The impact of the COVID-19 Pandemic on hypertension phenotypes (ESH ABPM COVID-19 study).

OBJECTIVE: The COVID-19 pandemic had a major impact on medical care. This study evaluated the influence of the pandemic on blood pressure (BP) control and hypertension phenotypes as assessed by office and 24-hour ambulatory BP monitoring (ABPM). DESIGN AND METHODS: Data were collected from 33 centers including Excellence Centers of the European Society of Hypertension. Two groups of patients with treated hypertension were compared. Pandemic group: including participants who had ABPM twice - at visit 2 during the COVID-19 pandemic and visit 1 performed 9-15 months prior to visit 2. Pre-pandemic group: had ABPM at two visits, performed before the pandemic within 9-15 months interval. We determined the following hypertension phenotypes: masked hypertension, white coat hypertension, sustained controlled hypertension (SCH) and sustained uncontrolled hypertension (SUCH). We analyzed the prevalence of phenotypes and their changes between visits. RESULTS: Data of 1419 patients, 616 (43 %) in the pandemic group and 803 (57 %) in the pre-pandemic group, were analyzed. At baseline (visit 1), the prevalence of hypertension phenotypes did not differ between groups. In the pandemic group, the change in hypertension phenotypes between two visits was not significant (p = 0.08). In contrast, in the pre-pandemic group, the prevalence of SCH increased during follow-up (28.8 % vs 38.4 %, p < 0.01) while the prevalence of SUCH decreased (34.2 % vs 27.8 %, p < 0.01). In multivariable adjusted analysis, the only factor influencing negative changes of hypertension phenotypes was the COVID-19 pandemic period. CONCLUSION: These results indicate a negative impact of the COVID-19 pandemic on BP control assessed by hypertension phenotypes.

Geographical differences in hydrochlorothiazide associated risk of skin cancer balanced against disability related to hypertensive heart disease.

BACKGROUND: Hypertension affects 25-30% of the world population. Hydrochlorothiazide (HCTZ) is among the most used and cheapest medications but was in 2018 labeled with a warning stating increased risk of non-melanoma skin cancer (NMSC). This study describes geographical differences in the association between HCTZ and NMSC in a perspective of hypertensive heart disease (HHD). METHODS: We conducted a systematic literature search (PubMed, Embase, Clinicaltrial.gov, and Clinicaltrial.eu) using PICO/PECO acronyms including case-control, cohort, and randomized controlled trials. We constructed a rate ratio of disability-adjusted life years (DALY) for HHD/NMSC in global burden of disease (GBD) regions. RESULTS: No increased risk of NMSC with use of HCTZ was found in Taiwan, India, and Brazil. A small (hazard ratio (HR)/odds ratio (OR) ≤ 1.5) but significantly increased risk was seen in Canada, USA, and Korea. An increased risk (1.5 < HR/OR ≤ 2.5) in Iceland, Spain, and Japan and a highly increased risk (HR/OR > 2.5 in UK, Denmark, Netherlands, and Australia. HHD is associated with a more than 10-fold DALY rate compared with NMSC in 13 of 21 GBD regions corresponding 77.2% of the global population. In none of these 13 regions were there an increased risk of HCTZ-associated NMSC. CONCLUSIONS: Despite limited information from many countries, our data point to large geographical differences in the association between HCTZ and NMSC. In all GBD regions, except Australasia, HHD constitutes a more than 5-fold DALY rate compared to NMSC. This disproportionate risk should be considered before avoiding HCTZ as part of the antihypertensive treatment.

Efficacy of antihypertensive treatment for target organ protection in patients with masked hypertension (ANTI-MASK): a multicentre, double-blind, placebo-controlled trial.

