厄贝沙坦治疗原发性高血压的临床疗效和靶器官保护

目的评价厄贝沙坦治疗原发性高血压的临床疗效及其对原发性高血压左心室肥厚(LVH)的逆转作用以及对肾功能的保护作用。方法 100例确诊为高血压病患者服用厄贝沙坦150 mg,每天1次,每周随访1次,治疗12周,监测治疗前及治疗中24 h动态血压水平及肾功能指标。用超声心动图测量LVH患者左心室肥厚的改善情况。结果厄贝沙坦治疗后,患者24 h平均收缩压及舒张压、日间及夜间收缩压及舒张压均有明显下降(P<0.01),血及尿β2-MG明显减少(P<0.01)。经厄贝沙坦治疗后左心室重量(left ventricular hypertraphy,LVMI)明显下降(P<0.01)。结论厄贝沙坦对原发性高血压患者有良好的平稳降压效果,对原发性高血压患者的LVH有逆转作用,且对其肾功能有良好的保护作用。     

氢氯噻嗪联合缬沙坦治疗原发性高血压的效果观察

目的探讨氢氯噻嗪联合缬沙坦治疗原发性高血压的临床效果。方法选取2012年1月～2013年1月本院收治的原发性高血压患者160例,将其随机分为观察组和对照组,各80例,对照组采用缬沙坦治疗．观察组在对照组治疗的基础上加用氢氯噻嗪,治疗1个月后比较两组患者的临床效果和血压变化。结果观察组总有效率为87．5％,明显高于对照组的75．0％,差异有统计学意义（P〈0．05）。治疗前,两组患者的DBP、SBP比较差异无统计学意义（P〉0．05）;治疗后,两组患者的DBP、SBP明显下降,与治疗前比较差异有统计学意义（P〈0．05）．且观察组下降较对照组显著,差异有统计学意义（P〈0．05）。两组患者不良反应发生率均为3．75％,差异无统计学意义（P〉0．05）。结论氢氯噻嗪联合缬沙坦治疗原发性高血压效果显著,无严重不良反应,值得临床推广应用。     

Valsartan: a novel angiotensin Type 1 receptor antagonist

Valsartan is a highly selective, orally available antagonist of the angiotensin Type 1 (AT₁)receptor. It is indicated for treatment of mild to moderate essential hypertension. Experimental studies have confirmed the abolition or attenuation of angiotensin II (AII)-related effects, such as vasoconstriction, cell growth promotion and aldosterone release. In humans, valsartan is rapidly absorbed with maximal plasma concentrations occurring 1 - 2 h after oral administration. The elimination half-life comes to about 7 - 8 h, valsartan is metabolised to a negligible extent and most of the drug is excreted via the faeces. There is no dose adjustment required for patients with a creatinine clearance >> 10 ml/min. The dose should not exceed 80 mg o.d. in patients with hepatic dysfunction, valsartan is not recommended for patients with severe hepatic dysfunction and/or biliary cirrhosis. At present, no clinically relevant pharmacokinetic drug interactions have been observed. Valsartan produces persistent blood pressure reductions in patients with mild to moderate hypertension, the recommended starting dose is 80 mg o.d. If required, the dose may either be increased to 160 mg o.d. or hydrochlorothiazide may be added. In comparison to other antihypertensive drugs valsartan therapy leads to similar blood pressure reductions, while exhibiting a favourable tolerability profile. Preliminary studies suggest beneficial effects in patients with hypertensive end-organ damage such as renal disease and left ventricular hypertrophy. Furthermore, the drug is evaluated for its efficacy in heart failure and patients post-myocardial infarction.     

