Patient-Level Pooled Analysis of Endovascular Ultrasound Renal Denervation or a Sham Procedure 6 Months After Medication Escalation: The RADIANCE Clinical Trial Program

Circulation · 2023 · 35 citations

• Medicine
• Surgery
• Internal medicine

BACKGROUND: The randomized, sham-controlled RADIANCE-HTN (A Study of the Recor Medical Paradise System in Clinical Hypertension) SOLO, RADIANCE-HTN TRIO, and RADIANCE II (A Study of the Recor Medical Paradise System in Stage II Hypertension) trials independently met their primary end point of a greater reduction in daytime ambulatory systolic blood pressure (SBP) 2 months after ultrasound renal denervation (uRDN) in patients with hypertension. To characterize the longer-term effectiveness and safety of uRDN versus sham at 6 months, after the blinded addition of antihypertensive treatments (AHTs), we pooled individual patient data across these 3 similarly designed trials. METHODS: Patients with mild to moderate hypertension who were not on AHT or with hypertension resistant to a standardized combination triple AHT were randomized to uRDN (n=293) versus sham (n=213); they were to remain off of added AHT throughout 2 months of follow-up unless specified blood pressure (BP) criteria were exceeded. In each trial, if monthly home BP was ≥135/85 mm Hg from 2 to 5 months, standardized AHT was sequentially added to target home BP <135/85 mm Hg under blinding to initial treatment assignment. Six-month outcomes included baseline- and AHT-adjusted change in daytime ambulatory, home, and office SBP; change in AHT; and safety. Linear mixed regression models using all BP measurements and change in AHT from baseline through 6 months were used. RESULTS: <0.001), respectively. There was no heterogeneity between trials. Safety outcomes were few and did not differ between groups. CONCLUSIONS: This individual patient-data analysis of 506 patients included in the RADIANCE trials demonstrates the maintenance of BP-lowering efficacy of uRDN versus sham at 6 months, with fewer added AHTs. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT02649426 and NCT03614260.

Endovascular Ultrasound Renal Denervation to Treat Hypertension

JAMA · 2023 · 171 citations

• Medicine
• Surgery
• Radiology

Importance: Two initial sham-controlled trials demonstrated that ultrasound renal denervation decreases blood pressure (BP) in patients with mild to moderate hypertension and hypertension that is resistant to treatment. Objective: To study the efficacy and safety of ultrasound renal denervation without the confounding influence of antihypertensive medications in patients with hypertension. Design, Setting, and Participants: Sham-controlled, randomized clinical trial with patients and outcome assessors blinded to treatment assignment that was conducted between January 14, 2019, and March 25, 2022, at 37 centers in the US and 24 centers in Europe, with randomization stratified by center. Patients aged 18 years to 75 years with hypertension (seated office systolic BP [SBP] ≥140 mm Hg and diastolic BP [DBP] ≥90 mm Hg despite taking up to 2 antihypertensive medications) were eligible if they had an ambulatory SBP/DBP of 135/85 mm Hg or greater and an SBP/DBP less than 170/105 mm Hg after a 4-week washout of their medications. Patients with an estimated glomerular filtration rate of 40 mL/min/1.73 m2 or greater and with suitable renal artery anatomy were randomized 2:1 to undergo ultrasound renal denervation or a sham procedure. Patients were to abstain from antihypertensive medications until the 2-month follow-up unless prespecified BP criteria were exceeded and were associated with clinical symptoms. Interventions: Ultrasound renal denervation vs a sham procedure. Main Outcomes and Measures: The primary efficacy outcome was the mean change in daytime ambulatory SBP at 2 months. The primary safety composite outcome of major adverse events included death, kidney failure, and major embolic, vascular, cardiovascular, cerebrovascular, and hypertensive events at 30 days and renal artery stenosis greater than 70% detected at 6 months. The secondary outcomes included mean change in 24-hour ambulatory SBP, home SBP, office SBP, and all DBP parameters at 2 months. Results: Among 1038 eligible patients, 150 were randomized to ultrasound renal denervation and 74 to a sham procedure (mean age, 55 years [SD, 9.3 years]; 28.6% female; and 16.1% self-identified as Black or African American). The reduction in daytime ambulatory SBP was greater with ultrasound renal denervation (mean, -7.9 mm Hg [SD, 11.6 mm Hg]) vs the sham procedure (mean, -1.8 mm Hg [SD, 9.5 mm Hg]) (baseline-adjusted between-group difference, -6.3 mm Hg [95% CI, -9.3 to -3.2 mm Hg], P < .001), with a consistent effect of ultrasound renal denervation throughout the 24-hour circadian cycle. Among 7 secondary BP outcomes, 6 were significantly improved with ultrasound renal denervation vs the sham procedure. No major adverse events were reported in either group. Conclusions and Relevance: In patients with hypertension, ultrasound renal denervation reduced daytime ambulatory SBP at 2 months in the absence of antihypertensive medications vs a sham procedure without postprocedural major adverse events. Trial Registration: ClinicalTrials.gov Identifier: NCT03614260.

