Antihypertensive monotherapy with nisoldipine CC is superior to enalapril in black patients with severe hypertension.

A single-center, prospective double-blind randomized trial was conducted to compare the efficacy and safety of the calcium channel blocker nisoldipine in a sustained release coat-core formulation (CC), titrated from 10 mg to 40 mg daily, with the angiotensin converting enzyme inhibitor enalapril, titrated from 10 to 40 mg daily, in the treatment of black South African patients with severe hypertension (sitting diastolic blood pressure [DBP] between 115 and 140 mm Hg, confirmed by 24-h ambulatory blood pressure monitoring). Treatment target was a sitting DBP < 95 mm Hg by the 9th week of treatment. This was followed by a 4-month open phase using nisoldipine CC 10 to 60 mg daily. Ninety-six patients had complete data at baseline, and at the end of the double-blind and open phases, and were included in this analysis. In both groups, all patients required titration up to the maximal dose of double-blind medication. Monotherapy with nisoldipine CC, but not enalapril, significantly reduced both sitting and 24-h ambulatory blood pressure (BP). Twenty-four-hour BP in the nisoldipine CC group decreased from 179+/-14 / 118+/-7 to 144+/-16 / 94+/-10 mm Hg (P < .0001) versus 181+/-13 / 117+/-5 to 171+/-17 / 110+/-11 mm Hg in the enalapril group (P = ns). The profound decrease in blood pressure achieved with nisoldipine CC was accompanied by a significant reduction in left ventricular [LV] mass index, observed after only 2 months of treatment (from 146+/-40 to 129+/-35 g/m2, P = .05). In contrast, enalapril had no effect on LV mass (from 139+/-36 to 142+/-50 g/m2, P = NS). The antihypertensive effect of nisoldipine CC was further demonstrated in the open phase, during which 24-h BP decreased from 180+/-14 / 118+/-6 mm Hg (at baseline) to 142+/-16 / 92+/-10 mm Hg at the end of the 16-week open phase (P < .0001). This effect was sustained with trough-to-peak ratio of 74% for systolic and 67% for diastolic BP, with further regression in LV mass. Reduction in 24-h systolic BP to < 135 mm Hg was associated with a greater degree of regression of LV mass index in patients treated with nisoldipine CC. The incidence of adverse events in both groups was low and both nisoldipine CC and enalapril were well tolerated. The incidence of significant ventricular arrhythmia was also low and did not change with treatment. In conclusion, our findings suggest that nisoldipine CC administered once daily could be considered as a suitable first-line antihypertensive agent in black patients with severe hypertension, based on its profound and sustained blood-pressure-lowering effect, associated with significant regression of left ventricular mass and its low side effect profile.

Once-daily fixed dose combinations of verapamil and trandolapril in black patients with mild to moderate hypertension: a new choice for first line treatment.

Using ambulatory blood pressure (BP) monitoring, a potent ACE-inhibitor/calcium channel blocker combination was tested in 21 Black patients (age 52 +/- 10 years; 10 males, 11 females) with mild to moderate hypertension (mean 12-hour daytime diastolic BP > or = 90 mmHg and < or = 114 mmHg). After a 14-day wash-out and a 14-day placebo run-in period, therapy was initiated with verapamil 180 mg plus trandolapril 2 mg. At monthly visits, if mean daytime diastolic BP remained > or = 90 mmHg, the dose combination was uptitrated stepwise to verapamil 240 mg plus trandolapril 4 mg, verapamil 360 mg plus trandolapril 4 mg, and finally hydrochlorothiazide 12.5 mg were added. Mean 24-hour BP dropped from 150 +/- 14/96 +/- 7 mmHg at baseline to 131 +/- 13/82 +/- 8 mmHg after 4 months treatment (p < 0.001). In 16 (76%) patients mean 24-hour diastolic BP was < 90 mmHg at the end of the trial and 15 (71%) patients achieved a reduction of > 10 mmHg. Five out of 5 patients finishing on dose I were controlled, 5/6 patients on dose II, 5/8 patients on dose III, and 1/2 patients who received additional hydrochlorothiazide. The 24-hour BP load fell from 72 +/- 8% at baseline to 35 +/- 25% in 4 months (p < 0.001). Mean diastolic BP drop for the 2 peak hours during daytime was 20 mmHg and for the last 2 hours of monitoring was 13 mmHg, resulting in a trough to peak ratio of 65%. There were no significant adverse events or biochemical abnormalities. It is concluded that the combination doses tested showed a sustained and marked antihypertensive effect throughout the 24-hour dosing interval, and the starting dose (verapamil 180 mg plus trandolapril 2 mg) seems appropriate in this group of patients.