Telmisartan/hydrochlorothiazide combination therapy in the treatment of essential hypertension

Telmisartan is an angiotensin-II receptor blocker that has demonstrated efficacy in the reduction of blood pressure in patients with hypertension. Patients with hypertension commonly require two or more antihypertensives to reduce their blood pressure to safe levels, and the choice of combination therapy should be informed by clinical trial data. Telmisartan is available in fixed-dose combination with hydrochlorothiazide (telmisartan/HCTZ) in doses of 40 mg/12.5 mg and 80 mg/12.5 mg. Telmisartan/HCTZ has been studied in a number of clinical trials in essential hypertension, for the most part using ambulatory blood pressure monitoring. It has been compared with monotherapy in full patient populations and in non-responders, and has been compared with other drug combinations. Telmisartan/HCTZ provides significantly greater reductions in blood pressure than monotherapy, and significantly increases the percentage of patients who achieve target blood pressure. The reduction in blood pressure achieved by adding HCTZ to telmisartan is greater than that achieved by adding HCTZ to atenolol, despite the fact that telmisartan and atenolol monotherapy had similar efficacy. Telmisartan/HCTZ provides significantly greater reductions than losartan plus HCTZ in 24-h mean blood pressure, primarily due to a significantly greater effect in the risky, early morning hours. Telmisartan/HCTZ is effective and well-tolerated in the elderly, diabetics and African-American patients. Ongoing studies are comparing the efficacy of telmisartan/HCTZ with valsartan plus HCTZ and amlodipine plus HCTZ in overweight, hypertensive diabetics and in patients with isolated systolic hypertension – two patient groups who are particularly at risk of target organ damage.     

Pharmacology of the angiotensin II receptor antagonist,eprosartan

The non-peptide angiotensin II receptor antagonists represent a new class of drugs with demonstrated efficacy in the treatment of hypertension. Eprosartan is a potent, orally active AT₁ receptor antagonist which is chemically distinct from losartan and other non-peptide angiotensin II receptor antagonists. Eprosartan has a high affinity for the angiotensin II AT₁ receptor, but does not interact with the AT₂ receptor, adrenergic receptors or other receptors involved in cardiovascular regulation. In contrast to most other angiotensin II antagonists, eprosartan is a true competitive antagonist of the AT₁ receptor. Eprosartan is effective in antagonising the cardiovascular and renal effects of exogenous angiotensin II in both experimental animals and humans. Furthermore, it is an effective antihypertensive agent when administered to renin-dependent hypertension animal models, and in patients with mild to severe hypertension. The antihypertensive effect of eprosartan is maintained over a 24-h interval following a single dose with no reported dose-dependent adverse side-effects.     

Losartan: a selective angiotensin II type 1 (AT1) receptor antagonist for the treatment of heart failure

Losartan (COZAARΟχιρχ^?) is the prototype of a new class of potent and selective angiotensin II (AII) type 1 (AT₁) receptor antagonists with the largest published preclinical and clinical data base. Since all of the AII antagonists are selective for the AT₁ receptor, these drugs should exhibit similar cardiovascular effects. However, since the pharmacokinetic/pharmacodynamic profiles of these agents and their degree of affinity for the AT₁ receptor differ, it is likely that differences in clinical profiles between these drugs exist and will require investigation. Losartan (parent compound), has moderate affinity for the AT₁ receptor (competitive inhibition). Losartan is well-absorbed orally as an active drug and is rapidly converted via oxidation in the human liver to a more potent metabolite (designated E3174) with an affinity 20- to 30-times greater for the AT₁ receptor (non-competitive inhibition). E3174 has a half-life of 6 - 9 h; elimination is via renal and hepatic routes. Antihypertensive and, in heart failure patients, haemodynamic activity is observed over a 24 h period with once daily dosing. Over 6 million patients have been treated for hypertension with continued excellent tolerability. Clinical experience in heart failure is growing, and recent data suggest an improved survival with losartan versus captopril, a drug from the angiotensin-converting-enzyme inhibitor class with proven benefit in this population. The current comprehensive losartan clinical end-point programme (4 large scale morbidity/mortality trials) should provide evidence regarding the efficacy of direct blockade of the AT₁ receptor with losartan compared to standard therapy: 1) The Losartan Heart Failure Survival Study - ELITE II, 2) The Losartan Post-Myocardial Infarction Survival Study - OPTIMAAL, 3) The Losartan Hypertension Survival Study - LIFE and 4) The Losartan Renal Protection Study - RENAAL.     

