Which anti-hypertensive to add to a beta-blocker: ACE inhibitor or diuretic?

Thirty-eight patients already treated with atenolol 50 mg once daily were randomly assigned to treatment with either hydrochlorothiazide (12.5-25 mg once daily) or lisinopril (10-20 mg once daily) for 8 weeks in a double-blind crossover study. Eight weeks' treatment with the combination of ACE inhibitor and beta-blocker or the diuretic and beta-blocker produced falls in blood pressure (lying: -8.4 +/- 15.4/ -7.3 +/- 80 mmHg and -6.1 +/- 15.3/ -5.2 +/- 8.8 mmHg [mean +/- SD] for lisinopril and hydrochlorothiazide respectively; standing: -10.2 +/- 14.2/8.2 +/- 9.2 mmHg and -6.8 +/- 14/ -6.3 +/- 10.3 mmHg for lisinopril and hydrochlorothiazide respectively) which were not statistically significantly different. Heart rate was significantly increased on the combination of beta-blocker and diuretic (lying: +4.3 +/- 10.7; standing: +3.2 +/- 10.0 beats/min) compared with a fall on beta-blocker+ACE inhibitor (lying; -0.5 +/- 7.6; standing: -1.5 +/- 7.4). Both therapeutic regimens were equally well tolerated. These results suggest that where patients fail to respond to monotherapy with a beta-blocker the addition of an ACE inhibitor may be as effective as the more traditional option of diuretic therapy.     

A double blind comparison of perindopril and atenolol in essential hypertension

A multicentre randomised double-blind trial was performed in order to compare the therapeutic efficacy and acceptability of the angiotensin converting enzyme (ACE) inhibitor perindopril with those of atenolol in mild to moderate hypertension. After one month of placebo, 173 patients with supine diastolic blood pressure (DBP) between 95 and 125 mmHg were randomised to receive perindopril 4 mg once daily or atenolol 50 mg once daily. Monthly assessments were made for three months. Treatment was adjusted at these visits if supine DBP was greater than 90 mmHg; the dose was first doubled (8 mg perindopril or 100 mg atenolol once daily) and then hydrochlorothiazide was added. The pretreatment blood pressure levels were similar in both groups. Supine DBP was 105.5 +/- 0.9 mmHg (n = 85) in the perindopril group and 106.9 +/- 0.9 mmHg (n = 88) in the atenolol group. At the end of the third month, the study target blood pressure (supine DBP less than or equal to 90 mmHg) was achieved in a significantly (P = 0.006) larger percentage of patients in the perindopril group (78%) than in the atenolol group (58%). This appeared to be due to a greater potentiation of the antihypertensive effect by the addition of diuretic to perindopril than to atenolol. The fall in systolic blood pressure was significantly greater in the perindopril group than in the atenolol group (supine: 26.5 +/- 2.0 mmHg vs. 20.6 +/- 2.0 mmHg; P = 0.042) although the fall in DBP was comparable (supine: perindopril 17.4 +/- 0.9 mmHg, atenolol 15.6 +/- 1.1 mmHg; P = 0.195).(ABSTRACT TRUNCATED AT 250 WORDS)     

Atenolol or propranolol in hypertensive patients poorly controlled on captopril and frusemide

Eighteen patients whose clinic blood pressure (BP) remained over 95 mmHg despite treatment with captopril 50 mg twice daily plus frusemide 40 mg twice daily were randomised in a crossover study to four weeks' treatment with once daily atenolol 100 mg, slow release propranolol 160 mg or placebo. The reduction in BP on atenolol was superior to that on both propranolol and placebo. The mean supine BP 24 hours post dosing were 177/110 mmHg (placebo), 173/109 mmHg (propranolol) and 164/100 mmHg (atenolol). The corresponding mean heart rates were 77 bpm (placebo), 63 bpm (propranolol) and 62 bpm (propranolol) and 62 bpm (atenolol). The difference in hypotensive efficacy between atenolol and propranolol is not readily explained but our study shows that atenolol has a clinically useful supplementary effect on BP. Refractory hypertension remains an important clinical problem and further studies are required to establish the optimum combination of drugs that should be used with captopril in order to achieve 'target' BP in patients with moderate to severe hypertension.     

