Antihypertensive Treatment Group Research Articles

Early vs Delayed Antihypertensive Treatment in Acute Single Subcortical Infarction

The China Antihypertensive Trial in Acute Ischemic Stroke II (CATIS-2) suggests that early antihypertensive treatment did not reduce the risk of dependency or death in acute ischemic stroke (AIS), compared with delayed treatment. Single subcortical infarction (SSI) is an important stroke subtype, and the association of antihypertensive timing with clinical outcomes is unclear. To investigate the association of early vs delayed antihypertensive treatment with clinical outcomes in patients with SSI, stratified by the presence of parent artery disease (PAD) stenosis. This secondary analysis of the CATIS-2 randomized clinical trial included 106 hospitals in China between June 2018 and July 2022. In CATIS-2, patients with AIS within 24 to 48 hours of symptoms onset and elevated systolic blood pressure were eligible. Patients with SSI detected in diffusion-weighted imaging were included in the current post hoc subgroup analysis. Patients were grouped into (1) SSI with PAD stenosis and (2) SSI without PAD stenosis. Statistical analysis was performed from July 2023 to May 2024. Early (immediate) vs delayed (starting on day 8) antihypertensive therapy. Primary outcome was the combination of functional dependency or death (modified Rankin Scale score ≥3) at 90 days. Among 997 patients with SSI in CATIS-2 (mean [SD] age, 62.4 [9.8] years; 612 [61.4%] men), 116 (11.6%) had SSI with PAD and 881 (88.4%) had SSI without PAD. There was no significant difference in the primary outcome between early and delayed antihypertensive treatment groups among all patients with SSI (8.8% vs 7.1%; OR, 1.25 [95% CI, 0.79-1.99]; P = .34). Among patients with SSI with PAD, early antihypertensive treatment was associated with increased risk of the primary outcome compared with delayed treatment (23.4% vs 7.7%; OR, 3.67 [95% CI, 1.14-11.86]; P = .03); this finding was not observed in patients with SSI without PAD (6.6% vs 7.1%; OR, 0.93 [95% CI, 0.55-1.57]; P = .77). Significant interaction with treatment and presence of PAD stenosis was detected for the primary outcome (P for interaction = .04). In this secondary analysis of a randomized clinical trial, early antihypertensive treatment was associated with an increased risk of functional dependency or death at 90 days among patients with SSI and coexisting PAD stenosis, compared with delayed antihypertensive treatment. Further studies are warranted for individualized BP management in patients with SSI by the presence of PAD. ClinicalTrials.gov Identifier: NCT03479554.

Efficacy of Immediate Antihypertensive Treatment in Patients With Acute Ischemic Stroke With Different Blood Pressure Genetic Variants.

It remains unclear whether blood pressure (BP) genetic variants could modify the efficacy of immediate antihypertensive treatment after acute ischemic stroke. We conducted a secondary analysis of the CATIS (China Antihypertensive Trial in Acute Ischemic Stroke) to investigate the effect of early antihypertensive treatment on clinical outcomes among patients with acute ischemic stroke according to 5 BP-associated genetic variants. The CATIS randomized 4071 patients with acute ischemic stroke with elevated systolic BP to receive antihypertensive treatment or discontinue all antihypertensive agents during hospitalization. Randomization was conducted centrally and was stratified by participating hospitals and use of antihypertensive medications. Five BP-associated single nucleotide polymorphisms (rs16849225, rs17030613, rs1173766, rs6825911, and rs35444 in FIGN-GRB14, ST7L-CAPZA1, NPR3, ENPEP, and near TBX3, respectively) were genotyped among 2590 patients. The primary outcome was a combination of death and major disability at 14 days or hospital discharge. A weighted BP genetic risk score was constructed by the 5 single nucleotide polymorphisms. At 14 days or hospital discharge, the primary outcome was not significantly different between antihypertensive treatment and control groups based on genotype subgroups for all 5 single nucleotide polymorphisms (all P>0.05 for interaction). In addition, the BP genetic risk score did not modify the effect of antihypertensive treatment. The odds ratios (95% CIs) for the primary outcome were 0.95 (0.71-1.26), 1.08 (0.80-1.44), and 0.91 (0.69-1.22) in patients with low, intermediate, and high BP genetic risk score, respectively (P=0.88 for interaction). Early antihypertensive treatment had a neutral effect on clinical outcomes among patients with acute ischemic stroke according to 5 BP-associated genetic variants. URL: https://www.clinicaltrials.gov; Unique identifier: NCT01840072.