Comparison of captopril-thiazide and enalapril-thiazide combinations in the management of mild to moderate black hypertensive patients: how important is diuretic dose and duration of action of the ACE-inhibitor?

A double-blind, randomized, parallel-group study was performed to compare the efficacy and tolerability of captopril-thiazide and enalapril-thiazide combinations. After a 3-week placebo run-in period, 47 Black patients with mild to moderate essential hypertension (mean 24-hour diastolic blood pressure (BP) > 90 mmHg and < 115 mmHg) were randomized to receive 1 of 2 combination tablets: captopril 50 mg plus hydrochlorothiazide 25 mg (CAP, n = 24) or enalapril 20 mg plus hydrochlorothiazide 12.5 mg (COR, n = 23) once daily. After 12 weeks of active treatment the mean 24-hour ambulatory BP was reduced from 152 +/- 11/99 +/- 6 to 133 +/- 13/86 +/- 7 mmHg (p < 0.005) in the CAP group and 157 +/- 15/100 +/- 6 to 141 +/- 18/90 +/- 12 in the COR group (p < 0.005). Target BP (24-hour diastolic BP < 90 mmHg) was achieved in 75% (18/24) of patients on CAP and 48% (11/23) on COR (p = n.s.). 24-hour BP load fell significantly with both CAP (from 69% to 34%, p < 0.001) and COR (from 67% to 37%, p < 0.001). Left ventricular mass index decreased by 7% with CAP and 11% with COR. Cardiac index and fractional shortening remained essentially unchanged in both groups. Both treatments were well tolerated and overall incidence of side effects was very low. It is concluded that both CAP and COR are effective, safe first-line antihypertensive choices in Black patients with mild to moderate hypertension with the former showing a trend towards greater efficacy than the latter.

Effects of amlodipine on 24-hour ambulatory blood pressure profiles, electrocardiographic monitoring, and left ventricular mass and function in black patients with very severe hypertension.

In a 3-month, open-label study, 54 consecutive black patients with very severe hypertension were treated with amlodipine. Very severe hypertension was defined as an average sitting diastolic blood pressure (BP) > or = 115 mmHg and < or = 140 mmHg as a mean of 10 readings over a 30-minute period using an automatic BP measuring device and a mean 24-hour diastolic ambulatory blood pressure (ABP) > or = 110 mmHg and < or = 140 mmHg). Serial changes in 24-hour ABP and electrocardiographic monitoring, left ventricular (LV) mass index, and LV systolic function were evaluated. Mean 24-hour ABP was reduced from 181 +/- 14/119 +/- 6 to 140 +/- 15/92 +/- 9 mmHg at 3 months (P < 0.0001). Target BP (mean 24-hour diastolic ABP < 90 mmHg) was achieved in 35% of the patients. The reduction in BP was sustained for 24 hours after drug administration. Simultaneous BP measurements using the automatic BP measuring device were significantly different from the ABP measurements before and after treatment, suggesting a marked "white coat" pressor effect. At baseline, frequent or complex ventricular arrhythmias (> 30 ventricular extrasystoles per hour, ventricular couplets) were present in 2 (4%) patients, with no significant change after treatment. Left ventricular mass index regressed from 140 +/- 50 to 111 +/- 30 g/m2 at 3 months (P < 0.03); LV performance was not adversely affected. Adverse effects were few and tended to disappear during the treatment period. All of the clinical laboratory parameters tested remained unchanged. In this group of patients, treatment with amlodipine showed a marked and sustained antihypertensive action as demonstrated by 24-hour ABP monitoring, and was well tolerated and associated with LV mass regression without adverse effect on systolic cardiac function. Further, a low rate of complex ventricular arrhythmias was documented.

Low dose hydrochlorothiazide (12.5 to 25 mg daily) as monotherapy in black patients with mild to moderate hypertension. Assessment by ambulatory blood pressure monitoring.

