BP-lowering Agents Research Articles

The impact of blood pressure lowering agents on the risk of worsening frailty among patients with diabetes mellitus: a cohort study

Patients with diabetes mellitus (DM) are at risk of developing frailty, but studies rarely addressed risk factors for frailty worsening. We investigated whether blood pressure (BP)-lowering agents influenced such risk in these patients. Adults with type 2 DM were identified from National Taiwan University Hospital, with the primary outcome, the worsening of frailty by ≧1 score increase of FRAIL scale determined. We used the Cox proportional hazards analysis to derive the risk of worsening frailty associated with BP-lowering agents. Among 41,440 patients with DM, 27.4% developed worsening frailty after 4.09 years of follow-up. Cox regression revealed that diuretics (hazard ratio (HR) 1.12, 95% confidence interval (CI) 1.06–1.18) and α-blocker (HR 1.14, 95% CI 1.06–1.23) users had a significantly higher risk of worsening frailty than non-users, whereas the risk was lower among β-blocker users (HR 0.93, 95% CI 0.88–0.98). It would be therefore prudent to weigh the advantages and disadvantages of using specific BP-lowering agent classes.

Uncontrolled hypertension and hypertensive urgency: One-year single-center emergency department experience.

The prevalence of uncontrolled hypertension remains a significant concern in public healthcare systems, including daily practices of emergency departments (ED). We aimed to characterize patients admitted to an ED for elevated blood pressure (BP) and to identify factors leading to hospitalization. This retrospective analysis included all patients admitted to an ED in a tertiary hospital in 2022 due to an acute BP rise without hypertensive emergencies. The studied group (n = 570) constituted 1.5% of all ED admissions in 2022. The median age was 67 years (Q1-Q3) (52-75), 68.9% were females. Systolic BP (200 mm Hg [180-212]) and diastolic BP (105 mm Hg [100-115]) at home were higher than during triage (173 mm Hg [160-190] and 95 mm Hg [84-103], respectively [P <0.0001]). Thirty-nine percent of the studied population had taken BP-lowering agents before ED admission (captopril in 91.8% of cases). In the ED, nitrendipine (54.2%), captopril (38.1%), furosemide (16.3%), urapidil (10.0%), and nitroglycerine (1.9%) were administered. Eventually, a median of 140/82 mm Hg BP was reached in the median time of 288 minutes (202-400). Hospitalization was necessary in 5.4% of patients. The need for furosemide or urapidil administration in the ED doubled the risk of hospitalization (OR, 2.0; P <0.01). Before ED admission, only 17.0% of patients received guidelines-recommended single-pill combination therapy, and 17.6% had already visited ED for uncontrolled hypertension (median of 388 days earlier). Elevated BP is a common reason for admission to the ED. Crucially, improvements in long-term hypertension treatment and education are needed to reduce the number of patients seeking ED care for elevated BP.

Efficacy and safety of a single-pill versus free combination of perindopril/indapamide/amlodipine: a multicenter, randomized, double-blind study in Chinese patients with hypertension.

In China, the prevalence of hypertension is high and the use of combination antihypertensive therapy is low, which contributes to inadequate blood pressure (BP) control. The availability of simplified treatments combining complementary BP-lowering agents may help more patients achieve their goals. This Phase III, multicenter, randomized, double-blind, noninferiority study included Chinese adults with mild-to-moderate hypertension. Following a 1-month run-in on perindopril/indapamide bi-therapy, patients with uncontrolled systolic/diastolic BP (≥140/90 mmHg) were randomized to perindopril 5 mg/indapamide 1.25 mg/amlodipine 5 mg (Per/Ind/Aml) single-pill combination (SPC) or perindopril 4 mg/indapamide 1.25 mg plus amlodipine 5 mg (Per/Ind + Aml) for 6 months. Uptitration was permitted from month 2 onwards. The primary efficacy objective was the noninferiority of Per/Ind/Aml in lowering office systolic BP at 2 months. The secondary objectives included the effectiveness of SPC on diastolic BP, uptitration efficacy, and office BP control (systolic/diastolic <140/90 mmHg). A subgroup of patients participated in 24-h ambulatory BP monitoring (ABPM). A total of 532 patients were randomized: Per/Ind/Aml ( n = 262) and Per/Ind + Aml ( n = 269). Overall, the mean (±SD) age was 55.7 ± 8.8 years, 60.7% were male, and the mean office systolic/diastolic BP at baseline on Per/Ind was 150.4/97.2 mmHg. Systolic BP decreased in both groups at 2 months from baseline: -14.99 ± 14.46 mmHg Per/Ind/Aml versus -14.49 ± 12.87 mmHg Per/Ind +Aml. A predefined noninferiority margin of 4 mmHg was observed ( P < 0.001). The effectiveness of the Per/Ind/Aml SPC was also demonstrated for all secondary endpoints. ABPM demonstrated sustained BP control over 24 h. Both treatments were well tolerated. Per/Ind/Aml is an effective substitute for Per/Ind + Aml, providing at least equivalent BP control over 24 h in a single pill, with comparable safety.