The efficacy and tolerability of losartan versus atenolol in patients with isolated systolic hypertension. Losartan ISH Investigators Group

OBJECTIVE: To compare the efficacy and tolerability of angiotensin II (Ang II) antagonist losartan and the beta-blocker atenolol in the treatment of patients with isolated systolic hypertension (ISH) after 16 weeks of treatment. METHODS: A double-blind, randomized, multi-country study was carried out in 273 patients with ISH. Patients with a sitting systolic blood pressure (SiSBP) of 160-205 mmHg, and a sitting diastolic blood pressure (SiDBP) < 90 mmHg at screening and at placebo baseline were subjected to a 4-week placebo period and then randomly grouped to receive 50 mg losartan or 50 mg atenolol once daily for 16 weeks. At 8 and 12 weeks, patients not controlled (SiDBP > or = 160 mmHg) were given additional treatment of 12.5 mg hydrochlorothiazide (HCTZ) once daily. RESULTS: Similar significant reductions in SiSBPs (mean +/- SD) were obtained with 50 mg losartan and 50 mg atenolol, from 173.7 +/- 10.3 and 173.5 +/- 10.7 mmHg at baseline to 149.0 +/- 15.5 and 148.2 +/- 15.3 mmHg after 16 weeks of losartan or atenolol treatment respectively. Sixty-seven percent of the losartan-treated and 64% of the atenolol-treated patients remained on monotherapy throughout the study. Only 1.5% of the losartan-treated patients withdrew because of a clinical adverse event (CAE) compared with 7.2% in the atenolol-treatment group (P= 0.035). Drug-related CAEs were observed significantly more frequently with atenolol than with losartan treatment (20.3 versus 10.4%; P = 0.029). CONCLUSION: It is concluded that 50 mg losartan and 50 mg atenolol produced comparable reductions in SiSBP in patients with ISH but losartan was better tolerated. This is the first demonstration of the therapeutic value of selective Ang II receptor blockade with losartan in the treatment of ISH.     

Comparative trial of nifedipine retard and atenolol in the treatment of elderly patients with mild to moderate hypertension

Forty-one elderly patients with mild to moderate hypertension (resting diastolic blood pressure 100-130 mmHg after an eight week placebo run-in phase) were randomised to a double-blind parallel group comparison of nifedipine retard 10 mg twice daily or atenolol 50 mg once daily. If the resting diastolic pressure exceeded 95 mmHg after four weeks of treatment the dose(s) were doubled for a further four weeks. Initial sitting blood pressures were 187 +/- 21/105 +/- 5 mmHg in the nifedipine group and 181 +/- 19/106 +/- 6 in the atenolol group. At four weeks, eight patients given nifedipine and nine given atenolol had their doses doubled. At eight weeks sitting blood pressures were 159 +/- 19/85 +/- 7 and 162 +/- 21/87 +/- 8 respectively, with 18/20 patients given nifedipine and 16/21 given atenolol having a sitting diastolic pressure equal to or less than 95 mmHg. One patient given nifedipine was withdrawn because of unacceptable ankle oedema and one given atenolol withdrawn because of worsening angina. Both drugs were equally acceptable to the patients and neither caused a change in their sense of well-being.     

Beneficial effect of lisinopril plus telmisartan in patients with type 2 diabetes, microalbuminuria and hypertension

