Endothelial vascular function in hypertensive patients after renin-angiotensin system blockade

It is unclear whether single and combined pharmacologic inhibition of the renin-angiotensin-aldosterone system have similar effects on endothelial function and blood pressure (BP). The authors evaluated 63 hypertensive patients divided into 4 groups (hydrochlorothiazide 25 mg/d; irbesartan [IRBE] 150 mg/d; quinapril [QUIN] 20 mg/d; or IRBE 150 mg/d + QUIN 20 mg/d) and 25 healthy normotensive subjects (normal) followed for 12 weeks. Endothelium-dependent dysfunction measured as flow-mediated dilation at Weeks 0 and 12 were: normal, 11.5%+/-2.4% vs 13.5%+/-2.0%; hydrochlorothiazide, 7.3%+/-2.0% vs 12.8%+/-3.1%; QUIN, 7.2%+/-2.8% vs 13.2%+/-2.1%; IRBE, 7.1%+/-2.8% vs 13.0%+/-2.9%; and IRBE + QUIN, 7.5%+/-1.9% vs 12.8%+/-3.0%. Nitroglycerin-mediated responses were: normal, 26.0%+/-1.9% vs 24.0%+/-2.5%; hydrochlorothiazide, 17.0%+/-2.2% vs 18.3%+/-2.6%; QUIN, 17.8%+/-3.2% vs 23.4%+/-3.0%; IRBE, 16.8%+/-3.6% vs 24.7%+/-2.0%; and IRBE + QUIN, 17.3%+/-3.0% vs 25.1%+/-2.5%. Antihypertensive therapy restored BP to normal and improved the endothelium-dependent and -independent dysfunction after renin-angiotensin-aldosterone system blockade. In a further finding, the combined effect of angiotensin-converting enzyme inhibition and angiotensin II type 1 receptor blockade was not superior to the action of either of these treatments separately.     

Aldosterone escape with diuretic or angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker combination therapy in patients with mild to moderate hypertension

Renin-angiotensin-aldosterone system (RAAS) hyperactivity is implicated in the development of hypertension and progressive damage in target organs. Chronic inhibition of the RAAS or use of thiazide-type diuretics may trigger an aldoster-one escape. The aim of this study was to assess this phenomenon in hypertensive patients treated with thiazide-type diuretics (hydrochlorothiazide [HCTZ]) or single or double blockade of the RAAS (irbesartan [IRBE], quinapril [QUIN], and IRBE+QUIN). Blood pressure levels were obtained by 24-hour ambulatory blood pressure monitoring. Plasma renin activity and aldosterone levels were determined by immunoradiometric assay. Blood pressure level was normalized in the 4 treatment groups; the HCTZ and IRBE+QUIN groups showed an increased plasma aldosterone level after 12 weeks (9.1+/-2.2 to 14.1+/-1.4 and 6.9+/-1.9 to 12.9+/-2.3 ng/dL, respectively; P<.05), whereas plasma renin activity was increased only in the HCTZ group (0.9+/-0.2-1.7+/-0.2 ng/mL/h; P<.05). The increase in plasma aldosterone level after 12 weeks of HCTZ and IRBE+QUIN therapy suggests early aldosterone escape.     