Abstract 13243: Different Efficacy of Angiotensin Receptor Blockers for Nocturnal Blood Pressure Reduction in Patients With Mild to Moderate Hypertension: A Systematic Review and Meta-Analysis

Introduction: High nocturnal blood pressure (BP) is correlated with an increased risk of cardiovascular events and is an important predictor of cardiovascular death in hypertensive patients. Thus, nocturnal BP control is of great importance for cardiovascular risk reduction. Hypothesis: As the most commonly prescribed BP-lowering agents, angiotensin II receptor blockers (ARBs) maybe have different efficacy for nocturnal BP reduction in patients with mild-to-moderate hypertension (MMH). Methods: We conducted a systematic search in PubMed, EMBASE, Cochrane Library and Web of Science from inception to August 8th, 2022, and collected the ambulatory BP study data of different ARBs (allisartan, candesartan, irbesartan, losartan, olmesartan, telmisartan and valsartan) in patients with MMH following PICOs principle. Data was extracted and the risk of bias of the included studies was evaluated accordingly, and R software (version 4.0.0) was used for statistical analysis. Results: Seventy-eight studies with 13,108 patients were included. The results of meta-analysis showed that allisartan, olmesartan, telmisartan were associated with greater reduction in nocturnal systolic BP, while valsartan, olmesartan and telmisartan demonstrated greater efficacy in reducing nocturnal diastolic BP. In the aspect of the nocturnal-diurnal BP drop ratio, only allisartan was greater than 1 (figure). Additionally, allisartan showed more advantages in the last 4-6 hours ambulatory BP drop, the proportion of patients with dipping BP pattern, and the 24 hours ambulatory BP drop as compared to other ARBs. Conclusions: For patients with MMH, allisartan, olmesartan and telmisartan have more advantages in nocturnal BP reduction among the ARBs, while allisartan can reduce nocturnal BP more than daytime BP and improve the dipping pattern, contribute to restore normal BP rhythm.

Medication Adherence and Blood Pressure Control Among Hypertensive Outpatients Attending a Tertiary Cardiovascular Hospital in Tanzania: A Cross-Sectional Study.

BackgroundNotwithstanding the availability of effective treatments, asymptomatic nature and the interminable treatment length, adherence to medication remains a substantial challenge among patients with hypertension. Suboptimal adherence to BP-lowering agents is a growing global concern that is associated with the substantial worsening of disease, increased service utilization and health-care cost escalation. This study aimed to explore medication adherence and its associated factors among hypertension outpatients attending a tertiary-level cardiovascular hospital in Tanzania.MethodsThe pill count adherence ratio (PCAR) was used to compute adherence rate. In descriptive analyses, adherence was dichotomized and consumption of less than 80% of the prescribed medications was used to denote poor adherence. Logistic regression analyses was used to determine factors associated with adherence.ResultsA total of 849 outpatients taking antihypertensive drugs for ≥1 month prior to recruitment were randomly enrolled in this study. The mean age was 59.9 years and about two-thirds were females. Overall, a total of 653 (76.9%) participants had good adherence and 367 (43.2%) had their blood pressure controlled. Multivariate logistic regression analysis showed; lack of a health insurance (OR 0.5, 95% CI 0.3–0.7, p<0.01), last BP measurement >1 week (OR 0.6, 95% CI 0.4–0.8, p<0.01), last clinic attendance >1 month (OR 0.4, 95% CI 0.3–0.6, p<0.001), frequent unavailability of drugs (OR 0.6, 95% CI 0.3–0.9, p = 0.03), running out of medication before the next appointment (OR 0.6, 95% CI 0.4–0.9, p = 0.01) and stopping medications when asymptomatic (OR 0.6, 95% CI 0.4–0.8, p<0.001) to be independent associated factors for poor adherence.ConclusionA substantial proportion of hypertensive outpatients in this tertiary-level setting had good medication adherence. Nonetheless, observed suboptimal blood pressure control regardless of a fairly satisfactory adherence rate suggests that lifestyle modification plays a central role in hypertension management.

