Clinical evaluation of amlodipine, a new long-acting calcium antagonist, in mild and moderate hypertension.

The antihypertensive efficacy of amlodipine was studied in 22 patients (16 female, six male) with mild-to-moderate hypertension. Following an initial two-week placebo run in, patients with a sitting diastolic blood pressure in the range 95-115 mmHg (12.7-15.3 kPa) began the 12-week active treatment phase with amlodipine at a dose of 5 mg once daily. If the sitting diastolic blood pressure was not reduced to less than or equal to 90 mmHg (12.0 kPa) after four weeks' treatment, the amlodipine dose could be adjusted to 10 mg once daily. The final four weeks of active treatment comprised of a maintenance phase during which the dose, which had produced the desired therapeutic response in each patient, remained constant. At the end of the trial, 18 patients (85.7%) were classified as therapeutic successes (reduction in diastolic blood pressure to less than or equal to 90 mmHg [12.0 kPa] with a greater than or equal to 5 mmHg [0.7 kPa] from baseline values or a greater than or equal to 10 mmHg [1.3 kPa] decrease from baseline). Of these patients, 16 received the 5 mg dose throughout the study and only two required an increase to 10 mg once daily. Patients generally tolerated amlodipine treatment well.     

Is initial dose titration of amlodipine worthwhile in patients with mild to moderate hypertension?

Amlodipine, a dihydropyrimidine calcium antagonist, is effective in the treatment of patients with mild to moderate hypertension at doses of 5-10 mg daily. The aim of the study reported here was to determine whether an early increase in dosage of amlodipine provided an advantage in terms of antihypertensive effect. This was a single-blind, randomised study in 115 patients with mild to moderate hypertension (diastolic blood pressure 95-114 mmHg) conducted at 10 centres with two parallel groups. Group I received amlodipine 5 mg once daily for the entire 10-week treatment period, while group II received amlodipine 5 mg once daily for two weeks, with the option to increase the dose to 10 mg once daily were the diastolic blood pressure to exceed 90 mmHg. The dose was increased in 40% of group II patients (20/50). Diastolic and systolic blood pressure decreased steadily until the end of the sixth week of treatment in both groups, with no statistically significant difference between the groups. The response rate (diastolic blood pressure < or = 90 mmHg) at the end of treatment was 84% in both groups. Because there is no advantage in an early increase in dosage of amlodipine in terms of antihypertensive effect, a dose increase should not be considered until after six weeks of treatment at 5 mg once daily.     

The relationship between terazosin dose and blood pressure response in hypertensive patients

A double-blind, randomized, placebo-controlled, multicenter study was conducted to describe the dose-response curve for terazosin on blood pressure. A total of 128 patients with mild to moderate essential hypertension (supine diastolic blood pressure, 100 to 114 mmHg) participated in the study. The study consisted of a 4-week single-blind placebo lead-in period and a 14-week double-blind treatment period. Patients were randomized in equal numbers to four parallel treatment groups: terazosin 1, 2, and 5 mg; terazosin 2, 5, and 10 mg; terazosin 20, 40, and 80 mg; and placebo. The 24-hour ambulatory blood pressure measurements were performed at the end of the placebo lead-in period and at the end of each 4-week fixed-dose period. The nonlinear, mixed-effect model computer program was used to analyze the dose-response relationship. There was a strong dose-response relationship between fall in blood pressure and the 1 to 10 mg terazosin dose, as well as a plateauing of response for terazosin doses above 10 mg. The maximum antihypertensive response (Emax) to terazosin was 10.7 mmHg for systolic blood pressure and 8.0 mmHg for diastolic blood pressure. The daily dose of terazosin, which produced 50% of the maximum response (ED50), was 3.0 mg for systolic blood pressure and 1.5 mg for diastolic blood pressure. The results of this study suggest that although some patients may benefit from terazosin doses of greater than 10 mg, doses up to 10 mg will maximize therapeutic benefit for most patients, with acceptable side effects.     