Patient-Level Pooled Analysis of Ultrasound Renal Denervation in the Sham-Controlled RADIANCE II, RADIANCE-HTN SOLO, and RADIANCE-HTN TRIO Trials

JAMA Cardiology · 2023 · 82 citations

• Medicine
• Internal medicine
• Remote sensing

Importance: Ultrasound renal denervation (uRDN) was shown to lower blood pressure (BP) in patients with uncontrolled hypertension (HTN). Establishing the magnitude and consistency of the uRDN effect across the HTN spectrum is clinically important. Objective: To characterize the effectiveness and safety of uRDN vs a sham procedure from individual patient-level pooled data across uRDN trials including either patients with mild to moderate HTN on a background of no medications or with HTN resistant to standardized triple-combination therapy. Data Sources: A Study of the ReCor Medical Paradise System in Clinical Hypertension (RADIANCE-HTN SOLO and TRIO) and A Study of the ReCor Medical Paradise System in Stage II Hypertension (RADIANCE II) trials. Study Selection: Trials with similar designs, standardized operational implementation (medication standardization and blinding of both patients and physicians to treatment assignment), and follow-up. Data Extraction and Synthesis: Pooled analysis using individual patient-level data using linear regression models to compare uRDN with sham across the trials. Main Outcomes and Measures: The primary outcome was baseline-adjusted change in 2-month daytime ambulatory systolic BP (dASBP) between groups. Results: A total of 506 patients were randomized in the 3 studies (uRDN, 293; sham, 213; mean [SD] age, 54.1 [9.3]; 354 male [70.0%]). After a 1-month medication stabilization period, dASBP was similar between the groups (mean [SD], uRDN, 150.3 [9.2] mm Hg; sham, 150.8 [10.5] mm Hg). At 2 months, dASBP decreased by 8.5 mm Hg to mean (SD) 141.8 (13.8) mm Hg among patients treated with uRDN and by 2.9 mm Hg to 147.9 (14.6) mm Hg among patients treated with a sham procedure (mean difference, -5.9; 95% CI, -8.1 to -3.8 mm Hg; P < .001 in favor of uRDN). BP decreases from baseline with uRDN vs sham were consistent across trials and across BP parameters (office SBP: -10.4 mm Hg vs -3.4 mm Hg; mean difference, -6.4 mm Hg; 95% CI, -9.1 to -3.6 mm Hg; home SBP: -8.4 mm Hg vs -1.4 mm Hg; mean difference, -6.8 mm Hg; 95% CI, -8.7 to -4.9 mm Hg, respectively). The BP reductions with uRDN vs sham were consistent across prespecified subgroups. Independent predictors of a larger BP response to uRDN were higher baseline BP and heart rate and the presence of orthostatic hypertension. No differences in early safety end points were observed between groups. Conclusions and Relevance: Results of this patient-level pooled analysis suggest that BP reductions with uRDN were consistent across HTN severity in sham-controlled trials designed with a 2-month primary end point to standardize medications across randomized groups. Trial Registration: ClinicalTrials.gov Identifier: NCT02649426 and NCT03614260.