The correlation between different antihypertensive treatments and prognosis of cardiovascular disease in hypertensive patients

ObjectiveTo determine the association between different antihypertensive regimens and cardiovascular disease (CVD) outcomes in hypertensive patients.MethodThis single center retrospective cohort study analyzed 602 hypertensive patients with complete medical records at Zhongnan Hospital of Wuhan University, China, from January 2016 to November 2022. Baseline data and follow-up data of the included patients were collected, including demographic and clinical characteristics and laboratory results.ResultsDuring the 5-year follow-up period, CVD outcomes occurred in 244 hypertensive patients (40.53%). Compared with patients receiving regular antihypertensive treatment, the incidence of adverse cardiovascular events in patients receiving irregular antihypertensive treatment was significantly higher (62 [55.86%] vs 182 [37.07%], HR 1.642, 95% CI 1.227–2.197, p < 0.001). In subgroup analysis, the results showed that the incidence of CVD was not identical (χ2 = 9.170, p = 0.010). The incidence of adverse cardiovascular events was highest in the single-drug antihypertensive treatment group (43.60%), followed by the multi-drug combination group (41.51%), and lowest in the two-drug combination group (29.58%). Kaplan–Meier curve showed that hypertensive patients treated with two-drug combination antihypertensive had longer overall survival time. We further compared the incidence of CVD between standard blood pressure and intensive blood pressure control, and found no significant difference in the incidence of adverse cardiovascular events between treatment to a systolic blood pressure (SBP) target of less than 140 mmHg compared with a SBP target of less than 120 mmHg (105 [43.93%] vs 35 [29.66%], HR 1.334, 95% CI 0.908–1.961, p = 0.142).ConclusionThe incidence of adverse cardiovascular events was significantly different among different antihypertension treatments. Kaplan–Meier survival curve showed that hypertensive patients receiving two-drug combination antihypertensive treatment had longer overall survival time.

S-46-3: ANTIHYPERTENSIVE TREATMENT IN MASKED HYPERTENSION FOR TARGET ORGAN PROTECTION (ANTI-MASK): A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL

Objective: Masked hypertension is associated with target organ damage and adverse outcomes. However, up to now there is no interventional evidence that antihypertensive therapy will be beneficial to the patients. Design and methods: The ANTIhypertensive treatment in MASKed hypertension for target organ protection (ANTI-MASK) trial is a multicenter, randomized, double-blind, placebo-controlled clinical trial (NCT02893358). Eligible patients were 30 to 70 years old, had untreated masked hypertension and at least one sign of target organ damage (TOD). Masked hypertension was defined as a normal office blood pressure (BP, &lt; 140/90 mmHg) and an elevated 24-hour (&gt; = 130/80 mmHg), daytime (&gt; = 135/85 mmHg) or nighttime BP (&gt; = 120/70 mmHg) at both screening visits. TOD included electrocardiogram diagnosed left ventricular hypertrophy (LVH), brachial-ankle pulse wave velocity (ba-PWV) &gt; = 1400 cm/s, or a random urinary albumin-to-creatinine ratio (ACR) &gt; = 2.5 mg/mmol in men and &gt; = 3.5 mg/mmol in women. Randomized patients were treated with alisartan 80 mg per day or placebo. If ambulatory BP was uncontrolled, drug dosage was doubled at the 2-month visit, and amlodipine 2.5 mg or matching placebo was added at the 4-month visit. The primary endpoint was the improvement rate of TOD after 12 months treatment, defined as the reverse (yes to no) of TOD or a significant decrease of ba-PWV or ACR by &gt; = 20% of the baseline level. Results: From Feb 2017 to Oct 2020, 317 patients with masked hypertension (43.2% women, mean age 54 years) were randomized in 13 hospitals in China. Overall, baseline office, 24-h, daytime and nighttime BPs averaged 130/81,137/85, 141/87, and 126/77 mmHg, respectively. At baseline, 98% had an elevated ba-PWV, 12% microalbuminuria, and 8% LVH. 252 patients completed the 12-month treatment and 65 (20.5%) withdrew from the trial. In the intention-to-treat analyses, the improvement rate of TOD was significantly higher in the antihypertensive treatment group than the placebo group (47.4% vs 26.1%, P &lt; 0.0001), as well as the decrease of the 24-h systolic/diastolic BPs (-9.1/-5.7 vs -1.5/-1.0 mmHg, P &lt; 0.0001). Conclusions: Antihypertensive treatment was beneficial for patients with masked hypertension in terms of TOD protection.

Effect of Immediate Antihypertensive Treatment on Clinical Outcomes in Acute Ischemic Stroke Patients With Different Renal Function Status.

It remains unclear whether different blood pressure management strategies should be administered for acute stroke patients with or without impaired renal function. We conducted a secondary analysis of the CATIS trial (China Antihypertensive Trial in Acute Ischemic Stroke) to investigate the effect of early antihypertensive treatment among patients with acute ischemic stroke according to the baseline renal function assessed by estimated glomerular filtration rates (eGFR). The CATIS trial randomly assigned 4071 acute ischemic stroke patients with systolic blood pressure between 140 and 220 mm Hg to receive antihypertensive treatment or to discontinue all antihypertensive medications during hospitalization. A primary outcome (composite outcome of death and major disability) and secondary outcomes were compared between antihypertensive treatment and control groups by baseline renal function levels of eGFR values of <60, 60 to 89, and ≥90 mL/min per 1.73 m2. At day 14 or hospital discharge, the primary outcome was not significantly different between the antihypertensive treatment and control groups in each subgroup stratified by renal function status (P=0.98 for homogeneity), and the odds ratios (95% CIs) were 1.23 (0.76-2.02) in patients with eGFR <60 mL/min per 1.73 m2, 0.94 (0.75-1.19) in patients with eGFR values of 60-89 mL/min per 1.73 m2, and 1.04 (0.88-1.24) in patients with eGFR ≥90 mL/min per 1.73 m2, respectively. In addition, early antihypertensive treatment was not associated with secondary clinical outcomes by baseline renal function (P>0.05 for all homogeneity). Early antihypertensive treatment had a neutral effect on clinical outcomes in ischemic stroke patients with different renal function status. URL: https://www. gov; Unique Identifier: NCT01840072.