Angiotensin-converting enzyme (ACE) inhibitors have favourable effects on hypertension and diabetic nephropathy, but persistent use may result in incomplete blockade of the renin-angiotensin system. Long-term effects of dual blockade using the ACE inhibitor lisinopril and the long-acting angiotensin II receptor blocker (ARB) telmisartan on blood pressure and albumin excretion rate (AER) were evaluated. Patients with type 2 diabetes mellitus, hypertension (systolic blood pressure [SBP] >or=140 mmHg or diastolic blood pressure [DBP] >or=90 mmHg) and microalbuminuria (AER 30-300 mg/24h) received 20mg of lisinopril or 80 mg of telmisartan once a day for 24 weeks. Patients were then randomised to continuing treatment with the respective monotherapy or with lisinopril plus telmisartan for a further 28 weeks. Significant (P<0.001) declines in SBP (11.1 mmHg versus 10.0 mmHg), DBP (5.6 mmHg versus 5.3 mmHg) and AER (98 mg/24 h versus 80 mg/24 h) were achieved with lisinopril (n=95) or telmisartan (n=97), respectively, after 24 weeks. Subsequent treatment with lisinopril plus telmisartan for 28 weeks resulted in further significant reductions (P<0.001) in SBP, DBP and AER compared with either monotherapy. All treatments were well tolerated. Lisinopril plus telmisartan thus provides superior blood pressure and AER control than either monotherapy. We conclude that use of dual blockade may provide a new approach to prevention of diabetic nephropathy in patients with type 2 diabetes, hypertension and microalbuminuria.     

Sustained antihypertensive actions of a dual angiotensin-converting enzyme neutral endopeptidase inhibitor, sampatrilat, in black hypertensive subjects.

Our objective was to evaluate the safety and antihypertensive efficacy of sampatrilat, a novel dual inhibitor of both angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP), in subjects poorly responsive to ACE inhibitor monotherapy. The ability of sampatrilat (50 to 100 mg daily) (n = 28) to lower blood pressure was compared with that of the ACE inhibitor lisinopril (10 to 20 mg daily) (n = 30) using a double-blind, randomized, parallel group study design over a 56-day treatment period in black hypertensives. Changes in systolic (SBP) and diastolic (DBP) blood pressure were determined using repeated ambulatory blood pressure (ABP) monitoring. Both sampatrilat and lisinopril decreased plasma ACE concentrations after 28 and 56 days. The decrease in plasma ACE concentrations (U/L) was greater after lisinopril (-9.33 +/- 0.52) as compared with sampatrilat (-6.31 +/- 0.70) (P = .0001) therapy. Lisinopril, but not sampatrilat, increased plasma renin activity. Lisinopril produced a transient decrease in mean 24-h ABP (mm Hg) at 28 days (SBP = -9.0 +/- 2.3, DBP = -5.7 +/- 1.3; P < .01), which returned to pretreatment values by 56 days of therapy. Alternatively, sampatrilat produced a sustained decrease in mean ABP over the 56-day treatment period (day 28: SBP = -7.3 +/- 1.8, DBP = -5.2 +/- 1.2; P < .01: day 56: SBP = -7.8 +/- 1.5; DBP = -5.2 +/- 0.95; P < 0.01) with a greater treatment effect on DBP than that of lisinopril at day 56 (P = .05). Treatment-emergent adverse events were noted to be similar between both treatment groups. We conclude that the antihypertensive actions of ACE/NEP inhibitor monotherapy in black subjects offers a novel therapeutic approach to patients otherwise resistant to the sustained antihypertensive actions of ACE inhibitor monotherapy.     

Effect of indomethacin on the antihypertensive efficacy of valsartan and lisinopril: a multicentre study