Review of Long-Term Blood Pressure Control After Intracerebral Hemorrhage: Challenges and Opportunities.

Blood pressure (BP) is the most important modifiable risk factor for intracerebral hemorrhage (ICH). Elevated BP is associated with an increased risk of ICH, worse outcome after ICH, and in survivors, higher risks of recurrent ICH, ischemic stroke, myocardial infarction, and cognitive impairment/dementia. As intensive BP control probably improves the chances of recovery from acute ICH, the early use of intravenous or oral medications to achieve a systolic BP goal of <140 mm Hg within the first few hours of presentation is reasonable for being applied in most patients. In the long-term, oral antihypertensive drugs should be titrated as soon as possible to achieve a goal BP <130/80 mm Hg and again in all ICH patients regardless of age, location, or presumed mechanism of ICH. The degree of sustained BP reduction, rather than the choice of BP-lowering agent(s), is the most important factor for optimizing risk reduction, with varying combinations of thiazide-type diuretics, long-acting calcium channel blockers, ACE (angiotensin-converting enzyme) inhibitors or angiotensin receptor blockers, being the mainstay of therapy. As most patients will require multiple BP-lowering agents, and physician inertia and poor adherence are major barriers to effective BP control, single-pill combination therapy should be considered as the choice of management where available. Increased population and clinician awareness, and innovations to solving patient, provider, and social factors, have much to offer for improving BP control after ICH and more broadly across high-risk groups. It is critical that all physicians, especially those managing ICH patients, emphasize the importance of BP control in their practice.

HIGH BLOOD PRESSURE IN THE EMERGENCY DEPARTMENT. A TOOL FOR DETECTION OF HYPERTENSION? A FOLLOW-UP STUDY OF UNSELECTED PATIENTS ATTENDING AN EMERGENCY DEPARTMENT

Objective: Hypertension is the most preventable cause of morbidity and mortality, but many individuals are not diagnosed and lack treatment control. High blood pressure (BP) in the emergency department (ED) is commonly observed but mostly used for short-term evaluation. We aimed to study the usefulness of high BP in the ED as a screening tool for undiagnosed hypertension. Design and method: We used the electronic medical record system to identify all patients that had attended the ED at a university hospital from 2018–01–01 to 2018–03–31 and from 2018-07-01 to 2018-09-30 with an obtained BP &gt; = 160/100 mm Hg measured in the ED. We excluded patients with previously diagnosed hypertension and patients on any BP-lowering medication. All patients identified where contacted two years after attending the ED, by mail with a letter of consent and a questionnaire with the following question: 1. Have you measured your BP after your visit to the ED? 2. Have you been diagnosed with hypertension? 3. If yes – what kind of BP-medication has been prescribed? Results: 5424 patients attended the ED during the 6-months-period. 2625 patients were excluded due to a BP &lt; 160/100 mm Hg, 1365 patients were excluded because of present BP-lowering medication, 523 patients were excluded because no BP was recorded, and 638 patients were deceased. A total of 271 patients were identified as suitable for the study and asked to participate. 167 individuals (62%) agreed to participate in the study and responded the questionnaire. Mean age of participants were 63,8 years and 50,2% were women. 135 patients (81%) had measured their BP after the ED-visit (question 1), and 48 (36%) of those had been diagnosed with hypertension (question 2). 96% of patients diagnosed with hypertension were on BP-lowering medication and 28% were on 2 or more different BP-lowering agents. Conclusions: To follow-up BP &gt; = 160/100 mm Hg after an ED-visit can reveal undiagnosed hypertension in one third of the patients. Given the amount of undiagnosed hypertension, an ED-measured BP might provide an important tool with potential to detect and start treatment of hypertension.

