[Nifedipine or nicardipine in management of threatened preterm delivery: an observational population-based study]. / Utilisation de la nifédipine et de la nicardipine dans le traitement de la menace d'accouchement prématurée: données observationnelles en population.

OBJECTIVE: For the first line tocolysis, calcium channel blockers (CCB)--oral nifedipine (Adalate®) or intravenous nicardipine (Loxen®)--are frequently used in France. No study compared nifedipine and nicardipine in management of threatened preterm delivery. From data of a French observational study, we compared factors associated with the use of nifedipine and nicardipine. Efficacy and tolerance of the two treatments were also compared. METHODS: It was a secondary analysis of EVAPRIMA study, a practice survey describing management of threatened preterm delivery in 107 French maternity units. Only women who received calcium channel blockers in their first line tocolytic therapy were included. We studied obstetrical factors associated with the choice of nifedipine or nicardipine. We also analyzed factors associated with a delivery within seven days following admission using univariate and multivariate analysis. Adverse secondary effects were compared between women who received nifedipine or nicardipine. RESULTS: Three hundred and four women received calcium channel blockers for their first line tocolytic therapy, in 73 maternity units: 93 (30.6%) women received oral nifedipine and 211 (69.4%) intravenous nicardipine. The same CCB was always prescribed in 69 maternity units. Admission after in utero transfer was less frequent among women who received nifedipine (6.5% versus 17.1%, P=0.01). Premature rupture of the membranes was also less frequent among women who received nifedipine (4.3% versus 13.7%, P=0.02), in comparison with women who received nicardipine. Median duration between admission for threatened preterm labor and delivery was longer when nifedipine was used (44 days versus 36 days, P=0.04). After adjustment on obstetrical factors, the risk to have a delivery within 7 days following admission was not significantly different between nifedipine and nicardipine groups (adjusted OR=0.5 [0.2-1.2]). Among women who received nifedipine only two cases (2.1%) of adverse event were reported with only one case needing a switch of treatment. Thirteen (6.2%) cases of adverse event were reported among women who received nicardipine (P=0.16); in three cases it motivated a switch. However, due to bias and limits inherent in such studies, our results should be interpreted cautiously. CONCLUSION: Nicardipine is the first choice for French obstetricians in management of severe threatened preterm delivery. However, intravenous nicardipine does not increase gestational duration in comparison with oral nifedipine.

Hemodynamic management and outcome of patients treated for cerebral vasospasm with intraarterial nicardipine and/or milrinone.

BACKGROUND: Vasospasm is a potentially devastating complication after aneurysmal subarachnoid hemorrhage. Although endovascular treatment with intraarterial nicardipine and milrinone is an accepted clinical treatment strategy, there is little information either on hemodynamic management during treatment or on outcome and consequences of the hemodynamic management. We tested 2 hypotheses: (1) intraarterial administration of nicardipine and milrinone to treat cerebral vasospasm would require increased administration of vasoconstrictor to support arterial blood pressure at target levels; and (2) high-dose vasopressors administered to increase blood pressure in these patients would lead to systemic acidosis and end-organ ischemic damage. METHODS: We conducted a single-center, retrospective review of consecutive patients with clinically symptomatic vasospasm after aneurysmal subarachnoid hemorrhage that failed medical management with "triple H therapy" and subsequently received intraarterial nicardipine and/or milrinone between March 2005 and July 2007. RESULTS: Of 160 endovascular interventions in 73 patients (aged 52 +/- 10 years; 50 women), 96 received only nicardipine, 5 only milrinone, and 59 both drugs. General anesthesia with muscle relaxation was performed for 93% of procedures. During treatment, both the number and dose of vasopressors required to maintain arterial blood pressure at target levels increased; the median dose of phenylephrine increased from 200 (n = 121) to 325 microg/min (n = 122), norepinephrine increased from 12 (n = 60) to 24.5 microg/min (n = 87), and vasopressin infusions increased from 7 to 24. Nonetheless, arterial blood pressure decreased 13% during treatment. In >90% of procedures, the postprocedure angiogram showed improved vessel caliber. A single patient demonstrated troponin T increase; no patients had a decrease in renal function, bowel or peripheral ischemia, systemic acidosis, or acute stroke. Overall mortality was 11%. CONCLUSIONS: Intraarterial administration of nicardipine and/or milrinone requires use of vasopressors to maintain arterial blood pressure. Despite high doses of vasoconstrictors, treatment has low mortality, minimal end-organ ischemic damage or systemic acidosis, and results in improved caliber of cerebral vessels affected by vasospasm.

