated to 10 mg od. RESULTS: All three treatments reduced 24-h BP as well as night-time and daytime BP levels from baseline. Twenty-four hour systolic blood pressure (SBP) was reduced by 15.9+/-1.0 mmHg (least-squares mean change+/-SE), 19.3+/-1.0 mmHg and 16.1+/-1.1 mmHg in the V160/HCTZ12.5, V160/HCTZ25 and A10 groups, respectively and 24-h diastolic blood pressure (DBP) was reduced by 9.3+/-0.6 mmHg, 11.4+/-0.6 mmHg and 9.6+/-0.7 mmHg in the three groups. The differences between the V160/HCTZ25 group and the A10 group were significant (p<0.05) for the changes in 24-h systolic BP as well as for changes in daytime systolic BP and night-time diastolic BP. Control rates defined as ABPM < or =130/80 mmHg were: 48.4%, 60.8% and 50.9% in the V160/HCTZ12.5, V160/25 and A10 groups, respectively. The differences in control rates between the V160/HCTZ25 group and the other two treatment groups were significant at p<0.05. CONCLUSIONS: The fixed-dose combination of valsartan 160 mg+HCTZ 25 mg od is an attractive therapeutic option measured on the effects on 24-h ABPM, night-time and daytime BP reduction and control rates in hypertensive patients at additional cardiovascular risk.     

24-Hour ambulatory blood pressure control with triple-therapy amlodipine, valsartan and hydrochlorothiazide in patients with moderate to severe hypertension

To determine the effectiveness and safety of once-daily combination therapy with amlodipine, valsartan and hydrochlorothiazide for reducing ambulatory blood pressure (ABP) in patients with moderate to severe hypertension, a multicenter, double-blind study was performed (N=2271) that included ABP monitoring in a 283-patient subset. After a single-blind, placebo run-in period, patients were randomized to receive amlodipine/valsartan/hydrochlorothiazide (10/320/25?mg), valsartan/hydrochlorothiazide (320/25?mg), amlodipine/valsartan (10/320?mg) or amlodipine/hydrochlorothiazide (10/25?mg) each morning for 8 weeks. Efficacy assessments included change from baseline in 24-h, daytime and night time mean ambulatory systolic BP (SBP) and diastolic BP (DBP). Statistically significant and clinically relevant reductions from baseline in all these parameters occurred in all treatment groups (P<0.0001, all comparisons versus baseline). At week 8, least squares mean reductions from baseline in 24-h, daytime and night time mean ambulatory SBP/DBP were 30.3/19.7, 31.2/20.5 and 28.0/17.8?mm?Hg, respectively, with amlodipine/valsartan/hydrochlorothiazide; corresponding reductions with dual therapies ranged from 18.8-24.1/11.7-15.5, 19.0-25.1/12.0-16.0 and 18.3-22.6/11.1-14.3?mm?Hg (P≤0.01, all comparisons of triple versus dual therapy). Treatment with amlodipine/valsartan/hydrochlorothiazide maintained full 24-h effectiveness, including during the morning hours; all hourly mean ambulatory SBP and mean ambulatory DBP measurements were ≤130/85?mm?Hg at end point. Amlodipine/valsartan/hydrochlorothiazide combination therapy was well tolerated. Once-daily treatment with amlodipine/valsartan/hydrochlorothiazide (10/320/25?mg) reduces ABP to a significantly greater extent than component-based dual therapy and maintains its effectiveness over the entire 24-h dosing period.     

Combination of hydrochlorothiazide or benazepril with valsartan in hypertensive patients unresponsive to valsartan alone.

