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The New England Journal of Medicine Sep 2016Limited data are available to guide the choice of a target for the systolic blood-pressure level when treating acute hypertensive response in patients with intracerebral... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
Limited data are available to guide the choice of a target for the systolic blood-pressure level when treating acute hypertensive response in patients with intracerebral hemorrhage.
METHODS
We randomly assigned eligible participants with intracerebral hemorrhage (volume, <60 cm(3)) and a Glasgow Coma Scale (GCS) score of 5 or more (on a scale from 3 to 15, with lower scores indicating worse condition) to a systolic blood-pressure target of 110 to 139 mm Hg (intensive treatment) or a target of 140 to 179 mm Hg (standard treatment) in order to test the superiority of intensive reduction of systolic blood pressure to standard reduction; intravenous nicardipine to lower blood pressure was administered within 4.5 hours after symptom onset. The primary outcome was death or disability (modified Rankin scale score of 4 to 6, on a scale ranging from 0 [no symptoms] to 6 [death]) at 3 months after randomization, as ascertained by an investigator who was unaware of the treatment assignments.
RESULTS
Among 1000 participants with a mean (±SD) systolic blood pressure of 200.6±27.0 mm Hg at baseline, 500 were assigned to intensive treatment and 500 to standard treatment. The mean age of the patients was 61.9 years, and 56.2% were Asian. Enrollment was stopped because of futility after a prespecified interim analysis. The primary outcome of death or disability was observed in 38.7% of the participants (186 of 481) in the intensive-treatment group and in 37.7% (181 of 480) in the standard-treatment group (relative risk, 1.04; 95% confidence interval, 0.85 to 1.27; analysis was adjusted for age, initial GCS score, and presence or absence of intraventricular hemorrhage). Serious adverse events occurring within 72 hours after randomization that were considered by the site investigator to be related to treatment were reported in 1.6% of the patients in the intensive-treatment group and in 1.2% of those in the standard-treatment group. The rate of renal adverse events within 7 days after randomization was significantly higher in the intensive-treatment group than in the standard-treatment group (9.0% vs. 4.0%, P=0.002).
CONCLUSIONS
The treatment of participants with intracerebral hemorrhage to achieve a target systolic blood pressure of 110 to 139 mm Hg did not result in a lower rate of death or disability than standard reduction to a target of 140 to 179 mm Hg. (Funded by the National Institute of Neurological Disorders and Stroke and the National Cerebral and Cardiovascular Center; ATACH-2 ClinicalTrials.gov number, NCT01176565 .).
Topics: Aged; Antihypertensive Agents; Cerebral Hemorrhage; Female; Glasgow Coma Scale; Humans; Hypertension; Infusions, Intravenous; Male; Middle Aged; Nicardipine; Treatment Failure; Treatment Outcome
PubMed: 27276234
DOI: 10.1056/NEJMoa1603460 -
American Journal of Hypertension Oct 2020Elevated blood pressure (BP) is pervasive among patients that visit emergency departments (EDs) for their care. (Review)
Review
BACKGROUND
Elevated blood pressure (BP) is pervasive among patients that visit emergency departments (EDs) for their care.
METHODS
In this review article, we outline the current approach to the management of these individuals and highlight the crucial role emergency medicine clinicians play in reducing the morbidity associated with elevated BP.
RESULTS
We highlight the critical importance of immediate treatment when elevated BP contributes to new or worsening end-organ injury but emphasize that such hypertensive emergencies are rare. For the vast majority of patients with elevated BP in the ED who do not have new or worsening end-organ injury from elevated BP, immediate BP reduction within the ED is not recommended or safe. Nonetheless, within weeks after an ED visit, there is a pressing need to improve the care of patients with elevated or previously undiagnosed hypertension. For many, it may be their only regular point of engagement with the healthcare system. To address this, we present novel perspectives that envision a new role for emergency medicine in chronic hypertension management-one that acknowledges the significant population-level gaps in BP control that contribute to disparities in cardiovascular disease and sets the stage for future changes in systems-based practice.