ASSOCIATION OF NDUFC2 POLYMORPHIC VARIANTS WITH LEFT VENTRICULAR HYPERTROPHY IN HUMAN HYPERTENSION

Objective: Previous experimental studies showed that a dysfunction of the NADH dehydrogenase (ubiquinone), the mitochondrial Complex I (CI), is associated with the development of left ventricular hypertrophy (LVH). A deficiency of Ndufc2 (a subunit of CI) impairs CI activity and causes severe mitochondrial dysfunction. The NDUFC2/rs11237379 polymorphic variant is associated with reduced gene expression and impaired mitochondrial function, contributing to increased susceptibility to vascular diseases. We examined the association of NDUFC2/rs11237379 and another NDUFC2 polymorphic variant (rs641836) with the development of LVH in hypertensive patients. Design and method: Two-hundred-fourty-six hypertensive subjects (147 male, 59.7%) with a mean age of 59 ± 15 years were studied. Seventy-nine individuals (32%) presented LVH. Results: The association analysis for both SNPs showed that hypertensive patients carrying the TT genotype at the NDUFC2/rs11237379 had a significant increase of echocardiographically assessed septal thickness (p = 0.001), posterior wall thickness (p = 0.003), relative wall thickness (RWT) (p = 0.01), LV mass/ body surface area (BSA) (p = 0.012) and LV mass/height2.(p = 0.0033) compared to subjects carrying either CC or CT genotypes. To better dissect the genetic effect, a covariate ANOVA was performed for each cardiac variable, considering age, gender, body mass index (BMI), office blood pressure (BP), antihypertensive treatment with a combination of 2 or more drugs and the number of BP-lowering agents as covariates. The adjustment for covariates revealed significant differences for septal thickness (p = 0.07), posterior wall thickness (p = 0.008), RWT (p = 0.021), LV mass/BSA (p = 0.03). With regard to NDUFC2/rs641836, hypertensive subjects carrying the mutant A allele had a significant increase of septal thickness (p = 0.001), posterior wall thickness (p = 0.001), RWT (p = 0.005), LV mass (p = 0.001), LV mass/BSA(p = 0.001), LV mass/height2.7(p = 0.002) compared to wild-type homozygotes. After adjustment for covariates, the results were significant for septal thickness (p = 0.017), posterior wall thickness (p = 0.011), LV mass (p = 0.003), LV mass/BSA (p = 0.002) and LV mass/height2.7(p = 0.010). Conclusions: Our results demonstrate for the first time a significant association of NDUFC2 variants with LVH in hypertensives and highlight a novel role of CI dependent mitochondrial dysfunction on increased susceptibility to cardiac damage in human hypertension. This study paves the way of a new pathophysiological mechanism of LVH which may lead to new clinical strategies.

Early lowering of blood pressure after acute intracerebral haemorrhage: a systematic review and meta-analysis of individual patient data

ObjectiveTo summarise evidence of the effects of blood pressure (BP)-lowering interventions after acute spontaneous intracerebral haemorrhage (ICH).MethodsA prespecified systematic review of the Cochrane Central Register of Controlled Trials, EMBASE and...

World Heart Federation Roadmap for Hypertension - A 2021 Update.

The World Heart Federation (WHF) Roadmap series covers a large range of cardiovascular conditions. These Roadmaps identify potential roadblocks and their solutions to improve the prevention, detection and management of cardiovascular diseases and provide a generic global framework available for local adaptation.A first Roadmap on raised blood pressure was published in 2015. Since then, advances in hypertension have included the publication of new clinical guidelines (AHA/ACC; ESC; ESH/ISH); the launch of the WHO Global HEARTS Initiative in 2016 and the associated Resolve to Save Lives (RTSL) initiative in 2017; the inclusion of single-pill combinations on the WHO Essential Medicines’ list as well as various advances in technology, in particular telemedicine and mobile health. Given the substantial benefit accrued from effective interventions in the management of hypertension and their potential for scalability in low and middle-income countries (LMICs), the WHF has now revisited and updated the ‘Roadmap for raised BP’ as ‘Roadmap for hypertension’ by incorporating new developments in science and policy. Even though cost-effective lifestyle and medical interventions to prevent and manage hypertension exist, uptake is still low, particularly in resource-poor areas. This Roadmap examined the roadblocks pertaining to both the demand side (demographic and socio-economic factors, knowledge and beliefs, social relations, norms, and traditions) and the supply side (health systems resources and processes) along the patient pathway to propose a range of possible solutions to overcoming them. Those include the development of population-wide prevention and control programmes; the implementation of opportunistic screening and of out-of-office blood pressure measurements; the strengthening of primary care and a greater focus on task sharing and team-based care; the delivery of people-centred care and stronger patient and carer education; and the facilitation of adherence to treatment. All of the above are dependent upon the availability and effective distribution of good quality, evidence-based, inexpensive BP-lowering agents.