Self-expanding Transcatheter vs Surgical Aortic Valve Replacement in Intermediate-Risk Patients

JAMA Cardiology · 2022 · 169 citations

• Medicine
• Surgery
• Cardiology

Importance: In patients with severe aortic valve stenosis at intermediate surgical risk, transcatheter aortic valve replacement (TAVR) with a self-expanding supra-annular valve was noninferior to surgery for all-cause mortality or disabling stroke at 2 years. Comparisons of longer-term clinical and hemodynamic outcomes in these patients are limited. Objective: To report prespecified secondary 5-year outcomes from the Symptomatic Aortic Stenosis in Intermediate Risk Subjects Who Need Aortic Valve Replacement (SURTAVI) randomized clinical trial. Design, Setting, and Participants: SURTAVI is a prospective randomized, unblinded clinical trial. Randomization was stratified by investigational site and need for revascularization determined by the local heart teams. Patients with severe aortic valve stenosis deemed to be at intermediate risk of 30-day surgical mortality were enrolled at 87 centers from June 19, 2012, to June 30, 2016, in Europe and North America. Analysis took place between August and October 2021. Intervention: Patients were randomized to TAVR with a self-expanding, supra-annular transcatheter or a surgical bioprosthesis. Main Outcomes and Measures: The prespecified secondary end points of death or disabling stroke and other adverse events and hemodynamic findings at 5 years. An independent clinical event committee adjudicated all serious adverse events and an independent echocardiographic core laboratory evaluated all echocardiograms at 5 years. Results: A total of 1660 individuals underwent an attempted TAVR (n = 864) or surgical (n = 796) procedure. The mean (SD) age was 79.8 (6.2) years, 724 (43.6%) were female, and the mean (SD) Society of Thoracic Surgery Predicted Risk of Mortality score was 4.5% (1.6%). At 5 years, the rates of death or disabling stroke were similar (TAVR, 31.3% vs surgery, 30.8%; hazard ratio, 1.02 [95% CI, 0.85-1.22]; P = .85). Transprosthetic gradients remained lower (mean [SD], 8.6 [5.5] mm Hg vs 11.2 [6.0] mm Hg; P < .001) and aortic valve areas were higher (mean [SD], 2.2 [0.7] cm2 vs 1.8 [0.6] cm2; P < .001) with TAVR vs surgery. More patients had moderate/severe paravalvular leak with TAVR than surgery (11 [3.0%] vs 2 [0.7%]; risk difference, 2.37% [95% CI, 0.17%- 4.85%]; P = .05). New pacemaker implantation rates were higher for TAVR than surgery at 5 years (289 [39.1%] vs 94 [15.1%]; hazard ratio, 3.30 [95% CI, 2.61-4.17]; log-rank P < .001), as were valve reintervention rates (27 [3.5%] vs 11 [1.9%]; hazard ratio, 2.21 [95% CI, 1.10-4.45]; log-rank P = .02), although between 2 and 5 years only 6 patients who underwent TAVR and 7 who underwent surgery required a reintervention. Conclusions and Relevance: Among intermediate-risk patients with symptomatic severe aortic stenosis, major clinical outcomes at 5 years were similar for TAVR and surgery. TAVR was associated with superior hemodynamic valve performance but also with more paravalvular leak and valve reinterventions.

Current interventional therapies in acute pulmonary embolism

Progress in Cardiovascular Diseases · 2021 · 7 citations

• Medicine
• Intensive care medicine
• Cardiology

Association of Race/Ethnicity, Gender, and Socioeconomic Status With Sodium-Glucose Cotransporter 2 Inhibitor Use Among Patients With Diabetes in the US

