Treatment of allergic rhinitis can improve blood pressure control.

Owing to high prevalence of arterial hypertension (AH) and allergic rhinitis (AR), these diseases frequently coexist. The study aimed to assess whether improvement of AR by conventional treatment can improve blood pressure (BP) control in this population. Sixty-eight subjects of both sexes aged 35-60 years with AR and AH were randomized into two groups to receive in addition to their antihypertensive medications: treatment group (n=34) Fluticasone nasal 50 microg/spray b.i.d. and Fenoxifenadine 180 mg tablets q.d., and control group (n=34) 0.9% NaCl nasal drops b.i.d. Office BP and AR severity (using the Relative Quality of Life Questionnaire (RQLQ)) and high-sensitive C-reactive protein (hs-CRP) were measured at study entry and after 8 weeks in both groups, without changing of antihypertensive medications. In Treatment group an improvement in RQLQ, significant reduction of systolic BP (SBP) (DSBP 7.4 +/- 4.3 mm Hg, P=0.006) and reduction of hs-CRP level (DCRP 2.05 +/- 1.08; P=0.028) were observed, whereas diastolic BP (DBP) remained unchanged (DDBP 0.9 +/- 1.7 mm Hg, P=0.7). There was a significant correlation between DRQLQ and DSBP (r=0.86; P=0.019) and between DCRP and DSBP (r=0.56; P=0.027). No statistically significant changes of RQLQ, BP and CRP were observed in the control group. In patients with coincidence of AH and AR, medications meant to improve AR attenuate low-grade systemic inflammation and can lower SBP, but not DBP.

Randomised controlled trial of dual blockade of renin-angiotensin system in patients with hypertension, microalbuminuria, and non-insulin dependent diabetes: the candesartan and lisinopril microalbuminuria (CALM) study.

OBJECTIVES: To assess and compare the effects of candesartan or lisinopril, or both, on blood pressure and urinary albumin excretion in patients with microalbuminuria, hypertension, and type 2 diabetes. DESIGN: Prospective, randomised, parallel group, double blind study with four week placebo run in period and 12 weeks' monotherapy with candesartan or lisinopril followed by 12 weeks' monotherapy or combination treatment. SETTING: Tertiary hospitals and primary care centres in four countries (37 centres). PARTICIPANTS: 199 patients aged 30-75 years. INTERVENTIONS: Candesartan 16 mg once daily, lisinopril 20 mg once daily. MAIN OUTCOME MEASURES: Blood pressure and urinary albumin:creatinine ratio. RESULTS: At 12 weeks mean (95% confidence interval) reductions in diastolic blood pressure were 9.5 mm Hg (7.7 mm Hg to 11.2 mm Hg, P<0.001) and 9.7 mm Hg (7.9 mm Hg to 11.5 mm Hg, P<0.001), respectively, and in urinary albumin:creatinine ratio were 30% (15% to 42%, P<0.001) and 46% (35% to 56%, P<0.001) for candesartan and lisinopril, respectively. At 24 weeks the mean reduction in diastolic blood pressure with combination treatment (16.3 mm Hg, 13.6 mm Hg to 18.9 mm Hg, P<0. 001) was significantly greater than that with candesartan (10.4 mm Hg, 7.7 mm Hg to 13.1 mm Hg, P<0.001) or lisinopril (mean 10.7 mm Hg, 8.0 mm Hg to 13.5 mm Hg, P<0.001). Furthermore, the reduction in urinary albumin:creatinine ratio with combination treatment (50%, 36% to 61%, P<0.001) was greater than with candesartan (24%, 0% to 43%, P=0.05) and lisinopril (39%, 20% to 54%, P<0.001). All treatments were generally well tolerated. CONCLUSION: Candesartan 16 mg once daily is as effective as lisinopril 20 mg once daily in reducing blood pressure and microalbuminuria in hypertensive patients with type 2 diabetes. Combination treatment is well tolerated and more effective in reducing blood pressure.

Interactions of angiotensin-converting enzyme, kinins and nitric oxide in circulation and the beneficial effects of ACE inhibitors in cardiovascular diseases.