OBJECTIVE : The aim of this open multicentric study was to investigate the efficacy and safety of the addition of an angiotensin converting enzyme (ACE) inhibitor (benazepril, 10 mg/day) or a diuretic (hydrochlorothiazide, 12.5 mg/day) for 4 weeks in patients with mild to moderate essential hypertension having been treated for 4 weeks by an angiotensin II antagonist (valsartan, 80 mg/day) but still having a diastolic blood pressure (BP) > 90 mmHg on this medication given alone. METHODS : A total of 327 patients were included in the trial and 153 patients (46%) had their diastolic BP 相似文献   

Antihypertensive efficacy of angiotensin receptor blockers in combination with hydrochlorothiazide: a review of the factorial-design studies

Most hypertensive patients require more than one drug for adequate blood pressure (BP) control. The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure recommends starting treatment with a thiazide diuretic or, when BP is >20/10 mm Hg above goal or in patients with diabetes, using two different antihypertensive agents. Searches of Medline, EMBASE, and BIOSIS databases identified four similarly designed, randomized, factorial studies comparing various doses of angiotensin II receptor blockers with hydrochlorothiazide as monotherapy and in combination. The methodology and results of these studies were compared. The primary efficacy end point in these studies was a decrease from baseline in mean diastolic BP after 8 weeks of therapy. All currently available angiotensin I receptor blocker/hydrochlorothiazide combinations evaluated (irbesartan, olmesartan medoxomil, telmisartan, and valsartan plus hydrochlorothiazide) produced significant systolic BP and diastolic BP reductions. Olmesartan medoxomil/hydrochlorothiazide 40 mg/25 mg provided the largest mean reduction in absolute and placebo-corrected systolic BP/diastolic BP. For all angiotensin II receptor blocker/hydrochlorothiazide combinations evaluated, > or =63% of patients achieved a diastolic BP response (diastolic BP <90 mm Hg or > or =10-mm Hg reduction). In conclusion, the combination of an angiotensin II receptor blocker and hydrochlorothiazide produces more substantial BP responses than monotherapy with either component.     

A noninferiority comparison of valsartan/hydrochlorothiazide combination versus amlodipine in black hypertensives

The objective of the study was to demonstrate that reduction in mean 24-hour diastolic blood pressure with 160 mg valsartan and 12.5 mg hydrochlorothiazide was not inferior to 10 mg amlodipine in hypertensive blacks. A total of 482 blacks with stage 1 and stage 2 hypertension (mean seated blood pressure 140 to 180/90 to 110 mm Hg) were enrolled in a double-blind, randomized, prospective study. After a placebo run-in period, patients were randomized to 160 mg valsartan or 5 mg amlodipine for 2 weeks, then force-titrated to 160 mg valsartan and 12.5 mg hydrochlorothiazide or 10 mg amlodipine for an additional 10 weeks. Blood pressure was assessed by 24-hour ambulatory blood pressure monitoring. Other assessments included quality of life, peripheral edema, and safety. Noninferiority of valsartan/hydrochlorothiazide to amlodipine was demonstrated by comparable reductions in mean 24-hour diastolic blood pressure with both treatments (-10.2+/-8.6 mm Hg versus -9.1+/-8.3 mm Hg, respectively; P<0.001 for noninferiority), as well as in mean 24-hour systolic blood pressure (-15.9+/-12.1 mm Hg versus -14.5+/-12.2 mm Hg; P<0.001 for noninferiority). The proportion of patients reporting adverse events and the incidence of most events were similar in both treatment groups, although more patients treated with amlodipine reported peripheral edema (5.8% versus 1.7%; P=0.03) and joint swelling (2.9% versus 0%; P=0.008) compared with valsartan/hydrochlorothiazide. We conclude that a starting dose of valsartan/hydrochlorothiazide (160/12.5 mg) is as effective as high-dose amlodipine (10 mg) in reducing blood pressure in blacks with stage 1 and stage 2 hypertension, and valsartan/hydrochlorothiazide is better tolerated.     