JAMA Network Open · 2021 · 331 citations

• Medicine
• Internal medicine
• Endocrinology

Importance: Sodium-glucose cotransporter 2 (SGLT2) inhibitors significantly reduce deaths from cardiovascular conditions, hospitalizations for heart failure, and progression of kidney disease among patients with type 2 diabetes. Black individuals have a disproportionate burden of cardiovascular and chronic kidney disease (CKD). Adoption of novel therapeutics has been slower among Black and female patients and among patients with low socioeconomic status than among White or male patients or patients with higher socioeconomic status. Objective: To assess whether inequities based on race/ethnicity, gender, and socioeconomic status exist in SGLT2 inhibitor use among patients with type 2 diabetes in the US. Design, Setting, and Participants: This retrospective cohort study of commercially insured patients in the US was performed from October 1, 2015, to June 30, 2019, using the Optum Clinformatics Data Mart. Adult patients with a diagnosis of type 2 diabetes, including those with heart failure with reduced ejection fraction (HFrEF), atherosclerotic cardiovascular disease (ASCVD), or CKD, were evaluated in the analysis. Main Outcomes and Measures: Prescription of an SGLT2 inhibitor. Multivariable logistic regression models were used to assess the association of race/ethnicity, gender, and socioeconomic status with SGLT2 inhibitor use. Results: Of 934 737 patients with type 2 diabetes (mean [SD] age, 65.4 [12.9] years; 50.7% female; 57.6% White), 81 007 (8.7%) were treated with an SGLT2 inhibitor during the study period. Between 2015 and 2019, the percentage of patients with type 2 diabetes treated with an SGLT2 inhibitor increased from 3.8% to 11.9%. Among patients with type 2 diabetes and cardiovascular or kidney disease, the rate of SGLT2 inhibitor use increased but was lower than that among all patients with type 2 diabetes (HFrEF: 1.9% to 7.6%; ASCVD: 3.0% to 9.8%; CKD: 2.1% to 7.5%). In multivariable analyses, Black race (adjusted odds ratio [aOR], 0.83; 95% CI, 0.81-0.85), Asian race (aOR, 0.94; 95% CI, 0.90-0.98), and female gender (aOR, 0.84; 95% CI, 0.82-0.85) were associated with lower rates of SGLT2 inhibitor use, whereas higher median household income (≥$100 000: aOR, 1.08 [95% CI, 1.05-1.10]; $50 000-$99 999: aOR, 1.05 [95% CI, 1.03-1.07] vs <$50 000) was associated with a higher rate of SGLT2 inhibitor use. These results were similar among patients with HFrEF, ASCVD, and CKD. Conclusions and Relevance: In this cohort study, use of an SGLT2 inhibitor treatment increased among patients with type 2 diabetes from 2015 to 2019 but remained low, particularly among patients with HFrEF, CKD, and ASCVD. Black and female patients and patients with low socioeconomic status were less likely to receive an SGLT2 inhibitor, suggesting that interventions to ensure more equitable use are essential to prevent worsening of well-documented disparities in cardiovascular and kidney outcomes in the US.

Racial, Ethnic, and Socioeconomic Inequities in Glucagon-Like Peptide-1 Receptor Agonist Use Among Patients With Diabetes in the US