缬沙坦联合氨氯地平或氢氯噻嗪对老年高血压患者血压变异性的影响

目的 比较缬沙坦联合氨氯地平或氢氯噻嗪对老年高血压患者血压变异性及一氧化氮、内皮素的影响.方法选取61例2、3级老年高血压患者,随机分为两组,分别给予缬沙坦+氨氯地平或缬沙坦+氢氯噻嗪行降压治疗,观察入选时、治疗第8周和第16周各种相关指示的变化.人选时检测血脂、空腹血糖、血尿酸,试验各个阶段监测24 h动态血压,检测血浆一氧化氮、内皮素水平.结果在患者入选时、治疗第8周和第16周三个时间点,缬沙坦+氨氯地平组和缬沙坦+氢氯噻嗪组24 h血压及白昼血压比较差异无统计学意义.治疗第16周,缬沙坦+氨氯地平组晨峰收缩压较缬沙坦+氢氯嚷嗪组明显降低[(22.6±8.8)mm Hg(1 mm Hg=0.133 kPa)比(26.3±13.7)mm Hg,P＜0.05];缬沙坦+氨氯地平组及缬沙坦+氢氯噻嗪组24 h收缩压变异性(SBPV)进行性降低[缬沙坦+氨氯地平组:(12.5±2.8)mm Hg比(10.2 ±2.2)mm Hg比(8.8±1.6)mm Hg,P＜0.01;缬沙坦±氢氯噻嗪组:(12.5±2.5)mmHg比(10.7±2.2)mm Hg比(9.6±2.0)mmHg,P＜0.01],缬沙坦+氨氯地平组及缬沙坦+氢氯噻嗪组白昼SBPV明显降低[缬沙坦+氨氯地平组:(12.2±3.0)mm Hg比(10.1±2.3)mm Hg比(8.4±1.9)mm Hg,P＜0.01;缬沙坦+氢氯噻嗪组:(11.8±2.7)mm Hg比(10.4±1.9)mm Hg比(9.6±2.2)mm Hg,P＜0.01],缬沙坦+氨氯地平组24 h舒张压变异性(DBPV)显著降低[(15.5±3.4)mm Hg比(13.0±3.5)mm Hg比(12.3±2.5)mm Hg,P＜0.01],缬沙坦+氢氯噻嗪组24 h DBPV无显著性变化;缬沙坦+氨氯地平组第16周白昼SBPV低于缬沙坦+氢氯噻嗪组[(8.4±1.9)mm Hg比(9.6 ±2.2)mm Hg,p＜0.05],缬沙坦+氨氯地平第8周、第16周的24 h DBPV、白昼DBPV低于缬沙坦+氢氯噻嗪组(P ＜0.01～0.05);缬沙坦+氨氯地平组一氧化氮进行性升高[(27.3±13.6)μmol/L比(47.2±16.3)μmol/L比(69.5±18.9)μmol/L,P＜0.01]、内皮素进行性降低[(45.3±8.0)ng/L比(37.4±3.9)ng/L比(34.2±4.4)ng/L,P＜0.01];缬沙坦+氢氯噻嗪组一氧化氮进行性升高[(33.5±13.9)μmol/L 比(49.7±21.9)μmol/L比(66.7 ±24.7)μmol/L,P＜0.01]、内皮素显著降低[(46.6±10.4)ng/L比(37.0±5.4)ng/L比(36.1±8.2)ng/L,P＜0.01].治疗第8周,缬沙坦+氨氯地平组收缩压变异性的降幅与一氧化氮的升幅有相关性(r =0.401,P=0.025).结论缬沙坦联合氨氯地平或氢氯噻嗪均能降低老年高血压患者血压变异性、改善血管内皮功能,缬沙坦联合氨氯地平可能更适合于老年高血压患者.     

Hydrochlorothiazide is not additive to verapamil in treating essential hypertension

Calcium channel blockers, a newer class of antihypertensive medications, have gained considerable acceptance as monotherapeutic agents, particularly in low renin hypertension where diuretics are also most effective. To study whether thiazide diuretics exert an additional antihypertensive effect in the setting of calcium channel blockade, we gave verapamil hydrochloride (360 mg/d) or hydrochlorothiazide (25 mg/d) alone and in combination in an open study to 13 hypertensive patients with mild to moderate essential hypertension. Both verapamil and hydrochlorothiazide lowered blood pressure (170 +/- 17/109 +/- 6 mm Hg pretreatment to 150 +/- 25/95 +/- 8 mm Hg with verapamil; 170 +/- 5/109 +/- 2 mm Hg pretreatment to 164 +/- 25/103 +/- 10 mm Hg with hydrochlorothiazide), but addition of hydrochlorothiazide to verapamil resulted in no added benefit (150 +/- 25/95 +/- 8 mm Hg vs 150 +/- 20/95 +/- 6 mm Hg). Furthermore, while hydrochlorothiazide lowered serum potassium values (4.2 +/- 0.25 mmol/L to 3.7 +/- 0.35 mmol/L) and stimulated plasma renin activity (1.5 +/- 1.3 ng/mL/h) pretreatment to 3.3 +/- 2.7 ng/mL/h with verapamil), verapamil only modestly elevated renin activity (1.5 +/- 1.3 ng/mL/h pretreatment to 2.7 +/- 2.5 ng/mL/h with verapamil) and did not lower potassium values. Altogether, the data suggest that in essential hypertension, at least for verapamil, concurrent diuretic therapy may not be helpful or warranted.     