CONCLUSIONS
Emergency medicine plays a key and evolving role in reducing morbidity associated with elevated BP.
Topics: Acute Disease; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Calcium Channel Blockers; Chronic Disease; Drug Therapy, Combination; Emergency Service, Hospital; Humans; Hypertension; Labetalol; Nicardipine; Nitroprusside; Practice Guidelines as Topic; Pyridines; Referral and Consultation; Sodium Chloride Symporter Inhibitors; Undiagnosed Diseases
PubMed: 32307541
DOI: 10.1093/ajh/hpaa068 -
Neurology India 2022Current recommendations prescribe either nicardipine or labetalol as the first-line treatment for acute hypertension due to ease of use, availability, and low price.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND OBJECTIVE
Current recommendations prescribe either nicardipine or labetalol as the first-line treatment for acute hypertension due to ease of use, availability, and low price. However, it is unclear if these drugs have different effectiveness and safety profiles. This systematic review and meta-analysis aimed to compare the efficacy and safety of labetalol and nicardipine in patients with acute stroke.
MATERIALS AND METHODS
MEDLINE via PubMed, Scopus, Embase, and Google Scholar databases were electronically searched for the eligible publications from inception until March 2022. All full-text journal papers in English which compared the efficacy of nicardipine with that of labetalol on lowering blood pressure (BP; or treating hypertension) in all subtypes of acute stroke were included. The Cochrane Collaboration tool was used to assess the risk of bias. Data were analyzed using specific statistical methods.
RESULTS
Following the abstract and full-text screening, this meta-analysis included five retrospective cohorts and one prospective pseudorandomized cohort. Nicardipine's effect on time at goal BP was significantly superior to that of labetalol in patients with acute stroke (0.275 standardized mean difference [SMD], 95% confidence interval [CI]: 0.112-0.438, P = 0.001). The incidence of adverse events was significantly higher in the nicardipine group than that in the labetalol group. The pooled odds ratio (OR) was 1.509 (95% CI: 1.077-2.113, I = 0.00%, P = 0.757). The quality of included studies was found to be low.
CONCLUSION
More prospective, comparative trials are needed to investigate the efficacy of BP management as well as clinical outcomes in acute stroke patients receiving continuous labetalol and nicardipine infusions.
Topics: Humans; Labetalol; Nicardipine; Antihypertensive Agents; Retrospective Studies; Prospective Studies; Blood Pressure; Treatment Outcome; Hypertension; Stroke
PubMed: 36352567
DOI: 10.4103/0028-3886.359214 -
Aging Feb 2021Glioblastoma multiforme (GBM) is the most invasive malignant central nervous system tumor with poor prognosis. Nicardipine, a dihydropyridine calcium channel antagonist,...
Glioblastoma multiforme (GBM) is the most invasive malignant central nervous system tumor with poor prognosis. Nicardipine, a dihydropyridine calcium channel antagonist, has been used as an adjuvant to enhance sensitivity to chemotherapeutic drugs. However, whether glioma stem cells (GSCs) can be sensitized to chemotherapy via combined treatment with temozolomide (TMZ) and nicardipine is unclear. In this study, surgical specimen derived GSCs SU4 and SU5 were applied to explore the sensitization effect of nicardipine on temozolomide against GSCs, and further explore the relevant molecular mechanisms. Our results showed that nicardipine can enhance the toxic effect of temozolomide against GSCs, promote apoptosis of GSCs, and inhibit autophagy of GSCs. The relevant mechanisms were related to activation of mTOR, and selective inhibition of mTOR by rapamycin could weaken the sensitization of nicardipine to temozolomide, which suggest that nicardipine can be applied as an adjuvant to inhibit autophagy in GSCs, and enhance apoptosis-promoting effect of temozolomide in GSCs as well. Nicardipine can inhibit autophagy by activating expression of mTOR, thus play tumor inhibition roles both and . Repurposing of nicardipine can help to improving therapeutic effect of TMZ against GBM, which deserves further clinical investigations.