Pharmacology of valsartan,an angiotensin II receptor antagonist

Valsartan is the second orally-active, non-peptide angiotensin II receptor blocker to reach the market in Europe and the USA for the treatment of hypertension. Preclinical studies have demonstrated that this blocker is specific for the AT₁ receptor and has no affinity for the angiotensin II AT₂ receptor. Experimentally, valsartan dose-dependently inhibits the vasoconstriction induced by angiotensin II and lowers blood pressure in renin-dependent models of hypertension. Pharmacologically, oral valsartan is characterised by a low bioavailability but a rapid absorption and distribution with a half-life in keeping with once-daily administration. Thus, after oral administration, the maximal plasma concentration is reached 2 h after dosing and the elimination half-life is about 6 h. Clinically, several dose-finding and comparative studies have demonstrated that valsartan is an effective and well-tolerated antihypertensive drug in patients with mild to moderate hypertension. Valsartan has also been shown to be effective in severe hypertension. Valsartan is at least as effective as ACE inhibitors, diuretics, beta-blockers and calcium antagonists. However, none of the side-effects observed with these latter agents, including cough and lower limb oedema, has been observed with the administration of valsartan. Three large clinical trials are now underway to demonstrate whether valsartan can reduce morbidity and mortality: one in hypertensives with a high cardiovascular risk profile (VALUE), one in patients with heart failure previously treated with an angiotensin-converting enzyme inhibitor (VAL-HeFT) and one in post-myocardial infarct patients (VALIANT). These studies will further define the place of valsartan beyond the treatment of hypertension.     

Pilot study of the uricosuric effect of DuP-753, a new angiotensin II receptor antagonist,in healthy subjects

Summary The uricosuric effect of DuP-753, a novel, specific angiotensin II receptor antagonist, has been explored in a healthy male Japanese volunteers, given single oral doses of 25, 50, 100 or 200 mg (n=6), or 100 mg (n=6) or placebo (n=3) once daily for 7 consecutive days.In the single-dose study, serum uric acid measured at 4 h after dosing showed a dose dependent decrease; the reductions from the corresponding pre-dose values were: 0.32 (25 mg), 0.77 (50 mg), 1.25 (100 mg) and 1.33 mg dl^–1 (200 mg). The urinary excretion of uric acid within the first 4 h after treatment was also increased in a dose-dependent manner, whereas the urinary excretion of creatinine remained unchanged.In the multiple-dose study, DuP-753 significantly decreased the serum uric acid concentration measured 4 h both after the first (pre-dose value: 5.68 vs 4 h after: 4.48 mg·dl^–1) and last administrations (4.42 mg·dl^–1). Simultaneously, the ratio of urinary uric acid to creatinine excretion was significantly increased within the first 4 h both after the first (DuP-753: 1.190 vs placebo: 0.576) and last administrations (1.02 vs 0.576).The findings suggest that DuP-753 posesses a uricosuric effect both after single and multiple doses in healthy subjects. The effect should be further examined in hypertensive patients.     

缬沙坦/氢氯噻嗪治疗原发性高血压有效性和安全性的Meta分析

目的评价复方缬沙坦（缬沙坦/氢氯噻嗪）治疗原发性高血压的有效性及安全性。方法计算机检索中国期刊全文数据库和中国生物医学文献数据库,使用RevMan4.2软件进行评价。结果共纳入12篇随机对照试验,Meta分析结果显示：复方缬沙坦与缬沙坦相比,有效率的差异有统计学意义[OR=2.94,95%CI（2.00,4.32）,P〈0.01],而不良反应发生率的差异无统计学意义[OR=0.91,95%CI（0.55,1.49）,P=0.70];与其它含氢氯噻嗪的复方制剂相比,有效率和不良反应发生率的差异均无统计学意义。结论复方缬沙坦治作为一种新型的固定剂量降压制剂,降压效果优良。     