Background: Masked hypertension is associated with target organ damage (TOD) and adverse health outcomes, but whether antihypertensive treatment improves TOD in patients with masked hypertension is unproven. Methods: In this multicentre, randomised, double-blind, placebo-controlled trial at 15 Chinese hospitals, untreated outpatients aged 30-70 years with an office blood pressure (BP) of <140/<90 mm Hg and 24-h, daytime or nighttime ambulatory BP of ≥130/≥80, ≥135/≥85, or ≥120/≥70 mm Hg were enrolled. Patients had ≥1 sign of TOD: electrocardiographic left ventricular hypertrophy (LVH), brachial-ankle pulse wave velocity (baPWV) ≥1400 cm/s, or urinary albumin-to-creatinine ratio (ACR) ≥3.5 mg/mmol in women and ≥2.5 mg/mmol in men. Exclusion criteria included secondary hypertension, diabetic nephropathy, serum creatinine ≥176.8 µmol/L, and cardiovascular disease within 6 months of screening. After stratification for centre, sex and the presence of nighttime hypertension, eligible patients were randomly assigned (1:1) to receive antihypertensive treatment or placebo. Patients and investigators were masked to group assignment. Active treatment consisted of allisartan starting at 80 mg/day, to be increased to 160 mg/day at month 2, and to be combined with amlodipine 2.5 mg/day at month 4, if the ambulatory BP remained uncontrolled. Matching placebos were used likewise in the control group. The primary endpoint was the improvement of TOD, defined as normalisation of baPWV, ACR or LVH or a ≥20% reduction in baPWV or ACR over the 48-week follow-up. The intention-to-treat analysis included all randomised patients, the per-protocol analysis patients who fully adhered to the protocol, and the safety analysis all patients who received at least one dose of the study medication. This study is registered with ClinicalTrials.gov, NCT02893358. Findings: Between February 14, 2017, and October 31, 2020, 320 patients (43.1% women; mean age ± SD 53.7 ± 9.7 years) were enrolled. Baseline office and 24-h BP averaged 130 ± 6.0/81 ± 5.9 mm Hg and 136 ± 8.6/84 ± 6.1 mm Hg, and the prevalence of elevated baPWV, ACR and LVH were 97.5%, 12.5%, and 7.8%, respectively. The 24-h BP decreased on average (±SE) by 10.1 ± 0.9/6.4 ± 0.5 mm Hg in 153 patients on active treatment and by 1.3 ± 0.9/1.0 ± 0.5 mm Hg in 167 patients on placebo. Improvement of TOD occurred in 79 patients randomised to active treatment and in 49 patients on placebo: 51.6% (95% CI 43.7%, 59.5%) versus 29.3% (22.1, 36.5%; p < 0.0001). Per-protocol and subgroup analyses were confirmatory. Adverse events were generally mild and occurred in 38 (25.3%) and 43 (26.4%) patients randomised to active treatment and placebo, respectively (p = 0.83). Interpretation: Our results suggest that antihypertensive treatment improves TOD in patients with masked hypertension, highlighting the need of treatment. However, the long-term benefit in preventing cardiovascular complications still needs to be established. Funding: Salubris China.

Effects of the discontinuation of antihypertensive treatment on neuropsychiatric symptoms and quality of life in nursing home residents with dementia (DANTON): a multicentre, open-label, blinded-outcome, randomised controlled trial.

BACKGROUND: Based on observational studies and randomised controlled trials (RCTs), the benefit-harm balance of antihypertensive treatment in older adults with dementia is unclear. OBJECTIVE: To assess whether discontinuing antihypertensive treatment reduces neuropsychiatric symptoms (NPSs) and maintains quality of life (QoL) in nursing home residents with dementia. DESIGN: Open-label, blinded-outcome RCT. Randomisation 1:1, stratified by nursing home organisation and baseline NPS. Trial registration: NL7365. SUBJECTS: Dutch long-term care residents with moderate-to-severe dementia and systolic blood pressure (SBP) ≤160 mmHg during antihypertensive treatment. Exclusion criteria included heart failure NYHA-class-III/IV, recent cardiovascular events/procedures or life expectancy <4 months (planned sample size n = 492). MEASUREMENTS: Co-primary outcomes NPS (Neuropsychiatric Inventory-Nursing Home [NPI-NH]) and QoL (Qualidem) at 16 weeks. RESULTS: From 9 November 2018 to 4 May 2021, 205 participants (median age 85.8 [IQR 79.6-89.5] years; 79.5% female; median SBP 134 [IQR 123-146] mmHg) were randomised to either antihypertensive treatment discontinuation (n = 101) or usual care (n = 104). Safety concerns, combined with lacking benefits, prompted the data safety and monitoring board to advice a premature cessation of randomisation. At 16-week follow-up, no significant differences were found between groups for NPI-NH (adjusted mean difference 1.6 [95% CI -2.3 to 5.6]; P = 0.42) or Qualidem (adjusted mean difference - 2.5 [95% CI -6.0 to 1.0]; P = 0.15). Serious adverse events (SAEs) occurred in 36% (discontinuation) and 24% (usual care) of the participants (adjusted hazard ratio 1.65 [95% CI 0.98-2.79]). All 32-week outcomes favoured usual care. CONCLUSION: Halfway through this study, a non-significant increased SAE risk associated with discontinuing antihypertensive treatment was observed, and an associated interim analysis showed that significant worthwhile health gain for discontinuation of antihypertensive treatment was unlikely. This unbeneficial benefit-harm balance shows that discontinuation of antihypertensive treatment in this context does not appear to be either safe or beneficial enough to be recommended in older adults with dementia.