Improving Blood Pressure Control: Increase the Dose of Diuretic or Switch to a Fixed‐Dose Angiotensin Receptor Blocker/Diuretic? The Valsartan Hydrochlorothiazide Diuretic for Initial Control and Titration to Achieve Optimal Therapeutic Effect (Val‐DICTATE) Trial

To assess the strategy of increasing the dose of a diuretic compared with using an angiotensin receptor blocker in combination with a diuretic, the authors performed a multicenter, randomized, parallel group trial in hypertensive patients (baseline blood pressure [BP], 153/97 mm Hg) whose BP remained uncontrolled on initial low-dose diuretic monotherapy (hydrochlorothiazide [HCTZ] 12.5 mg Hg). Patients with stage 1 and 2 hypertension were randomized to treatment with valsartan/HCTZ (160/12.5 mg) or to doubling of the HCTZ dose (25 mg). The primary end point was the percentage of patients whose clinic BP values were <140/90 mm Hg following 4 weeks of double-blind therapy. A significantly higher proportion (P<.001) of hypertensive patients met BP control levels in the valsartan/HCTZ (160/12.5 mg) group compared with the HCTZ 25 mg group (37% vs 16%). Changes from baseline in BP were significantly greater (P<.001) for both systolic BP and diastolic BP in the combination therapy arm compared with the diuretic monotherapy arm (-12. 4/-7.5 mm Hg in valsartan/HCTZ 160/12.5 mg group vs -5.6/-2.1 mm Hg in HCTZ 25 mg group). Tolerability and adverse events were similar in the 2 treatment groups. This study suggests that in the management of hypertension, utilizing an angiotensin receptor blocker/diuretic combination was more effective in lowering BP and achieving BP goals when compared with increasing the dose of the diuretic.     

复方缬沙坦与血脂康联合治疗原发性高血压的临床研究

目的评价复方缬沙坦(缬沙坦80mg/氢氯噻嗪12.5mg)联合血脂康(600mg)治疗轻、中度原发性高血压患者的疗效和安全性。方法采用随机、双盲对照研究。将280例轻、中度高血压患者随机分为缬沙坦组和对照组。缬沙坦组患者给予复方缬沙坦(缬沙坦80mg/氢氯噻嗪12.5mg,1次/d)和血脂康(600mg,2次/d)治疗,对照组患者降压药物单用缬沙坦(80mg,1次/d)。治疗中每周测量血压。在治疗8周和结束时评价药物安全性和有效性。结果对于轻、中度原发性高血压患者,缬沙坦组较对照组血压进一步下降,达标率显著高于对照组。治疗结束时平均坐位收缩压均降低5mmHg,平均坐位舒张压多下降3mmHg,缬沙坦组和对照组患者中,血压控制<140/90mmHg者分别占54.1%和40.7%。结论轻、中度原发性高血压患者采用复方缬沙坦联合血脂康治疗,降压效果和达标率均优于单用缬沙坦。     

Comparison of aliskiren/hydrochlorothiazide combination therapy with hydrochlorothiazide monotherapy in older patients with stage 2 systolic hypertension: results of the ACTION study

Patients with stage 2 systolic hypertension require sizable blood pressure (BP) reductions to achieve recommended targets. This randomized double-blind study compared a single-pill combination of the direct renin inhibitor aliskiren and hydrochlorothiazide (aliskiren/HCTZ) with HCTZ monotherapy in older patients (older than 55 years) with systolic BP ≥160 mm Hg and <200 mm Hg. After a 1- to 4-week washout, 451 patients were randomized to once-daily aliskiren/HCTZ 150/12.5 mg or HCTZ 12.5 mg for 1 week, and then double the doses for 7 weeks. Overall baseline BP was 168.8/91.4 mm Hg. At week 4 (primary) end point, aliskiren/HCTZ provided significantly greater BP reductions from baseline than HCTZ monotherapy (29.6/9.3 mm Hg vs 22.3/6.8 mm Hg) and resulted in a greater proportion of patients achieving BP goal of <140/90 mm Hg (51.1% vs 33.3%). Aliskiren/HCTZ therapy provides substantial BP reductions and may thus be a useful treatment option for older patients with stage 2 hypertension.     

