Intensive blood pressure lowering with nicardipine and outcomes after intracerebral hemorrhage: An individual participant data systematic review

2021 ◽  
pp. 174749302110446
Author(s):  
Kazunori Toyoda ◽  
Sohei Yoshimura ◽  
Mayumi Fukuda-Doi ◽  
Adnan I Qureshi ◽  
Renee’ Hebert Martin ◽  
...  
Keyword(s):  
Systematic Review ◽  
Blood Pressure ◽  
Intracerebral Hemorrhage ◽  
Systolic Blood Pressure ◽  
Hematoma Expansion ◽  
Antihypertensive Activity ◽  
Individual Participant Data ◽  
Modified Rankin Scale ◽  
Risk Of Death ◽  
Individual Participant

Background and aims Nicardipine has strong, rapidly acting antihypertensive activity. The effects of acute systolic blood pressure levels achieved with intravenous nicardipine after onset of intracerebral hemorrhage on clinical outcomes were determined. Methods A systematic review and individual participant data analysis of articles before 1 October 2020 identified on PubMed were performed (PROSPERO: CRD42020213857). Prospective studies involving hyperacute intracerebral hemorrhage adults treated with intravenous nicardipine whose outcome was assessed using the modified Rankin Scale were eligible. Outcomes included death or disability at 90 days, defined as the modified Rankin Scale score of 4–6, and hematoma expansion, defined as an increase ≥6 mL from baseline to 24-h computed tomography. Summary of review Three studies met the eligibility criteria. For 1265 patients enrolled (age 62.6 ± 13.0 years, 484 women), death or disability occurred in 38.2% and hematoma expansion occurred in 17.4%. Mean hourly systolic blood pressure during the initial 24 h was positively associated with death or disability (adjusted odds ratio (aOR) 1.12, 95% confidence interval (CI) 1.00–1.26 per 10 mmHg) and hematoma expansion (1.16, 1.02–1.32). Mean hourly systolic blood pressure from 1 h to any timepoint during the initial 24 h was positively associated with death or disability. Later achievement of systolic blood pressure to ≤140 mmHg increased the risk of death or disability (aOR 1.02, 95% CI 1.00–1.05 per hour). Conclusions Rapid lowering of systolic blood pressure by continuous administration of intravenous nicardipine during the initial 24 h in hyperacute intracerebral hemorrhage was associated with lower risks of hematoma expansion and 90-day death or disability without increasing serious adverse events.

Statistical analysis plan for pooled individual patient data from two landmark randomized trials (INTERACT2 and ATACH-II) of intensive blood pressure lowering treatment in acute intracerebral hemorrhage

2018 ◽  
Vol 14 (3) ◽  
pp. 321-328 ◽  
Author(s):  
Tom J Moullaali ◽  
Xia Wang ◽  
Renee' H Martin ◽  
Virginia B Shipes ◽  
Adnan I Qureshi ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Intracerebral Hemorrhage ◽  
Systolic Blood Pressure ◽  
Functional Recovery ◽  
Modified Rankin Scale ◽  
Blood Pressure Lowering ◽  
Safety Outcomes ◽  
Pressure Lowering ◽  
Acute Intracerebral Hemorrhage ◽  
Intensive Blood Pressure

Background There is persistent uncertainty over the benefits of early intensive systolic blood pressure lowering in acute intracerebral hemorrhage. In particular, over the timing, target, and intensity of systolic blood pressure control for optimum balance of potential benefits (i.e. functional recovery) and risks (e.g. cerebral ischemia). Aims To determine associations of early systolic blood pressure lowering parameters and outcomes in patients with a hypertensive response in acute intracerebral hemorrhage. Secondary aims are to identify the modifying effects of patient characteristics and an optimal systolic blood pressure lowering profile. Methods Individual participant data pooled analyses of two large, multicenter, randomized controlled trials specifically undertaken to assess the effects of early intensive systolic blood pressure reduction on clinical outcomes in acute intracerebral hemorrhage: the Intensive Blood Pressure in Acute Intracerebral Hemorrhage Trial (INTERACT2) and the Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH-II) trial. Combined data will include baseline characteristics; systolic blood pressure in the first 24 h; process of care measures; and key efficacy and safety outcomes. Outcomes The primary outcome is functional recovery, defined by an ordinal distribution of scores on the modified Rankin scale at 90 days post-randomization. Secondary outcomes include various standard binary cut-points for disability-free survival on the modified Rankin scale, and health-related quality of life at 90 days. Safety outcomes include symptomatic hypotension requiring corrective therapy and early neurologic deterioration within 24 h, and deaths, any serious adverse event, and cardiac and renal serious adverse events, within 90 days. Discussion A pre-determined protocol was developed to facilitate successful collaboration and reduce analysis bias arising from prior knowledge of the findings. Clinical trial registration URL: http://www.clinicaltrials.gov . Unique identifiers for INTERACT2 (NCT00716079) and ATACH-II (NCT01176565).