Hypertension and Heart Failure: From Pathophysiology to Treatment.

Hypertension represents one of the primary and most common risk factors leading to the development of heart failure (HF) across the entire spectrum of left ventricular ejection fraction. A large body of evidence has demonstrated that adequate blood pressure (BP) control can reduce cardiovascular events, including the development of HF. Although the pathophysiological and epidemiological role of hypertension in the development of HF is well and largely known, some critical issues still deserve to be clarified, including BP targets, particularly in HF patients. Indeed, the management of hypertension in HF relies on the extrapolation of findings from high-risk hypertensive patients in the general population and not from specifically designed studies in HF populations. In patients with hypertension and HF with reduced ejection fraction (HFrEF), it is recommended to combine drugs with documented outcome benefits and BP-lowering effects. In patients with HF with preserved EF (HFpEF), a therapeutic strategy with all major antihypertensive drug classes is recommended. Besides commonly used antihypertensive drugs, different evidence suggests that other drugs recommended in HF for the beneficial effect on cardiovascular outcomes exert advantageous blood pressure-lowering actions. In this regard, type 2 sodium glucose transporter inhibitors (SGLT2i) have been shown to induce BP-lowering actions that favorably affect cardiac afterload, ventricular arterial coupling, cardiac efficiency, and cardiac reverse remodeling. More recently, it has been demonstrated that finerenone, a non-steroidal mineralocorticoid receptor antagonist, reduces new-onset HF and improves other HF outcomes in patients with chronic kidney disease and type 2 diabetes, irrespective of a history of HF. Other proposed agents, such as endothelin receptor antagonists, have provided contrasting results in the management of hypertension and HF. A novel, promising strategy could be represented by small interfering RNA, whose actions are under investigation in ongoing clinical trials.

Potential Impact of Bioactive Peptides from Foods in the Treatment of Hypertension.

SCOPE: High blood pressure (BP) is the main preventable risk factor for cardiovascular diseases (CVDs). Much research is aimed at finding natural alternatives to control or prevent hypertension (HT), since some hypertensive patients do not respond to current pharmacological treatments or show undesirable side effects. METHODS AND RESULTS: Forty relevant articles have been selected from various scientific literature databases. The results reveal that angiotensin-converting enzyme (ACE) inhibition is the most reported mechanism of action of antihypertensive peptides. The active peptides have a great variety of origins. Biopeptides with a molecular weight of <3 kDa, short chain <20 amino acids, and a hydrophobic amino acid sequence at the C- and N-terminus exhibit higher antihypertensive activity. They also show good stability to enzymatic hydrolysis and gastrointestinal digestion, and no toxicity. To determine antihypertensive effectiveness, in vitro and in vivo animal studies are the most frequent developed, with few in silico studies and only one human clinical trial. CONCLUSION: There is interesting potential for antihypertensive peptides as promising natural candidates for the development of functional foods, nutraceuticals and drugs for preventive or therapeutic treatment of hypertension. The aim of this review is to study the role of food-derived bioactive peptides in HT.

The impact of long-term antihypertensive treatment on wound healing after major non-cardiac surgery in patients with cardiovascular diseases: A meta-analysis.