Review of three studies to determine the efficacy and tolerance of cicletanine in the short- and long-term treatment of essential hypertension

A double-blind multicentre study was performed initially to assess the effect of 4 weeks' treatment of cicletanine in daily doses of 12.5, 25, 50 and 100 mg, for the treatment of 60 patients with mild to moderate essential hypertension. A significant reduction in blood pressure was achieved with each dosage. Analysis of the responder rate indicated a significant dose-response relationship which was clinically relevant only for the 50 and 100 mg doses. The minimum therapeutic dosage of cicletanine for the treatment of essential hypertension was concluded to be 50 mg daily. A further 12-week study was performed in 40 patients with mild to moderate essential hypertension, commencing with a daily dose of cicletanine (50 mg) and increasing the dosage if necessary to 100 mg and 200 mg daily after 4 and 8 weeks, respectively. Blood pressure control was achieved in all patients and in the majority (70%) with a daily dosage of 100 mg cicletanine. Treatment was continued in all patients until a total duration of 2 years had been completed. Cicletanine was shown to be very well tolerated and a significant reduction in blood pressure was achieved at 6, 9, 12, 18 and 24 months. During the second year of treatment, all the patients were stabilized with a daily dosage of 50 mg cicletanine. These results are consistent with a previously reported study in 25 patients with mild to moderate essential hypertension. Twelve weeks of treatment with cicletanine (50 mg daily) produced a significantly greater reduction in blood pressure than a combination of 5 mg amiloride hydrochloride and 50 mg hydrochlorothiazide daily. This reduction was more significant for the diastolic than the systolic blood pressure measurements. A diastolic blood pressure of 90 mmHg, or less, was achieved in all patients receiving treatment with cicletanine (50 mg daily), except for two patients where the dosage was increased to 100 mg daily.     

Sustained release verapamil in hypertension. Results from a noninvasive ambulatory blood pressure monitoring and a clinical study

Summary The antihypertensive effect of a new sustained-release matrix formulation of verapamil 200 mg was investigated in a dose-response study in patients with mild to moderate essential hypertension. Noninvasive ambulatory blood pressure measurements were recorded over 24 h in 6 patients with diastolic blood pressure 100 mmHg. The patients received sustained-release verapamil 200 mg once daily and twice daily in a randomized order. Each medication period lasted 2 weeks. Verapamil 200 mg twice daily had a better antihypertensive effect than the same dose once daily. After a 6-week placebo period 27 patients with a diastolic blood pressure 100 mmHg were included in a double-blind clinical trial. The patients received sustained release verapamil 200 mg once daily and twice daily in a randomized crossover manner. Each medication period lasted 6 weeks, with an intervening 6-week placebo period. A diastolic blood pressure of 95 mmHg was achieved in 6 patients with the once-daily regimen and in 14 with the twice-daily regimen. The mean fall in diastolic blood pressure was 4 and 9 mmHg, respectively (p<0.05). We conclude that sustained-release verapamil 200 mg once daily gives a satisfactory blood pressure response only in a minority of patients, while 200 mg twice daily has a significantly better antihypertensive effect. Both doses were well tolerated.     

Crossover comparison of moxonidine and clonidine in mild to moderate hypertension

Summary The antihypertensive effect of moxonidine·HCl·H₂O (MOX) was compared with that of clonidine·HCl (CLON) in a randomized double-blind crossover study in 20 hypertensive outpatients (BP range 154–178/96–108 mmHg). After 2 weeks without antihypertensive medication, either MOX 0.2 mg daily or CLON 0.2 mg daily was given and the dose was titrated until the diastolic blood pressure fell below 90 mmHg. The first treatment period was continued for 2 weeks and, after crossover without a wash-out period, it was followed by the second treatment for a further 2 weeks. Within the first 4 days of administration 0.2–0.4 mg of either agent caused a significant decrease in BP (p<0.001) from a mean of 166/100 mmHg to 149/86 mmHg after CLON (approx. –10/–14%), and 163/99 mmHg to 146/84 mmHg after MOX (approx. –10/–15%). No significant difference in the fall in BP or pulse rate was detected between the two drugs. In the mean daily dose of 0.3 mg both drugs showed the same antihypertensive activity, but on CLON a higher incidence of side effects (p=0.003) was noted, and after discontinuation of therapy a more rapid rise in BP (systolic BP p<0.01, diastolic BP p<0.02) was found. 17 patients on CLON complained of side effects, especially tiredness and dry mouth, whilst only 6 patients on MOX were affected (p=0.003).     