The efficacy of low dose (12.5 to 25 mg daily) hydrochlorothiazide (HCTZ) was evaluated by ambulatory blood pressure monitoring (ABPM) in 19 mild to moderate hypertensive (mean daytime 12-h diastolic BP > or = 90 mm Hg and < 115 mm Hg) South African black patients. After a 3-week placebo run-in period, HCTZ was administered for 8 weeks as monotherapy. The mean daytime ABPM was reduced from 159 +/- 13/105 +/- 6 to 145 +/- 11/97 +/- 10 mm Hg (P < .005). Only 6/19 (32%) patients achieved BP control. The 24-h BP load fell from 69% at baseline, to 53% with 12.5 mg HCTZ and to 47% with 25 mg HCTZ daily. There were no side effects but the increase of HCTZ to 25 mg daily was followed by adverse changes (P < .05) in serum potassium levels. It is concluded that low dose of HCTZ monotherapy has only a moderate effect on the BP control and 24-h BP load while the higher 25 mg dose is associated with significant decrease in serum potassium level.

Frequency of prosthetic valve-related complications with very low level warfarin anticoagulation combined with dipyridamole after valve replacement using St. Jude Medical prostheses.

The safety of a very low level of anticoagulation combined with dipyridamole in a rheumatic population (mean age 31 +/- 13 years) with the St. Jude Medical (SJM) prosthesis has not yet been tested. Furthermore, no data are available on the safety of relatively infrequent monitoring of anticoagulation levels and of the necessity for different therapeutic targets according to valve position, number of risk factors, and other baseline risk factors for thromboembolism. In this study, the performance of the SJM prosthesis was tested using a target international normalized ratio (INR) of 2.0 to 2.5 combined with dipyridamole 300 mg/day applied uniformly to all patients. Clinical, biochemical, and echocardiographic data were acquired prospectively in 200 consecutive patients at 3-month intervals. Follow-up (mean 27 +/- 13 months) was complete in 95% of patients. Thirteen patients died (2.9%/patient year). Severe left ventricular dysfunction was the cause of death in 10 of 13 patients. Probability of survival (Kaplan-Meier) was 0.92 at 36 months and of event-free survival 0.84 at 36 months. The median INR was 2.0 +/- 0.9. Valve obstruction did not occur, and there were 3 thromboembolic events (0.6%/patient year). Incidence of bleeding was 1.6%/patient year (n = 7) and was major (hemorrhagic stroke) in 1 (0.2%/patient year). Thus, the SJM prosthesis performs very well despite the use of very low level warfarin anticoagulation combined with dipyridamole. A 3-month assessment of the anticoagulation level is safe. Left ventricular dysfunction rather than valve-related complications is the leading cause of mortality in this population.

Effect of isradipine in black patients with very severe hypertension. 24-hour ambulatory blood pressure monitoring and echocardiographic evaluation.

Fifty consecutive black patients with very severe hypertension (sitting diastolic blood pressure > or = 120 mm Hg and systolic > or = 210 mm Hg by the conventional cuff method) were treated in an open-label study (without a placebo or active drug control group) for 3 months with a long-acting preparation of isradipine (Dynacirc SRO), during which time serial changes in 24-h ambulatory blood pressure monitoring (ABPM), left ventricular (LV) mass index, and LV systolic function were evaluated. Mean 24-h ABPM was reduced from 184 +/- 13/119 +/- 6 to 148 +/- 18/96 +/- 11 mm Hg at 3 months (P < .0001). The reduction in BP was sustained for 24 h after dosing. Simultaneous BP measurements using a conventional cuff method and Dinamap were significantly different from the ABPM pre- and posttherapy, suggesting a marked "white coat" pressor effect. LV mass index regressed from 143 +/- 36 to 122 +/- 32 g/m2 at 3 months (P < .02). Heart rate and mean body weight were unchanged. Left ventricular performance was not adversely affected. Cardiac index and fractional shortening changed insignificantly, from 2.6 +/- 0.6 to 2.7 +/- 0.5 L/min/m2, and from 28 +/- 6 to 31 +/- 7%, respectively. Adverse effects were few and tended to disappear during the treatment period. All of the clinical laboratory parameters tested remained unchanged. We conclude that in this group of patients long-acting isradipine 1) showed a marked and sustained antihypertensive action demonstrated by 24-h ABPM; and 2) was well tolerated and associated with LV mass regression without adverse effect on systolic cardiac function.(ABSTRACT TRUNCATED AT 250 WORDS)

Nifedipine versus captopril in the management of moderate hypertension in black patients.