Topics: Antineoplastic Agents, Alkylating; Apoptosis; Autophagy; Brain Neoplasms; Calcium Channel Blockers; Glioma; Humans; Neoplastic Stem Cells; Nicardipine; Temozolomide; Tumor Cells, Cultured
PubMed: 33621205
DOI: 10.18632/aging.202539 -
The Cochrane Database of Systematic... Feb 2016Calcium channel blockers are the most commonly prescribed drugs for people with primary Raynaud's phenomenon. Primary Raynaud's phenomenon is a common condition... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Calcium channel blockers are the most commonly prescribed drugs for people with primary Raynaud's phenomenon. Primary Raynaud's phenomenon is a common condition characterised by an exaggerated vasospastic response to cold or emotion: classically the digits (fingers and toes) turn white, then blue, then red. This is an update of the review first published in 2014.
OBJECTIVES
To assess the effects of different calcium channel blockers for primary Raynaud's phenomenon as determined by attack rates, severity scores, participant-preference scores and physiological measurements.
SEARCH METHODS
For this update the Cochrane Vascular Trial Search Co-ordinator searched the Specialised Register (last searched January 2016) and the Cochrane Register of Studies (CENTRAL) (2015, Issue 12). In addition the TSC searched clinical trials databases.
SELECTION CRITERIA
Randomised controlled trials evaluating the effects of oral calcium channel blockers for the treatment of primary Raynaud's phenomenon.
DATA COLLECTION AND ANALYSIS
Three review authors independently assessed the trials for inclusion and their quality, and extracted the data. Data extraction included adverse events. We contacted trial authors for missing data.
MAIN RESULTS
We included seven randomised trials with 296 participants. Four trials examined nifedipine and the remainder nicardipine. Comparisons were with placebo in six trials and with both dazoxiben and placebo in one trial (only the nifedipine versus placebo data were used within this review). Treatment with oral calcium channel blockers was minimally effective in primary Raynaud's phenomenon at decreasing the frequency of attacks (standardised mean difference of 0.23; 95% confidence interval (CI) 0.08 to 0.38, P = 0.003). This translates to 1.72 (95% CI 0.60 to 2.84) fewer attacks per week on calcium channel blockers compared to placebo. One trial provided details on duration of attacks reporting no statistically significant difference between the nicardipine and placebo groups (no P value reported). Only two trials provided any detail of statistical comparisons of (unvalidated) severity scores between treatment groups: one of these trials (60 participants) reported a mean severity score of 1.55 on placebo and 1.36 on nicardipine, difference 0.2 (95% CI of difference 0 to 0.4, no P value reported) and the other trial (three participants only with primary Raynaud's phenomenon) reported a median severity score of 2 on both nicardipine and placebo treatment (P > 0.999) suggesting little effect on severity. Participant-preference scores were included in four trials, but in only two were results specific to participants with primary Raynaud's phenomenon, and scoring systems differed between trials: scores differed between treatments in only one trial, in which 33% of participants on placebo and 73% on nifedipine reported improvement in symptoms (P < 0.001). Physiological measurements were included as outcome measures in five trials (different methodologies were used in each): none of these trials found any statistically significant between-treatment group differences. Treatment with calcium channel blockers appeared to be associated with a number of adverse reactions, including headaches, flushing and oedema (swelling). Overall, the trials were classed as being at low or unclear risk of bias; and the quality of the evidence presented was moderate for number of attacks, very low for duration of attacks, high for severity scores and low for patient preference scores.
AUTHORS' CONCLUSIONS
The randomised controlled trials included in this review provide moderate quality evidence that oral calcium channel blockers are minimally effective in the treatment of primary Raynaud's phenomenon as measured by the frequency of attacks and high-quality evidence that they have little effect on severity. We are unable to comment on duration of attacks or on patient preference due to the very low and low quality of evidence as a result of small sample sizes in the included studies and the variable data quality of outcome measures.