厄贝沙坦/氢氯噻嗪复方片治疗难治性高血压的临床疗效

目的 评价厄贝沙坦/氢氯噻嗪复方片治疗难治性高血压的疗效和不良反应.方法 纳入2007年8月至2011年6月空军航空医学研究所附属医院难治性高血压患者96例,随机分为A组[（氨氯地平10mg/d＋美托洛尔50mg/d＋厄贝沙坦/氢氯噻嗪复方片1片,每片含厄贝沙坦150mg和氢氯噻嗪12.5mg）,n=52]和B组（氨氯地平10mg/d＋美托洛尔50mg/d＋氢氯噻嗪50mg/d,n=44）.分别记录两组治疗前、治疗第2周、第4周和第12周的血压、心率,同时检测治疗前和治疗12周后患者的血钾、血糖、血脂、血肌酐和血尿酸水平,并进行分析.结果 与治疗前比较,两组治疗后血压均明显降低（P均＜0.05）,B组血压下降更迅速,治疗2周后收缩压A vs.B（48.1 mmHg vs.136.1 mmHg）但A组血压保持稳定的时间较长,治疗12周后有效率更高（A vs.B：75.0% vs.31.9%）.12周后,A组血压达目标水平比率75.0%,低血压发生率5.8%,B组血压达目标水平31.9%,低血压占13.6%.与A组相比,B组血钾降低更明显,血尿酸升高更明显,差异有统计学意义（P＜0.05）.结论 厄贝沙坦/氢氯噻嗪复方片对难治性高血压患者具有较好的降压效果,且作用平稳,不良反应发生率低.     

Aldosterone breakthrough during aliskiren,valsartan, and combination (aliskiren + valsartan) therapy

Aldosterone levels increase in 30%–40% of patients on angiotensin-converting enzyme inhibitors and/or angiotensin receptor blockers over the long term. This “aldosterone breakthrough” may carry important clinical consequences given aldosterone's nonepithelial, pro-fibrotic actions. The renin inhibitor, aliskiren, by suppressing the renin-angiotensin-aldosterone system (RAAS) proximally, may limit breakthrough compared to conventional RAAS blockade. This open-label study (NCT01129557) randomized subjects to aliskiren 300 mg daily (A), valsartan 320 mg daily (V), or aliskiren 150 mg + valsartan 160 mg daily (A+V) for 9 months. Eligible subjects had proteinuria >300 mg/day, estimated glomerular filtration rate (eGFR) >45 mL/min/1.73 m², and systolic blood pressure (BP) >130 or diastolic BP >80 mm Hg. Serum and 24-hour urine aldosterone (indexed to 24-hour urine Na) were checked before initiation of therapy and at 3, 6, and 9 months. Aldosterone breakthrough was defined as a sustained increase from baseline aldosterone by study end. The study was intended to enroll 120 subjects but was terminated early by the sponsor. We present here the results of 33 subjects who completed the protocol, of which 12 were randomized to A, 11 were randomized to V, and 10 were randomized to A+V. Mean baseline eGFR was 75.5 (±23.3) mL/min/1.73 m²; baseline proteinuria was 3104 (±2943) mg/day; and baseline BP was 134.7 (±10.5)/84.8 (±8.4) mm Hg. Three (27%) subjects on V, three (25%) subjects on A, and three (30%) subjects on A+V had aldosterone breakthrough. Mean proteinuria reduction was 31% from baseline in all subjects: 30% in subjects with breakthrough vs. 32% in subjects without breakthrough. Mean BP reduction was 11.0/8.8 mm Hg in all subjects: 8.4/6.1 mm Hg in subjects with breakthrough vs. 12.0/9.8 mm Hg in subjects without breakthrough. Aliskiren, alone or in combination with valsartan, did not reduce the incidence of aldosterone breakthrough in subjects with hypertension and proteinuria compared with conventional RAAS blockade.     