Renin-angiotensin-aldosterone systems play a critical role in the development and progression of cardiovascular diseases, and inhibitors of angiotensin-converting enzyme have proven effective for the treatment of these diseases. Since angiotensin II receptor antagonists can inhibit the effects of angiotensin II via ACE-independent pathways, e.g., chymase, they were considered to be more effective than ACEIs. On the other hand, ACE inhibitors can increase bradykinin, and thus, nitric oxide, which may cause potent cardioprotection, inhibition of smooth muscle proliferation and attenuation of inflammation mechanisms. It appears that angiotensin II receptor antagonists and ACEIs may mediate cardioprotection in different ways. This is the rationale to explore the possibility of a combined administration of both drugs for the treatment of chronic heart failure and other cardiovascular pathology. In this review we try to analyze the role of ACE, kinins and chymase inhibition in the pathophysiology and treatment of cardiovascular diseases.

The effect of an endothelin-receptor antagonist, bosentan, on blood pressure in patients with essential hypertension. Bosentan Hypertension Investigators.

BACKGROUND: Endothelin is a powerful vasoconstrictor peptide derived from the endothelium. We evaluated the contribution of endothelin to blood-pressure regulation in patients with essential hypertension by studying the effect of an endothelin-receptor antagonist, bosentan. METHODS: We studied 293 patients with mild-to-moderate essential hypertension. After a placebo run-in period of four to six weeks, patients were randomly assigned to receive one of four oral doses of bosentan (100, 500, or 1000 mg once daily or 1000 mg twice daily), placebo, or the angiotensin-converting-enzyme inhibitor enalapril (20 mg once daily) for four weeks. Blood pressure was measured before and after treatment. RESULTS: As compared with placebo, bosentan resulted in a significant reduction in diastolic pressure with a daily dose of 500 or 2000 mg (an absolute reduction of 5.7 mm Hg at each dose), which was similar to the reduction with enalapril (5.8 mm Hg). There were no significant changes in heart rate. Bosentan did not result in activation of the sympathetic nervous system (as determined by measurement of the plasma norepinephrine level) or the renin-angiotensin system (as determined by measurements of plasma renin activity and angiotensin II levels). CONCLUSIONS: An endothelin-receptor antagonist, bosentan, significantly lowered blood pressure in patients with essential hypertension, suggesting that endothelin may contribute to elevated blood pressure in such patients. The favorable effect of treatment with bosentan on blood pressure occurred without reflexive neurohormonal activation.

Mibefradil in the treatment of systemic hypertension: comparative studies with other calcium antagonists.

This paper summarizes the results of 4 double-blind studies of antihypertensive therapy in which mibefradil was compared with other commonly used calcium antagonists (diltiazem CD, amlodipine, nifedipine SR, and nifedipine GITS) at the recommended dose range. A total of 640 patients were included, with 361 randomized to mibefradil, 98 to diltiazem CD, 119 to amlodipine, 71 to nifedipine SR, and 36 to nifedipine GITS. Trials included an active treatment phase of 6 or 12 weeks in duration. Compared with diltiazem CD or nifedipine SR, mibefradil demonstrated statistically significant greater efficacy. Decreases in sitting diastolic blood pressure (SDBP) after treatment with mibefradil 100 mg once daily were 14.0 +/- 7.8 mm Hg compared with 9.5 +/- 7.5 mm Hg with diltiazem CD 360 mg once daily (p = 0.001), and 12.8 +/- 8.4 mm Hg compared with 8.1 +/- 19.2 mm Hg with nifedipine SR 40 mg twice daily (p = 0.014). Patients on mibefradil also had higher normalization (SDBP reduced to < or = 90 mm Hg) and response (SDBP reduction > or = 10 mm Hg or normalization) rates than did those on diltiazem CD or nifedipine SR. The overall incidence of adverse events was similar among these 3 compounds, but the number of premature withdrawals due to adverse events was greater with both comparators than with mibefradil. Treatment with 100 mg mibefradil or 10 mg amlodipine once daily resulted in statistically significant decreases from baseline in SDBP of 11.5 +/- 8.2 mm Hg and 13.2 +/- 7.9 mm Hg, respectively, which were statistically equivalent. However, patients treated with amlodipine had a considerably greater incidence of leg edema than did those treated with mibefradil (33.6% vs 4.2%, respectively). Similarly, 100 mg mibefradil was equivalent in efficacy to 60 mg nifedipine GITS once daily, but patients on mibefradil experienced fewer vasodilatory related adverse events. In summary, mibefradil demonstrated superior efficacy to diltiazem CD and nifedipine SR and equivalent efficacy to amlodipine and nifedipine GITS in the treatment of hypertension.