OBJECTIVE : To compare the effect on antihypertensive efficacy produced by the addition of indomethacin to the angiotensin II (Ang II) antagonist, valsartan, or to the angiotensin-converting enzyme inhibitor, lisinopril, in hypertensive patients with chronic osteoarthritis. SUBJECTS AND METHODS : One hundred and twenty-eight patients (52 men and 76 women) aged 25-82 years (mean age 55.7 years), with diastolic blood pressure (DBP) > 100 mmHg at the end of a 2-week placebo washout period were allocated randomly to groups to receive valsartan (80-160 mg once daily) or lisinopril (10-20 mg once daily). At the end of 10 weeks of treatment, patients with DBP < 90 mmHg, while continuing to receive valsartan or lisinopril treatment, were allocated randomly to groups to receive either indomethacin (50 mg three times a day) or the corresponding placebo for 2 weeks, with a 1-week washout period between the two treatments, according to a double-blind, crossover design. After the initial washout period, patients were examined at the end of the 4th, 8th and 10th weeks of randomized treatment with valsartan and lisinopril, at the end of the first crossover period and then at the beginning and at the end of the second crossover period. At each visit, sitting and standing blood pressure were measured by standard mercury sphygmomanometer. RESULTS : The addition of indomethacin blunted the blood pressure-decreasing effect of both antihypertensive drugs. Although indomethacin produced greater increases in both systolic and DBP values in the lisinopril-treated patients (5.45/3.22 mmHg) than in the valsartan-treated ones (2.12/1.87 mmHg), no significant difference between the two drugs was found. CONCLUSIONS : From a theoretical standpoint, these findings suggest that prostaglandins may play a part in the antihypertensive action of Ang II antagonists. From a practical standpoint, hypertensive patients treated with valsartan or with lisinopril should be monitored to detect changes in blood pressure control while receiving indomethacin.     

Weighted Fourier analysis of blood pressure curves after lisinopril versus atenolol administration in young hypertensives

OBJECTIVE: To evaluate and compare the effects of lisinopril versus atenolol administration on the diurnal blood pressure profile and the nocturnal blood pressure fall in young mild-to-moderate essential hypertensives.METHODS: Thirty patients were studied. After a 2-week placebo run-in period, they were single-blind randomly assigned to receive 20 mg lisinopril or 100 mg atenolol. Using a SpaceLabs 90207 device, their ambulatory blood pressure was measured before and after 12 weeks of therapy. The readings were analysed using Fourer series with four harmonics. RESULTS: Lisinopril and atenolol administration significantly decreased office and ambulatory blood pressure values compared with the placebo period. The daily blood pressure curves obtained from Fourier analysis showed that the circadian rhythm was not altered by lisinopril and atenolol administration. From the night:day ratio for the nocturnal blood pressure fall, we found that atenolol administration minimized the average night-time blood pressure dip by increasing the number of non-dippers. In contrast, lisinopril administration did not modify the day-night difference, preserving the nocturnal blood pressure fall. CONCLUSION: Lisinopril and atenolol administration as a first-step treatment of young essential hypertensives produced comparable degrees of diurnal control of arterial pressure. The blood pressure fall at night in patients treated with atenolol was slightly less than that found with lisinopril treatment.     

A double-blind study of the blood pressure lowering effect of a thiazide diuretic in hypertensive patients already on nifedipine and a beta-blocker

Twelve hypertensive patients who were already on treatment with atenolol (100 mg once daily) and nifedipine as tablets (20 mg twice daily) were entered into a double-blind, randomized crossover study of the addition of 1 month's treatment with either bendrofluazide (5 mg once daily) or a matching placebo. The addition of bendrofluazide to the combination of atenolol and nifedipine did not cause any statistically significant fall in the blood pressure 2 h after the last dose of nifedipine compared to treatment with placebo [bendrofluazide: 135.2 +/- 5.1/89.8 +/- 2.5 (mean +/- s.e.), versus placebo: 132.1 +/- 4.6/89.9 +/- 3.1 mmHg; P = NS]. However, 12 hours after the last dose of nifedipine blood pressure tended to be lower whilst on bendrofluazide compared with placebo. Plasma urate levels were significantly higher on the diuretic compared to placebo (461 +/- 27 versus 396 +/- 21 mumol P less than 0.001). Plasma potassium was lower on the diuretic compared to placebo (3.59 +/- 0.12 vs 3.76 +/- 0.10) but this difference just failed to reach statistical significance. The results of this study suggest that a thiazide diuretic has little additive effect on blood pressure in patients already on treatment with atenolol and nifedipine, particularly when nifedipine is maximally effective. However, the addition of a diuretic does have potentially deleterious metabolic effects.     

24-hour efficacy of once-daily diltiazem in essential hypertension.