The efficacy of nifedipine (20 to 40 mg twice daily) and captopril (25 to 50 mg twice daily) was assessed during a 12-week single-blind randomized trial in 41 moderately hypertensive black patients (mean 24-h diastolic blood pressure [BP] > or = 90 mm Hg and < 115 mm Hg). Nifedipine and captopril were administered as monotherapy in increasing dosage while a diuretic was added after 8 weeks in patients who failed to reach the target BP (24-h mean diastolic BP < 90 mm Hg) on monotherapy. After 8 weeks of monotherapy, the mean 24-h ambulatory BP was reduced from 156 +/- 12/101 +/- 5 to 128 +/- 11/84 +/- 7 mm Hg (P < .0001) in the nifedipine group while it remained essentially unchanged (156 +/- 15/101 +/- 7 to 158 +/- 17/102 +/- 9) in the captopril group. Left ventricular (LV) mass index was also reduced significantly (P < .05) in the nifedipine group, while cardiac index and fractional shortening changed marginally. The addition of diuretic in the captopril group (16/21 patients) resulted in a significant fall in BP to 123 +/- 11/81 +/- 7. Only 2/20 patients in the nifedipine group required the addition of diuretic. The overall incidence of side effects was similar with both treatments but the addition of diuretic in the captopril group was followed by adverse changes in serum sodium (P < .01), urea (P < .05), and creatinine (P < .01) levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Somatosensory evoked potentials quantify clinical improvement of cerebral vasospasm after intravenous administration of nimodipine.

The calcium antagonist nimodipine (Nimotop; Bayer AG Leverkusen) has been shown to prevent cerebral vasospasm after aneurysm surgery. Ten patients with clinical and angiographic evidence of vasospasm showed accompanying delays in central conduction time, quantified by somatosensory evoked potential measurements, but nimodipine infusion markedly improved neurological status and level of consciousness in all cases within 10-60 minutes. Conduction time was simultaneously reduced on the affected side. No focal deficits developed during therapy (mean 7.1 days) with nimodipine, which also appears to be effective in relieving existing vasospasm. Evoked potentials provided a noninvasive quantitative parameter that correlated well with vasospastically induced clinical signs.

Survey of clinical experience with nimodipine in patients with subarachnoid hemorrhage.

The present studies show that nimodipine prevents and/or improves permanent ischemic neurological deficits in patients with subarachnoid hemorrhage. This was particularly marked in four double-blind, placebo-controlled studies in which statistically significant reductions in mortality and morbidity as consequence of cerebral vasospasm were found. The drug has been shown to increase cerebral blood flow, to reduce vasoconstriction, although not to fully prevent angiographic vasospasm, and to improve central conduction time. Nimodipine did not increase the rate of rebleeding. Its administration during anesthesia does not result in management problems. In general, nimodipine was well tolerated. Side effects were recorded mainly in open studies using the intravenous formulation and consisted mainly of decreases in blood pressure and headaches. Transient increases in liver enzymes may be due to the organic solvent. Hence, all results indicate that patients with subarachnoid hemorrhage will benefit from preventive or therapeutic nimodipine treatment.

A comparison of the acute hemodynamic effects of nifedipine and nisoldipine in patients with ischemic reduced left ventricular function.

Nisoldipine (BAY k 5552) like nifedipine, is a dihidropyridine compound with strong calcium blocking activity. The purpose of this study was to measure and compare the absolute hemodynamic effects of these two drugs before and at 30 min, 60 min and 120 min after oral intake in 20 ischemic heart disease patients with radionuclide gated cardiac scintigraphy. No significant change was seen in end diastolic volume index with either of the drugs. With nifedipine the stroke volume index (SVI) increased significantly from the basal value at 30 min (P = 0.004) and 60 min (P = 0.034) yet not significantly at 120 min. The same trend was seen in left ventricular ejection fraction (LVEF) with significant increases at 30 min (P = 0.02) and 60 min (P = 0.025) yet not at 120 min. The cardiac index increased significantly at 30 min (P = 0.001), 60 min (P = 0.002) and 120 min (P = 0.025) but the latter value was significantly lower than the 30 min value indicating the maximal effect had already passed. With nisoldipine the SVI increased significantly at 60 min (P = 0.004) and 120 min (P = 0.001) but not at 30 min. These changes were again reflected by a significant increase in LVEF at 60 min (P = 0.021) and 120 min (P = 0.002) without significant increase at 30 min. The increase in CI was highly significant at 60 min (P = 0.003) and 120 min (P = 0.001) without significant change at 30 min. Nisoldipine proved to be a potent calcium antagonist with slower onset and longer duration of action than nifedipine.