奥美沙坦:一种新的血管紧张肽Ⅱ受体拮抗剂

奥美沙坦 (olmesartan)是最新的血管紧张肽Ⅱ受体 (AT1)拮抗剂 ,对不同程度的高血压均有很好的降压作用 ,病人对其亦有很好的耐受性。本文对该药的药效学、药动学和临床应用等研究作一综述     

Effect of the non peptide angiotensin II antagonist,GR117289C on the vasoconstrictor actions of angiotensin II in the human forearm

AIMS: GR117289C is a non peptide, selective angiotensin (AT1) receptor antagonist. The purpose of this study was to determine whether this agent, given orally, could attenuate the vasoconstrictor effects of angiotensin II(AII) infused locally into the forearm circulation in man. METHODS: Eight healthy male subjects were studied on four occasions in a randomized, double-blind, placebo controlled, crossover study. Five hours (approximate time of peak dynamic effect) following dosing with GR117289C (300 mg, 100 mg, 10 mg or placebo), A II was infused in incremental doses (0, 0.1, 0.4, 1.6, 6.2, 25 and 100 pmol min-1) into the left brachial artery, each for 10 min. Forearm blood flow was measured using venous occlusion plethysmography. RESULTS: GR117289C inhibits the vasoconstrictor effects of A II in a dose dependent manner. The active treatment: placebo ratios of forearm blood flow in the infused arm during the highest dose of AII (100 pmol min-1) were: GR117289C 10 mg, 1.12 (95% C.I. 0.81-1.55; P = 0.478), 100 mg, 1.43 (95% C.I. 1.01-2.01; P = 0.042) and 300 mg, 1.62 (95% C.I. 1.17-2.24; P = 0.006). There was no significant difference in blood pressure between each of the treatment groups and placebo. CONCLUSIONS: GR117289C is a pharmacologically active, oral A II antagonist in healthy men.     

依那普利联合氢氯噻嗪治疗原发性高血压的临床疗效观察

目的观察依那普利联合氢氯噻嗪在原发性高血压治疗中的应用效果。方法选择2010年1月～2012年1月笔者所在医院收住的原发性高血压患者作为研究对像,共60例。随机分为治疗组(依那普利联合氢氯噻嗪)和对照组(依那普利)各30例,比较两组的降压效果。结果治疗后4、8周后,两组的收缩压、舒张压分别较治疗前明显降低,且治疗组较对照组降低更明显,差异有统计学意义(P<0.05)。结论依那普利联合氢氯噻嗪治疗原发性高血压效果好,不良反应少,值得推广和应用。     

厄贝沙坦与厄贝沙坦／氢氯噻嗪复方制齐佾疗轻中度原发性高血压的疗效对比观察

目的评价厄贝沙坦与厄贝沙坦／氢氯噻嗪复方制剂治疗高血压病的疗效。方法轻中度原发性高血压患者共106例,随机分为两组,一组为厄贝沙坦治疗组（n=52）,服用厄贝沙坦150mg,1次／日;另一组为厄贝沙坦／氢氯噻嗪复方制剂组（n=54）,服用厄贝沙坦150rng和氢氯噻嗪12．5mg的复方制剂,1次／日。结果治疗12周后．厄贝沙坦／氢氯噻嗪复方制剂降压的总有效率为83．3％（45／54）,厄贝沙坦降压的总有效率为78．8％（41／52）,两组血钾、LDL-C、血糖较入组时无明显变化,组间差异无统计学意义,未观察到严重不良反应。结论厄贝沙坦／氢氯噻嗪复方制剂治疗轻中度原发性高血压患者的控制率和达标率较高．较单用厄贝沙坦未增加不良反府．     

厄贝沙坦氢氯噻嗪片治疗原发性高血压的临床评价

目的探讨厄贝沙坦氢氯噻嗪片治疗原发性高血压的临床疗效。方法收集我院已治疗原发性高血压患者108例,随机分为:观察组54例和对照组54例。观察组采用药物为厄贝沙坦氢氯噻嗪片,对照组所采用药物为厄贝沙坦。治疗完成后,观察、分析两组临床疗效。结果观察组的总有效率为94.44%,对照组的总有效率为75.93%,两组临床疗效差异有统计学意义(P<0.05)。结论在原发性高血压的治疗方面,厄贝沙坦氢氯噻嗪片的临床疗效显著优于厄贝沙坦,具有良好的临床疗效,值得推广。     

