Nicardipine Is a Safe, Efficacious, and Cost-Effective Antihypertensive for Neonates and Young Infants Undergoing Cardiac Surgery.

OBJECTIVE: The use of nicardipine in congenital cardiac surgery has been guarded given the calcium sensitivity of immature myocardium and paucity of clinical data. Reports of nicardipine use have excluded neonates with single ventricles. The goal of this study was to compare the use of nicardipine and sodium nitroprusside for postoperative blood pressure control in young patients recovering from cardiac surgery. METHODS: All neonates (<30 days) and young infants (31-180 days) who received either sodium nitroprusside or nicardipine as first-line therapy for blood pressure control were retrospectively reviewed. Some patients had multiple index operations and each index operation was counted separately regarding treatment with sodium nitroprusside or nicardipine. RESULTS: A total of 59 patients underwent 70 procedures (24 as neonates and 46 as infants). Nicardipine was administered as initial therapy following 33 procedures (n = 28 patients), and sodium nitroprusside was administered as initial therapy following 37 index procedures (n = 31 patients). The duration of treatment was longer (P = .025) when sodium nitroprusside was the initial treatment. Five (15%) patients that received nicardipine required a second blood pressure management agent, and seven (19%) patients that received sodium nitroprusside required a second agent (P = .66). No adverse events related to titratable antihypertensive therapy were recorded in any treatment group. The use of nicardipine resulted in significant medication cost reduction. Based on average wholesale price, patient costs for sodium nitroprusside use were $182,952 ($5,544/pt), while costs for nicardipine were only $24,960 ($780/pt). CONCLUSIONS: Nicardipine can be safely used as a first-line antihypertensive in infants. The use of nicardipine as initial antihypertensive therapy rather than sodium nitroprusside can lead to a significant reduction in medication costs without jeopardizing clinical outcomes.

Comparison of efficacy and safety of intracoronary nicardipine and adenosine for fractional flow reserve assessment of coronary stenosis.

BACKGROUND: Administration of intracoronary (IC) adenosine allows an easily feasible, inexpensive, and more rapid alternative method for fractional flow reserve (FFR). It is common practice in many centers worldwide. Nicardipine is a strong coronary vasodilator but its efficacy and safety for assessing FFR is not established. The purpose of present study was to compare the efficacy and safety of IC nicardipine and adenosine for assessing FFR. METHODS: One hundred and fifty-nine patients with a total of 193 vessels undergoing clinically indicated FFR assessment of intermediate coronary stenoses were included. For the initial assessment of FFR, hyperemia was induced by an IC adenosine. After a washout period of 3 min, FFR was reassessed using 200 µg of IC nicardipine. RESULTS: Hyperemic efficacy among two different stimuli was compared. The mean FFR with IC adenosine was 0.83 ± 0.09 and that with an IC nicardipine was 0.84 ± 0.09. The median FFR with an IC adenosine was 0.83 (0.78-0.91) and that with an IC nicardipine was 0.85 (0.79-0.91) (p-value 0.246). Both FFR values showed an excellent correlation (R2 = 0.982, p < 0.001). Nicardipine produced fewer changes in heart rate, less chest pain and less flushing than adenosine. Transient atrioventricular block occurred in 29 patients with IC adenosine and none with IC nicardipine. CONCLUSIONS: IC bolus injection of nicardipine could be introduced as a safe and practical alternative method of inducing hyperemia during FFR measurements. Compared to IC adenosine, IC nicardipine has a similar hyperemic efficacy and excellent side-effect profile.

Early Achievement of Blood Pressure Lowering and Hematoma Growth in Acute Intracerebral Hemorrhage: Stroke Acute Management with Urgent Risk-Factor Assessment and Improvement-Intracerebral Hemorrhage Study.