Risk of hypertension and treatment on out-of-hospital cardiac arrest incidence: A case-control study.

Hypertension (HTN) is a high risk factor for major cardiovascular adverse events. This study aimed to investigate the effect of HTN risk on out-of-hospital cardiac arrest (OHCA) incidence and determine whether the effect of HTN on OHCA incidence differs according to antihypertensive medication.This case-control study used the Korean Cardiac Arrest Resuscitation Consortium and Korean Community Health Survey (CHS). Cases were defined as emergency medical service-treated adult OHCA patients presumed to have a cardiac etiology from 2015 to 2017. Patients without information on HTN diagnosis were excluded from the study. The Korean CHS database's controls were matched at a 1:2 ratio with strata, including age, gender, and county of residence. Multivariable conditional logistic regression analysis was conducted to estimate HTN risk and antihypertensive treatment on OHCA incidence,A total of 2633 OHCA patients and 5266 community-based controls were enrolled in this study. Among them, 1176 (44.7%) patients and 2049 (38.9%) controls were diagnosed with HTN. HTN was associated with an increased risk of OHCA (adjusted odds ratio [AOR]: 1.19 [1.07–1.32]). On comparing HTN with or without the antihypertensive treatment group with the non-HTN-diagnosed group (as a reference), the HTN without treatment group had the highest AOR (95% confidence interval) (3.41 [2.74–4.24]). The AOR in the HTN treatment group was reduced to that in the non-HTN-diagnosed group (0.96 [0.86–1.08]).HTN increased OHCA risk, and the HTN without treatment group had the highest OHCA risk. Conversely, OHCA risk decreased to the non-HTN-diagnosed group level with HTN treatment.

ANTIHYPERTENSIVE TREATMENT IN MASKED HYPERTENSION FOR TARGET ORGAN PROTECTION (ANTI-MASK): A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL

Objective: Masked hypertension is associated with target organ damage and adverse outcomes. However, up to now there is no interventional evidence that antihypertensive therapy will be beneficial to the patients. Design and method: The ANTIhypertensive treatment in MASKed hypertension for target organ protection (ANTI-MASK) trial is a multicenter, randomized, double-blind, placebo-controlled clinical trial (NCT02893358). Eligible patients were 30 to 70 years old, had untreated masked hypertension and at least one sign of target organ damage (TOD). Masked hypertension was defined as a normal office blood pressure (BP, &lt; 140/90 mmHg) and an elevated 24-hour (&gt; = 130/80 mmHg), daytime (&gt; = 135/85 mmHg) or nighttime BP (&gt; = 120/70 mmHg) at both screening visits. TOD included electrocardiogram diagnosed left ventricular hypertrophy (LVH), brachial-ankle pulse wave velocity (ba-PWV) &gt; = 1400 cm/s, or a random urinary albumin-to-creatinine ratio (ACR) &gt; = 2.5 mg/mmol in men and &gt; = 3.5 mg/mmol in women. Randomized patients were treated with alisartan 80 mg per day or placebo. If ambulatory BP was uncontrolled, drug dosage was doubled at the 2-month visit, and amlodipine 2.5 mg or matching placebo was added at the 4-month visit. The primary endpoint was the improvement rate of TOD after 12 months treatment, defined as the reverse (yes to no) of TOD or a significant decrease of ba-PWV or ACR by &gt; = 20% of the baseline level. Results: From Feb 2017 to Oct 2020, 317 patients with masked hypertension (43.2% women, mean age 54 years) were randomized in 13 hospitals in China. Overall, baseline office, 24-h, daytime and nighttime BPs averaged 130/81, 137/85, 141/87, and 126/77 mmHg, respectively. At baseline, 98% had an elevated ba-PWV, 12% microalbuminuria, and 8% LVH. 252 patients completed the 12-month treatment and 65 (20.5%) withdrew from the trial. In the intention-to-treat analyses, the improvement rate of TOD was significantly higher in the antihypertensive treatment group than the placebo group (47.4% vs 26.1%, P &lt; 0.0001), as well as the decrease of the 24-h systolic/diastolic BPs (-9.1/-5.7 vs -1.5/-1.0 mmHg, P &lt; 0.0001). Conclusions: Antihypertensive treatment was beneficial for patients with masked hypertension in terms of TOD protection.