Control of blood pressure in hypertensive patients with felodipine extended release or nifedipine retard.

1. This multicentre hospital study compared the antihypertensive efficacy and the tolerability of once daily felodipine extended release (ER) with twice daily nifedipine retard (R) in hypertensive patients inadequately controlled on metoprolol monotherapy. 2. One hundred patients, aged 20-70 years, whose seated diastolic blood pressure was 100-115 mmHg after 4 to 6 weeks of metoprolol (200 mg day-1) monotherapy, were randomised, double-blind, to receive felodipine ER 10 mg once daily or nifedipine R 20 mg twice daily for 8 weeks. The dosage of felodipine or nifedipine was doubled if seated diastolic blood pressure exceeded 95 mmHg, 2 or 4 weeks after randomisation. Metoprolol 200 mg once daily was taken throughout the trial. 3. Fifty-one patients received felodipine ER and 49 nifedipine R; 46 and 45 respectively completed the 8 week trial. About half of patients on each treatment needed the higher dose. The baseline characteristics of the felodipine and nifedipine groups were generally well balanced. 4. Seated diastolic blood pressure was reduced by 17 mmHg for felodipine (24 h post-dose) and by 9 mmHg for nifedipine (12 h post-dose), a difference between treatments of 8 mmHg (95% confidence interval 5 to 12 mmHg, P less than 0.0001). The attained blood pressures at the end of the study (felodipine 90 +/- 10, mmHg, mean +/- s.d.; nifedipine 95 +/- 10) were also significantly different (95% confidence interval for the 5 mmHg difference, -9 to -1 mmHg, P less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)     

ANGIOTENSIN-CONVERTING ENZYME INHIBITION AS FIRST-LINE TREATMENT FOR HYPERTENSION

1. Perindopril (4 mg) was compared with atenolol (50 mg), captopril (25 mg b. d.) or a diuretic (hydrochlorothiazide 50 mg and amiloride 5 mg) in three studies involving a total of 503 hypertensive patients with a diastolic blood pressure (DBP) of 95–125 mmHg.
2. A 4 week single-blind placebo period preceded 12 weeks of active treatment. Dose titration was at weeks 4 and 8 if supine DBP >90 mmHg. The dose was doubled and if necessary a diuretic was added in the atenolol or captopril comparisons, and atenolol was added in the diuretic study.
3. The fall in supine blood pressure (BP) was 27/17 mmHg with perindopril and 21/16 mmHg for atenolol. Monotherapy controlled 55% of patients on perindopril and 48% on atenolol, increasing to 78% and 58% with the addition of hydrochlorothiazide, respectively. Captopril caused a BP fall of 19/12 mmHg compared with 27/18 mmHg for perindopril, with 49% of both groups being controlled on monotherapy.
4. Diuretic addition produced a greater antihypertensive effect with perindopril (75%) compared with 57% for captopril in achieving control. Perindopril caused a comparable fall in supine BP to the diuretic combination 27/19 mmHg and 31/18 mmHg, but the fall in erect systolic BP was significantly greater for the diuretic. At 3 months, 85% of the diuretic group and 78% of the perindopril group achieved the target BP.
5. A multicentre trial of 856 patients treated with perindopril (690 patients treated for 1 year or more) has shown that BP control is maintained in the long term with a low incidence of side-effects (7.9%) causing withdrawal from treatment. These studies demonstrate that perindopril compares favourably with standard first-line therapy for mild to moderate hypertension.     

Felodipine extended release in mild to moderate hypertension

A multi-centre study was carried out to examine the antihypertensive effect and adverse event profile of felodipine in an extended-release (ER) formulation given once daily as monotherapy. Doses of 5 mg, 10 mg or 20 mg felodipine ER were compared with placebo in 183 patients with mild or moderate hypertension. All antihypertensive medication was discontinued on entering a 4-week placebo run-in period. If, at the end of the run-in period, supine diastolic blood pressure was in the range greater than 95 less than 120 mmHg, patients were randomly allocated to double-blind treatment with felodipine, 5 mg, 10 mg or 20 mg, or placebo, to be taken once daily for 4 weeks. Supine and standing blood pressure, heart rate and body weight were measured every 2 weeks during the trial. Assessments were made 24 hours after intake of the study drug. Adverse events were recorded at each review. Over the 4-week treatment period, a dose-related decrease in supine diastolic blood pressure was observed, this reduction occurring already during the first 2 weeks of active treatment. In the placebo group and the felodipine 5 mg, 10 mg and 20 mg groups, supine blood pressure (systolic/diastolic) decreased by 7/6 mmHg, 9/8 mmHg, 12/10 mmHg and 14/11 mmHg, respectively. Supine diastolic blood pressure reduction in the felodipine 10 mg group and both systolic and diastolic blood pressure reductions in the 20 mg group were significantly greater than with placebo. Standing diastolic blood pressure reduction was significantly greater in all three dose groups on felodipine compared with placebo.(ABSTRACT TRUNCATED AT 250 WORDS)     