The safety and effectiveness of a once daily formulation of diltiazem hydrochloride (diltiazem CD) in the treatment of essential hypertension was assessed in a total of 127 patients with supine diastolic blood pressures (DBP) of 95 to 110 mmHg randomized to diltiazem CD (n = 61) or placebo (n = 66). Patients were titrated to doses of 120, 240, or 360 mg to achieve DBP reduction to less than 90 mmHg. At end study diltiazem CD changed trough supine SBP and DBP by -8.4 +/- 1.7 (p = 0.0009) and -8.6 +/- 1.1 mmHg (p = 0.0075), respectively. Heart rate was not significantly changed (-1.3 +/- 1.1 beats/min, p = 0.4362). The average dose of diltiazem CD was 268 mg with 69% achieving a clinical response. A subset of 47 patients underwent ambulatory blood pressure monitoring to assess the consistency of the effect over the full 24-h dosing interval. Diltiazem CD lowered DBP and SBP throughout the dosing interval. The overall side effect profile was similar to placebo. This study provides evidence of 24-h efficacy of this new, once daily formulation of diltiazem.     

Lisinopril and enalapril in hypertension: a comparative study using ambulatory monitoring

Detecting differences in the effect of two antihypertensive agents is bedevilled by the inherent variability of blood pressure itself. Using an ambulatory blood pressure monitoring technique, we compared, in a cross-over design study, the effects of four weeks' treatment with enalapril, 10 mg once daily, to lisinopril, 10 mg once daily, on the blood pressure of 19 patients with mild to moderate hypertension. A significant reduction in blood pressure was shown by both drugs. However, lisinopril produced a greater fall in mean 24 hour systolic pressure than did enalapril (difference; 5.94 (C.I. -0.77 to -11.1) mmHg, P = 0.027). The difference of 3.3 mmHg (C.I. +0.54 to -7.10) in diastolic pressure between the two agents, though in the same direction, was not significant. Plasma renin activity did not predict the responses to either agent. Studying the prevailing information for these two drugs one might expect there to be little difference between them when administered once daily in terms of antihypertensive effect. The explanation for the superiority of lisinopril may lie in the slightly longer pharmacokinetic half-life and possibly in differences in tissue distribution or persistence. The side effects of both drugs were mild and of similar frequency to those recorded during placebo treatment, illustrating the generally well tolerated nature of this class of antihypertensive therapy. The use of ambulatory blood pressure monitoring provides a method that can detect small, but possibly important differences between drugs. In the clinical setting it allows a more thorough assessment of a particular patient's response to therapy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Felodipine in elderly hypertensives. Dutch GP Multicentre Study Group

Elderly hypertensive patients (n = 52), with a supine diastolic blood pressure (DBP) greater than or equal to 100 mmHg, were randomised to four weeks' double-blind, parallel-group treatment with felodipine or placebo in order to compare the antihypertensive efficacy and tolerability of these compounds. The starting dose of felodipine was 2.5 mg twice daily, which was increased to 5 mg twice daily after two weeks' treatment if the supine DBP was still greater than 95 mmHg. In the felodipine group, mean supine blood pressure (BP) was reduced from 176/101 to 167/92 and 165/88 mmHg after two and four weeks, respectively. The corresponding figures in the placebo group were a reduction from 177/103 to 174/102 and 172/98 mmHg. The difference in reduction in DBP between the groups was statistically significant. The proportion of responders was also significantly greater in the felodipine group. The dose-increase was performed in 34% of the patients on felodipine and in 69% of the patients on placebo. Both treatments were well tolerated, and only one patient was withdrawn from the felodipine group and two from the placebo group. Ankle swelling was the most common adverse event of felodipine.     