Effect of immediate blood pressure reduction on post-stroke depression in ischemic stroke patients: A substudy of CATIS trial

BackgroundSeveral prospective studies have identified that hypertension is an important risk factor of post-stroke depression (PSD). However, the effect of immediate antihypertensive treatment on the risk of PSD in patients with acute ischemic stroke remains unknown. MethodsIn this prespecified depression substudy of the China Antihypertensive Trial in Acute Ischemic Stroke (CATIS) randomized clinical trial, a total of 642 patients with acute ischemic stroke within 48 h of onset and elevated systolic BP at 7 sites of CATIS were included. Patients were randomly assigned to receive antihypertensive treatment (n = 318) or to control group (n = 324). The primary outcome was depression (Hamilton Rating Scale for Depression score≥8) at 3-month posttreatment follow-up. ResultsAt 24 h after randomization, the mean systolic BP was reduced by 21.6 mm Hg (12.5%) in the treatment group and 13.9 mm Hg (7.9%) in the control group (difference, -7.7 mm Hg [95% CI, -10.2 to -5.2]; P<0.001). The mean systolic BP levels at 7 days (P<0.001) and 14 days (P<0.001) after randomization in treatment group were also significantly lower than those in control group. At 3-month posttreatment follow-up, 122 patients (38.4%) in antihypertensive treatment group and 131 patients (40.4%) in control group developed PSD (odds ratio, 0.92 [95% CI, 0.67 to 1.26]; P = 0.59). LimitationsAll patients in the CATIS trial were Chinese, which might limit the generalizability of our findings to other populations. ConclusionsEarly antihypertensive treatment had no effect on the risk of PSD at 3 months among patients with acute ischemic stroke and elevated BP.

The impact of antihypertensive use in the treatment of acute ischemic stroke in patients receiving alteplase.

Treatment of acute ischemic stroke (AIS) with intravenous alteplase within 4.5 h of symptom onset is associated with neurologic improvement. High baseline blood pressure (BP) and BP variability during the first 24 h of AIS is associated with increased early adverse events and death. The purpose of this study is to characterize the incidence of poor neurologic outcome in patients treated with alteplase for AIS who received antihypertensive medications prior to and within the first 24 h following alteplase administration compared with patients who did not. This was a multicenter, retrospective cohort of patients >18 years diagnosed with AIS from January 1, 2011 through December 31, 2015 who received one or more antihypertensive medication in the first 24 h of AIS in patients receiving alteplase compared to controls. The primary endpoint was poor neurologic outcome at 90 days, according to modified Rankin Scale ≥3. Univariate analysis was conducted using Chi-square, Fisher's exact test, or Mann-Whitney U test. Multivariable logistic regression was conducted to determine independent predictors of poor outcome. Of the 587 patients evaluated, 351 (59.7%) were included, of which 127 (36.2%) received antihypertensive(s). More patients in the antihypertensive treatment group had a history of hypertension (88.2% vs. 69.6%, p < 0.01), diabetes (37% vs. 25.5%, p = 0.03) and chronic kidney disease (19.7% vs. 8.5%, p < 0.01). Intravenous push labetalol was most commonly administered (81.2%), followed by nicardipine (44.1%), and hydralazine (22%). More patients in the antihypertensive treatment group experienced poor neurologic outcome at 90 days (53.5% vs. 38.8%, p < 0.01), however, this finding was not observed after multivariable logistic regression. Antihypertensive treatment in the first 24 h of AIS was associated with poor neurologic outcomes at 90 days. However, after controlling for other clinical factors in a multivariable logistic regression, this association was no longer observed.

Pharmacological treatment of hypertension in people without prior cerebrovascular disease for the prevention of cognitive impairment and dementia.