Effect of cilazapril with orwithout low dose thiazide on LDLperoxidationin hypertensive patients

BackgroundThis study aims to address the question, “Does equivalent blood pressure (BP) reduction by cilazapril alone or in combination with low dose of both cilazapril and hydrochlorothiazide have an equal effect on lowering oxidation of plasma LDL?”MethodsFifteen patients with untreated arterial hypertension were enrolled. Patients received 5 mg/d cilazapril (C5) for 6 weeks and were treated with a combination of 2.5 mg/d cilazapril and 12.5 mg/d hydrochlorothiazide (C2.5,HCTz) for an additional 2 months to achieve the same BP reduction as in the initial period. Treatment with a combination of 5 mg/d cilazapril and 12.5 mg/d hydrochlorothiazide (C5,HCTz) was administered for an additional 6 weeks.ResultsTreatment with C5 or in combination with C2.5,HCTz lowered systolic BP by the same magnitude (P < .05). Treatment with C5,HCTz decreased systolic BP an additional 7% and diastolic BP by 6% (P < .05). The LDL of 15 hypertensive patients demonstrated a 16.7% shorter lag time to initiation of peroxidation and 8.5% higher malonyldialdehyde levels at point of maximal peroxidation than LDL from 10 healthy controls (P < .05). Treatment with C5 decreased LDL tendency to peroxidation (lag time was prolonged by 43%, P < .05; malonyldialdehyde levels decreased by 8.3%). The combined treatment of C2.5,HCTz achieved the same BP reduction, but did not increase LDL resistance to peroxidation. Treatment with C5,HCTz achieved the same reduction in malonyldialdehyde levels in LDL than C5 therapy, but prolonged lag time by 17% (P < .05).ConclusionsThe decreased tendency of LDL to peroxidation in hypertensive patients treated by cilazapril is due to the inherent effect of cilazapril, and not to a reduction in BP.     

Losartan improves exercise tolerance in patients with diastolic dysfunction and a hypertensive response to exercise.

OBJECTIVES: The aim of the study was to test the hypothesis that angiotensin II (Ang II) blockade would improve exercise tolerance in patients with diastolic dysfunction and a marked increase in systolic blood pressure (SBP) during exercise. BACKGROUND: Diastolic dysfunction may be exacerbated during exercise, especially if there is a marked increase in SBP. Angiotensin II may contribute to the hypertensive response to exercise and impair diastolic performance. METHODS: We performed a randomized, double-blind, placebo-controlled, crossover study of two weeks of losartan (50 mg q.d.) on exercise tolerance and quality of life. The subjects were 20 patients, mean age 64 +/- 10 years with normal left ventricular systolic function (EF >50%), no ischemia on stress echocardiogram, mitral flow velocity E/A <1, normal resting SBP (<150 mm Hg), and a hypertensive response to exercise (SBP >200 mm Hg). Exercise echocardiograms (Modified Bruce Protocol) and the Minnesota Living With Heart Failure questionnaire were administered at baseline, and after each two-week treatment period, separated by a two-week washout period. RESULTS: Resting blood pressure (BP) was unaltered by placebo or losartan. During control, patients were able to exercise for 11.3 +/- 2.5 (mean +/- SD) min, with a peak exercise SBP of 226 +/- 24 mm Hg. After two weeks of losartan, baseline BP was unaltered, but peak SBP during exercise decreased to 193 +/- 27 mm Hg (p < 0.05 vs. baseline and placebo), and exercise time increased to 12.3 +/- 2.6 min (p < 0.05 vs. baseline and placebo). With placebo, there was no improvement in exercise duration (11.0 +/- 2.0 min) or peak exercise SBP (217 +/- 26 mm Hg). Quality of life improved with losartan (18 +/- 22, p < 0.05) compared to placebo (22 +/- 26). CONCLUSIONS: In patients with Doppler evidence of diastolic dysfunction at rest and a hypertensive response to exercise, Ang II receptor blockade blunts the hypertensive response to exercise, increases exercise tolerance and improves quality of life.     