The addition of mibefradil to chronic hydrochlorothiazide therapy in hypertensive patients is associated with a significant antihypertensive effect.

OBJECTIVE: To evaluate the antihypertensive efficacy, tolerability, safety, and dose-response characteristics of the novel calcium antagonist, mibefradil, in combination with a diuretic regimen. DESIGN: A multinational, double-blind, randomised, placebo-controlled, parallel-design trial. METHODS: Three hundred and seven patients whose mild-to-moderate essential hypertension remained uncontrolled after 4 weeks of treatment with hydrochlorothiazide (HCTZ) 25 mg/day and placebo were randomised to receive combined treatment with HCTZ and once-daily doses of 12.5, 25, 50, or 100 mg of mibefradil or placebo. After 8 weeks of combined treatment, HCTZ was withdrawn and the mibefradil groups continued on their respective doses for an additional 6 weeks. RESULTS: After 8 weeks, the addition of once-daily doses of mibefradil to the initial HCTZ regimen resulted in clinically relevant, dose-related reductions in sitting diastolic blood pressure (SDBP) and sitting systolic blood pressure (SSBP) at trough, which were significantly greater in the 50 and 100 mg dose groups compared to the placebo group (P < or = 0.003). Placebo-corrected treatment effects on SDBP and SSBP at the end of the combined treatment period relative to baseline were, respectively, -4.1 and -8.0 mm Hg in the 50 mg mibefradil group and -9.5 and -8.0 mm Hg in the 100 mg mibefradil group. Therapeutic response rates to combination mibefradil and HCTZ therapy were high and dose related, reaching 82% for SDBP in the 100 mg group. CONCLUSIONS: The addition of once-daily doses of 50 or 100 mg of mibefradil to patients whose hypertension is not controlled by HCTZ alone is well tolerated and effective in improving BP control.

A randomised, double-blind trial comparing mibefradil and amlodipine: two long-acting calcium antagonists with similar efficacy but different tolerability profiles. Mibefradil International Study Group.

OBJECTIVE: To compare the efficacy and tolerability of mibefradil and amlodipine in patients with uncomplicated mild-to-moderate essential hypertension. DESIGN: A double-blind, randomised, parallel group multicentre trial. METHODS: 239 patients received 50 mg mibefradil or 5 mg amlodipine for 4 weeks, followed by a forced titration to 100 mg mibefradil or 10 mg amlodipine for an additional 8 weeks. Patients then entered a 4-week withdrawal period either on therapy or switched to placebo. RESULTS: Statistically equivalent reductions in trough sitting diastolic blood pressure (SDBP) were observed after 12 weeks of once-daily treatment with 50/100 mg mibefradil (-11.5 +/- 8.2 mm Hg) and 5/10 mg amlodipine (-13.2 +/- 7.9 mm Hg). The number of patients with normalised SDBP (< or = 90 mm Hg) increased 23.3% in the mibefradil group and 19.5% in the amlodipine group (approximately 74% in both groups). Patients on mibefradil or amlodipine during the withdrawal period had significantly larger decreases in SDBP than those on placebo. Patients on mibefradil had a decrease in heart rate of 5.5 bpm. Patients on amlodipine had no change in heart rate; however, cessation of amlodipine was associated with a decrease in heart rate. CONCLUSIONS: Mibefradil was as effective as amlodipine in reducing BP; both compounds were effective treatments of hypertension.

Rhabdomyolysis in paraphenylenediamine intoxication.

Edema of the upper airways and rhabdomyolysis developed in a young patient as a consequence of paraphenylenediamine poisoning. Treatment with adrenaline, steroids and enforced diuresis prevented tracheostomy and renal failure.

Time dependency of the antihypertensive efficacy of the new renin inhibitor Ro 42-5892.