Regional Differences in Early BP Management After Acute Ischemic Stroke in the ENCHANTED International Randomized Controlled Trials.

Background and Aims: Epidemiological studies show significant variations in hypertension management within and between countries. The level of regional variation in early blood pressure (BP) management after acute stroke is uncertain.Methods: Data are from the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED), a partial-factorial, international randomized controlled trial of thrombolysis-eligible acute ischemic stroke (AIS) patients with elevated systolic BP (SBP >150 mmHg) assigned to intensive (target SBP 130-140 mmHg) vs. guideline-recommended (SBP <180 mmHg) treatment; BP management was compared among four regions: Western countries (Italy/United Kingdom/Spain/Australia), China (mainland), other Asia (Hong Kong/Taiwan/Singapore/Thailand/Vietnam/India), and South America (Chile/Brazil/Colombia).Results: These analyses included 2,196 AIS [38% women, mean age 67 (12) years] patients. Commonly used intravenous BP-lowering agents were labetalol, nitroglycerin, and topical nitrates in Western countries; urapidil and sodium nitroprusside in China; nicardipine in other Asian countries; and sodium nitroprusside and labetalol in South America. Chinese patients were less likely to receive BP-lowering treatment in the first 24 h and be treated with multiple agents although they had smaller magnitude of SBP reduction and lower SBP variability.Conclusion: Regional variations in early BP management in acute stroke translated into differences in early BP control parameters.

411-P: Fibroblast Growth Factor 23 and Diabetic Kidney Disease Phenotypes in Type 2 Diabetes

Fibroblast growth factor 23 (FGF23) targets tubular epithelial cells to promote phosphaturia and it has been associated with adverse outcomes in chronic kidney disease (CKD). Emerging data suggest that FGF23 plays a specific role in type 2 diabetes (T2D). We evaluated intact FGF23 (iFGF23) levels (plasma EDTA; chemiluminescence immunoassay) in 182 T2D subjects with no-DKD (n = 46), with albuminuria alone (ACR ≥30 mg/g; DKD stages 1-2, n = 48), with eGFR &amp;lt;60 ml/min/1.73m2 alone (Alb-DKD; n = 42) and with both albuminuria and eGFR &amp;lt;60 (Alb+DKD; n = 46). There was no difference in ACR between DKD stages 1-2 and Alb+DKD (97 [IQR 49-329] and 268 [62-736] mg/g); eGFR (CKD-EPI formula based on creatinine [eGFRcreat = 49 [45-54] and 45 [35-52] ml/min/1.73m2] or based on creatinine and cystatin-C) did not differ between Alb-DKD and Alb+DKD. Age, DD, HbA1c, triglycerides, uric acid and fibrinogen increased across DKD groups, while HDL cholesterol decreased, with no other significant difference in clinical and laboratory parameters. BP-lowering agents, RAS blockers and lipid-lowering drugs were slightly more frequent in albuminuric groups. Alb+DKD had the highest levels of inflammatory biomarkers: uric acid, hs-CRP and fibrinogen. In the whole cohort, iFGF23 was significantly and directly correlated with these 3 biomarkers. iFGF23 increased steeply (p&amp;lt;0.0001) across DKD groups (no DKD: 48.2 [IQR 37.3-61.5] pg/ml; DKD stages 1-2: 53.0 [42.5-61.4]; Alb-DKD: 60.4 [45.1-73.4] and Alb+DKD 76.6 [60.1-96.3]), with iFGF23 of Alb+DKD higher as compared to no-DKD (p&amp;lt;0.0001), DKD stages 1-2 (p&amp;lt;0.0001), and also Alb-DKD (p=0.008). In the whole cohort, iFGF23 was mildly associated with ACR (r = 0.260; p=0.001) and more strongly inversely related with eGFRcreat (r = -0.483, p&amp;lt;0.0001). Our results suggest that, for the same degree of eGFR reduction, higher iFGF23 levels in Alb+DKD as compared to Alb-DKD might be expression of more advanced renal damage and/or of an overwhelming inflammation. Disclosure M. Garofolo: Consultant; Self; Eli Lilly and Company. C. Pelosini: None. D. Lucchesi: None. P. Falcetta: None. M. Sessa: None. S. Del prato: Advisory Panel; Self; Eli Lilly and Company, Novo Nordisk, Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Speaker’s Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Merck Sharp &amp; Dohme Corp., Novartis Pharmaceuticals Corporation, Sanofi. G. Penno: Advisory Panel; Self; Eli Lilly and Company.