scholarly journals Outcomes in Antiplatelet‐Associated Intracerebral Hemorrhage in the TICH‐2 Randomized Controlled Trial

2021 ◽  
Author(s):  
Zhe Kang Law ◽  
Michael Desborough ◽  
Ian Roberts ◽  
Rustam Al‐Shahi Salman ◽  
Timothy J. England ◽  
...  
Keyword(s):  
Intracerebral Hemorrhage ◽  
Tranexamic Acid ◽  
Functional Outcome ◽  
Antiplatelet Therapy ◽  
Controlled Trial ◽  
Hematoma Expansion ◽  
Modified Rankin Scale ◽  
Double Blind ◽  
Risk Of Death ◽  
Increased Risk

Background Antiplatelet therapy increases the risk of hematoma expansion in intracerebral hemorrhage (ICH) while the effect on functional outcome is uncertain. Methods and Results This is an exploratory analysis of the TICH‐2 (Tranexamic Acid in Intracerebral Hemorrhage‐2) double‐blind, randomized, placebo‐controlled trial, which studied the efficacy of tranexamic acid in patients with spontaneous ICH within 8 hours of onset. Multivariable logistic regression and ordinal regression were performed to explore the relationship between pre‐ICH antiplatelet therapy, and 24‐hour hematoma expansion and day 90 modified Rankin Scale score, as well as the effect of tranexamic acid. Of 2325 patients, 611 (26.3%) had pre‐ICH antiplatelet therapy. They were older (mean age, 75.7 versus 66.5 years), more likely to have ischemic heart disease (25.4% versus 2.7%), ischemic stroke (36.2% versus 6.3%), intraventricular hemorrhage (40.2% versus 27.5%), and larger baseline hematoma volume (mean, 28.1 versus 22.6 mL) than the no‐antiplatelet group. Pre‐ICH antiplatelet therapy was associated with a significantly increased risk of hematoma expansion (adjusted odds ratio [OR], 1.28; 95% CI, 1.01–1.63), a shift toward unfavorable outcome in modified Rankin Scale (adjusted common OR, 1.58; 95% CI, 1.32–1.91) and a higher risk of death at day 90 (adjusted OR, 1.63; 95% CI, 1.25–2.11). Tranexamic acid reduced the risk of hematoma expansion in the overall patients with ICH (adjusted OR, 0.76; 95% CI, 0.62–0.93) and antiplatelet subgroup (adjusted OR, 0.61; 95% CI, 0.41–0.91) with no significant interaction between pre‐ICH antiplatelet therapy and tranexamic acid (P interaction=0.248). Conclusions Antiplatelet therapy is independently associated with hematoma expansion and unfavorable functional outcome. Tranexamic acid reduced hematoma expansion regardless of prior antiplatelet therapy use. Registration URL: https://www.isrctn.com ; Unique identifier: ISRCTN93732214.

Abstract WP399: Delayed Response to Intensive Blood Pressure Lowering and Poor Clinical Outcomes in Acute Intracerebral Hemorrhage

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Kanta Tanaka ◽  
Masatoshi Koga ◽  
Adnan I Qureshi ◽  
Haruko Yamamoto ◽  
Kazunori Toyoda
Keyword(s):  
Blood Pressure ◽  
Intracerebral Hemorrhage ◽  
Clinical Outcomes ◽  
Early Response ◽  
Hematoma Expansion ◽  
Delayed Response ◽  
Blood Pressure Lowering ◽  
Risk Of Death ◽  
Pressure Lowering ◽  
Acute Intracerebral Hemorrhage