Comparison of indapamide and hydrochlorothiazide plus amiloride as a third drug in the treatment of arterial hypertension

Summary In a randomized, double-blind crossover trial, indapamide (IND) 2.5 mg and hydrochlorothiazide 25 mg+amiloride 2.5 mg (HCTZ+a) were found to be equally effective in reducing blood pressure (BP) in 13 patients with moderate to severe hypertension already receiving chronic treatment with a beta blocker and a vasodilatator (supine BP during run-in: 169/103±21/5 mmHg; on IND: 149/91±21/14 mmHg; on HCTZ+A 144/88±23/5 mmHg). Both drugs induced insignificant reductions in body weight, and no change in plasma volume was seen.Serum potassium was significantly reduced on both regimens—the values recorded on IND being significantly lower than those seen on HCTZ+A. Values below 3.0 mmol/l were found in two patients receiving IND, but no subjective side effects were reported. Hyperuricemia occurred with the same frequency on both regimens.It is concluded that IND, just like the thiazide diuretics, is useful as the third drug in patients needing triple drug therapy to control BP, but metabolic adverse effects are not avoided by the choice of this drug.     

Efficacy and Safety of Long-Term Treatment With the Combination of Amlodipine Besylate and Olmesartan Medoxomil in Patients With Hypertension

The authors report on the 44-week open-label extension of the 8-week, double-blind Combination of Olmesartan Medoxomil and Amlodipine Besylate in Controlling High Blood Pressure (COACH) trial in 1684 patients. Initial therapy was amlodipine (AML) plus olmesartan medoxomil (OM) 5+40 mg/d, up-titrated to AML+OM 10+40 mg/d plus hydrochlorothiazide (HCTZ) 12.5 mg then 25 mg if patients did not achieve blood pressure (BP) goal (<140/90 mm Hg or <130/80 mm Hg in patients with diabetes). Baseline mean BP decreased from 164/102 mm Hg to 131/82 mm Hg at end of study, with an overall 66.7% of patients, including those with diabetes, achieving BP goal. The BP goal achievement was 80% for AML+OM 5+40 mg/d, 70.6% for AML+OM 10+40 mg/d, 66.6% for AML+OM+HCTZ 10+40+12.5 mg/d, and 46.3% for AML+OM+HCTZ 10+40+25 mg/d. Study medication was safe and well tolerated. Combination antihypertensive therapy with AML+OM±HTCZ, up-titrated as necessary, allowed a majority of patients to achieve BP goal.     

工作场所干预条件下不同药物组合的降压效果

目的比较分析工作场所干预条件下,不同药物组合对高血压患者的降压效应。方法 2009-04-2010-05对开滦集团有限责任公司井下及井下辅助单位在岗患高血压的职工进行综合干预[共5367例,其中男性4023例,女性67例,年龄(45.5±6.5)岁]。干预措施包括免费发放降压药物,宣传教育和行政干预。免费发放的降压药为下列组合之一:①尼群地平5mg2次/d+卡托普利12.5mg2次/d(A组,1115例);②尼群地平5mg2次/d+螺内酯20mg1次/d(B组,704例);③氢氯噻嗪12.5mg1次/d+卡托普利12.5mg2次/d(C组,794例);④氢氯噻嗪12.5mg1次/d+螺内酯20mg1次/d(D组,1477例)。干预期间每2周随访1次并测量血压,观察干预前后的血压变化情况。结果干预后收缩压[(134.1±13.1)比(147.6±17.5)mmHg]、舒张压[(86.6±8.9)比(96.9±10.9)mmHg]下降(均P<0.01)。A、B、C、D组收缩压分别下降(14.1±23.3)、(11.4±23.0)、(12.1±21.7)和(14.8±20.9)mmHg,舒张压分别下降(9.5±15.5)、(7.4±14.8)、(10.2±14.4)和(12.1±13.6)mmHg,组间比较差异有统计学意义(均P<0.01),D组血压下降值大于其他组。A、B、C、D组的总有效率分别为67.0%、62.9%、68.5%和77.3%,D组的总有效率高于其他组(P<0.01)。结论工作场所不同抗高血压药物组合能有效降低高血压患者的血压水平。     

Efficacy and safety of irbesartan/HCTZ combination therapy as initial treatment for rapid control of severe hypertension