Blood pressure lowering effects of alpha-lipoic acid supplementation: a meta-analysis of randomized controlled trials

Background: The aim of the present meta-analysis was to detect the effect of a-lipoic acid (ALA) supplementation on systolic and diastolic blood pressure (BP). Material and methods: The related records were selected from several electronic databases from the earliest date 1980 until October 2019. The heterogeneities were assessed by I 2 test (I 2 < 50%) and X 2 test on Cochrane’s Q statistic. Standardized mean difference (SMD) and their 95% confidence intervals (CIs) were considered for net change in systolic blood pressure (SBP) and diastolic blood pressure (DBP). Subgroup analyses were also conducted by baseline BP, health status, doses of supplementation, study duration and supplement utilization. Results: As a result, a total of 10 studies with 612 subjects were included in the final analysis. Alpha-lipoic acid supplementation significantly reduced SBP (SMD = –0.50, 95% CI: –0.84, –0.16, p = 0.004) and DBP (SMD = –0.40, 95% CI: –0.71, –0.09, p = 0.01), compared to the controls, with the reduction of 6.1 mm Hg and 3.6 mm Hg of the mean SBP and DBP, respectively. Heterogeneities were explored in both SBP and DBP. Moreover, a statistically significant reduction in BP was detected in elevated BP and hypertensive patients as compared with the normotensive subjects. Conclusion: ALA supplementation could be considered as a BP-lowering agent, especially in subjects with higher blood pressure.

Therapeutic Variation in Lowering Blood Pressure: Effects on Intracranial Pressure in Acute Intracerebral Haemorrhage.

Intracerebral haemorrhage (ICH) is associated with high morbidity and mortality. Blood pressure (BP) control is one of the main management strategies in acute ICH. Limited data currently exist regarding intracranial pressure (ICP) in acute ICH. The relationship between BP lowering and ICP is yet to be fully elucidated. We conducted a systematic review to investigate the effects of BP lowering on ICP in acute ICH. The study protocol was registered on PROSPERO (CRD42019134470). Following PRISMA guidelines, MEDLINE, EMBASE and CENTRAL were searched for studies on ICH with BP and ICP or surrogate measures. 1096 articles were identified after duplicates were removed; 18 studies meeting the inclusion criteria. Dihydropyridine calcium channel blockers (CCBs) were the most common agent used to lower BP, but had a varying effect on ICP. Other BP-lowering agents used also had a varying effect on ICP. Further work, including large observational or randomized interventional studies, is needed to develop a better understanding of the effect of BP lowering on ICP in acute ICH, which will assist the development of more effective management strategies. The study protocol was registered on PROSPERO (CRD42019134470) on 29/05/2019.

Blood Pressure Effects of Canagliflozin and Clinical Outcomes in Type 2 Diabetes and Chronic Kidney Disease: Insights From the CREDENCE Trial.