Topics: Calcium Channel Blockers; Humans; Nicardipine; Nifedipine; Randomized Controlled Trials as Topic; Raynaud Disease
PubMed: 26914257
DOI: 10.1002/14651858.CD002069.pub5 -
Frontiers in Pharmacology 2021Metastasis represents an advanced stage of cancers, and matrix metalloproteinases are critical regulators. Calcium signal is crucial for appropriate cell behaviors. The...
Metastasis represents an advanced stage of cancers, and matrix metalloproteinases are critical regulators. Calcium signal is crucial for appropriate cell behaviors. The efficacy and effects of calcium channel blockers in treating cancers are individually differ from each other. Here, we attempt to investigate the effects of nicardipine, a FDA-approved calcium channel blocker, in advanced breast cancers. We analyzed the influence of nicardipine on the colony-forming ability of triple negative breast cancer cell lines. Using cell culture inserts, cell migration was also examined. The expression of regulatory proteins was evaluated by real-time PCR, Western blot, and ELISA. We have confirmed that nicardipine inhibits the breast cancer cells migration and colony formation. In addition, we also revealed that nicardipine increases the Nrf2 and HO-1 expression. The inhibition of HO-1 abrogates nicardipine-reduced matrix metalloproteinase-9 expression. Moreover, the end products of HO-1, namely, CO, Fe2+, and biliverdin (will converted to bilirubin), also decreases the expression of matrix metalloproteinase-9. These findings suggest that nicardipine-mediated matrix metalloproteinase-9 reduction is regulated by Nrf2/HO-1 axis and its catalytic end products. Therefore, nicardipine may be a potential candidate for repurposing against advanced breast cancers.
PubMed: 34483918
DOI: 10.3389/fphar.2021.710978 -
Journal of Rural Medicine : JRM Jan 2022Nitroglycerin is a first-line treatment for hypertensive acute heart failure syndrome (AHFS). However, nicardipine is frequently used to treat hypertensive emergencies,...
Nitroglycerin is a first-line treatment for hypertensive acute heart failure syndrome (AHFS). However, nicardipine is frequently used to treat hypertensive emergencies, including AHFS. In this study, we compared the effectiveness of nicardipine and nitroglycerin in patients with hypertensive AHFS. This single-center, retrospective, observational study was conducted at the intensive care unit of a Japanese hospital. Patients diagnosed with AHFS and systolic blood pressure 140 mmHg on arrival between April 2013 and March 2021 were included. The outcomes were the time to optimal blood pressure control, duration of continuous infusion of antihypertensive agents, duration of positive pressure ventilation, need for additional antihypertensive agents, length of hospital stay, and body weight changes. Outcomes were compared between the nicardipine and nitroglycerin groups. We also compared these outcomes between the groups after excluding patients who received renal replacement therapy. Fifty-eight patients were enrolled (26 and 32 patients were treated with nitroglycerin and nicardipine, respectively). The nicardipine group had a shorter time to optimal blood pressure control (2.0 [interquartile range, 2.0-8.5] h vs. 1.0 [0.5-2.0] h), shorter duration of continuous anti-hypertensive agent infusion (3.0 [2.0-5.0] days vs. 2.0 [1.0-2.0] days), less frequent need for additional anti-hypertensive agents (1 patients [3.1%] vs. 11 patients [42.3%]), and shorter length of hospital stay (17.5 [10.0-33.0] days vs. 9.0 [5.0-15.0] days) than the nitroglycerin group. The duration of positive pressure ventilation and body weight changes were similar between the groups. The outcomes were similar after excluding patients who received renal replacement therapy. : Nicardipine may be more effective than nitroglycerin for treating hypertensive AHFS.
PubMed: 35047100
DOI: 10.2185/jrm.2021-045 -
Pharmaceutics Mar 2023Impaired transport activity of hepatic OATP1B1 and OATP1B3 due to drug-drug interactions (DDIs) often leads to increased systemic exposure to substrate drugs (e.g.,...