Severe hypertension is difficult to control. This prospective, randomized, double-blind, active-controlled, multicenter trial compared efficacy and safety of once-daily irbesartan/hydrochlorothiazide (HCTZ) combination therapy with irbesartan monotherapy in severe hypertension. Patients who were untreated or uncontrolled on monotherapy (seated diastolic blood pressure [BP] ≥110 mm Hg) received fixed-dose irbesartan 150 mg/HCTZ 12.5 mg combination therapy for 7 weeks, force-titrated to irbesartan 300 mg/HCTZ 25 mg at week 1 (n=468); or irbesartan 150 mg monotherapy, force-titrated to 300 mg at week 1 (n=269). Significantly more patients on combination therapy achieved seated diastolic BP <90 mm Hg at week 5 (primary end point) compared with monotherapy recipients (47.2% vs 33.2%; P= .0005). Likewise, significantly more patients attained goals per the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) (<140/90 mm Hg) at week 5 (34.6% vs 19.2%, respectively; P< .0001), while the mean difference between combination and monotherapy in seated diastolic BP and seated systolic BP was 4.7 mm Hg and 9.7 mm Hg ( P< .0001). Greater and more rapid BP reduction with irbesartan/HCTZ was achieved without additional side effects.     

Safety and Tolerability of Fixed-Dose Irbesartan/Hydrochlorothiazide for Rapid Control of Severe Hypertension

This prospective, double-blind, multicenter trial compared the safety and tolerability of irbesartan/hydrochlorothiazide (HCTZ) fixed-dose combination therapy with irbesartan monotherapy in patients with severe hypertension (seated diastolic blood pressure (SeDBP) ≥110 mm Hg, mean BP 172/113 mm Hg at baseline). Patients were randomized 2:1 to 7 weeks' irbesartan/HCTZ 150/12.5 mg to 300/25 mg (n = 468) or irbesartan 150 mg to 300 mg (n = 227). The incidence of treatment-related adverse events (AEs) was similar with combination and monotherapy (11.3% and 10.1%), and most AEs were mild-to-moderate. The combined incidence of prespecified AEs was lower with irbesartan/HCTZ than with irbesartan (8.8% vs. 11.5%). There were no treatment-related serious AEs or deaths. At week 5, more patients achieved SeDBP < 90 mm Hg compared to irbesartan (47% vs. 33%; P = 0.0005). Despite more rapid and aggressive BP lowering, initial fixed-dose irbesartan/HCTZ demonstrated a comparable AE profile to irbesartan monotherapy in patients with severe hypertension.     

Increasing the doses of both diuretics and angiotensin receptor blockers is beneficial in subjects with uncontrolled systolic hypertension

BACKGROUND:

Blood pressure (BP) control is frequently difficult to achieve in patients with predominantly elevated systolic BP. Consequently, these patients frequently require combination therapy including a thiazide diuretic such as hydrochlorothiazide (HCTZ) and an agent blocking the renin-angiotensin-aldosterone system. Current clinical practice usually limits the daily dose of HCTZ to 25 mg. This often leads to the necessity of using additional antihypertensive agents to control BP in a high proportion of patients.

OBJECTIVES:

To compare the efficacy of two doses of losartan (LOS)/HCTZ combinations in patients with uncontrolled ambulatory systolic hypertension after six weeks of treatment with LOS 100 mg/HCTZ 25 mg (LOS100/HCTZ25).

METHODS:

Following a two- to four-week washout period, subjects with a mean clinic sitting systolic BP of 160 mmHg or higher and a mean ambulatory daytime systolic BP (MDSBP) of 135 mmHg or higher on LOS100/HCTZ25 (n=105; 33 women and 72 men) were randomly assigned to receive LOS 150 mg/HCTZ 25 mg (group 1; n=53) or LOS 150 mg/HCTZ 37.5 mg (LOS150/HCTZ37.5, group 2; n=52). The primary end point was the difference in MDSBP reductions.

RESULTS:

At the end of the six-week treatment period, the respective additional decreases in MDSBP were 1.2 mmHg (P=0.335) on LOS 150 mg/HCTZ 25 mg and 5.6 mmHg (P<0.0001) on LOS150/HCTZ37.5 (difference of 4.4 mmHg; P=0.011). Daytime systolic ambulatory BP goal (lower than 130 mmHg) achievement tended to be higher (25% versus 17%; P=0.313) with LOS150/HCTZ37.5, while it was significantly higher (65% versus 43%; P=0.024) for mean daytime diastolic BP (lower than 80 mmHg). No deleterious metabolic changes were observed.