BACKGROUND: Previous studies have revealed that hematoma growth mainly occurs during the first 6 h after the onset of spontaneous intracerebral hemorrhage (ICH). Early lowering of blood pressure (BP) may be beneficial for preventing hematoma growth. However, relationships between timing of BP lowering and hematoma growth in ICH remain unclear. We investigated associations between timing of BP lowering and hematoma growth for ICH. METHODS: The Stroke Acute Management with Urgent Risk-factor Assessment and Improvement (SAMURAI)-ICH Study was a multicenter, prospective, observational study investigating the safety and feasibility of early (within 3 h from onset) reduction of systolic BP (SBP) to < 160 mm Hg with intravenous nicardipine for acute hypertension in cases of spontaneous ICH. The present study was a post hoc analysis of the SAMURAI-ICH study. We examined relationships between time from onset, imaging, and initiation of treatment to target SBP achievement and hematoma growth (absolute growth ≥6 mL) in ICH patients. Target SBP achievement was defined as the time at which SBP first became < 160 mm Hg. RESULTS: Among 211 patients, hematoma growth was seen in 31 patients (14.7%). The time from imaging to target SBP and time from treatment to target SBP were significantly shorter in patients without hematoma growth than in those with (p = 0.043 and p = 0.032 respectively), whereas no significant difference was seen in time from onset to SBP < 160 mm Hg between groups (p = 0.177). Patients in the lower quartiles of time from imaging to target SBP and time from treatment to target SBP showed lower incidences of hematoma growth (p trend = 0.023 and 0.037 respectively). The lowest quartile of time from imaging to target SBP (< 38 min) was negatively associated with hematoma growth on multivariable logistic regression (OR 0.182; 95% CI 0.038-0.867; p = 0.032). CONCLUSIONS: Early achievement of target SBP < 160 mm Hg is associated with a lower risk of hematoma growth in ICH.

Intravenous nicardipine dosing for blood pressure lowering in acute intracerebral hemorrhage: the Stroke Acute Management with Urgent Risk-factor Assessment and Improvement-Intracerebral Hemorrhage study.

BACKGROUND: Intravenous nicardipine is commonly used to reduce elevated blood pressure in acute intracerebral hemorrhage (ICH). We determined factors associated with nicardipine dosing and the association of dose with clinical outcomes in hyperacute ICH. METHODS: Hyperacute (<3 hours from onset) ICH patients with initial systolic blood pressure (SBP) greater than 180 mm Hg were included. All patients initially received 5 mg/hour of intravenous nicardipine. The dose was adjusted to maintain SBP between 120 and 160 mm Hg. Associations of maximum hourly and total doses with early neurologic deterioration (END), hematoma expansion (>33%), and modified Rankin Scale score 4-6 at 3 months were assessed. RESULTS: Two hundred six patients (81 women, 65.8 ± 11.8 years) were studied. Initial SBP was 201.9 ± 15.9 mm Hg. Maximum and total nicardipine doses were 9.1 ± 4.2 mg/hour and 123.7 ± 100.2 mg/day, respectively. Multivariate analyses revealed that men (standardized regression coefficient [ß] = .20, P = .0030 for maximum dose; ß = .25, P = .0002 for total dose), age (ß = -.28, P = .0002; ß = -.25, P = .0005), and initial SBP (ß = .19, P = .0018; ß = .18, P = .0021) were independently associated with both maximum and total doses. Body weight (ß = .20, P = .0084) was independently associated with total dose. After multivariate adjustment, maximum dose (per 1 mg/hour; odds ratio [OR], 1.25; 95% confidence interval [CI], 1.09-1.45) was independently, and total dose (per 10 mg/day; OR, 1.06; 95% CI, .998-1.132) tended to be independently, associated with END. Nicardipine dose was not associated with hematoma expansion or 3-month outcome. CONCLUSIONS: Nicardipine dose is roughly predictable with sex, age, body weight, and initial SBP in acute ICH. The maximum dose was associated with neurologic deterioration.

Systolic blood pressure lowering to 160 mmHg or less using nicardipine in acute intracerebral hemorrhage: a prospective, multicenter, observational study (the Stroke Acute Management with Urgent Risk-factor Assessment and Improvement-Intracerebral Hemorrhage study).