This is an update of a Cochrane Review first published in 2006 (McGuinness 2006), and previously updated in 2009 (McGuinness 2009). Hypertension is a risk factor for dementia. Observational studies suggest antihypertensive treatment is associated with lower incidences of cognitive impairment and dementia. There is already clear evidence to support the treatment of hypertension after stroke. To assess whether pharmacological treatment of hypertension can prevent cognitive impairment or dementia in people who have no history of cerebrovascular disease. We searched the Specialised Register of the Cochrane Dementia and Cognitive Improvement Group, CENTRAL, MEDLINE, Embase, three other databases, as well as many trials registries and grey literature sources, most recently on 7 July 2020. We included randomised controlled trials (RCTs) in which pharmacological interventions to treat hypertension were given for at least 12 months. We excluded trials of pharmacological interventions to lower blood pressure in non-hypertensive participants. We also excluded trials conducted solely in people with stroke. Two authors independently assessed trial quality and extracted data. We contacted study authors for additional information. We collected information regarding incidence of dementia, cognitive decline, change in blood pressure, adverse effects and quality of life. We assessed the certainty of evidence using GRADE. We included 12 studies, totaling 30,412 participants, in this review. Eight studies compared active treatment with placebo. Of the four non-placebo-controlled studies, two compared intensive versus standard blood pressure reduction. The two final included studies compared different classes of antihypertensive drug. Study durations varied from one to five years. The combined result of four placebo-controlled trials that reported incident dementia indicated no evidence of a difference in the risk of dementia between the antihypertensive treatment group and the placebo group (236/7767 versus 259/7660, odds ratio (OR) 0.89, 95% confidence interval (CI) 0.72 to 1.09; very low certainty evidence, downgraded due to study limitations and indirectness). The combined results from five placebo-controlled trials that reported change in Mini-Mental State Examination (MMSE) may indicate a modest benefit from antihypertensive treatment (mean difference (MD) 0.20, 95% CI 0.10 to 0.29; very low certainty evidence, downgraded due to study limitations, indirectness and imprecision). The certainty of evidence for both cognitive outcomes was downgraded on the basis of study limitations and indirectness. Study durations were too short, overall, to expect a significant difference in dementia rates between groups. Dementia and cognitive decline were secondary outcomes for most studies. Additional sources of bias include: the use of antihypertensive medication by the placebo group in the placebo-controlled trials; failure to reach recruitment targets; and early termination of studies on safety grounds. Meta-analysis of the placebo-controlled trials reporting results found a mean change in systolic blood pressure of -9.25 mmHg (95% CI -9.73, -8.78) between treatment (n = 8973) and placebo (n = 8820) groups, and a mean change in diastolic blood pressure of -2.47 mmHg (95% CI -2.70, -2.24) between treatment (n = 7700) and placebo (n = 7509) groups (both low certainty evidence downgraded on the basis of study limitations and inconsistency). Three trials - SHEP 1991, LOMIR MCT IL 1996 and MRC 1996 - reported more withdrawals due to adverse events in active treatment groups than placebo groups. Participants on active treatment in Syst Eur 1998 were less likely to discontinue treatment due to side effects, and participants on active treatment in HYVET 2008 reported fewer 'serious adverse events' than in the placebo group. There was no evidence of a difference in withdrawals rates between groups in SCOPE 2003, and results were unclear for Perez Stable 2000 and Zhang 2018. Heterogeneity precluded meta-analysis. Five of the placebo-controlled trials provided quality of life (QOL) data. Heterogeneity again precluded meta-analysis. SHEP 1991, Syst Eur 1998 and HYVET 2008 reported no evidence of a difference in QOL measures between active treatment and placebo groups over time. The SCOPE 2003 sub-study (Degl'Innocenti 2004) showed a smaller drop in QOL measures in the active treatment compared to the placebo group. LOMIR MCT IL 1996 reported an improvement in a QOL measure at twelve months in one active treatment group and deterioration in another. High certainty randomised controlled trial evidence regarding the effect of hypertension treatment on dementia and cognitive decline does not yet exist. The studies included in this review provide low certainty evidence (downgraded primarily due to study limitations and indirectness) that pharmacological treatment of hypertension, in people without prior cerebrovascular disease, leads to less cognitive decline compared to controls. This difference is below the level considered clinically significant. The studies included in this review also provide very low certainty evidence that pharmacological treatment of hypertension, in people without prior cerebrovascular disease, prevents dementia.

Therapeutic effect of early intensive antihypertensive treatment on rebleeding and perihematomal edema in acute intracerebral hemorrhage.

To observe the effect of early intensive blood pressure (BP)-lowering treatment on rebleeding and perihematomal edema (PE) in patients with acute intracerebral hemorrhage (ICH). A total of 121 patients with ICH were randomly assigned to an early intensive antihypertensive treatment group (IG) (n=62) or control group (CG) (n=59). For both groups, 25mg of urapidil injection was slowly administered intravenously in 6hours of the onset. For the IG, 100mg of urapidil and 30mL of 0.9% sodium chloride were then slowly administered. Repeat computed tomography imaging was performed at 24hours, 72hours, day 7, and day 14 to detect any rebleeding via changes in hematoma volume and the changes in PE. Finally, NIHSS scores and Barthel Index (BI) were calculated at 24hours, 72hours, day 7, day 14, day 30, and day 90. The average hematoma volume in IG patients was significantly smaller than that of CG patients after 24hours (P<.05). The volume of PE in the CG increased more than in the IG within 24hours of onset, but was not statistically significant (P>.05); however, this trend was statistically significant after 72hours (P<.05). On day 30 and day 90, the average NIHSS score of IG patients was lower than that of CG patients, and the BI was higher (P<.05) than that of CG patients. There was no significant difference in mortality between the two groups. Early intensive antihypertensive treatment in ICH patients reduces rebleeding and PE, improving short-term quality of life.

Abstract TP403: Blood Pressure Reduction on Two-Year Mortality and Major Disability in Patients With Acute Ischemic Stroke According to Time to Treatment

Introduction: The optimal time to initiate antihypertensive therapy among patients with acute ischemic stroke remains uncertain. We tested the effects of blood pressure (BP) reduction on two-year mortality and major disability in acute ischemic stroke patients according to time from onset to initiation of antihypertensive treatment. Methods: The China Antihypertensive Trial in Acute Ischemic Stroke, a randomized, single-blind, blinded end-points trial, was conducted in 4,071 patients with ischemic stroke within 48 hours of onset and elevated systolic BP (SBP). Patients were randomly assigned to receive antihypertensive treatment (n=2,038) or to discontinue all antihypertensive medications (n=2,033) during hospitalization. Post-treatment follow-ups were conducted at 3, 12, and 24 months after hospital discharge. The primary outcome was a composite of death and major disability at the two-year follow-up visit. Results: At 24 hours after randomization, the differences in SBP reductions were 8.7, 9.5, and 9.6 mmHg between the antihypertensive treatment and control groups among patients receiving treatment within less than 12, 12-23, and 24-48 hours after stroke onset, respectively (P&lt;0.001 in all subgroups). At two-year follow-up, study outcomes were obtained in 1,945 (95.4%) participants in the treatment group and 1,925 (94.7%) in the control group. The event rates of primary outcome were not statistically significantly different between the antihypertensive treatment group and the control group according to time to treatment (Table). Conclusions: Among patients with acute ischemic stroke, BP reduction with antihypertensive medications during hospitalization did not reduce or increase the composite outcome of death and major disability over two years according to time to initiation of treatment.