Treatment of mild-to-moderate hypertension with calcium channel blockers: a multicentre comparison of once-daily nifedipine GITS with once-daily amlodipine

BACKGROUND: Hypertension is one of the most important causes of cardiovascular disease, and treatment of hypertension leads to a significant reduction in cardiovascular mortality and morbidity. Although calcium channel blockers are regarded as an important part of the therapeutic armamentarium against cardiovascular diseases, and are among the most frequently prescribed antihypertensive medications, concern has been aroused about these drugs, particularly the short-acting dihydropyrldine derivatives. However, the value of nifedipine GITS(Adalat-Crono), the long-acting dihydropyrldine, is in need of being re-established. OBJECTIVE: To compare the effectiveness, safety and tolerability of once-daily nifedipine and amlodipine treatment in patients with mild-to-moderate essential hypertension. DESIGN: Randomised multicentre trial with an open comparison of treatments for 12 weeks, with a preceding placebo run-in period of 2 weeks (patients on beta-blockers at the time of enrollment entered a mandatory 2-week wash-out period before being allowed In the placebo run-in period;this wash-out period was one week for patients using any antihypertensive medication other than beta-blockers). SETTING: Nine centres (all university hospitals) in Turkey. PATIENTS: 155 patients with essential hypertension(diastolic blood pressure 95-109 mmHg). INTERVENTIONS: Initial treatment (step 1) consisted of 30 mg nifedipine GlTS (n = 76; (Adalat-Crono tablets), or 5 mg amlodipine (n = 79; Norvasct5-mg tablets), either administered once daily, as a morning dose, or f the blood pressure was not below 140/90 mmHg, or the reduction In diastolic blood pressure was lower than 10 mmHg after a treatment period of 6 weeks, the dose was increased (Step 2) to 60 mg once daily in the nifedipine group, or 10 mg once daily in the amlodipine group. MAIN EFFICACY PARAMETER: Diastolic blood pressure at trough after 12 weeks of active compound therapy adjusted to baseline. RESULTS: After 12 weeks of treatment, the mean diastolic blood pressure was 83.1 and 81.9 mmHg,in the nifedipine and amlodipine groups, respectively (p = 0.436). The mean decrease in systolic blood pressure (28.5 +/- 11.9 and 28.2 +/- 11.2 mmHg in the nifadipine and amlodipine groups, respectively) and the mean decrease in diastolic blood pressure (16.4A +/- 7.0 and 17.5 +/- 6.9 mmHg in the nifedipine and amlodipine groups, respectively), as well as the responder rates (88.1%and 92.1%, in the nifediplne and amlodipine groups, respectively) were comparable at the end of the study. No significant differences between groups were detected In the efficacy parameters assessed in this study. Both drugs were well tolerated. The overall incidence of adverse events was 7.9% in the nifadipine group and 10.1% In the amlodipine group. However, more patients discontinued treatment prematurely in the amlodipine group (13 patients; 19.7%), than in the nifedipine group (four patients; 5.6%). CONCLUSIONS: The results of this study demonstrated that once-daily nifedipine in GITS formation and amlodipine are comparably safe and effective treatment options in patients with mild-to-moderate essential hypertension.     

The response to the first dose of an angiotensin converting enzyme inhibitor in uncomplicated hypertension--a placebo controlled study utilising ambulatory blood pressure recording.