People with type 2 diabetes and chronic kidney disease experience a high burden of hypertension, but the magnitude and consistency of blood pressure (BP) lowering with canagliflozin in this population are uncertain. Whether the effects of canagliflozin on kidney and cardiovascular outcomes vary by baseline BP or BP-lowering therapy is also unknown. The CREDENCE trial (Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation) randomized people with type 2 diabetes and chronic kidney disease to canagliflozin or placebo. In a post hoc analysis, we investigated the effect of canagliflozin on systolic BP across subgroups defined by baseline systolic BP, number of BP-lowering drug classes, and history of apparent treatment-resistant hypertension (BP ≥130/80 mm Hg while receiving ≥3 classes of BP-lowering drugs, including a diuretic). We also assessed whether effects on clinical outcomes differed across these subgroups. The trial included 4401 participants, of whom 3361 (76.4%) had baseline systolic BP ≥130 mm Hg, and 1371 (31.2%) had resistant hypertension. By week 3, canagliflozin reduced systolic BP by 3.50 mm Hg (95% CI, -4.27 to -2.72), an effect maintained over the duration of the trial, with similar reductions across BP and BP-lowering therapy subgroups (all P interaction ≥0.05). Canagliflozin also reduced the need for initiation of additional BP-lowering agents during the trial (hazard ratio, 0.68 [95% CI, 0.61-0.75]). The effect of canagliflozin on kidney failure, doubling of serum creatinine, or death caused by kidney or cardiovascular disease (hazard ratio, 0.70 [95% CI, 0.59-0.82]) was consistent across BP and BP-lowering therapy subgroups (all P interaction ≥0.35), as were effects on other key kidney, cardiovascular, and safety outcomes. In people with type 2 diabetes and chronic kidney disease, canagliflozin lowers systolic BP across all BP-defined subgroups and reduces the need for additional BP-lowering agents. These findings support use of canagliflozin for end-organ protection and as an adjunct BP-lowering therapy in people with chronic kidney disease. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02065791.

Comparative Efficacy and Safety of BP-Lowering Pharmacotherapy in Patients Undergoing Maintenance Dialysis: A Network Meta-Analysis of Randomized, Controlled Trials.

Elevated BP is an important risk factor for cardiovascular disease, with a prevalence of over 80% in patients undergoing maintenance dialysis. We assessed the comparative BP-lowering efficacy and the safety of BP-lowering drugs in patients undergoing maintenance dialysis. We performed a frequentist random effects network meta-analysis of randomized, controlled trials evaluating BP-lowering agents in adult patients undergoing maintenance dialysis. Electronic databases (CENTRAL, MEDLINE, and Embase) were systematically searched (up to August 2018) for relevant trials. The main outcome was systolic BP reduction. Forty trials (4283 participants) met our inclusion criteria. Angiotensin-converting enzyme inhibitors, β-blockers, calcium-channel blockers, and aldosterone antagonists lowered systolic BP to a greater extent than placebo, with effect sizes ranging from -10.8 mm Hg (95% confidence interval, -14.8 to -6.7 mm Hg) for the aldosterone antagonists to -4.3 mm Hg (95% confidence interval, -7.2 to -1.5 mm Hg) for angiotensin-converting enzyme inhibitors. Aldosterone antagonists and β-blockers were superior to angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, calcium-channel blockers, and renin inhibitors at lowering systolic BP. Compared with angiotensin-converting enzyme inhibitors, aldosterone antagonists and β-blockers lowered systolic BP by 6.4 mm Hg (95% confidence interval, -11.4 to -1.4 mm Hg) and 4.4 mm Hg (95% confidence interval, -7.4 to -1.3 mm Hg), respectively. Systolic BP reduction was not different with angiotensin receptor blockers, α-blockers, and calcium-channel blockers compared with angiotensin-converting enzyme inhibitors. Renin inhibitors were less effective. Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and aldosterone antagonists incurred risks of drug discontinuation due to adverse events and hypotension. BP-lowering agents significantly reduced systolic BP in patients undergoing maintenance dialysis. β-Blockers and aldosterone antagonists may confer larger reductions, although treatment with aldosterone antagonists may be limited by adverse events.

54 Acute Blood Pressure Lowering in Spontaneous Acute Intra-cerebral Haemorrhage: A Re-audit in a Tertiary Referral Stroke Centre