Abstract WP435: Blood Pressure Reduction on Two-Year Mortality and Major Disability in Acute Ischemic Stroke With Various Severities

Introduction: We conducted a prespecified subgroup analysis to assess whether disease severity modifies the effect of early antihypertensive treatment on two-year mortality and major disability in acute ischemic stroke patients. Methods: The China Antihypertensive Trial in Acute Ischemic Stroke, a randomized, single-blind, blinded end-points trial, was conducted in 4,071 patients with ischemic stroke within 48 hours of onset and elevated systolic BP (SBP). Patients were randomly assigned to receive antihypertensive treatment (n=2,038) or to discontinue all antihypertensive medications (n=2,033) during hospitalization. Post-treatment follow-ups were conducted at 3, 12, and 24 months after hospital discharge. The primary outcome was a composite of death and major disability at the two-year follow-up visit. Results: At 24 hours after randomization, mean SBP differences (95% CIs) were -8.5 (-10.0 to -7.1), -9.8 (-11.4 to -8.3), and -9.1 (-14.4 to -3.8) mmHg between the treatment and control groups (all P &lt;0.001) for patients with a baseline NIHSS score of 0-4, 5-15, and ≥16, respectively. At day 7 after randomization, the corresponding mean SBP differences were -9.3 (-10.5 to -8.2), -9.1 (-10.3 to -7.8), and -10.1 (-15.1 to -5.1) mm Hg between the treatment and control groups (all P &lt;0.001). The event rates of primary outcome were not statistically significantly different between the antihypertensive treatment group and the control group according to baseline NIH stroke score or Rankin score (Table). Conclusions: Among patients with acute ischemic stroke, BP reduction with antihypertensive medications during hospitalization did not reduce or increase the composite outcome of death and major disability over two years according to disease severity at baseline.

A3154 Effects of Lipid - lowering Therapy on Blood Pressure and Arteriosclerosis in Elderly Patients with Obese Hypertension

Objectives: To investigate the effect of lipid-lowering on therapeutic effect and arteriosclerosis in elderly patients with different types of obesity. Methods: According to the factorial design, the subjects were randomly divided into four groups: 89 cases (group A) with lipid-lowering and depressing abdominal obesity group, 75 cases (group B) with lipid-lowering and blood pressure non-abdominal obesity group, Eighty-seven obese patients (group C) and 71 non-obese obese patients (group D). Antihypertensive therapy to give candesartan, rosuvastatin, simple antihypertensive treatment given candesartan, placebo. Regular follow-up of 1 year. Results: ¢ÙAfter treatment, body mass index, waist circumference, triglyceride, total cholesterol, fasting blood glucose, alanine aminotransferase, ankle brachial index, and ankle-brachial index decreased significantly in abdominal obesity group and non-abdominal obesity group The decreasing degree of lipid-lowering and antihypertensive treatment group was better than that of pure antihypertensive treatment group, the difference was statistically significant (P < 0.05). ¢Ú There was significant difference in clinical curative effect among all groups (P < 0.05), the systolic blood pressure in group C was significantly different from that in group B and group D (P < 0.05), and the difference between group B and group A and group C was statistically Significance (P < 0.05). The diastoli Conclusion: The lipid-lowering effect of lipid-lowering therapy on elderly patients with obesity and hypertension is significant, which can significantly reduce obesity-related indicators such as blood pressure, blood lipids, blood glucose and other symptoms, and effectively improve the symptoms of atherosclerosis without obvious adverse reactions. For these patients, To achieve more effective treatment.

Abstract P328: Effect of Sitagliptin on the Hemodynamic and Metabolic Response to a Mixed Meal in Individuals With Type 2 Diabetes and Hypertension

Dipeptidyl peptidase IV (DPP4) inhibitors such as sitagliptin are anti-diabetes drugs that may also have cardiovascular effects. We tested the hypothesis that there is an interactive effect between sitagliptin and angiotensin-converting enzyme (ACE) inhibition on blood pressure (SBP, DBP, MAP) and heart rate (HR) after a meal. We enrolled 52 type 2 diabetics (T2DM) with hypertension. The mean age was 56.1±10.2 years. 58.5% were men, 28.3% were black and 67.9% were white. Individuals were randomized to one of three BP agents: ramipril 10mg/d, valsartan 320mg/d [a renin-angiotensin-aldosterone system (RAAS) inhibiting drug without enzyme activity], and amlodipine 10mg/d (a RAAS-independent control) for 15 weeks. On the 5 th , 10 th , and 15 th week of anti-hypertensive therapy each participant underwent one-week crossover treatment with sitagliptin 100 mg/d + placebo, placebo + placebo, and sitagliptin + aprepitant 80 mg/d (a substance P receptor blocker, as DPP4 and ACE degrade substance P). On the last day of each treatment, participants were given a mixed meal (712 calories: 45% from fat, 33% carbohydrate, 22% protein). There was no difference in pre-prandial BP among the three crossover treatments. Following the meal, SBP (p=0.002) and MAP (p&lt;0.001) were significantly decreased during either DPP4 inhibitor crossover treatment compared to placebo. In particular, in patients treated with an ACE inhibitor, post-prandial SBP (0.015) and MAP (p=0.021) were lower during DPP4 inhibition. This was true after controlling for significant effects of race (p=0.002) and gender (p=0.0007). Post-prandial HR was not affected by DPP4 inhibition during ACE inhibition. The effect of DPP4 inhibition on fasting glucose but not on postprandial glucose differed among anti-hypertensive treatment groups. DPP4 inhibition decreased the formation of PYY3-36 from PYY following the meal. There is an interactive effect between DPP4 inhibition and anti-hypertensive therapy on post-prandial BP and metabolic parameters.