CONCLUSIONS:

In patients with uncontrolled systolic ambulatory hypertension receiving LOS100/HCTZ25, increasing both HCTZ and LOS dosages simultaneously to LOS150/HCTZ37.5 may be an effective strategy that does not affect metabolic parameters.     

Comparison of acebutolol with and without hydrochlorothiazide versus carvedilol with and without hydrochlorothiazide in black patients with mild to moderate systemic hypertension.

In the present study, we assessed the antihypertensive efficacy of acebutolol 200 mg versus carvedilol 25 mg once daily, given as monotherapy for 3 months to 40 black patients (20 patients in each group, mean age 53+/-10 years, 24 women) with mean blood pressure (BP) during the day >90 and <110 mm Hg. Patients in whom blood pressure could not be controlled took medication, which was increased at 3-month intervals as follows: step 2, acebutolol 200 mg or carvedilol 25 mg plus hydrochlorothiazide 12.5 mg once daily; step 3, acebutolol 400 mg or carvedilol 50 mg plus hydrochlorothiazide 25 mg once daily. Overall, significant but modest BP reduction was achieved with both beta blockers at 3 months. In the acebutolol group, 24-hour BP decreased from 142+/-15/94+/-7 mm Hg to 138+/-16/89+/-8 mm Hg (p<0.005 for diastolic BP at 3 months vs baseline). Mean day BP decreased from 145+/-15/98+/-5 mm Hg to 140+/-14/93+/-7 mm Hg (p<0.05 for systolic BP and p<0.0005 for diastolic BP at 3 months vs. baseline). In the carvedilol group, 24-hour BP decreased from 145+/-11/93+/-6 to 138+/-16/87+/-9 mm Hg (p<0.05 for systolic BP and p<0.005 for diastolic BP at 3 months vs baseline). Mean day BP decreased from 149+/-10/99+/-5 to 141+/-16/91+/-87 mm Hg (p<0.05 for systolic BP and p<0.0005 for diastolic BP at 3 months vs baseline). At 12 months, most patients required combination therapy to achieve BP control. The control (mean day diastolic BP <90 mm Hg) and response (mean day diastolic BP decrease > or =10 mm Hg) rates at 12 months were 59% and 82% in the acebutolol and 78% and 78% in the carvedilol groups, respectively. In conclusion, acebutolol or carvedilol in combination with hydrochlorothiazide, rather than acebutolol or carvedilol alone, should be considered as first-line antihypertensive therapy in black patients with mild to moderate hypertension.     

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.     

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。     

Rapid improvement of nitric oxide bioavailability after lipid-lowering therapy with cerivastatin within two weeks

OBJECTIVES: We investigated whether improvement of endothelial dysfunction in hypercholesterolemia can be achieved with short-term lipid-lowering therapy. BACKGROUND: Impaired endothelium-dependent vasodilation plays a pivotal role in the pathogenesis of atherosclerosis and acute coronary syndromes. METHODS: In a randomized, double-blind, placebo-controlled trial, we studied 37 patients (52 +/- 11 yrs) with low density lipoprotein cholesterol > or = 160 mg/dl (196 +/- 44 mg/dl) randomly assigned to either cerivastatin (0.4 mg/d) or placebo. Endothelium-dependent vasodilation of the forearm vasculature was measured by plethysmography and intra-arterial infusion of acetylcholine (ACh 12, 48 microg/min) and endothelium-independent vasodilation by intra-arterial infusion of nitroprusside (3.2, 12.8 microg/min). RESULTS: Low density lipoprotein cholesterol decreased after two weeks of treatment (cerivastatin -33 +/- 4% vs. placebo + 2 +/- 4%, x +/- SEM, p < 0.001). Endothelium-dependent vasodilation improved after two weeks of therapy with cerivastatin compared with baseline (ACh 12 microg/min: + 22.3 +/- 5.2 vs. + 11.2 +/- 1.9 ml/min/100 ml, p < 0.01; ACh 48 microg/min: +31.2 +/- 6.3 vs. +19.1 +/- 3.1 ml/min/100 ml, p < 0.05). In contrast, changes in forearm blood flow to ACh were similar before and after therapy in the placebo group (ACh 12 microg/min: + 12.9 +/- 3.6 vs. + 9.0 +/- 1.9 ml/min/100 ml, NS; ACh 48 microg/min: +20.7 +/- 3.7 vs. 19.4 +/- 2.9 ml/min/100 ml, NS). Endothelium-dependent vasodilation improved in comparison with placebo (ACh 48 microg/min: +203 +/- 85% [cerivastatin] vs. -26 +/- 71% [placebo], p < 0.05). This improvement in endothelium-dependent vasodilation was no longer observed when the nitric oxide-synthase inhibitor N(G)-monomethyl-L-arginine was coinfused (ACh 48 microg/min + N(G)-monomethyl-L-arginine 4 micromol/min -48 +/- 85% [cerivastatin]). CONCLUSIONS: Short-term lipid-lowering therapy with cerivastatin can improve endothelial function and NO bioavailability after two weeks in patients with hypercholesterolemia.     