Diltiazem compared with metoprolol as add-on-therapies to diuretics in hypertension. Swedish Diltiazem-Metoprolol Multicentre Study Group

In a randomized, double-blind, parallel group study, diltiazem was compared with metoprolol as add-on therapy to diuretic treatment in 115 patients with hypertension. Following a placebo and diuretic period of four weeks, patients were randomized to either slow release diltiazem 90 mg twice daily or metoprolol 100 mg once daily using a double dummy technique. If after four weeks a target supine diastolic blood pressure (DBP) less than or equal to 90 mmHg pressure was not reached, the doses of diltiazem and metoprolol were doubled. Supine inclusion systolic/diastolic blood pressures (SBP/DBP) at randomization were 158 +/- 13 (mean +/- SD)/102 +/- 5 mmHg in the diltiazem group and 158 +/- 17/101 +/- 6 mmHg in the metoprolol group. Active therapy significantly lowered SBP and DBP in both groups by 7-10%. Heart rate was significantly lowered in both groups, although the effect of metoprolol was more pronounced. Response rates (supine DBP less than or equal to 90 mmHg and/or decreased by greater than or equal to 10%) were 43% on diltiazem 90 mg twice daily and 52% on metoprolol 100 mg once daily, increasing to 82% and 62%, respectively, after dose escalations. No serious side effects were seen, but three patients, two on diltiazem and one on metoprolol, were withdrawn from the study due to severe headache, nausea and bradycardia respectively. of mild to moderate adverse reactions, tiredness was most frequent, occurring in 14.5% and 15.8% on active diltiazem and metoprolol therapy, respectively. We conclude that both diltiazem and metoprolol lower BP when added to diuretics in hypertensive patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

非洛地平与赖诺普利的降压效应及对左室肥厚逆转作用的对比

目的：评价并比较非洛地平及赖诺普利治疗轻、中度原发性高血压（ＥＨ）的降压疗效及对左心室肥厚的逆转作用。方法：选择１２８例轻、中度ＥＨ患者,入选前服用安慰剂２周,随机分为非洛地平组６６例和赖诺普利组６２例。非洛地平组服用非洛地平５～１０ｍｇ／ｄ,赖诺普利组服用赖诺普利１０～２０ｍｇ／ｄ,每日１次,疗程２４周。两组均在治疗前及治疗后的２、１２、２４周分别进行偶测血压、２４ｈ动态血压及超声心动图检查。结果：非洛地平和赖诺普利均能显著降低血压,两药对偶测血压的下降幅度差异无显著性（Ｐ＞０．０５）。非洛地平能有效控制清晨高峰期血压。收缩压、舒张压的谷／峰比值分别是７２％、６７％。非洛地平降低２４ｈ平均血压和白昼血压的幅度大于赖诺普利,而夜间血压降低的幅度显著低于白昼。两药治疗２４周后,室间隔厚度、左心室后壁厚度、左室心肌重量及左室重量指数较治疗前显著改善（Ｐ＜０．００１）。两组药物副反应均较轻。结论：非洛地平能有效降低ＥＨ患者的血压,降低靶器官损害的危险性。     

Antihypertensive effect of valsartan 80 mg and hydrochlorothiazide 12.5 mg evaluated by ambulatory blood pressure monitoring

OBJECTIVE: The aim of the study was to evaluate by ambulatory blood pressure measurement (ABPM) the 24 hours antihypertensive efficacy of the fixed combination therapy, valsartan 80 mg + hydrochlorothiazide 12.5 mg (V + H), once daily, after 6 weeks of treatment, in patients with mild to moderate hypertension. STUDY DESIGN: It was a French, multicenter, double blind, randomized trial in parallel groups comparing V + H and placebo. After an initial two weeks placebo period, patients were assigned to receive either V + H or placebo for six weeks. Were eligible those with clinical arterial blood pressure, measured by sphygmomanometer, between 160/95 and 209/114 mmHg after monotherapy. A 26 hours ABPM, with Spacelabs 90,207, was done at J0 and J42 (one measurement every 15 minutes, in day time and at night). Responders were defined as a fall in day diastolic blood pressure > or = 5 mmHg and/or day diastolic blood pressure < 90 mmHg with ABPM. RESULTS: 123 of the 138 randomized patients had two interpretative measurements. Their average age was 59 + 10 years. 57% (78) of them were males and their average ABPM before treatment was 143 +/- 15/88 +/- 11 mmHg. With V + H, the reduction of the systolic and the diastolic blood pressure measured by ABPM, was significantly more important than with placebo (SBP: -15.4 +/- 10.9 mmHg versus -0.6 +/- 7.7 mmHg, p < 0.001; DBP: -9.1 +/- 7 mmHg versus -0.4 +/- 5.4 mmHg, p < 0.001). Pulse pressure (PP) was also significantly reduced with the combination therapy V + H, but it was not modified with placebo (-6.3 + 5.5 mmHg versus -0.2 + 4.1 mmHg, p < 0.001). ABPM responder rate was 73% with V + H versus 24% with placebo (p < 0.001). Trough/peak ratio was 80.3% for systolic blood pressure and 57.3% for diastolic blood pressure. The combination V + H was as well tolerated as placebo. CONCLUSION: The fixed combination V + H used for treatment of hypertension, after failure of monotherapy, is very effective in reducing pulse pressure, systolic and diastolic blood pressure, over 24 hours, homogeneously, and is as well tolerated as placebo.     