Efficacy of the combination of amlodipine and valsartan in patients with hypertension uncontrolled with previous monotherapy: the Exforge in Failure after Single Therapy (EX-FAST) study

In this randomized, double-blind, multicenter study, patients whose blood pressure (BP) was uncontrolled by monotherapy were switched directly to amlodipine/valsartan 5/160 mg (n=443) or 10/160 mg (n=451). After 16 weeks, BP control (levels <140/90 mm Hg or <130/80 mm Hg for diabetics) was achieved in 72.7% (95% confidence interval [CI], 68.6-76.9) of patients receiving amlodipine/valsartan 5/160 mg and in 74.8% (95% CI, 70.8-78.9) receiving amlodipine/valsartan 10/160 mg. Incremental reductions from baseline in mean sitting systolic and diastolic BP were significantly greater with the higher dose (20.0+/-0.7 vs 17.5+/-0.7 mm Hg; P=.0003 and 11.6+/-0.4 vs 10.4+/-0.4 mm Hg; P=.0046). Incremental BP reductions were also achieved with both regimens irrespective of previous monotherapy, hypertension severity, diabetic status, body mass index, and age. Peripheral edema was the most frequent adverse event. These results provide support for the BP-lowering benefits of complementary antihypertensive therapy with amlodipine and valsartan in patients with hypertension uncontrolled by previous monotherapy.     

Comparison of the antihypertensive efficacy of irbesartan/HCTZ and valsartan/HCTZ combination therapy: impact of age and gender

This analysis aimed to explore whether low-dose irbesartan/hydrochlorothiazide (HCTZ) has superior blood pressure (BP)-lowering efficacy over low-dose valsartan/HCTZ in the elderly and across both genders. This is a post-hoc analysis of data from a multicenter, parallel group, open-label, blinded-endpoint study in patients with hypertension uncontrolled with HCTZ monotherapy. The reduction in systolic BP (SBP)/diastolic BP (DBP) and rate of BP control achieved following 8 weeks of treatment with irbesartan/HCTZ 150/12.5 mg or valsartan/HCTZ 80/12.5 mg were analyzed for older (≥65 years) vs. younger (<65 years) patients and for men vs. women. Blood pressure measurements were by home BP monitoring (HBPM). In the age and gender subgroups, both treatments significantly decreased home SBP and DBP (p < 0.0001). The reduction in home SBP and DBP was numerically greater with irbesartan/HCTZ compared to valsartan/HCTZ for all subgroups: the difference in DBP was significant for all except the elderly (p < 0.05), and the difference in SBP was significant in the elderly and in men (p < 0.03). In all subgroups, more patients achieved BP control (HBPM ≤135/85 mmHg) in the irbesartan/HCTZ arm (range 45%-58%) than in the valsartan/HCTZ arm (range, 23%-39%; p < 0.02). Both combination therapies were well tolerated and safety parameters were similar in both age and gender subgroups. More patients with mild or moderate hypertension, uncontrolled in HCTZ monotherapy alone, had their BP controlled with irbesartan/HCTZ 150/12.5 mg than with valsartan/HCTZ 80/12.5 mg, irrespective of age or gender.     

Amlodipine and valsartan combined and as monotherapy in stage 2, elderly, and black hypertensive patients: subgroup analyses of 2 randomized, placebo-controlled studies