Early antihypertensive treatment and clinical outcomes in acute ischemic stroke: subgroup analysis by baseline blood pressure.

We studied the effect of early antihypertensive treatment on death, major disability, and vascular events among patients with acute ischemic stroke according to their baseline SBP. We randomly assigned 4071 acute ischemic stroke patients with SBP between 140 and less than 220 mmHg to receive antihypertensive treatment or to discontinue all antihypertensive medications during hospitalization. A composite primary outcome of death and major disability and secondary outcomes were compared between treatment and control stratified by baseline SBP levels of less than 160, 160-179, and at least 180 mmHg. At 24 h after randomization, differences in SBP reductions were 8.8, 8.6 and 7.8 mmHg between the antihypertensive treatment and control groups among patients with baseline SBP less than 160, 160-179, and at least 180 mmHg, respectively (P < 0.001 among subgroups). At day 14 or hospital discharge, the primary and secondary outcomes were not significantly different between the treatment and control groups among subgroups. However, there was a significant interaction between antihypertensive treatment and baseline SBP subgroups on death (P = 0.02): odds ratio (95% CI) of 2.42 (0.74-7.89) in patients with baseline SBP less than 60 mmHg and 0.34 (0.11-1.09) in those with baseline SBP at least 180 mmHg. At the 3-month follow-up, the primary and secondary clinical outcomes were not significantly different between the treatment and control groups by baseline SBP levels. Early antihypertensive treatment had a neutral effect on clinical outcomes among acute ischemic stroke patients with various baseline SBP levels. Future clinical trials are warranted to test BP-lowering effects in acute ischemic stroke patients by baseline SBP levels. ClinicalTrials.gov Identifier: NCT01840072.

Abstract WP328: Suppression of Tachycardia and Cost Effectiveness of Bisoprolol Transdermal Patch Addition to Intravenous Nicardipine in Antihypertensive Treatment for Acute Intracerebral Hemorrhage

Introduction: In patients with hypertensive intracerebral hemorrhage (ICH), intravenous (i.v.) Nicardipine is often used to lower the blood pressure. However, reflex tachycardia is a well-known side effect. Bisoprolol transdermal patch, a beta-blocker to be percutaneously absorbed, recently became commercially available in Japan. It can be used for patients with acute ICH with vomiting or dysphagia. The aim of this study is to evaluate suppressing effect of tachycardia and cost effectiveness of adding Bisoprolol transdermal patch to i.v. Nicardipine in patients with hypertensive ICH. Methods: We randomly assigned patients who were admitted to our department from January 2015 through April 2017 because of acute ICH to single antihypertensive treatment group (i.v. Nicardipine only) or combination treatment group (Bisoprolol transdermal patch and i.v. Nicardipine). The primary outcome was heart rate during 24 hours after admission. Key secondary outcomes were dose of Nicardipine (drug costs), neurological prognosis as defined by modified Rankin scale 0 to 2, and adverse drug reactions. Results: A total of 59 patients were randomized into two groups; 35 patients were assigned to single antihypertensive treatment group and 24 patients were assigned to combination treatment group. There were no significant differences between two groups in baseline characteristics on admission (age, body weight, hematoma volume, NIHSS, systolic blood pressure, heart rate). Mean heart rate during 24 hours after admission were significantly lower in combination treatment group (78.10±11.43 vs. 86.13±12.46, P=0.021). Hourly heart rate of combination treatment group was significantly lower in 5 to 24 hours later from start of treatment. Dose of Nicardipine was tended to be lower in combination treatment group (80.54±65.93 vs. 119.7±96.80mg, P=0.10), and costs of antihypertensive drug was tended to be lower in combination treatment group (5708±4569 vs. 8292±6708 yen, P=0.13). Neurological prognosis showed no difference (P=0.72), and bradycardia occurred in three patients of combination treatment group. Conclusions: Adding Bisoprolol transdermal patch to Nicardipine can decrease heart rate and may reduce drug costs in antihypertensive treatment for acute ICH.

Blood pressure reduction in acute ischemic stroke according to time to treatment: a subgroup analysis of the China Antihypertensive Trial in Acute Ischemic Stroke trial.