1. The importance of total dose to the initial hypotensive response with an angiotensin converting enzyme inhibitor (quinapril) was assessed using a suggested 'maintenance' dose (20 mg) or matched placebo in a randomised double-blind study in patients with uncomplicated hypertension. 2. Thirty-two patients were recruited who were not on therapy or had not received diuretic therapy in their existing drug treatment in the preceding 4 weeks. Secondary causes of hypertension had previously been excluded and sustained clinic blood pressures of SBP greater than 160 mmHg and/or DBP greater than 90 mmHg were taken as indications for a trial of adjuvant or monotherapy with an ACE inhibitor. 3. After uneventful supervised therapy with quinapril in an open pilot study (n = 5) 27 patients entered a double-blind, randomised, crossover study of quinapril or placebo using ambulatory monitoring to assess BP response. 4. All patients remained asymptomatic and both therapy and monitoring were well tolerated. A smooth onset of antihypertensive effect was noted with an overall 24 h placebo corrected fall in systolic BP of 9.9 mmHg (7.2-12.6 95% CI) and diastolic BP of 6.4 mmHg (4.2-8.8) with no significant effect on heart rate. Individual placebo corrected maximal responses during the first 8 h following quinapril showed a wide range for both systolic (+1.56 to 44.0 mmHg) and diastolic (+2.3 to -35.6 mmHg) pressure. Larger falls tended to be associated with higher baseline pretreatment pressures but in no case did absolute systolic pressure fall below 100 mmHg during the first 8 h following administration of placebo or quinapril.(ABSTRACT TRUNCATED AT 250 WORDS)     

Antihypertensive effect of metoprolol in diuretic-treated,mild primary hypertension

Metoprolol tartrate was administered to 41 patients with mild essential hypertension already treated with a diuretic for a period of 2 weeks. In the majority of those patients, other step 2 antihypertensive agents either failed to control high blood pressure or caused adverse reactions. All other antihypertensive agents except diuretics were discontinued during the 2-week wash-out period. Patients with a diastolic blood pressure of 95 to 104 mmHg (inclusive) received oral metoprolol at a dose of 50mg twice daily for 2 weeks. Subsequently, metoprolol titration was individualized on a bi-weekly basis until either the diastolic blood pressure was = 90 mmHg and/or a maximal daily dose of 300mg of metroprolol was reached. The analysis of efficacy and safety was done for a total period of 14 weeks. Diastolic blood pressure and heart rates were significantly reduced (P≤0.05) in all treatment groups. Minor adverse reactions such as mild fatigue in 11 patients, nervousness in 2, and leg cramps in 2 patients were reported. Transient skin rash, dizziness, headache, chest pain, insomnia, and cold extremities were also reported in one patient each. It is concluded from the present study that metropolol (in twice daily dose) in combination with a diuretic is safe, effective, and well tolerated in the treatment of mild hypertension.     

The relationship of dose to the antihypertensive response of verapamil-sustained release in patients with mild to moderate essential hypertension. The Verapamil-SR Study Group

The dose-response relationship of verapamil-SR was studied in 221 hypertensive patients. This double-blind, parallel-group, placebo-controlled study compared placebo to 60 mg, 120 mg, 240 mg and 480 mg daily of verapamil-SR. After 6 weeks of therapy, peak diastolic blood pressure was similar in the placebo group and the verapamil-SR 60 mg group, 93.0 and 92.0 mmHg, respectively. The 120 mg, 240 mg and 480 mg verapamil-SR groups produced significantly lower diastolic blood pressure, 89.8, 85.3 and 83.7 mmHg (P less than 0.01), respectively. At trough, placebo and verapamil-SR 60 mg groups and 120 mg groups had diastolic blood pressures of 96.6, 97.0 and 97.1 mmHg, respectively. Diastolic blood pressure with the 240 mg dose (92.4 mmHg) was significantly lower than with the 120 mg dose (P less than 0.01). The 480 mg dose resulted in a diastolic blood pressure of 88.6 mmHg, which was significantly lower than the 240 mg dose (P less than 0.01). The responder rate with 240 mg at peak was 82%. The trough to peak ratio was 0.58. Plasma concentrations were highly correlated with dose (r greater than 0.8; P less than 0.01); but not with diastolic blood pressure (r greater than 0.4; P less than 0.01). Headache and constipation, although not significantly different from placebo, were the most commonly reported adverse reactions in the verapamil-SR groups, 6.3% (placebo--6.7%) and 5.1% (placebo--4.4%), respectively. Graded doses of verapamil-SR produced a dose-response curve in hypertensive patients with a greater than 80% responder rate at the 240 mg dose.(ABSTRACT TRUNCATED AT 250 WORDS)     