Safety and feasibility of intra-arterial nicardipine for the treatment of subarachnoid hemorrhage-associated vasospasm: initial clinical experience with high-dose infusions.

BACKGROUND AND PURPOSE: Delayed cerebral ischemia from vasospasm is a major complication after aneurysmal subarachnoid hemorrhage (SAH), but complications and/or low efficacy are associated with current therapy. We report our initial experience with intra-arterial use of a calcium channel blocker, nicardipine. MATERIALS AND METHODS: A retrospective review of a consecutive series of patients with clinical and angiographic vasospasm treated with intra-arterial nicardipine was performed. Standard criteria for definition of significant, intractable vasospasm after aneurysmal SAH were used. After catheter angiographic confirmation of vasospasm, arteries showing severe narrowing were targeted for superselective catheterization. Nicardipine was infused at a high dose rate (0.415-0.81 mg/min). Contrast injections were performed at 2-5-mg intervals to assess effective response (a 60% increase in arterial diameter of the most severely decreased in caliber vessel compared with the very first angiographic run). RESULTS: Eleven consecutive patients underwent a total of 20 procedures; most had SAH with high Hunt and Hess grades (III or IV). All had depressed level of consciousness; others had paresis (7/20, 35%), aphasia (1/20, 5%), and facial nerve palsy (1/20, 5%). Between 10 and 40 mg of nicardipine was used. A 60% increase in diameter of the main affected artery compared with the initial diameter measured in the initial angiographic run was achieved in all procedures. Clinical improvement (resolved focal symptoms or increased Glasgow Coma Score) occurred in 10 of 11 patients (91%). One patient died from complications of the initial hemorrhage. No complications occurred after 16 of 20 procedures (80%); minor complications without sequelae occurred after the remaining procedures. Follow-up of at least 2 months in 10 survivors revealed minor or no deficits in most patients with a Glasgow Outcome Score of 1 or 2 in 9 of 10 patients (90%). CONCLUSION: In this small series, high-dose intra-arterial nicardipine infusion to treat SAH-associated vasospasm seems to be safe and effective.

[The efficacy and safety of slow-release nicardipine vs nifedipine in angina]. / Efficacia e tollerabilità della nicardipina a lenta liberazione vs nifedipina nell'angina.

This controlled, double-blind, completely randomized study assessed the efficacy and safety of nicardipine and nifedipine, both in slow-release formulations, in patients with unstable angina. Thirty patients (28 M, 2F) were included in the final analysis, mean age 56.5 +/- 9.1 years (SD), mean weight 73.5 +/- 9.2 kg, mean height 171.5 +/- 6.5 cm, all with unstable angina. Nicardipine was given at a daily dosage of 80-120 mg, and nifedipine 40-60 mg, for up to one month. At the end of treatment with nicardipine supine systolic and diastolic blood pressure (SBP and DBP) dropped respectively 7.7% and 5.5% at 8 am and 8.6% and 7.1% at 8 pm. Nifedipine reduced SBP and DBP by respectively 6.5% and 13.1% at 8 am and 5.3% and 9.4% at 8 pm. There was no clinical or statistical difference between the treatments. Heart rate did not change appreciably during either treatment. On completion of nicardipine treatment, 87.5% of patients had suffered no angina attacks, compared with 66.7% for nifedipine. The remaining 12.5% of patients treated with nicardipine presented only one mild angina attack per day, while the other 33.3% of the nifedipine patients had one moderate angina attack per day. No untoward effects were reported with nicardipine; one patient receiving nifedipine presented cardiopalmus and another complained of headache. These results indicate that nicardipine is at least as safe and effective as nifedipine in the treatment of unstable angina.

Long-acting nicardipine for elderly hypertensive patients: effect on diurnal variation of blood pressure.