OBJECTIVE: Optimal blood pressure (BP) control in acute intracerebral hemorrhage (ICH) remains controversial. We determined the effects of SBP lowering to 160 mmHg or more using intravenous nicardipine for acute ICH patients. METHODS: This is a prospective, multicenter, observational study conducted in Japan, with the lack of control groups. Patients with supratentorial ICH within 3 h of onset, admission SBP 180 mmHg or more, Glasgow Coma Scale (GCS) 5 or more, and hematoma volume less than 60 ml were initially treated with intravenous nicardipine to maintain SBP between 120 and 160 mmHg with 24-h frequent BP monitoring. The primary endpoints were neurological deterioration within 72 h [GCS decrement ≥ 2 points or National Institutes of Health Stroke Scale (NIHSS) increment ≥ 4 points; estimated 90% confidence interval (CI) on the basis of previous studies: 15.2-25.9%] and serious adverse effects (SAE) to stopping intravenous nicardipine within 24 h (1.8-8.9%). The secondary endpoints included hematoma expansion more than 33% at 24 h (17.1-28.3%), modified Rankin Scale (mRS) 4 or more (54.5-67.9%) and death at 3 months (6.0-13.5%). RESULTS: We enrolled 211 Japanese patients (81 women, 65.6 ± 12.0 years old). At baseline, BP was 201.8 ± 15.7/107.9 ± 15.0 mmHg. Median hematoma volume was 10.2 ml (interquartile range 5.6-19.2), and NIHSS score was 13 (8-17). Neurological deterioration was identified in 17 patients (8.1%), SAE in two (0.9%), hematoma expansion in 36 (17.1%), mRS 4 or more in 87 (41.2%), and death in four (1.9%). All the results were equal to or below the estimated lower 90% CI. CONCLUSION: SBP lowering to 160 mmHg or less using nicardipine appears to be well tolerated and feasible for acute ICH.

Intravenous labetalol compared with intravenous nicardipine in the management of hypertension in critically ill patients.

BACKGROUND: Critically ill patients with acute hypertension often require titratable rapid blood pressure (BP) reductions using parenteral administration of drugs. There are few comparative studies available to make informed drug product selection decisions. The purpose of this study was to evaluate the short-term clinical outcomes and costs of intravenous labetalol or intravenous nicardipine in the management of hypertension in critically ill patients. METHODS: This study was a retrospective analysis of consecutive patients receiving intravenous labetalol or intravenous nicardipine in the intensive care unit with acute elevations in either systolic (>160 mm Hg) or diastolic (>90 mm Hg) BP. Patient demographics, clinical characteristics, and short-term clinical outcomes were abstracted from the medical record. Hospital costs were calculated from hospital billing forms. RESULTS: A total of 189 patients receiving labetalol and 193 patients receiving nicardipine were included in the analysis. The average hourly dose was 37.3 ± 9.4 mg/h for labetalol compared with 7.1 ± 5.6 mg/h for nicardipine (P < .001). The average total dose of labetalol was 170.9 ± 32.6 mg compared with 112.2 ± 29.1 mg for nicardipine (P = .02). The duration of therapy was significantly shorter for labetalol (8.2 ± 6.2 hours) compared with nicardipine (15.8 ± 4.4 hours) (P = .03). There were a greater number of dose titrations with labetalol (6.1 ± 6.2) than with nicardipine (4.7 ± 4.9), but this difference was not significantly different (P = .29). There were no significant differences in the magnitude of the average change in systolic (P = .79) or diastolic (P = .82) BP between labetalol and nicardipine. The proportion of patients achieving their BP targets was significantly greater with nicardipine (83%) than with labetalol (67%) (P = .04). The proportion of patients requiring an alternate antihypertensive agent was significantly greater with labetalol than with nicardipine (31% vs 17%; P = .02). The total number of all-cause adverse events was significantly greater with labetalol (61%) than with nicardipine (48%) (P = .04). Labetalol was associated with a significantly greater incidence of hypotension and bradycardia or atrioventricular block compared with nicardipine. There was no significant difference in the frequency of other adverse events between these 2 drugs. The median hospital costs were not significantly different between patients receiving labetalol and patients receiving nicardipine. CONCLUSION: Our study suggests that nicardipine is a more effective antihypertensive agent than labetalol in an unselected group of patients who develop hypertension in the intensive care unit setting. A major advantage of nicardipine compared with labetalol was fewer adverse effects. Nicardipine was associated with less hypotension and bradycardia or atrioventricular block, resulting in a lower rate of drug discontinuation compared with labetalol.