Antihypertensive properties of tiapamil (RO 11-1781)--a new calcium antagonist--in patients with mild and moderate essential hypertension

An open, non-comparative study, with a new calcium antagonist-tiapamil, was undertaken in 22 patients with mild and moderate essential hypertension (stage I-II WHO). After a two-week placebo period, patients were treated with tiapamil, 300-600 mg twice daily during a period of six weeks (Dose-finding period). Thereafter patients were continued on tiapamil during a 54 week period (Long-term follow-up). In some patients it was necessary to add the diuretic hydrochlorothiazide to obtain adequate control of the arterial hypertension. Monotherapy with tiapamil normalized supine diastolic blood pressure after the first six weeks in 17 of the 21 evaluable patients, and reduced it by greater than or equal to 10 mmHg (1.3 kPa) from baseline without normalization in two patients. In the two remaining cases the decrease was less than 10 mmHg. The optimal dose administered at six weeks in those patients who responded to treatment (normalization or decrease by greater than or equal to 10 mmHg.) was 600 mg/day in 32% of the cases, 750-900 mg/day in 47% and more than 900 mg/day in 21%. After completion of the dose-finding part, 19 patients continued treatment for a further 54 weeks. In 16 out of 19 patients hydrochlorothiazide was added to enhance the antihypertensive effect. All three patients who received tiapamil monotherapy throughout the trial, had normalized supine diastolic blood pressure on completing the study. In the 16 patients with the combination therapy, the addition of hydrochlorothiazide led in two patients to no further decrease in supine diastolic blood pressure, to an additional decrease by less than 10 mmHg in ten patients and by greater than or equal to 10 mmHg in four in comparison with the values obtained before starting combination therapy. At the end of the study 11 of these 16 patients had normalized supine diastolic blood pressure. The mean daily dose was 900 +/- 45 mg of tiapamil and 39 +/- 4 mg of hydrochlorothiazide. Both monotherapy and the combination regimen were well tolerated, and no effects attributable to drug interactions were observed. It may be concluded that tiapamil in oral doses of 300-600 mg twice daily is an effective antihypertensive agent with an excellent tolerance when administered for a period of 54 weeks.     

Relative potency of a beta-blocking and a calcium entry blocking agent as antihypertensive drugs in black patients

Summary The short-term efficacy of nitrendipine (N) as a first stage antihypertensive drug in black patients has been assessed and compared with acebutolol (A) in a double-blind study. Forty patients were randomized and after a 4 week run-in period on placebo, the active treatment was administered for 6 weeks starting with 20 mg N or 200 mg A once daily. The dose was increased up to 60 mg N or 600 mg A as needed. Nitrendipine appeared to be more efficient than acebutolol in reducing blood pressure and the N-induced fall in blood pressure was achieved after 2 weeks. After 2 and 6 weeks on N, the recumbent blood pressure was decreased by 13% and 12% for the systolic and by 14% and 11% for the diastolic pressure. The concurrent decreases in the A group averaged 4% and 5% for the systolic and 5% and 10% for the diastolic pressure after 2 and 6 weeks. Pulse rate and plasma renin activity in the N group were slightly increased and body weight was decreased at the end of the active treatment period.     

Antihypertensive effect of low-dose hydrochlorothiazide alone or in combination with quinapril in black patients with mild to moderate hypertension