The effect of long-acting nicardipine tablets on diurnal variation of blood pressure was compared with that of standard nicardipine tablets and long-acting nifedipine tablets by 24-hour ambulatory blood pressure monitoring in 35 patients with hypertension. Long-acting nicardipine decreased systolic blood pressure in each age group, and there was no difference in its anti-hypertensive effect when compared with the other two drugs. All three drugs had no effect on the amplitude of daily blood pressure variation, and all three drugs decreased the baseline blood pressure in each age group when compared with untreated patients. In addition, no change was observed in the decrement of baseline blood pressure after switching from the other two drugs to long-acting nicardipine. Long-acting nicardipine had less effect on diurnal blood pressure variation than standard nicardipine tablets, which are administered three times daily. In each age group, long-acting nicardipine also more effectively inhibited the increase in cardiac work resulting from the morning rise phenomenon when compared with standard nicardipine tablets. These findings suggest that long-acting nicardipine may be a more useful preparation for the treatment of essential hypertension, particularly in elderly patients.

Are the calcium antagonists really useful in cerebral aneurysmal surgery? A retrospective study.

From 1983 to 1990, 234 patients with one or several cerebral arterial aneurysms were surgically treated in our department. Since 1983, we have been performing surgery as early as possible. As soon as the subarachnoid hemorrhage diagnosis is confirmed by computed tomography (or if unconfirmed, by lumbar puncture), we assume that each patient may have an aneurysm. Between 1987 and 1990, 111 patients were treated by vascular volume expansion (maintenance of central venous pressure above 5 cm H2O with 4% albumin or Ringer-lactate or, if necessary, with 20% albumin), which we supplemented with calcium antagonists (nimodipine in 60 patients and nicardipine in 51 patients). Two months after being discharged, each patient is examined by a neurosurgeon and, on the same day, is subjected to a neuropsychological evaluation and a computed tomographic scan of the brain. A few months after this consultation, a working-position/family-activities questionnaire is issued to the patient. All of the results studied on the basis of postoperative mortality, second-month computed tomographic scan ischemia, neuropsychological evaluation, and return to work show no significant difference between the groups with or without calcium antagonists or between the nimodipine and nicardipine subgroups.

[Comparison of nicardipine and nifedipine in treatment of Chinese senile hypertension placebo-control, double-blind, randomized and crossover study].

The purpose of this placebo-control, double-blind, randomized and crossover study is to evaluate the effect of nicardipine and nifedipine in Chinese senile hypertension. Among totally 37 senile hypertensive patients enrolled, 26 patients (25 males, 1 female) from 55 to 78 years of age (mean 65) who had finished one part or whole protocol were studied. Totally 18 cases after 6-week treatment of nicardipine (Perdipine) had blood pressure decrease significantly from 152.6 +/- 12.3/99.6 +/- 5.7 to 140.4 +/- 15.6/93.8 +/- 8.1 mmHg in supine position (P < 0.05), and from 153.3 +/- 12.7/98.7 +/- 7.7 to 139.2 +/- 13.5/90.7 +/- 7.6 mmHg in standing position (p < 0.05). Twenty-five cases after 6-week treatment of nifedipine (Towarat) also had significant blood pressure decrease from 155.0 +/- 13.3/99.5 +/- 8.4 to 144.2 +/- 10.0/95.3 +/- 9.2 mmHg in supine position (P < 0.05), and from 151.5 +/- 17.8/100.6 +/- 9.5 to 138.6 +/- 12.8/90.4 +/- 8.3 mmHg in standing position (p < 0.05). Heart rate was unchanged in both groups. Both nicardipine and nifedipine decreased blood pressure and increased heart rate significantly with the first dose of medication in the morning (P < 0.05). There was 6.5% and 9.0% decrease of systolic and diastolic blood pressure with nicardipine in supine position, 10.1% and 11.2% decrease with nifedipine in supine position, 6.3% and 7.2% decrease with nicardipine in standing position, and 9.7% and 10.6% decrease with nifedipine in standing position. The major side-effects were palpitation (20%) and lower abdominal distension (16%) with nicardipine; and nausea or vomiting (22%) and dizziness (15%) with nifedipine.(ABSTRACT TRUNCATED AT 250 WORDS)

Dose-escalation study of intravenous nicardipine in patients with aneurysmal subarachnoid hemorrhage.