Hypertension is a prevalent condition that poses significant challenges in the perioperative management of patients undergoing major non-cardiac surgery, particularly concerning wound healing and scar formation. This meta-analysis assesses the impact of long-term antihypertensive treatment on postoperative wound healing, examining data from seven studies involving patients who received such treatments compared to untreated controls. Our findings reveal that long-term antihypertensive therapy is associated with significantly improved wound healing outcomes, as indicated by lower REEDA scores (I2 = 96%, SMD = -25.71, 95% CI: [-33.71, -17.70], p < 0.01) 1 week post-surgery and reduced scar formation, demonstrated by lower Manchester Scar Scale scores (I2 = 93%, SMD = -37.29, 95% CI: [-44.93, -29.64], p < 0.01) 2 months post-surgery. These results underscore the potential benefits of antihypertensive treatment in enhancing surgical recovery and offer insights into optimising perioperative care for hypertensive patients.

The lowest well tolerated blood pressure: A personalized target for all?

The optimal blood pressure (BP) target for prevention of cardiovascular complications of hypertension remains uncertain. Most Guidelines suggest different targets depending on age, comorbidities and treatment tolerability, but the underlying evidence is not strong. Results of randomized strategy trials comparing lower (i.e., more intensive) versus higher (i.e., less intensive) BP targets should drive the definition. However, these trials tested different BP targets based on systolic BP, diastolic BP or combined systolic and diastolic BP goals. Overall, the more intensive treatment targets reduced the risk of major cardiovascular complications of hypertension when compared with the less intensive targets, despite a higher incidence of unwanted effects including, but not limited to, hypotension, electrolyte abnormalities and renal dysfunction. Consequently, some Guidelines defined low BP thresholds (i.e., 120/70 mmHg) not to exceed downward because of the expectation that unwanted effects may outweigh the outcome benefits. The present review discusses the evidence underlying the choice of BP targets, which remains an important step in the management of hypertensive patients. We conclude that, on the ground of the heterogeneity of available data in support to fixed BP targets, their definition should be personalized in all patients and based on best trade-off between efficacy and safety, i.e., the lowest well tolerated BP.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: Early antihypertensive treatment had a neutral effect on clinical outcomes among patients with acute ischemic stroke according to 5 BP-associated genetic variants. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01840072.

Alcohol Consumption and Antihypertensive Treatment Effect in Male Patients With Hypertension.

BACKGROUND: Alcohol consumption is a proven risk factor of hypertension. In the present analysis, we investigated the use of antihypertensive medications and blood pressure control in male alcohol drinkers and non-drinkers with hypertension (systolic/diastolic blood pressure 160-199/100-119 mm Hg). METHODS: The study participants were patients enrolled in a 12-week therapeutic study and treated with the irbesartan/hydrochlorothiazide combination 150/12.5 mg once daily, with the possible up-titration to 300/12.5 mg/day and 300/25 mg/day at 4 and 8 weeks of follow-up, respectively, for blood pressure control of <140/90 mm Hg or <130/80 mm Hg in patients with diabetes mellitus. Alcohol consumption was classified as non-drinkers and drinkers. RESULTS: The 68 alcohol drinkers and 168 non-drinkers had similar systolic/diastolic blood pressure at baseline (160.8 ±â€…12.1/99.8 ±â€…8.6 vs. 161.8 ±â€…11.0/99.2 ±â€…8.6, P ≥ 0.55) and other characteristics except for current smoking (80.9% vs. 47.6%, P < 0.0001). In patients who completed the 12-week follow-up (n = 215), the use of higher dosages of antihypertensive drugs was similar at 4 weeks of follow-up in drinkers and non-drinkers (10.6% vs. 12.4%, P = 0.70), but increased to a significantly higher proportion in drinkers than non-drinkers at 12 weeks of follow-up (54.7% vs. 36.6%, P = 0.01). The control rate of hypertension tended to be lower in alcohol drinkers, compared with non-drinkers, at 4 weeks of follow-up (45.6% vs. 58.9%, P = 0.06), but became similar at 12 weeks of follow-up (51.5% vs. 54.8%, P = 0.65). CONCLUSION: Alcohol drinkers compared with non-drinkers required a higher dosage of antihypertensive drug treatment to achieve similar blood pressure control. CLINICAL TRIAL REGISTRY NUMBER: NCT00670566 at www.clinicaltrials.gov.