In this study, using 24-hour ambulatory blood pressure (BP) monitoring, the authors assessed the potential for BP control using hydrochlorothiazide (HCTZ, 12.5 mg daily), given as a monotherapy over 12 months to 49 black South African patients with mild to moderate hypertension (mean day diastolic blood pressure [DBP] > or = 90 and < 115 mmHg). Uncontrolled patients received fixed combination of quinapril/HCTZ 10/12.5, 20/12.5, and 20/25 mg, with dose titration at 3 monthly intervals if BP control was not achieved (day DBP < 90 mmHg). Overall, profound and sustained BP reduction was observed at the end of the study. The 24-hour BP decreased from 151 +/- 14/98 +/- 7 to 136 +/- 15/87 +/- 9 mmHg (p < 0.0001 at end of study vs. baseline); the mean day BP decreased from 155 +/- 14/104 +/- 7 to 140 +/- 15/91 +/- 10 mmHg (p < 0.0001 at end of study vs. baseline). The overall control (mean day DBP < 90 mmHg) and response (decrease in day DBP > or = 10 mmHg) rates were 49% and 61%, respectively. At the end of the study, only 2 patients (4%) remained on treatment with HCTZ. Out of the initial 12 patients controlled on HCTZ at 3 months (12/49, 24%), 5 patients remained controlled at 6 months and only 1 patient at 12 months. In contrast, quinapril/HCTZ combinations maintained their antihypertensive effect up to 9 months, with a significant number of patients (22/49, 45%) requiring the highest dose of the combination (20/25 mg daily). In conclusion, low-dose HCTZ should not be recommended as monotherapy in black patients with mild to moderate hypertension due to the fact that the BP-lowering effect is attenuated already at 6 months of treatment, with most patients requiring the addition of the ACE inhibitor.     

A multi-centre,placebo controlled comparative study between 200 mg and 400 mg celiprolol in patients with mild to moderate essential hypertension

Summary

A two-centre, double-blind, placebo controlled, randomized 3-way crossover study was undertaken to assess the efficacy, tolerability and safety of celiprolol in mild to moderate essential hypertension. A 4-week single-blind placebo run-in/ screening period, during which no antihypertensive medication was given, was followed by 3 consecutive 4-week treatment periods with placebo or celiprolol (200?mg or 400?mg daily). At the end of the 4-week placebo run-in/screening period, 26 hospital out-patients with a seated mean blood pressure (systolic/ diastolic) of 161.4/101.7 mmHg and a mean pulse rate of 75 beats/min entered the double-blind crossover phase of the study. Results showed that there was no significant difference in seated mean systolic or diastolic blood pressure between 200?mg celiprolol daily (149.2/92.3 mmHg) and 400?mg celiprolol daily (149.1/ 92.5 mmHg). However, mean seated systolic and diastolic blood pressures were significantly (p<0.05) lower on celiprolol than on placebo (157.1/98.2 mmHg). Neither dose of celiprolol had a significant effect on seated pulse rate. No patient was withdrawn due to an adverse event and no laboratory assessment outside the normal range was reported to be of any clinical significance. It is concluded that oral celiprolol, 200?mg or 400?mg daily, is effective and well tolerated for controlling mild to moderate essential hypertension. Since both doses had very similar effects on blood pressure there is no advantage in this group of patients for the 400?mg daily dose of celiprolol.     

Antihypertensive efficacy of twice daily controlled release diltiazem using 24 hour intra-arterial blood pressure monitoring

The aim of the study was to examine the efficacy of a new controlled release formulation of diltiazem administered in a twice-daily dose in patients with essential hypertension using 24 hour intra-arterial ambulatory blood pressure monitoring.Sixteen patients (2 female) of mean age 53 years with mild to moderate essential hypertension, defined as a supine resting diastolic cuff blood pressure 95 mm Hg, were recruited to a sequential dose ranging study of controlled release (CR) diltiazem. After a six week run-in period without any anti-hypertensive medication, intra-arterial blood pressure monitoring with 60° tilt, isometric handgrip and bicycle exercise testing were performed. Patients were then treated for one week with CR diltiazem 120 mg b.i.d. If supine resting diastolic cuff blood pressure fell by <10 mm Hg compared to the last run-in value and remained >90 mm Hg, the dose was increased to 240 mg b.i.d. for a week, and if necessary to 360 mg b.i.d. for a week. Patients continued for further one month on the dose of CR diltiazem at which they achieved target blood pressure reduction. At the end of this maintenance treatment, 24 hour intra-arterial blood pressure monitoring was repeated.Twelve patients were satisfactorily controlled on 120 mg b.i.d. CR diltiazem, three on 240 mg twice daily and one on 360 mg twice daily. During rest and exercise, blood pressure and heart rate were significantly lower after treatment with CR diltiazem than before treatment. The hypotensive effect of diltiazem was maintained throughout the 12 hour dosing interval and the early morning blood pressure response was blunted. No adverse effects or ECG abnormalities were reported.It was concluded that CR diltiazem 120 mg, administered twice daily to a total daily dose of between 240 mg and 720 mg, is effective and well tolerated in the treatment of mild to moderate essential hypertension.     