Ambulatory blood pressure monitoring for the assessment of nicardipine as a third drug in severe essential hypertension.

The antihypertensive efficacy of sustained-release nicardipine compared to placebo as third-line therapy has been assessed by ambulatory blood pressure monitoring in severely hypertensive patients with clinically unsatisfactory blood pressure control on 50 mg hydrochlorothiazide o.d. and 75 mg captopril b.d. Forty-two patients, 31 m and 11 f, with supine diastolic blood pressure 95-115 mm Hg after a 4 week run-in period on open hydrochlorothiazide and captopril, were randomly allocated to sustained-release nicardipine 45-60 mg/d or placebo. At a visit to the clinic blood pressure and heart rate were measured 12 h after the evening dose by a trained observer unaware of the treatment. Twenty-four hour ambulatory monitoring was performed at the end of baseline and after 8 weeks of blinded medication. There was no significant change in BD at the visit or on ambulatory monitoring in the placebo treated patients. In contrast, nicardipine produced a significant reduction in both blood pressures without affecting heart rate. Nicardipine also decreased the mean 24-h blood pressure by 14/10 mm Hg in patients whose clinical hypertension had been confirmed by ambulatory blood pressure monitoring but by only 3/2 mm Hg in ambulant patients who were normotensive on two-drug therapy. One patient experienced an episode of severe symptomatic hypotension while on nicardipine. Otherwise, the numbers and percentages of patients from each group reporting adverse experiences were similar. It is concluded that nicardipine appears to be an effective antihypertensive agent when used as third line therapy with diuretics and angiotensin converting enzyme inhibitors in patients with severe hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Inotropic effect of nicardipine in patients with heart failure: assessment by left ventricular end-systolic pressure-volume analysis.

Nicardipine, a new dihydropyridine calcium channel blocker, has been investigated for the treatment of coronary artery disease and heart failure. To assess the inotropic effect of nicardipine in humans independent of its vasodilator effect, equihypotensive doses of intravenous nitroprusside (mean infusion rate 65 +/- 13 micrograms/min) and nicardipine (mean dose 5.2 +/- 0.4 mg) were administered to 15 patients with heart failure (New York Heart Association functional classes II to IV, radionuclide left ventricular ejection fraction 0.15 +/- 0.02). Left ventricular micromanometer pressure and simultaneous radionuclide left ventricular volume were obtained at baseline, during nitroprusside infusion, during a second baseline period and during nicardipine infusion. Heart rate did not change significantly with either nitroprusside or nicardipine. Mean systemic arterial pressure decreased by an average of 21 mm Hg with both drugs. A greater decrease in left ventricular end-diastolic pressure occurred with nitroprusside (27 +/- 2 to 14 +/- 2 mm Hg, p less than 0.01) than with nicardipine (27 +/- 2 to 23 +/- 3 mm Hg, p less than 0.05), and pulmonary capillary wedge pressure decreased significantly only with nitroprusside. Cardiac index increased from 1.8 +/- 0.1 to 2.1 +/- 0.1 liters/min per m2 (p less than 0.05) with nitroprusside and to a greater extent from 1.7 +/- 0.1 to 2.4 +/- 0.1 liters/min per m2 (p less than 0.01) with nicardipine. Left ventricular ejection fraction increased with nicardipine (0.15 +/- 0.01 to 0.19 +/- 0.01, p less than 0.01), but not with nitroprusside. Peak positive first derivative of left ventricular pressure (dP/dt) decreased by 9% with both agents.(ABSTRACT TRUNCATED AT 250 WORDS)