Trial of Intensive Blood-Pressure Control in Older Patients with Hypertension.

BACKGROUND: The appropriate target for systolic blood pressure to reduce cardiovascular risk in older patients with hypertension remains unclear. METHODS: In this multicenter, randomized, controlled trial, we assigned Chinese patients 60 to 80 years of age with hypertension to a systolic blood-pressure target of 110 to less than 130 mm Hg (intensive treatment) or a target of 130 to less than 150 mm Hg (standard treatment). The primary outcome was a composite of stroke, acute coronary syndrome (acute myocardial infarction and hospitalization for unstable angina), acute decompensated heart failure, coronary revascularization, atrial fibrillation, or death from cardiovascular causes. RESULTS: Of the 9624 patients screened for eligibility, 8511 were enrolled in the trial; 4243 were randomly assigned to the intensive-treatment group and 4268 to the standard-treatment group. At 1 year of follow-up, the mean systolic blood pressure was 127.5 mm Hg in the intensive-treatment group and 135.3 mm Hg in the standard-treatment group. During a median follow-up period of 3.34 years, primary-outcome events occurred in 147 patients (3.5%) in the intensive-treatment group, as compared with 196 patients (4.6%) in the standard-treatment group (hazard ratio, 0.74; 95% confidence interval [CI], 0.60 to 0.92; P = 0.007). The results for most of the individual components of the primary outcome also favored intensive treatment: the hazard ratio for stroke was 0.67 (95% CI, 0.47 to 0.97), acute coronary syndrome 0.67 (95% CI, 0.47 to 0.94), acute decompensated heart failure 0.27 (95% CI, 0.08 to 0.98), coronary revascularization 0.69 (95% CI, 0.40 to 1.18), atrial fibrillation 0.96 (95% CI, 0.55 to 1.68), and death from cardiovascular causes 0.72 (95% CI, 0.39 to 1.32). The results for safety and renal outcomes did not differ significantly between the two groups, except for the incidence of hypotension, which was higher in the intensive-treatment group. CONCLUSIONS: In older patients with hypertension, intensive treatment with a systolic blood-pressure target of 110 to less than 130 mm Hg resulted in a lower incidence of cardiovascular events than standard treatment with a target of 130 to less than 150 mm Hg. (Funded by the Chinese Academy of Medical Sciences and others; STEP ClinicalTrials.gov number, NCT03015311.).

Superiority of polatuzumab vedotin over other novel agents in previously untreated ABC-type diffuse large B-cell lymphoma: a network meta-analysis of 20 RCTs.

Because of lacking of head-to-head comparison among polatuzumab (Pola) vedotin and other novel agents for untreated diffuse large B-cell lymphoma (DLBCL), the optimal option remains undefined. We searched twelve relevant published reports, covering 8376 subjects. Interestingly, the PFS benefit with Pola-R-CHP over other regimens was found prominently in those B-cell-like type (ABC-type) patients. For those ABC-type patients, the PFS advantage with Pola-R-CHP was statistically significant, when compared to R-CHOP+Bort (HR: 0.52, P=0.02), R-CHOP+Ibru (HR: 0.43, P=0.001), R-CHOP+Lena (HR: 0.51, P=0.009), G-CHOP (HR: 0.46, P=0.008), and R-CHOP (HR: 0.40, P<0.001). Meanwhile, for those germinal center B-cell-like (GCB) type patients, no PFS advantage with Pola-R-CHP was found when compared to R-CHOP+Bort (HR: 1.18, P=0.46), R-CHOP+Lena (HR: 1.21, P=0.45), G-CHOP (HR: 1.39, P=0.14), R-CHOP-14 (HR: 0.94, P=0.82), and R-CHOP (HR: 1.00, P=1). The PFS advantage with Pola-R-CHP over other regimens might be confined to those patients of ABC-type DLBCL.

Daratumumab added to standard of care in patients with newly diagnosed multiple myeloma: A network meta-analysis.