Abstract Background Acute blood pressure (BP) lowering to a target of &lt;150mmHg systolic improves outcomes in patients with acute spontaneous intra-cerebral haemorrhage (sICH). It is thought that the beneficial effect of BP-lowering in sICH is time-sensitive and mediated through the prevention of haematoma expansion. The American Heart Association guidelines state that BP lowering to &lt;150 mmHg or lower is safe and can improve functional outcome. Our aim was to re-evaluate the performance of clinicians in meeting target SBP levels of &lt;150mmHg in patients with acute sICH within 1 hour of presentation, following the introduction of a BP-lowering protocol in our centre. Methods We undertook a retrospective chart review of consecutive patients with an acute sICH admitted to our centre between September 2017 and May 2018. Any patient who did not receive active medical management from the outset of presentation due to immediate initiation of palliative measures were excluded. The time from presentation to target BP and BP measured at 1 hour were recorded. Any protocol violations were also documented Results 11 patients were included (mean age 77.5years, 55% female). The mean BP at presentation and 1 hour was 186/93mmHg and 161/93mmHg respectively. The median and mean times from presentation to first achieved target BP was 129 and 120minutes respectively. At least 1 protocol violation occurred in 66.6% of cases. The most common protocol violation was the failure to escalate to an intravenous infusion of a BP-lowering agent in a timely manner when bolus therapy had failed. Conclusion An introduction of a BP protocol for patients with an acute sICH did not improve performance on achieving rapid SBP-lowering to target levels of &lt;150mmHg. Strategies to improve awareness of this protocol are required to improve adherence and its successful implementation.

The prevalence and predictors of resistant hypertension in high‐risk overweight and obese patients: A cross‐sectional study based on the 2017 ACC/AHA guidelines

Obesity is significantly associated with uncontrolled blood pressure and resistant hypertension (RH). There are limited studies on the prevalence and determinants of RH in patients with higher body mass index (BMI) values. Since the hypertension guidelines changed in 2017, the prevalence of RH has become unknown and now is subject to be estimated by further studies. We conducted a cross-sectional study in an urban Federally Qualified Health Center in New York City aiming to estimate the prevalence of RH in high-risk overweight and obese patients based on the new hypertension definition, BP threshold ≥130/80mm Hg, and also to describe the associated comorbid conditions in these patients. We identified 761 eligible high-risk overweight and obese subjects with hypertension between October 2017 and October 2018. Apparent treatment-RH was found in 13.6% among the entire study population. This represented 15.4% of those treated with BP-lowering agents. True RH confirmed with out-of-office elevated BP was found in 6.7% of the study population and 7.4% among patients treated with BP-lowering agents. Prevalence was higher with higher BMI values. Those with true RH were more likely to be black, to have diabetes mellitus requiring insulin, chronic kidney disease stage 3 or above and diastolic heart failure. In conclusion, obesity is significantly associated with RH and other significant metabolic comorbid conditions.

ESC Council on hypertension position document on the management of hypertensive emergencies.

Hypertensive emergencies are those situations where very high blood pressure (BP) values are associated with acute organ damage, and therefore, require immediate, but careful, BP reduction. The type of acute organ damage is the principal determinant of: (i) the drug of choice, (ii) the target BP, and (iii) the timeframe in which BP should be lowered. Key target organs are the heart, retina, brain, kidneys, and large arteries. Patients who lack acute hypertension-mediated end organ damage do not have a hypertensive emergency and can usually be treated with oral BP-lowering agents and usually discharged after a brief period of observation.

Combined use of polypill components in patients with type 2 diabetes mellitus.

Objectives A polypill containing aspirin, a statin and blood pressure (BP)-lowering agents has been proposed for the prevention of cardiovascular disease. To increase adherence and reduce the gaps between indicated and used therapy, a polypill might be of interest for patients with type 2 diabetes (T2DM). Our aim was to assess the prevalence of the combined use of polypill components in patients with T2DM over time. Methods The combined use of polypill components was assessed between 1996 and 2015 in patients with T2DM in the prospective SMART cohort ( n = 1828). The results were dichotomized into patients without ( n = 568) and with ( n = 1260) vascular disease. The patient characteristics associated with the use of polypill components were evaluated. Results In total, 19% of patients with T2DM without vascular disease received a statin and ≥2 BP-lowering agents ('cardiovascular polypill') and 13% received additional oral glucose-lowering therapy ('diabetic polypill'). Of the patients with T2DM with vascular disease, 42% received the combination of an antiplatelet agent, a statin and ≥2 BP-lowering agents ('cardiovascular polypill') and 30% received additional glucose-lowering therapy ('diabetic polypill'). The prevalence of the use of the cardiovascular and diabetic polypill combination has substantially increased between 1996 and 2015 to 36 and 32% in patients without vascular disease and to 67 and 57% in patients with vascular disease. Conclusions Patients with T2DM frequently use polypill components, often together with oral glucose-lowering agents, and this rate of use has increased steadily between 1996 and 2015. Introducing a cardiovascular or diabetic polypill for patients with T2DM seems to be highly relevant.