Differential effects of the angiotensin-converting enzyme inhibitor lisinopril versus the beta-adrenergic receptor blocker atenolol on hemodynamics and left ventricular contractile function in experimental mitral regurgitation

OBJECTIVES: The goal of this study was to determine the therapeutic efficacy of angiotensin-converting enzyme (ACE) inhibitors and beta-adrenergic receptor blockers in experimental chronic mitral regurgitation (MR), gaining knowledge using methods difficult to apply in humans. BACKGROUND: Both ACE inhibitors and beta-blockers are cornerstones in the treatment of human congestive heart failure. However, the roles of these treatments for chronic MR is unclear. METHODS: Mitral regurgitation was created in 11 closed-chest dogs. Three months after the creation, the ACE inhibitor lisinopril 20 mg was given orally daily. After three months of lisinopril therapy, the beta-blocker atenolol was added to lisinopril for another three months. Atenolol was begun at a dose of 12.5 mg daily and increased gradually to 100 mg daily. Hemodynamics and left ventricular (LV) function were assessed throughout the study. RESULTS: Regurgitant fraction was consistently >50% over the course of this study. Pulmonary capillary wedge pressure and LV end-diastolic pressure were significantly increased after three months of MR and decreased during both lisinopril and the combined therapy in which it was not different from baseline. Left ventricular contractility measured by the end-systolic stiffness constant was depressed from 3.66 +/- 0.20 to 2.65 +/- 0.12 (p < 0.05) at three months of MR and rose insignificantly after lisinopril treatment (2.99 +/- 0.17). When atenolol was added, it rose significantly and returned to normal (3.50 +/- 0.22, p < 0.05). CONCLUSIONS: Although lisinopril significantly reduced preload, its effect on LV contractility was insignificant in experimental MR. Conversely, atenolol, when added to lisinopril, achieved maximum hemodynamic benefit and also restored LV contractility.     

Adding hydrochlorothiazide to olmesartan dose dependently improves 24-h blood pressure and response rates in mild-to-moderate hypertension