A Qualitative Study on Patients' Views on Hypertension and Antihypertensive Medications.

Purpose: Few studies explored what patients initiated on blood pressure medication in primary care think about their disease and their medications. The aim of this study was to gain an understanding of hypertensive patients' views on and experiences of hypertension and the use of antihypertensive medications. Methods: A qualitative study based on open-ended questions from a survey on medication adherence, which captured treated hypertensive patients' perspective on their condition and treatment. Data were collected for 219 patients on antihypertensive medication, ≥ 30 years old, who consulted 25 primary health care centers in Stockholm, Sweden, during 2016. Thematic analysis with both inductive and deductive approach was applied. Results: We identified 21 codes from the data and grouped them under the World Health Organization's five dimensions of adherence: condition-, therapy-, health care team and system-, patient-, and socioeconomic-related factors. The analyses revealed that many patients with hypertension have limited knowledge of their disease, are afraid of drug side effects and experience various issues in primary health care that may negatively impact adherence, including short doctor appointments, prescribing without communication and room for improvement in individualization of therapy and a person-centered approach. Conclusion: Many patients with hypertension have limited understanding of their hypertension and fear of adverse events from their antihypertensive medications. There is also room for improvement in how the patients are managed in primary health care. Interventions should focus on these issues to promote a better blood pressure target achievement.

Blood pressure control in hypertensive sleep apnoea patients of the European Sleep Apnea Database cohort - effects of positive airway pressure and antihypertensive medication.

Aims: We analysed longitudinal blood pressure (BP) data from hypertensive obstructive sleep apnoea (OSA) patients in the European Sleep Apnea Database cohort. The study investigated the interaction between positive airway pressure (PAP)-induced BP change and antihypertensive treatment (AHT). Methods and results: Hypertensive patients with AHT [monotherapy/dual therapy n = 1283/652, mean age 59.6 ± 10.7/60.6 ± 10.3 years, body mass index (BMI) 34.2 ± 6.5/34.8 ± 7.0 kg/m2, apnoea-hypopnoea index 46 ± 25/46 ± 24 n/h, proportion female 29/26%, respectively] started PAP treatment. Office BP at baseline and 2- to 36-month follow-up were assessed. The interaction between AHT drug classes and PAP on BP was quantified and the influences of age, gender, BMI, co-morbidities, BP at baseline, and study site were evaluated. Following PAP treatment (daily usage, 5.6 ± 1.6/5.7 ± 1.9 h/day), systolic BP was reduced by -3.9 ± 15.5/-2.8 ± 17.7 mmHg in mono/dual AHT and diastolic BP by -3.0 ± 9.8/-2.7 ± 10.8 mmHg, respectively, all P < 0.0001. Systolic and diastolic BP control was improved following PAP treatment (38/35% to 54/46% and 67/67% to 79/74%, mono/dual AHT, respectively). PAP treatment duration predicted a larger BP improvement in the monotherapy group. Intake of renin-angiotensin blockers [angiotensin converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB)] alone or in any AHT combination was associated with better BP control. The AHT-dependent BP improvement was independent of confounders. Conclusion: In this pan-European OSA patient cohort, BP control improved following initiation of PAP. Longer PAP treatment duration, was associated with a favourable effect on BP. Our study suggests that ACEI/ARB, alone or in combination with other drug classes, provides a particularly strong reduction of BP and better BP control when combined with PAP in OSA.

Association between baseline blood pressure and the incidence of lenvatinib-induced hypertension in patients with thyroid cancer.