Background and purpose: We aimed to highlight temporal trajectories of systolic blood pressure (SBP) in patients with acute intracerebral hemorrhage (ICH) to investigate the clinical relevance of heterogeneity in responses to blood pressure lowering therapy. Methods: A post-hoc analysis of ATACH-2 trial, in which ICH patients were randomly assigned to intensive or standard SBP lowering with intravenous administration of nicardipine. Using data for all 1000 patients enrolled from 110 clinical sites, temporal changes of hourly maximum SBP up to 24 hours after randomization were analyzed with the group-based trajectory modeling (GBTM). Model selection was mainly based on the Bayesian Information Criteria. The primary outcome was death or disability (modified Rankin Scale score 4-6) at 3 months. Secondary outcomes included hematoma expansion within 24 hours and acute kidney injury (AKI). AKI was defined as an increase in serum creatinine by ≥0.3 mg/dl or to ≥1.5 times baseline within 48 hours. The outcomes were compared between the trajectory groups using multivariable logistic models with random-effects by clinical sites. Results: Of the analyzed 1000 patients, death or disability, hematoma expansion, and AKI were encountered in 367, 161, and 101 patients, respectively. GBTM revealed 4 SBP trajectory groups: early response-low SBP (38.2%), moderate SBP (16.8%), delayed response-low SBP (14.2%), and high SBP (30.8%). Nicardipine dosage was highest in the delayed response-low SBP group, 81.7% of which were from the intensive SBP lowering group. The risk of death or disability was higher only in the delayed response-low SBP group (adjusted odds ratio [aOR] 2.86; 95% confidence interval [CI] 1.66-4.93) than in the early response-low SBP group. The risk of hematoma expansion was not significantly different among the groups. The delayed response-low SBP group had higher risk of AKI (aOR 2.78; 95% CI 1.46-5.31; reference, the early response-low SBP group). Conclusions: An SBP trajectory group with delayed SBP lowering despite intensive treatment was associated with increased risk of death or disability at 3 months. Resistance to intensive SBP lowering may predict poor clinical outcomes, and intensive SBP control in these cases will increase the risk of AKI.

scholarly journals Acute hypertensive response in patients with intracerebral hemorrhage pathophysiology and treatment

2017 ◽  
Vol 38 (9) ◽  
pp. 1551-1563 ◽  
Author(s):  
Adnan I Qureshi ◽  
Mushtaq H Qureshi
Keyword(s):  
Blood Pressure ◽  
Intracerebral Hemorrhage ◽  
Systolic Blood Pressure ◽  
Cerebral Hemorrhage ◽  
Blood Pressure Reduction ◽  
Systemic Blood Pressure ◽  
Current Evidence ◽  
Hematoma Expansion ◽  
Pressure Reduction ◽  
Small Magnitude

Acute hypertensive response is a common systemic response to occurrence of intracerebral hemorrhage which has gained unique prominence due to high prevalence and association with hematoma expansion and increased mortality. Presumably, the higher systemic blood pressure predisposes to continued intraparenchymal hemorrhage by transmission of higher pressure to the damaged small arteries and may interact with hemostatic and inflammatory pathways. Therefore, intensive reduction of systolic blood pressure has been evaluated in several clinical trials as a strategy to reduce hematoma expansion and subsequent death and disability. These trials have demonstrated either a small magnitude benefit (second intensive blood pressure reduction in acute cerebral hemorrhage trial and efficacy of nitric oxide in stroke trial) or no benefit (antihypertensive treatment of acute cerebral hemorrhage 2 trial) with intensive systolic blood pressure reduction compared with modest or standard blood pressure reduction. The differences may be explained by the variation in intensity of systolic blood pressure reduction between trials. A treatment threshold of systolic blood pressure of ≥180 mm with the target goal of systolic blood pressure reduction to values between 130 and 150 mm Hg within 6 h of symptom onset may be best supported by current evidence.

scholarly journals Sex Differences in Blood Pressure–Lowering Therapy and Outcomes Following Intracerebral Hemorrhage

Stroke ◽  
2020 ◽  
Vol 51 (8) ◽  
pp. 2282-2286 ◽  
Author(s):  
Mayumi Fukuda-Doi ◽  
Haruko Yamamoto ◽  
Masatoshi Koga ◽  
Yuko Y. Palesch ◽  
Valerie L. Durkalski-Mauldin ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Sex Differences ◽  
Relative Risk ◽  
Intracerebral Hemorrhage ◽  
Antihypertensive Drugs ◽  
Hematoma Expansion ◽  
Unique Identifier ◽  
Risk Of Death ◽  
Lowering Therapy ◽  
Relative Risk Of Death