OBJECTIVE: To test whether adding hydrochlorothiazide (HCTZ) (12.5 or 25 mg) to olmesartan 20 mg improves 24-h blood pressure in patients whose conventional diastolic blood pressure is inadequately controlled by olmesartan monotherapy. PATIENTS: Male and female patients > or = 18 years with mean sitting diastolic blood pressure (DBP) of 100-115 mmHg, mean sitting systolic blood pressure (SBP) greater than 150 mmHg, mean 24-h DBP of at least 84 mmHg, and at least 30% of DBP daytime readings > 90 mmHg. INTERVENTIONS: Four weeks of single-blind treatment with olmesartan 20 mg once daily, followed in non-responders by 8 weeks of randomized double-blind treatment with placebo or HCTZ (12.5 or 25 mg) once-daily, added to olmesartan. RESULTS: HCTZ 25 mg added to olmesartan 20 mg decreased mean daytime DBP significantly more (P = 0.0012) than placebo added to olmesartan 20 mg. Compared to olmesartan monotherapy, mean 24-h DBP and SBP were significantly reduced by combination therapy with olmesartan/HCTZ 20/12.5 mg (-1.9 mmHg, P = 0.0167 and -3.9 mmHg, P = 0.0018, respectively) and 20/25 mg (-3.7 and -7.4 mmHg respectively, P < 0.0001 for both). Mean 24-h DBP and SBP and mean night-time SBP reductions were significantly greater for HCTZ 25 mg than for HCTZ 12.5 mg. Response rates (mean daytime DBP assessed by ambulatory blood pressure measurement < or = 85 mmHg) approximately doubled following the addition of HCTZ (12.5 mg = 57.6% and 25 mg = 69.5%). CONCLUSION: Combination of olmesartan 20 mg with HCTZ provides significantly better 24-h blood pressure reduction than olmesartan monotherapy in patients with mild-to-moderate hypertension. Moreover, increasing the dose of HCTZ from 12.5 to 25 mg is a reasonable step to reach better daytime and night-time blood pressure control.     

Treatment with irbesartan or atenolol improves endothelial function in essential hypertension

OBJECTIVES: To investigate if antihypertensive treatment could improve endothelium-dependent vasodilatation in hypertensive patients, and whether the angiotensin II subtype-1 (AT1)-receptor antagonist irbesartan and the beta1-receptor antagonist atenolol would differ in this respect. SUBJECTS AND METHODS: Thirty-four patients (28 men and six women) with mild-to-moderate essential hypertension (diastolic blood pressure 90-120 mmHg) were randomized to once daily 150-300 mg irbesartan or 50-100 mg atenolol in a double-blind fashion, preceded by a placebo run-in period. Forearm blood flow (FBF) was assessed by venous occlusion plethysmography during local intra-arterial infusions of methacholine and sodium nitroprusside, to evaluate endothelium-dependent and endothelium-independent vasodilatation, respectively. Measurements of FBF were undertaken at the end of the run-in placebo period and repeated after 3 months of active antihypertensive treatment. RESULTS: Irbesartan and atenolol induced a similar decline in blood pressure (from 171/107 to 158/98 mmHg, P < 0.05), and improved endothelium-dependent vasodilatation (e.g. an increase in FBF response to 4 microg/min methacholine from 325 +/- 29% to 411 +/- 41%, P < 0.05), with no difference between the two study drugs. No significant changes in endothelium-independent vasodilatation were induced by irbesartan or by atenolol. CONCLUSIONS: The present study shows that 3 months of antihypertensive therapy with irbesartan or atenolol improves endothelium-dependent vasodilatation.     

Quality of life, side effects and efficacy of lisinopril compared with metoprolol in patients with mild to moderate essential hypertension.

In a double-blind, parallel-group multicentre study in general practice, lisinopril (10-20 mg once daily) was compared with metoprolol (100-200 mg once daily) in 360 patients whose diastolic blood pressure (DBP) was in the range 91-115 mmHg despite diuretic treatment. Following a three week run-in period during which the diuretic was withdrawn, monotherapy with either lisinopril or metoprolol was given for two months with dose doubled after one month if DBP remained greater than 90 mmHg. Quality of life was assessed using established and validated questionnaires at the time of cessation of diuretic treatment and again after two months's active treatment. Both metoprolol and lisinopril achieved statistically significant BP reduction relative to baseline (P less than 0.001). Significantly fewer adverse events were experienced on lisinopril and metoprolol than on diuretic treatment. Frequency of withdrawals due to adverse events were statistically significantly lower on lisinopril than metoprolol P = 0.01. Before treatment approximately 35% of the patients had quality of life problems measured by General Health Questionnaire (GHQ), which was reduced to 17% on lisinopril and 23% on metoprolol. Thus both metoprolol and lisinopril were effective and safe in the treatment of mild to moderate essential hypertension with lisinopril being better tolerated. From patients' self-assessments of quality of life, lisinopril was found to be superior to metoprolol in some aspects of emotional, cognitive and social functioning.