A dose-escalation study of the calcium ion entry blocking drug nicardipine was performed using large dose infusions in 67 patients with recent aneurysmal subarachnoid hemorrhage (SAH). A safe, potentially therapeutic dose of the drug was determined. Patients admitted within 7 days of SAH from a documented cerebral aneurysm were entered into the study if no spasm was present on the initial angiogram. Nicardipine was administered as a continuous intravenous infusion throughout the 14-day period after SAH, regardless of the timing of surgery. To determine the safest possible dose, nicardipine was administered at seven dose levels from 0.01 to 0.15 mg/kg/hr. The total daily doses ranged from 27.7 mg to 375.0 mg. A follow-up angiogram was carried out on all 67 patients 7 to 10 days after SAH. Computerized tomography and neurological examinations were used to determine the presence of cerebral infarction. No major adverse effects, unexpected reactions, or permanent sequelae could be attributed to nicardipine. A decline in blood pressure was noted following administration of the drug. This occurred more frequently among patients given the largest dose but did not produce clinical problems or require discontinuation of the drug. Favorable outcomes were noted in 52 patients (78%). Vasospasm was found by arteriography in 31 patients (46%). A dose-related trend was noted: only eight (24%) of 33 patients treated at the highest dose level (approximately 10 mg/hr) developed arteriographic evidence of vasospasm. Symptomatic vasospasm was diagnosed in only two (6%) of 33 patients treated with this dose. Of the 34 patients receiving the lower dose levels, angiographic spasm was observed in 68% and symptomatic vasospasm in 27%. No deaths due to vasospasm occurred. Nicardipine appears to prevent both vasospasm and cerebral ischemia after SAH. A multicenter randomized double-blind trial to test this hypothesis is planned.

A randomized double-blind crossover study of nicardipine and nifedipine in patients with angina pectoris and concomitant essential hypertension.

The two dihydropyridine calcium antagonists, nicardipine and nifedipine, were compared in 12 patients with both stable angina pectoris and systemic hypertension using a double-blind, crossover protocol. After a 2-week placebo run-in period, each patient was randomized to either nicardipine or nifedipine; each drug was titrated up to either blood pressure normalization, appearance of adverse effects, or maximal dosage (40 mg, three times a day with nicardipine and 30 mg, three times a day with nifedipine) and then administered for 4 weeks. Maximal symptom-limited exercise tests were performed at the end of the placebo run-in and each treatment period, 3 and 8 hours after drug administration. Nicardipine and nifedipine were used at the mean doses of 100 +/- 20 mg/day and 57 +/- 20 mg/day, respectively. Both drugs reduced, significantly and similarly, standing and supine blood pressure, frequency of anginal episodes, and nitroglycerin consumption. At 3 hours after drug administration, exercise duration and time to 1-mm ST depression increased significantly from 402 +/- 84 and 306 +/- 108 seconds, respectively, with placebo; to 533 +/- 135 and 442 +/- 138 seconds during nicardipine; and to 518 +/- 118 and 437 +/- 133 seconds during nifedipine, with a concomitant reduction of peak ST depression. Both submaximal and maximal exercise diastolic blood pressure were significantly reduced by the two calcium antagonists whereas systolic blood pressure was decreased only at submaximal but not at maximal exercise; the heart rate was not significantly modified by the two drugs at any exercise stage.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of the efficacy of nicardipine, a new calcium channel blocker, with nifedipine in the treatment of mild to moderate essential hypertension.

Thirty-nine patients with mild to moderate essential hypertension participated in a parallel, single-blind study comparing 6 weeks' treatment of nicardipine hydrochloride (90 mg/day) with nifedipine (40 mg/day). Nicardipine-treated patients commenced therapy with a significantly higher mean supine diastolic blood pressure than the nifedipine-treated patients. There was a statistically significant fall in blood pressure (systolic and diastolic) on both treatments at the 3 and 6 week follow-up visits. On adjusting the results for the baseline inequality, no statistically significant differences were found between treatment groups. Seven patients withdrew from nifedipine therapy and six patients withdrew from nicardipine therapy due to adverse events. The results show that nicardipine hydrochloride at 90 mg/day is an effective anti-hypertensive agent. The incidence and nature of adverse events were similar on the two treatments.