依那普利联合氢氯噻嗪治疗高血压的临床疗效观察

目的探讨依那普利联合氢氯噻嗪治疗高血压的疗效。方法选择2009年6月～2011年6月来笔者所在医院治疗的原发性高血压患者60例,按照随机数字表法分为观察组和对照组各30例,观察组患者每日晨服马来酸依那普利胶囊、氢氯噻嗪,对照组仅予马来酸依那普利胶囊口服,比较两组的降压效果以及不良反应情况。结果观察组的降压效果总有效率为96.7%,明显高于对照组,差异有统计学意义(P<0.05)。结论依那普利联合氢氯噻嗪治疗高血压疗效确切,安全性好,值得推广和应用。     

Angiotensin II receptor blockers for the treatment of hypertension

The rising incidence of stroke, congestive heart failure (CHF) and end stage renal disease (ESRD) has signalled a need to increase awareness, treatment and control of hypertension. There continues to be a need for effective antihypertensive medications since hypertension is a major precursor to various forms of cardiovascular disease. The renin-angiotensin (AT) aldosterone system (RAAS) is a key component to the development of hypertension and can be one target of drug therapy. Angotensin II (ATII) receptor blockers (ARBs) are the most recent class of agents available to treat hypertension, which work by by inhibiting ATII at the receptor level. Currently, national consensus guidelines recommend that ARBs should be reserved for hypertensive patients who cannot tolerate angiotensin converting enzyme (ACE) inhibitors (ACEIs). ARBs, however, are moving to the forefront of therapy with a promising role in the area of renoprotection and CHF. Recent trials such as the The Renoprotective Effect of the Angiotensin-Receptor Antagonist Irbesartan in Patients with Nephropathy Due to Type 2 Diabetes Trial (IDNT), the Effect of Irbesartan on the Development of Diabetic Nephropathy in Patients with Type 2 Diabetes (IRMA2), and The Effects of Losartan on Renal and Cardiovascular Outcomes in Patients with Type 2 Diabetes and Nephropathy (RENAAL) study have demonstrated the renoprotective effects of ARBs in patients with Type 2 diabetes. The Valsartan Heart Failure Trial (Val-HeFT) adds to the growing body of evidence that ARBs may improve morbidity and mortality in CHF patients. As a class, ARBs are well tolerated and have a lower incidence of cough and angioedema compared to ACEIs. This article reviews the differences among the ARBs, existing efficacy data in hypertension, and explores the role of ARBs in CHF and renal disease.     

养血清脑颗粒联合缬沙坦氢氯噻嗪治疗老年原发性高血压的临床研究

目的 探讨养血清脑颗粒联合缬沙坦氢氯噻嗪片治疗老年原发性高血压的临床疗效。方法 选取2020年6月—2021年11月在保定市第一医院收治的82例老年原发性高血压患者为观察对象,根据随机数字表法将所有患者分为对照组和治疗组,每组各41例。对照组口服缬沙坦氢氯噻嗪片,1片/次,1次/d;治疗组在对照组治疗的基础上温水冲服养血清脑颗粒,1袋/次,3次/d。两组患者连续治疗3个月。观察两组的临床疗效,比较两组的血压指标、血流动力学指标、血清指标。结果 治疗后,治疗组患者的总有效率为95.12%,对照组的总有效率为80.49%,组间比较差异有统计学意义（P＜0.05）。治疗后,两组的24 h收缩压（24 h SBP）、24 h舒张压（24 h DBP）、24 h收缩压标准差（24 h SSD）、24 h舒张压标准差（24 h DSD）明显低于治疗前（P＜0.05）,且治疗组24 h SBP、24 h DBP、24 h SSD、24 h DSD低于对照组（P＜0.05）。治疗后,两组的体循环阻力（SVR）低于治疗前,心排血量（CO）、心脏指数（CI）高于治疗前（P＜0.05）;并且治疗组的SVR低于对照组,CO、CI高于对照组,差异有统计学意义（P＜0.05）。治疗后,两组的血清同型半胱氨酸（Hcy）、内皮素-1（ET-1）水平低于治疗前,一氧化氮（NO）水平高于治疗前（P＜0.05）;治疗组的Hcy、ET-1水平低于对照组,NO水平高于对照组（P＜0.05）。结论 养血清脑颗粒联合缬沙坦氢氯噻嗪片治疗老年原发性高血压的疗效确切,能有效控制血压,改善血流动力学指标和血管内皮功能,安全性良好。     