Differential Preincubation Effects of Nicardipine on OATP1B1- and OATP1B3-Mediated Transport in the Presence and Absence of Protein: Implications in Assessing OATP1B1- and OATP1B3-Mediated Drug-Drug Interactions.
Impaired transport activity of hepatic OATP1B1 and OATP1B3 due to drug-drug interactions (DDIs) often leads to increased systemic exposure to substrate drugs (e.g., lipid-lowering statins). Since dyslipidemia and hypertension frequently coexist, statins are often concurrently used with antihypertensives, including calcium channel blockers (CCBs). OATP1B1/1B3-related DDIs in humans have been reported for several CCBs. To date, the OATP1B1/1B3-mediated DDI potential of CCB nicardipine has not been assessed. The current study was designed to assess the OATP1B1- and OATP1B3-mediated DDI potential of nicardipine using the R-value model, following the US-FDA guidance. IC values of nicardipine against OATP1B1 and OATP1B3 were determined in transporter-overexpressing human embryonic kidney 293 cells using [H]-estradiol 17β-D-glucuronide and [H]-cholecystokinin-8 as substrates, respectively, with or without nicardipine-preincubation in protein-free Hanks' Balanced Salt Solution (HBSS) or in fetal bovine serum (FBS)-containing culture medium. Preincubation with nicardipine for 30 min in protein-free HBSS buffer produced lower IC and higher R-values for both OATP1B1 and OATP1B3 compared to in FBS-containing medium, yielding IC values of 0.98 and 1.63 µM and R-values of 1.4 and 1.3 for OATP1B1 and OATP1B3, respectively. The R-values were higher than the US-FDA cut-off value of 1.1, supporting that nicardipine has the potential to cause OATP1B1/3-mediated DDIs. Current studies provide insight into the consideration of optimal preincubation conditions when assessing the OATP1B1/3-mediated DDIs in vitro.
PubMed: 36986880
DOI: 10.3390/pharmaceutics15031020 -
Medicine Dec 2022To evaluate the effect of continuous infusion of nicardipine on the management of uncontrolled blood pressure (BP) during postpartum period. This retrospective study...
To evaluate the effect of continuous infusion of nicardipine on the management of uncontrolled blood pressure (BP) during postpartum period. This retrospective study included 209 women diagnosed in hospital with hypertensive disorders during pregnancy and had uncontrolled BP after delivery between January 2018 to December 2020 Uncontrolled BP was defined as persistent elevation of systolic BP ≥ 160 mm Hg or diastolic BP ≥ 110 mm Hg. Patients were divided into 2 groups: nicardipine (N = 53; continuous nicardipine infusion and additional bolus of labetalol or hydralazine) and control (N = 156; consecutive bolus of labetalol or hydralazine). BP data were analyzed using the Mann-Whitney U and χ2 tests by dividing the time interval of 4 hours by the delivery time. The highest BP trends showed that the mean values of both systolic and diastolic BP immediately before delivery were higher in the nicardipine group than in the control. After 8 to 12 hours following delivery, both systolic and diastolic BP were lower in the nicardipine group than in the control. Subsequently, 16 to 20 hours after delivery, both systolic and diastolic BP were significantly lower in the nicardipine group than in the control (137/80 vs 141/84 mm Hg). Initially, the proportions of uncontrolled BP in the nicardipine group were higher than those in the control; however, it then became lower at all time intervals 8 hours after delivery. The proportions of patients who received additional antihypertensive agents and the median cumulative dosages were lower in the nicardipine group than in the control. Continuous infusion of nicardipine can help manage uncontrolled BP during the postpartum period.
Topics: Pregnancy; Humans; Female; Nicardipine; Labetalol; Retrospective Studies; Hypertension; Antihypertensive Agents; Blood Pressure; Hydralazine; Postpartum Period
PubMed: 36595745
DOI: 10.1097/MD.0000000000032381