Antihypertensive efficacy,safety, and tolerability of the oral direct renin inhibitor aliskiren in patients with hypertension: a pooled analysis

The antihypertensive efficacy and safety of the direct renin inhibitor aliskiren were assessed in a pooled analysis of data from seven randomized, multicenter studies. Data were available for 7,045 patients (mean age 52.5 to 59.8 years, 50.2 to 72.5% men) with mild-to-moderate hypertension (mean sitting diastolic blood pressure [msDBP] 95 to 109 mm Hg) over treatment durations of 6 to 8 weeks. In placebo-controlled trials, aliskiren reduced mean sitting systolic blood pressure/msDBP from baseline by 8.6 to 12.1/7.2 to 10.3 mm Hg (75 mg), 8.7 to 13.0/7.8 to 10.3 mm Hg (150 mg), 14.1 to 15.8/10.3 to 12.3 mm Hg (300 mg), and 15.7 to 15.8/11.5 to 12.5 mm Hg (600 mg), compared with 2.9 to 10.0/3.3 to 8.6 mm Hg for placebo. Aliskiren demonstrated comparable efficacy in men and women, in patients aged <65 years or ≥65 years, and lowered blood pressure (BP) effectively in all racial subgroups. Combination of aliskiren 150 mg or 300 mg with ramipril, amlodipine, or hydrochlorothiazide provided significant additional BP reductions compared with the respective monotherapies. The overall incidence of adverse events with aliskiren monotherapy was similar to placebo (39.8% vs. 40.2%, respectively). The incidence of diarrhea with aliskiren was higher than placebo due to a significantly higher rate with aliskiren 600 mg (P < .0001 vs. placebo). In conclusion, aliskiren 150 mg or 300 mg provides highly effective and consistent BP lowering with placebo-like tolerability in patients with mild-to-moderate hypertension.     

Blood Pressure Control by Drug Group in the Antihypertensive and Lipid‐Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)

Blood pressure (BP) control rates and number of antihypertensive medications were compared (average follow‐up, 4.9 years) by randomized groups: chlorthalidone, 12.5–25 mg/d (n=15,255), amlodipine 2.5–10 mg/d (n=9048), or lisinopril 10–40 mg/d (n=9054) in a randomized double‐blind hypertension trial. Participants were hypertensives aged 55 or older with additional cardiovascular risk factor(s), recruited from 623 centers. Additional agents from other classes were added as needed to achieve BP control. BP was reduced from 145/83 mm Hg (27% control) to 134/76 mm Hg (chlorthalidone, 68% control), 135/75 mm Hg (amlodipine, 66% control), and 136/76 mm Hg (lisinopril, 61% control) by 5 years; the mean number of drugs prescribed was 1.9, 2.0, and 2.1, respectively. Only 28% (chlorthalidone), 24% (amlodipine), and 24% (lisinopril) were controlled on monotherapy. BP control was achieved in the majority of each randomized group—a greater proportion with chlorthalidone. Over time, providers and patients should expect multidrug therapy to achieve BP <140/90 mm Hg in a majority of patients.