Evaluation of long-term efficacy and acceptability of indapamide SR in elderly hypertensive patients

OBJECTIVE: To assess the long-term antihypertensive efficacy and acceptability of indapamide SR 1.5 mg in elderly hypertensive patients (> or = 65 years). STUDY DESIGN: Open, 12-month, follow-up study of 444 patients, treated with indapamide SR, who were responders and/or achieved target BP levels following a 3-month, randomised, controlled, double-blind short-term comparison of indapamide SR versus hydrochlorothiazide 25 mg and amlodipine 5 mg. RESULTS: The long-term decrease in systolic blood pressure (SBP)/diastolic blood pressure (DBP) after 12 months follow-up with indapamide SR was -24.0/-13.1 mmHg from baseline (M0). The percentage of patients that achieved target BP levels (DBP < 95 mmHg, SBP < or = 160 mmHg) was 80.1% [84.3% for isolated systolic hypertension (ISH) subgroup], and the response rate (BP < 140/90 mmHg or decrease in supine diastolic BP > or = 10 mmHg or in supine systolic BP > or = 20 mmHg) 81.5%. Blood pressure (BP) remained stable throughout the 12 months follow-up period (M3-M15), whatever the previous treatment received during the 3-month, doubleblind period (M0-M3). Clinical and biological acceptability was good. A low occurrence of withdrawals (7.2%), was reported. CONCLUSION: Over the course of the long-term, 12-month follow-up study, indapamide SR was shown to be an effective and well tolerated antihypertensive therapy, even after a switch from amlodipine or hydrochlorothiazide, in patients aged 65 years-80 years with systolo-diastolic hypertension (SDH) or ISH.     

Efficacy and tolerability of the perindopril/indapamide combination therapy for hypertension: the PRIMUS study

BACKGROUND: Tight blood pressure (BP) control is required to reduce cardiovascular morbidity and mortality. OBJECTIVE: To evaluate the efficacy and tolerability of the first line combination perindopril/indapamide in hypertension in daily practice. DESIGN AND METHODS: In this prospective, open-label, observational trial, 1892 general practitioners in Germany recruited patients with hypertension (n = 8023; mean age 59.6 years, 48.1% males, body mass index 27.6 kg/m2, systolic BP >or= 140 mmHg and/or diastolic BP >or= 90 mmHg) between October 2002 and December 2004. Patients received perindopril 2 mg/indapamide 0.625 mg for 12 weeks. BP measured in the general practice setting, safety, and tolerability were evaluated after 4 and 12 weeks. RESULTS: At baseline, most patients had moderate to severe hypertension (78%); initial BP was 164.6/95.8 mmHg. At inclusion, 38% of the patients were newly diagnosed hypertensives (mean BP 166.1/97.2 mmHg) and 58% of patients had uncontrolled BP despite preexisting antihypertensive treatment (163.5/94.9 mmHg). Previous treatment consisted of beta-blockers (49.5%), ACE inhibitors (36.4%), calcium-antagonists (29.3%), diuretics (28.8%), AT-I receptor antagonists (7.1%), and other treatments (8.1%). In the entire study cohort, treatment with perindopril/indapamide significantly decreased systolic BP (27.9 mmHg), diastolic BP (13.7 mmHg), and pulse pressure (14.2 mmHg), compared with baseline (p < 0.0001); 96% of patients responded to treatment and in 50% of patients BP was normalized (< 140/90 mmHg). Treatment dose was doubled in 9.5% of patients. Similar results were found in various subgroup analyses (newly diagnosed patients, the elderly, and patients with isolated systolic hypertension, additional cardiovascular risk factors, associated diseases, or target organ damage). The most frequent adverse events (< 1% of patients) were dry cough and nausea. CONCLUSIONS: The open-label, observational study PRIMUS, extends the existing evidence that the first line combination treatment of hypertension with perindopril/indapamide is effective, safe, and well tolerated in a representative cross-section of patients with newly diagnosed or pretreated but uncontrolled hypertension in daily practice.