The effects of KT3-671, a new angiotensin II (AT 1) receptor blocker in mild to moderate hypertension

AIMS: To compare the antihypertensive effect, and tolerability and safety of once daily doses of KT3-671 with that of placebo in patients with mild to moderate uncomplicated essential hypertension. METHODS: A randomised, multicentre, double blind, parallel-group comparison of KT3-671 with placebo. Hypertensive patients [Ambulatory Blood Pressure Monitoring (ABPM), mean daytime DBP > 90 mmHg, Office sitting mean DBP 95-114 after a 7-28 day washout period] entered a 2-week, single blind, run-in phase. Patients eligible for the double-blind phase were randomised to receive KT3-671 40 mg, 80 mg, 160 mg or placebo once daily over 4 weeks. The primary end-point was trough mean sitting office DBP. The study had 90% power to detect a 5 mmHg change between treatments and placebo at the 5% level of significance. The secondary end-points were 24 hour, daytime and night time mean ABPM. RESULTS: Office DBP was significantly lower with KT3-671 40 mg but not the other 2 dosage groups (-3.2; 95% CL -6.1 : -0.3 P < 0.03). Office SBP was significantly reduced with all dosage groups (40 mg -5.9, 95% CL -11 : -0.9; 80 mg -4.9, 95% CL -9.9 : 0.1 and 160 mg -5.7, 95% CL -10.8 : -0.7 P < 0.05). All doses of KT3-671 reduced systolic and diastolic ABPM. The number of patients with treatment related adverse events were comparable to placebo (38.8% KT3-671 vs 32.8% placebo). There was some evidence of a dose-response relationship with fall in nocturnal ABPM. CONCLUSIONS: Oral KT3-671 was well tolerated. KT3-671 reduced office systolic BP at all doses and diastolic BP at some of the doses. Due to greater precision and power, the falls in mean ambulatory systolic and diastolic pressure were all significantly lower than placebo.     

比较比索洛尔-氢氯噻嗪复合剂与缬沙坦对原发性高血压24小时动态血压的影响研究

目的:比较比索洛尔-氢氯噻嗪复合剂(Bisoprolol//HCTZ)与缬沙坦(Valsartan)对原发性高血压患者24小时动态血压的影响。方法:44例原发性高血压患者分别随机入组比索洛尔2.5~5 mg/氢氯噻嗪6.25 mg复合剂治疗组和缬沙坦80~160 mg治疗组,用法:1次/d,连续服药16周,每4周对患者进行用药前后24小时动态血压(ABP)进行监测。结果:44例患者入组(男性23例,女性21例)中,23例入组比索洛尔/氢氯噻嗪复合剂治疗组,21例入组缬沙坦治疗组。与治疗前相比,两组的动态血压都有显著的降低,24小时SBP/DBP(-16.9/-10.3 mmHg和-17.7/-10.9 mmHg),白天SBP/DBP分别为(-17.1/-9.4 mmHg和-17.6/-9.8 mmHg),夜晚SBP/DBP分别为(-17.0/-11.5 mmHg和-16.4/-11.6 mmHg)。结论:低剂量组合的比索洛尔和氢氯噻嗪对于原发性高血压患者24小时动态血压的降低有显著效果。     

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

ABSTRACT

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

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

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

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

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