Patients with difficult to control hypertension typically require 2 or more agents to achieve goal blood pressure (BP) levels. Fixed-dose combination therapies with lower doses generally are well tolerated and more effective than higher-dose monotherapy. The authors performed prespecified and post hoc subgroup analyses of 2 double-blind, randomized, placebo-controlled trials that assessed the efficacy and safety of amlodipine and valsartan, alone and in combination, in patients with mild to moderate hypertension. Patients were randomized to amlodipine (study 1: 2.5 or 5 mg/d; study 2: 10 mg/d), valsartan (study 1: 40, 80, 160, or 320 mg/d; study 2: 160 or 320 mg/d), combination therapy across the same dose ranges, or placebo. Analyses were performed on changes from baseline in mean sitting systolic and diastolic BP and the occurrence of adverse events in specific subgroups of patients (ie, those with stage 2 hypertension [post hoc], the elderly [65 years or older], and blacks [both prespecified]). Amlodipine + valsartan combination therapy was associated with greater BP-lowering effects in the subgroups compared with each respective monotherapy and placebo. These findings were consistent with the primary efficacy analysis results from the overall study populations. Combination regimens were generally well tolerated by all patient subgroups.     

A multicenter, randomized double-blind study of valsartan/hydrochlorothiazide combination versus amlodipine in patients with mild to moderate hypertension

OBJECTIVE : To compare the antihypertensive efficacy and tolerability of a once-daily fixed valsartan/hydrochlorothiazide (HCTZ) combination and amlodipine in subjects with mild-to-moderate hypertension. SUBJECTS AND SETTING : In this multicentre, double-blind, randomized, comparative trial, 690 patients with sitting systolic blood pressure (BP) > or = 160 mmHg and sitting diastolic BP > or = 95 mmHg at the end of a 2-week placebo wash-out period were randomized to valsartan-based treatment (n = 342) or amlodipine (n = 348). METHODS : The patients received valsartan 80 mg o.d. or amlodipine 5 mg o.d for 4 weeks; in the case of an unsatisfactory blood pressure response, the treatments could be respectively changed to the fixed combination of valsartan 80 mg + HCTZ 12.5 mg o.d. or amlodipine 10 mg o.d. for a further 8 weeks. RESULTS : Both treatment approaches decreased systolic blood pressure and diastolic blood pressure to the same extent. The rate of responders to treatment at the end of fourth week (before up-titration) was 57.4% among the valsartan-treated patients and 61.9% among the amlodipine-treated patients (ns). At the end of the study, the rate of responders was not significantly different between the two groups (74.9 versus 72.1%). Valsartan-based treatment had a slightly lower incidence of adverse events (1.5 versus 5.5%; P = 0.006). CONCLUSIONS : The results of this trial demonstrate that the valsartan/hydrochlorothiazide combination and amlodipine are equally effective in lowering BP, and that the combination is better tolerated.     

Effects of the angiotensin II receptor blockers telmisartan vs valsartan in combination with hydrochlorothiazide 25 mg once daily for the treatment of hypertension

To attain recent goals of blood pressure (BP) control, multiple drug therapy combinations are required, including higher doses of thiazide diuretics in combination with other classes of antihypertensive drug therapy. Thus, the authors evaluated the antihypertensive effects of telmisartan vs valsartan when combined with hydrochlorothiazide (HCTZ) 25 mg in a large (N=1066), placebo-controlled trial in patients with stage 1 or 2 hypertension. The primary end points were the changes from baseline in seated diastolic and systolic BP at the end of the 8-week treatment period. Safety end points included adverse events, changes in laboratory parameters, and pulse rate. Changes from baseline in BP following telmisartan-HCTZ (-24.0/-17.6 mm Hg) were significantly greater than both placebo (-4.4/-6.8 mm Hg) and valsartan-HCTZ (-21.2/-16.1 mm Hg) (vs placebo, P<.001 for systolic and diastolic BP; vs valsartan-HCTZ, P=.004 for systolic BP and P=.019 for diastolic BP). The total number of patients with at least 1 adverse event reported were similar among the 3 treatment groups (placebo, 49%; telmisartan-HCTZ, 43%; and valsartan-HCTZ, 38%). In conclusion, telmisartan-HCTZ at doses of 80/25 mg lowered both systolic and diastolic BP to a greater extent than valsartan-HCTZ at doses of 160/25 mg. These data support using a higher dose of a thiazide diuretic (25 mg) with a long-acting angiotensin receptor blocker as a useful strategy for improving hypertension control.