The objective of this study was to assess the antihypertensive efficacy of the new renin inhibitor Ro 42-5892 in patients with essential hypertension treated with 100 mg once daily orally. This was a double-blind, placebo-controlled, parallel group trial. After three weeks of wash-out and one week of single-blind placebo run-in periods, 25 patients with mild to moderate essential hypertension (sitting DBP between 95 and 114 mmHg) were randomised to receive either placebo (n = 12) or 100 mg of Ro 42-5892 (n = 13) once daily for eight days. On the eighth day, four hours after the oral administration, patients were randomised to receive intravenously either placebo or 10 mg of Ro 42-5892. BP and heart rate were measured repeatedly (hourly for eight hours and at the 24th hour post-dose) on the first and last days of active treatment. Compared with the placebo group, a slight decrease in sitting DBP was observed after the first dose in the Ro 42-5892 group. The decrease in sitting DBP reached significant levels only at six to eight hours post-dosing. In contrast, on the last day of active treatment, a larger, faster and longer decrease in sitting DBP was observed in the Ro 42-5892 group. Thus, the peak effect (-8.9 +/- 1.9 vs. -2.9 +/- 1.3 mmHg, P < 0.01) was reached 1.5 hours post-dosing and the trough effect (24 hours post-dosing) was slightly but significantly lower when compared with the placebo group (-3.0 +/- 1.0 vs -0.3 +/- 0.8 mmHg, P < 0.05, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of placebo on office and on 24 hour noninvasive ambulatory blood pressure measurements.

Elevated BP in the clinical but not during daily activities (white coat hypertension) is a well recognised problem encountered in the diagnosis of mild hypertension. The aim of this study is to evaluate this phenomenon with a study population of 90 mild hypertensive patients subjected to 24h BP measurement, and to assess the effect of placebo on both the office and the daytime continual BP monitored values. For this purpose, 90 patients were evaluated after four weeks of single-blind placebo (Phase I) and, of these, 27 patients were evaluated after a further four weeks of double-blind placebo administration (Phase II). During Phase I treatment the mean office SBP (163.9 mmHg) and the mean office DBP (104.5 mmHg) were significantly higher than the average of the six readings obtained during the first two hours of automatic continual BP monitoring (158.6 and 98 mmHg respectively, P < 0.001) (white coat effect). These differences were much more pronounced when the comparison was made between office measurements and the average daytime values (SBP 152.8 mmHg, DBP 93.1 mmHg). At the end of Phase II, the average values of BP measurements obtained both in the office and from continual monitoring were significantly lower (placebo effect). However, the difference between the office and the daytime values persisted. Thus, notwithstanding the reduction in the BP measurements following placebo administration, the white coat effect persists.

Effects of an orally active renin inhibitor, Ro 42-5892, in patients with essential hypertension.

Ro 42-5892 (Ro) is a new renin inhibitor that has been shown to be an orally effective compound in primates and in the first exploratory studies in humans. However, no firm conclusions could be drawn from the human trials and therefore the present study was designed to evaluate the antihypertensive efficacy of the compound in a double-blind, placebo-controlled trial. After a 3 week wash-out period and a 1 week single-blind placebo period, 24 patients were randomized to receive once daily orally either placebo or 600 mg Ro 42-5892 (N = 12/group) for 8 days. On the last day of treatment, an intravenous infusion of placebo or 100 mg Ro was given in a double-blind fashion, 4 h after the oral administration. Blood pressure (BP), heart rate (HR), plasma renin activity (PRA), immunoreactive renin (IRR), and plasma Ro levels were measured repeatedly on the first and last days of treatment. After the first oral intake of Ro, sitting diastolic BP dropped significantly from 30 min to 24 h post-dose when compared to placebo (-10.2 +/- 1.2 mm Hg v - 0.4 +/- 2.0 mm Hg at peak and -6.9 +/- 1.8 mm Hg v 1.7 +/- 0.9 mm Hg at trough; P < .01 respectively). The trough effects of Ro and placebo after the 7th and 8th doses were -5.1 +/- 1.6 mm Hg v -0.2 +/- 1.0 mm Hg; P < .05 and -5.4 +/- 1.3 mm Hg v 2.3 +/- 1.2 mm Hg; P < .01, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Antihypertensive duration of action of cilazapril in patients with mild to moderate essential hypertension.