PURPOSE: To investigate the activity and safety of daratumumab added to standard of care and evaluate the relative efficacy of DRd vs DVMP and other regimens on survival endpoints for untreated myeloma, we undertook this meta-analysis. METHODS: We searched published reports that described the activity and safety of daratumumab added to standard of care for untreated myeloma. RESULTS: Six daratumumab trials were identified, covering 5106 subjects. Daratumumab containing combinations for untreated myeloma attained an impressive complete response or better (≥CR) rate of 24%, very good partial response or better (≥VGPR) rate of 67%, overall response rate (ORR) of 92%. Daratumumab added to standard of care significantly improved progression free survival (PFS): the HR for PFS was 0.52 [0.44, 0.61], P < .001. The HR for overall survival (OS) was 0.73 [0.52, 1.04], P = .09. In the network meta-analysis for patients ineligible for autologous stem-cell transplantation (ASCT), DRd regimen produced significant PFS advantage vs other first-line treatments (VMP HR:0.39 P < .001, Rd HR:0.55 P < .001, MPT HR:0.38 P < .001, and MP HR:0.22 P < .001); DVMP regimen also produced significant PFS advantage vs VMP (HR:0.50 P < .001), MPT (HR:0.49 P < .001), and MP (HR:0.28 P < .001). Among these first-line regimens (DRd, DVMP, VMP, Rd, MPT, and MP), DRd regimen had the highest probability to be the best intervention, with 83.4% and 91.0% probability to reach the longest PFS and OS, respectively. Toxicity consisted primarily of myelosuppression. And, the vital non-hematologic adverse events (AEs) were peripheral sensory neuropathy (41% of all grades) and upper respiratory tract infection (39% of all grades). CONCLUSIONS: Daratumumab added to standard of care could produce clinical benefits in newly diagnosed patients with multiple myeloma. DRd and DVMP could be good combination options for those patients ineligible for ASCT.

Comparison of venetoclax and ivosidenib/enasidenib for unfit newly diagnosed patients with acute myeloid leukemia and IDH1/2 mutation: a network meta-analysis.

Because of lacking of head-to-head comparison between venetoclax and IDH1/IDH2 inhibitors (ivosidenib/enasidenib) for newly diagnosed unfit patients with acute myeloid leukemia (AML), the optimal option for these patients still remains undefined. We searched relevant published reports. Three RCTs with 180 IDH1 mutant and 165 IDH2 mutant patients were identified. Indirect comparison of OS using fixed effects network meta-analysis (NMA) models indicated venetoclax plus azacitidine (Ven-Aza) significantly improved survival than enasidenib plus azacitidine (Ena-Aza) (HR:0.30, p = 0.005) for those newly diagnosed patients with AML and IDH2 Mutation. And, for those IDH2 mutation patients, Ven-Aza also had the highest probability of 98.3% (OS analysis) and 84.0% (CR/CRi analysis) to be the best intervention among these first-line treatment regimens (Ven-Aza, Ena-Aza and Aza). And, there was a favorable trend towards Ven-Aza in survival analysis (HR:0.69, p = 0.42), when compared to ivosidenib plus azacitidine (Ivo-Aza) for those newly diagnosed patients with AML and IDH1 Mutation. For those IDH1 Mutation, venetoclax plus azacitidine (Ven-Aza) had the highest probability of 65.8% (OS analysis) and 73.0% (CR/CRi analysis) to be the best intervention among these first-line treatment regimens (Ven-Aza, ivosidenib plus azacitidine (Ivo-Aza) and azacitidine (Aza)). In conclusion, venetoclax plus azacitidine could be a good option for unfit newly diagnosed patients with acute myeloid leukemia and IDH1/2 mutation. Considering our limits (only trial data-based network meta-analysis et al.), future trials directly comparing these regimens are warranted.

Changes in Home Blood Pressure Monitored Among Elderly Patients With Hypertension During the COVID-19 Outbreak: A Longitudinal Study in China Leveraging a Smartphone-Based Application.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has impacted clinical care worldwide. Evidence of how this health crisis affected common conditions like blood pressure (BP) control is uncertain. METHODS: We used longitudinal BP data from an ongoing randomized clinical trial to examine variations in home BP monitored via a smartphone-based application (app) in a total of 7394 elderly patients with hypertension aged 60 to 80 years stratified by their location in Wuhan (n=283) compared with other provinces of China (n=7111). Change in morning systolic BP (SBP) was analyzed for 5 30-day phases during the pandemic, including preepidemic (October 21 to November 20, 2019), incubation (November 21 to December 20, 2019), developing (December 21, 2019 to January 20, 2020), outbreak (January 21 to February 20, 2020), and plateau (February 21 to March 21, 2020). RESULTS: Compared with non-Wuhan areas of China, average morning SBP (adjusted for age, sex, body mass index) in Wuhan patients was significantly higher during the epidemic growth phases, which returned to normal at the plateau. Between-group differences in ΔSBP were +2.5, +3.0, and +2.1 mm Hg at the incubation, developing, and outbreak phases of COVID-19 (P<0.001), respectively. Sensitivity analysis showed a similar trend in trajectory pattern of SBP in both the intensive and standard BP control groups of the trial. Patients in Wuhan also had an increased regimen change in antihypertensive drugs during the outbreak compared with non-Wuhan patients. Expectedly, Wuhan patients were more likely to check their BP via the app, while doctors were less likely to monitor the app for BP control during the pandemic. CONCLUSIONS: Our data demonstrate that the COVID-19 pandemic was associated with a short-term increase in morning SBP among elderly patients with hypertension in Wuhan but not other parts of China. Further study will be needed to understand if these findings extended to other parts of the world substantially affected by the virus. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03015311.