The optimal time to initiate antihypertensive therapy among patients with acute ischemic stroke remains uncertain. We tested the effects of blood pressure reduction among patients with acute ischemic stroke according to time from onset to initiation of antihypertensive treatment. We randomly assigned 4071 acute ischemic stroke patients with elevated SBP to receive antihypertensive treatment or to discontinue all antihypertensive medications during hospitalization. The primary outcome was a combination of death and major disability, and secondary outcomes included the modified Rankin score, recurrent stroke, vascular disease events, and all-cause mortality. At 24 h after randomization, the differences in SBP reductions were 8.7, 9.5, and 9.6 mmHg between the antihypertensive treatment and control groups among patients receiving treatment within less than 12, 12-23, and 24-48 h after stroke onset, respectively (P < 0.001 in all subgroups). At day 14 or hospital discharge, the primary and secondary outcomes were not significantly different between the treatment and control groups in all subgroups. At the 3-month follow-up, death or major disability [odds ratio (OR) 0.73; 95% confidence interval (CI) 0.55-0.96; P = 0.03], recurrent stroke (OR 0.25; 95% CI 0.08-0.74; P = 0.01), and vascular events (OR 0.41; 95% CI 0.18-0.95; P = 0.04) were significantly reduced in the antihypertensive treatment group only among participants who received treatment between 24 and 48 h. Blood pressure reduction might reduce 3-month death and major disability and recurrent stroke among patients with acute ischemic stroke who receive antihypertensive treatment between 24 and 48 h after stroke onset. ClinicalTrials.gov Identifier: NCT01840072.

Abstract 65: Effects of Immediate Blood Pressure Reduction on Two-Year Mortality and Major Disability in Patients With Acute Ischemic Stroke

Although elevated blood pressure (BP) is very common in patients with acute ischemic stroke, the management of hypertension among them remains controversial. We tested the effect of immediate BP reduction on two-year mortality and major disability in acute ischemic stroke patients. The China Antihypertensive Trial in Acute Ischemic Stroke, a randomized, single-blind, blinded end-points trial, was conducted in 4,071 patients with ischemic stroke within 48 hours of onset and elevated systolic BP (SBP). Patients were randomly assigned to receive antihypertensive treatment (n=2,038) or to discontinue all antihypertensive medications (n=2,033) during hospitalization. Post-treatment follow-ups were conducted at 3, 12, and 24 months after hospital discharge. The primary outcome was a composite of death and major disability at the two-year follow-up visit. Mean SBP was reduced by 21.8 in the treatment group and 12.7 mm Hg in the control group within 24 hours after randomization (P&lt;0.001). Mean SBP was 137.3 mm Hg in the treatment group and 146.5 in the control group at day 7 after randomization (P&lt;0.001). At two-year follow-up, study outcomes were obtained in 1945 (95.4%) participants in the treatment group and 1925 (94.7%) in the control group. 78.8% of the patients in the treatment group and 72.6% in the control group reported the use of antihypertensive medications (p&lt;0.001). SBP was 138.8 mmHg in the antihypertensive treatment group and 139.7 in the control group (p=0.02). Among patients in the antihypertensive treatment group, 24.5% (476/1945) died or had a major disability, compared with 22.1% (425/1925) in the control group (odds ratio 1.14 [95% CI 0.99 to 1.33], p=0.078). Hazard ratios for all-cause mortality (1.01 [0.81, 1.25], p=0.95), recurrent stroke (0.91 [0.73, 1.13], p=0.40), and vascular events (0.97 [0.79, 1.19], p=0.76) were not statistically significant comparing the antihypertensive treatment group to the control group. The effect of antihypertensive treatment did not differ by pre-defined subgroups. In conclusion, among patients with acute ischemic stroke, BP reduction with antihypertensive medications during hospitalization did not reduce or increase the composite outcome of death and major disability over two years.

Effects of early blood pressure reduction on cognitive function in patients with acute ischemic stroke

The effect of early blood pressure reduction on cognitive function in patients with acute ischemic stroke remains unknown. We tested whether antihypertensive treatment would reduce cognitive impairment in patients with acute ischemic stroke. In the China Antihypertensive Trial in Acute Ischemic Stroke, patients with elevated blood pressure were randomly assigned to receive antihypertensive treatment or to discontinue all hypertensive medications within 48 h of onset. Cognitive function was measured by the Mini-Mental State Examination and Montreal Cognitive Assessment at 3 months after randomization in a subsample of 638 participants. Mean systolic blood pressure was reduced by 21.5 mmHg in the antihypertensive treatment group and 13.9 mmHg in the control group within 24 h after randomization (P < 0.001). Mean systolic blood pressure was 134.9 mmHg in the antihypertensive treatment group and 141.6 mmHg in the control group at day 14 after randomization (P < 0.001). Median Mini-Mental State Examination score was 26 and Montreal Cognitive Assessment score was 22 in both the antihypertensive treatment and control groups at 3 months. An Mini-Mental State Examination < 24 was present in 30.9% of patients in the antihypertensive treatment group compared with 29.7% in the control group (odds ratio = 1.06; 95% confidence interval 0.75-1.48; P = 0.75). Likewise, proportions of patients with Montreal Cognitive Assessment < 26 were similar between the antihypertensive treatment (70.6%) and control (70.7%) groups (odds ratio = 0.99; 95% confidence interval 0.70-1.40; P = 0.96). These data indicated that early blood pressure reduction with antihypertensive medication in patients with acute ischemic stroke had no effect on cognitive impairment at 3 months.