Background and Purpose: Evidence regarding sex differences in clinical outcomes and treatment effect following intracerebral hemorrhage is limited. Using the ATACH-2 trial (Antihypertensive Treatment in Intracerebral Hemorrhage-2) data, we explored whether sex disparities exist in outcomes and response to intensive blood pressure (BP)–lowering therapy. Methods: Eligible intracerebral hemorrhage subjects were randomly assigned to intensive (target systolic BP, 110–139 mm Hg) or standard (140–179 mm Hg) BP-lowering therapy within 4.5 hours after onset. Relative risk of death or disability corresponding to the modified Rankin Scale score of 4 to 6 was calculated, and interaction between sex and treatment was explored. Results: In total, 380 women and 620 men were included. Women were older, more prescribed antihypertensive drugs before onset, and had more lobar intracerebral hemorrhage than men. Hematoma expansion was observed less in women. After multivariable adjustment, the relative risk of death or disability in women was 1.19 (95% CI, 1.02–1.37, P =0.023). The relative risk of death or disability between intensive versus standard BP-lowering therapy was 0.91 (95% CI, 0.74–1.13) in women versus 1.13 (95% CI, 0.92–1.39) in men ( P for interaction=0.11), with inconclusive Gail-Simmon test ( P =0.16). Conclusions: Women had a higher risk of death or disability following intracerebral hemorrhage. The benefit of intensive BP-lowering therapy in women is inconclusive, consistent with the overall results of ATACH-2. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01176565.

Abstract WP398: Occurrence of Acute Kidney Injury in Patients With Intracerebral Hemorrhage Undergoing Systolic Blood Pressure Reduction

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Adnan I Qureshi ◽  
Wei Huang ◽  
Iryna Lobanova ◽  
Hunain Aslam ◽  
Werdah Zafar
Keyword(s):  
Blood Pressure ◽  
Acute Kidney Injury ◽  
Intracerebral Hemorrhage ◽  
Serum Creatinine ◽  
Systolic Blood Pressure ◽  
Standard Treatment ◽  
Blood Pressure Reduction ◽  
Kidney Injury ◽  
Hematoma Expansion ◽  
Open Label

Background: Aggressive systolic blood pressure (SBP) reduction may precipitate acute kidney injury (AKI) because of underlying hypertensive nephropathy, in subjects with intracerebral hemorrhage (ICH). Rate and determinants of AKI during acute hospitalization among ICH subjects were analyzed using a post hoc analysis of randomized, multicenter, two-groups, open-label clinical trial. Methods: Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH) 2 trial data was analyzed. Subjects with ICH (volume <60 cm 3 ) and a Glasgow Coma Scale (GCS) score of 5 or more were randomized to a SBP target of 110 to 139 mm Hg (intensive treatment) or a target of 140 to 179 mm Hg (standard treatment). IV nicardipine was given within 4.5 hours of symptom onset to lower SBP. Serum creatinine was ascertained at baseline, 24, 48 and 72 hours after randomization. AKI was classified based on increase in serum creatinine levels from baseline, stage 1 ≥ 0.3 mg/dl (≥ 26.4umol/L) or (>1.5 to 2-fold), stage 2 (>2 to 3-fold) and stage 3 (>3-fold) were identified. Results: Of 1000 randomized subjects, 158 developed AKI (65% were men; mean age of 61.5±13.2 years). Severity of AKI was grade I, II, III in 15.3%, 0.1%, and 0.4% patients, respectively. The rate of AKI was similar in intensive and standard treatment group (16.4% versus 15.2%, P=N.S). AKI incidence was significantly higher in subjects with baseline creatinine greater than 1.2 mg/dl (36% compared to 14%, OR 3.4, 95% CI 2.3-4.9, P= <0.0001). There was no significant association between subjects with AKI and hypertension (RR 1.1, 95% CI 1-1.2, P=0.15) or diabetes mellitus type 2 (RR 0.72, 95% CI 1.5-1.1, P=0.12). Patients with GCS ≤ 12 had significantly lower chances of developing AKI (RR 0.5, 95% CI 0.4-0.9, P=0.01). The incidence of hematoma expansion (OR 2.5, 95% CI 0.6-11, P=0.2) was not significantly higher in the subjects with AKI. No significant association was observed between occurrence of AKI and death or disability (modified Rankin score 4-6) at 3 months post randomization (RR 1.1, 95% CI 0.9-1.3, P=0.44). Conclusions: Mild AKI is frequent among intracerebral hemorrhage subjects undergoing SBP reduction. However, the rate of AKI was not different between subjects who were randomized to intensive or standard treatments.

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