JAMA Health Forum · 2021 · 255 citations

• Medicine
• Internal medicine
• Demography

Importance: Randomized clinical trials have shown that glucagon-like peptide-1 receptor agonists (GLP-1 RAs) cause significant weight loss and reduce cardiovascular events in patients with type 2 diabetes (T2D). Black patients have a disproportionate burden of obesity and cardiovascular disease and have a higher rate of cardiovascular-related mortality. Racial and ethnic disparities in health outcomes are largely attributable to the pervasiveness of structural racism, and patients who are marginalized by racism have less access to novel therapeutics. Objectives: To evaluate GLP-1 RA uptake among a commercially insured population of patients with T2D; identify associations of race, ethnicity, sex, and socioeconomic status with GLP-1 RA use; and specifically examine its use among the subgroup of patients with atherosclerotic cardiovascular disease (ASCVD) because of the known benefit of GLP-1 RA use for this population. Design Setting and Participants: This was a retrospective cohort analysis using data from OptumInsight Clinformatics Data Mart of commercially insured adult patients with T2D (with or without ASCVD) in the US. Data from October 1, 2015, to June 31, 2019, were included, and the analyses were performed in July 2020. We estimated multivariable logistic regression models to identify the association of race, ethnicity, sex, and socioeconomic status with GLP-1 RA use. Main Outcome and Measure: A prescription for a GLP-1 RA. Results: Of the 1 180 260 patients with T2D (median [IQR] age, 69 [59-76] years; 50.3% female; 57.7% White), 90 934 (7.7%) were treated with GLP-1 RA during the study period. From 2015 to 2019, the percentage of T2D patients treated with an GLP-1 RA increased from 3.2% to 10.7%. Among patients with T2D and ASCVD, use also increased but remained low (2.8%-9.4%). In multivariable analyses, lower rates of GLP-1 RA use were found among Asian (aOR, 0.59; 95% CI, 0.56-0.62), Black (adjusted odds ratio [aOR] 0.81; 95% CI, 0.79-0.83), and Hispanic (aOR, 0.91; 95% CI, 0.88-0.93) patients with T2D. Female sex (aOR, 1.22; 95% CI, 1.20-1.24) and higher zip code-linked median household incomes (>$100 000 [OR, 1.13; 95% CI, 1.11-1.16] and $50 000-$99 999 [OR, 1.07; 95% CI, 1.05-1.09] vs <$50 000) were associated with higher GLP-1 RA use. These results were similar to those found among patients with ASCVD. Conclusions and Relevance: In this cohort study of US patients with T2D, GLP-1 RA use increased, but remained low overall for treatment of T2D, particularly among patients with ASCVD who are likely to derive the most benefit. Asian, Black, and Hispanic patients and those with low income were less likely to receive treatment with a GLP-1 RA. Strategies to lower barriers to GLP-1 RA use, such as lower cost, are needed to prevent the widening of well-documented inequities in cardiovascular disease outcomes in the US.

Ultrasound renal denervation for hypertension resistant to a triple medication pill (RADIANCE-HTN TRIO): a randomised, multicentre, single-blind, sham-controlled trial

The Lancet · 2021 · 400 citations

• Medicine
• Internal medicine
• Pharmacology

Impact of COVID‐19 pandemic on STEMI care: An expanded analysis from the United States

Catheterization and Cardiovascular Interventions · 2020 · 91 citations

• Medicine
• Medical emergency
• Virology

OBJECTIVE: To evaluate the impact of COVID-19 pandemic migitation measures on of ST-elevation myocardial infarction (STEMI) care. BACKGROUND: We previously reported a 38% decline in cardiac catheterization activations during the early phase of the COVID-19 pandemic mitigation measures. This study extends our early observations using a larger sample of STEMI programs representative of different US regions with the inclusion of more contemporary data. METHODS: Data from 18 hospitals or healthcare systems in the US from January 2019 to April 2020 were collecting including number activations for STEMI, the number of activations leading to angiography and primary percutaneous coronary intervention (PPCI), and average door to balloon (D2B) times. Two periods, January 2019-February 2020 and March-April 2020, were defined to represent periods before (BC) and after (AC) initiation of pandemic mitigation measures, respectively. A generalized estimating equations approach was used to estimate the change in response variables at AC from BC. RESULTS: Compared to BC, the AC period was characterized by a marked reduction in the number of activations for STEMI (29%, 95% CI:18-38, p < .001), number of activations leading to angiography (34%, 95% CI: 12-50, p = .005) and number of activations leading to PPCI (20%, 95% CI: 11-27, p < .001). A decline in STEMI activations drove the reductions in angiography and PPCI volumes. Relative to BC, the D2B times in the AC period increased on average by 20%, 95%CI (-0.2 to 44, p = .05). CONCLUSIONS: The COVID-19 Pandemic has adversely affected many aspects of STEMI care, including timely access to the cardiac catheterization laboratory for PPCI.

<i>JAMA Network Open</i> Peer Reviewers in 2019

JAMA Network Open · 2020 · 1 citations

• Political Science
• Psychology
• Political Science