The efficacy of cilazapril monotherapy was evaluated in 2 multicentre double-blind dose-response trials. After 4 weeks of a single-blind placebo run-in period, patients with uncomplicated mild to moderate essential hypertension and a sitting diastolic blood pressure of 100 to 115 mm Hg, 24 hours after the last placebo dose (trough), were randomised to take either placebo or cilazapril 2.5 mg or 5 mg for 4 weeks (study 1, 86 patients) or 8 weeks (study 2, 78 patients). Sitting diastolic blood pressure was checked every 2 weeks at trough in both studies and at peak in study 2. The reductions in sitting diastolic blood pressure from baseline at trough, and the difference from placebo, were clinically and statistically significant for both cilazapril groups in the 2 studies. The reduction in blood pressure in both active treatment groups was similar, but the response rate with cilazapril 5 mg was greater than that with 2.5 mg. More than 50% of the peak effect was still present at trough for both cilazapril groups. It is concluded that both dosages of cilazapril are effective and reduce blood pressure compared with placebo over a 24-hour period.

Resource savings from non-pharmacological control of hypertension.

Treatment of acute cardiovascular illness is expensive, and a preventative approach may be cheaper. Since pharmacological costs account for a large proportion of costs in prevention programmes, a non-pharmacological approach such as that used by us in Ashkelon on mild hypertensives, relying on stress management, weight management and exercise aimed at reducing risk factors, might prove to be more cost-effective. After six months on a 1,000 calorie/day diet, 69 obese subjects (initial body mass index greater than 28 kg/m2) had reduced their weight by an average of 7.3 kg (P less than 0.005). This weight reduction contributed to a significant decrease in systolic blood pressure (SBP) from 157.3 to 137.6 mmHg (P less than 0.005) and diastolic blood pressure (DBP) from 101.1 to 85.2 mmHg (P less than 0.005), which was sustained at two-year follow-up. Pharmacological treatment could be stopped in about one-quarter of these cases. In non-obese mild-hypertensives, deep muscle relaxation and biofeedback techniques were prescribed. Significant decreases in SBP (153.1 to 138.3 mmHg, P less than 0.005) and DBP (101.2 to 90.1 mmHg, P less than 0.005) were achieved at six months. In nine out of 19 cases pharmacological treatment was stopped after six to eight months. Smoking cessation was achieved by individual instruction together with stress management techniques, physical exercise and a nicotine-based chewing gum. After six months 18 out of 30 heavy smokers had stopped smoking, and the remaining 12 had reduced their cigarette consumption.(ABSTRACT TRUNCATED AT 250 WORDS)

The antihypertensive effect of atenolol and bopindolol in the elderly.

The antihypertensive efficacy and tolerability of two betablockers: atenolol and bopindolol, was compared in a group of 30 elderly subjects aged 64.8 +/- 4.6 years. The daily dose of the two agents was relatively low. Atenolol 50-100 mg and bopindolol 0.5-1.0 mg sufficed to cause reduction of DBP to the target of less than or equal to 95 mm Hg, when applied as monotherapy. This was achieved in 75% of cases with bopindolol and in 93% of cases with atenolol. Atenolol, 50-100 mg/dd, lowered blood pressure from 173.7 +/- 13.2/103.7 +/- 3.0 (weekly) to 155.5 +/- 16.5/86.5 +/- 8.2 mm Hg (week 12) (P less than 0.005) while bopindolol, 0.5-1.0 mg, lowered blood pressure from 171.6 +/- 11.3/104.1 +/- 3.6 to 158.7 +/- 20.9/86.1 +/- 6.0 mm Hg (P less than 0.005). Heart rate was reduced from 80.5 (week 4) to 66.7 +/- 7.3 (week 12) by atenolol (P less than 0.0001), and from 83.7 +/- 11.8 (week 4) to 71.1 +/- 7.5 (week 12) by bopindolol (P less than 0.0001). Between treatment differences: comparisons yielded P values which were not sufficiently low to reject the null hypothesis of no difference between the two treatments. Well-being and short-term memory were not affected by either agent and tolerability of both drugs was good. These findings demonstrate that both bopindolol and atenolol are useful agents for control of hypertension in the elderly.

Normoglycemic diabetic retinopathy and nephropathy.

End-stage renal failure is one of the major complications of diabetes and a significant cause of death in this population. At present, its cause is unknown, and consequently, attempts to prevent it are arbitrary. It has been suggested that improved control of blood glucose and hypertension may prevent the onset of renal failure in patients with diabetes mellitus. We present a case in which, despite near-normal levels of blood glucose and blood pressure, a relentless downhill course ensued resulting in severe renal failure and near blindness as a result of diabetic nephropathy and retinopathy.