BACKGROUND: Hypertension is the most frequently occurring adverse event of lenvatinib, recognized relatively early in its course. However, the trend in blood pressure after the initiation of lenvatinib and the outcomes with antihypertensive treatment are unclear. This study aimed to clarify the association between baseline blood pressure and the incidence of lenvatinib-induced hypertension in patients with thyroid cancer. METHODS: This retrospective study included 65 patients without hypertension at the time of lenvatinib initiation. Patients were divided into two groups: those who developed hypertension grade ≥3 (HTN group) and those who did not develop hypertension grade ≥3 (non-HTN group). RESULTS: Of the 65 patients, 46 (71%) developed hypertension grade ≥3. In both HTN and non-HTN groups, blood pressure significantly increased the day after lenvatinib initiation. There was no significant difference in the elevated values of both the changes in systolic blood pressure (ΔSBP) and diastolic blood pressure (ΔDBP) between the two groups, with an average increase of 20 mmHg in SBP and 13 mmHg in DBP from baseline. The median (range) time to the onset of hypertension grade ≥3 was 2 days (1-12 days). In the multivariable analysis, patients with normal (SBP 120-129 mmHg and/or DBP 80-84 mmHg) or high-normal baseline blood pressure (SBP 130-139 mmHg and/or DBP 85-89 mmHg) were at higher risk of developing hypertension grade ≥3 than those with optimal baseline blood pressure (SBP <120 mmHg and DBP <80 mmHg) (odds ratio [OR], 5.07; 95% confidential interval [CI] 1.09-23.54 and OR, 7.48; 95% CI, 1.67-33.51, respectively). CONCLUSIONS: Lenvatinib-induced hypertension appears the day after administration, and higher baseline blood pressure is a significant risk factor for developing hypertension grade ≥3. In cases of increased blood pressure with lenvatinib, early initiation of antihypertensives may prevent treatment interruption due to hypertension and maintain the therapeutic intensity of lenvatinib.

Blood Pressure Variability as a Risk Factor for Cardiovascular Disease: Which Antihypertensive Agents Are More Effective?

Blood pressure oscillations during different time scales, known as blood pressure variability (BPV), have become a focus of growing scientific interest. BPV can be measured at long-term (seasonal variability or visit-to-visit), at mid-term (differences in consecutive days or weeks) or at short-term (day-night differences or changes induced by other daily activities and conditions). An increased BPV, either at long, mid or short-term is associated with a poor cardiovascular prognosis independently of the amount of blood pressure elevation. There is scarce evidence on the effect of different antihypertensive treatments on BPV, but some observational and interventional studies suggest that calcium channel blockers in general, and particularly amlodipine, either in monotherapy or combined with renin-angiotensin system blockers, can reduce BPV more efficiently than other antihypertensive drugs or combinations. Nevertheless, there are several aspects of the relationship between BPV, antihypertensive treatment, and clinical outcomes that are still unknown, and more work should be performed before considering BPV as a therapeutical target in clinical practice.

Magnitude of Systolic Blood Pressure Reduction and Early Achieved Blood Pressure and Clinical Outcomes After Acute Ischemic Stroke.

Background We aimed to evaluate the relationships between the magnitude of systolic blood pressure (SBP) reduction and achieved SBP in the acute phase of ischemic stroke onset and subsequent clinical outcomes. Methods and Results This study was a secondary analysis of CATIS (China Antihypertensive Trial in Acute Ischemic Stroke), a multicenter randomized controlled trial of 4071 patients with acute ischemic stroke. SBP reduction was defined as the proportional SBP changes from baseline to 24 hours after randomization, and achieved SBP was the mean of SBP measurements at day 7. The study outcomes included functional outcome of death or major disability (modified Rankin Scale score ≥3), death, and cardiovascular events at 3 months after recruitment. Compared with the reference group of increase or no change in SBP within the first 24 hours, the odds ratios (95% CIs) of functional outcome of death or major disability were 0.62 (0.47-0.83) and 0.61 (0.42-0.87) for the reduction of 11% to 20% and >20%, respectively. Compared with participants in highest achieved SBP group (≥160 mm Hg) at day 7, odds ratios or hazard ratios of lower achieved SBP (<130 mm Hg) were 0.54 (95% CI, 0.37-0.80) for functional outcome, and 0.36 (95% CI, 0.17-0.80) for death or cardiovascular events. Conclusions A moderate magnitude of SBP reduction and a lower early achieved SBP were associated with a decreased risk of poor functional outcome, death, and cardiovascular events after acute ischemic stroke. Further studies are warranted to confirm these findings. REGISTRATION: URL: ClinicalTrials.gov; Unique identifier: NCT01840072.