Prevention of Heart Failure in Hypertension-the Role of Coronary Heart Disease Events Treated With Versus Without Revascularization: The ALLHAT Study.

In modern clinical practice, less than half of patients with new-onset heart failure (HF) undergo ischemic evaluation and only a minority undergo revascularization. We aimed to assess the proportion of the effect of hypertension (antihypertensive treatment) on incident HF to be eliminated by prevention of coronary heart disease (CHD) event treated with or without revascularization, considering possible treatment-mediator interaction. The causal mediation analysis of Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) included 42,418 participants (age 66.

Mortality and Morbidity Among Individuals With Hypertension Receiving a Diuretic, ACE Inhibitor, or Calcium Channel Blocker: A Secondary Analysis of a Randomized Clinical Trial.

Importance: The long-term relative risk of antihypertensive treatments with regard to mortality and morbidity is not well understood.

Objective: To determine the long-term posttrial risk of primary and secondary outcomes among trial participants who were randomized to either a thiazide-type diuretic, calcium channel blocker (CCB), or angiotensin-converting enzyme (ACE) inhibitor with up to 23 years of follow-up.

Design, Setting, And Participants: This prespecified secondary analysis of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), a multicenter randomized, double-blind, active-controlled clinical trial, followed up with participants aged 55 years or older with a diagnosis of hypertension and at least 1 other coronary heart disease risk factor for up to 23 years, from February 23, 1994, to December 31, 2017.

The 18-year risk of cancer, angioedema, insomnia, depression, and erectile dysfunction in association with antihypertensive drugs: post-trial analyses from ALLHAT-Medicare linked data.

Purpose: This study aimed to determine the 18-year risk of cancer, angioedema, insomnia, depression, and erectile dysfunction in association with antihypertensive drug use.

Methods: This is a post-trial passive follow-up study of Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) participants between 1994 and 1998 that was conducted by linking their follow-up data with Medicare claims data until 2017 of subjects who were free of outcomes at baseline on 1 January 1999. The main outcomes were the occurrence of cancer (among  = 17,332), angioedema (among  = 17,340), insomnia (among  = 17,340), depression (among  = 17,330), and erectile dysfunction (among  = 7,444 men) over 18 years of follow-up.

Orthostatic Hypotension, Hypertension Treatment, and Cardiovascular Disease: An Individual Participant Meta-Analysis.

Importance: There are ongoing concerns about the benefits of intensive vs standard blood pressure (BP) treatment among adults with orthostatic hypotension or standing hypotension.

Objective: To determine the effect of a lower BP treatment goal or active therapy vs a standard BP treatment goal or placebo on cardiovascular disease (CVD) or all-cause mortality in strata of baseline orthostatic hypotension or baseline standing hypotension.

Data Sources: Individual participant data meta-analysis based on a systematic review of MEDLINE, EMBASE, and CENTRAL databases through May 13, 2022.

Primary Peritoneal Mesothelioma: Diagnostic Challenges of This Lethal Imposter.

Primary Peritoneal Mesothelioma is a rapidly aggressive and rare neoplasm that arises from the lining of mesothelial cells of the peritoneum and spreads extensively within the confines of the abdominal cavity. The pathogenesis of all forms of mesothelioma is strongly associated with industrial pollutants, of which asbestos is the principal carcinogen. Characteristically, asbestos exposure has a strong relationship with mesothelioma of the pleura, but the peritoneal cavity is the second most commonly affected site.

A Dynamic Risk Model for Multitype Recurrent Events.

Recurrent events can occur more than once in the same individual; such events may be of different types, known as multitype recurrent events. They are very common in longitudinal studies. Often there is a terminating event, after which no further events can occur.

Risk of Developing Alzheimer's Disease and Related Dementias in ALLHAT Trial Participants Receiving Diuretic, ACE-Inhibitor, or Calcium-Channel Blocker with 18 Years of Follow-Up.

Background: There is no any large randomized clinical trial of antihypertensive drug treatment with 18-year passive follow-up to examine the risk of Alzheimer's Disease (AD) or Related Dementias (ADRD).

Methods: Post-trial passive follow-up study of Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) participants in 1994-1998 by linking with their Medicare claims data through 2017 among 17,158 subjects in 567 U.S.

Autologous Cardiac Stem Cell Injection in Patients with Hypoplastic Left Heart Syndrome (CHILD Study).

Mortality in infants with hypoplastic left heart syndrome (HLHS) is strongly correlated with right ventricle (RV) dysfunction. Cell therapy has demonstrated potential improvements of RV dysfunction in animal models related to HLHS, and neonatal human derived c-kit cardiac-derived progenitor cells (CPCs) show superior efficacy when compared to adult human cardiac-derived CPCs (aCPCs). Neonatal CPCs (nCPCs) have yet to be investigated in humans.

The Blood Pressure Lowering Treatment Trialists' Collaboration: methodological clarifications of recent reports.

Epidemiological evidence has consistently shown that people with higher systolic or diastolic blood pressure are at greater risk of cardiovascular diseases. However, there has been limited randomized evidence to determine the role of blood pressure level at treatment initiation in the reduction of cardiovascular diseases risk. The extent to which other characteristics of individuals, such as prior disease history, age or sex, should be taken into account has also been controversial.

Antihypertensive drug effects on long-term blood pressure: an individual-level data meta-analysis of randomised clinical trials.

Objective: Evidence from randomised trials of pharmacological treatments on long-term blood pressure (BP) reduction is limited. We investigated the antihypertensive drug effects on BP over time and across different participant characteristics.

Methods: We conducted an individual patient-level data meta-analysis of 52 large-scale randomised clinical trials in the Blood Pressure Lowering Treatment Trialists' Collaboration using mixed models to examine treatment effects on BP over 4 years of mean follow-up.

Applications of Covariate Adjusted Nonparametric Methods to CCTRN Clinical Trials.

CCTRN is a Cardiovascular Cell Therapy Research Network. There were three randomized double blinded controlled stem cell clinical trials conducted in its first phase. The main results of these three clinical trials were published with conventional parametric models such as T test and nonparametric test such as Wilcoxon rank sum test without adjusting covariates.

Effects of Posttrial Antihypertensive Drugs on Morbidity and Mortality: Findings from 15-Year Passive Follow-Up after ALLHAT Ended.

Background: Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) ended in 2002, but it is important to study its long-term outcomes during the posttrial period by incorporating posttrial antihypertensive medication uses in the analysis.

Purposes: The primary aim is to explore the patterns of antihypertensive medication use during the posttrial period from Medicare Part-D data over the 11-year period from 2007 to 2017. The secondary aim is to examine the potential effects of these posttrial antihypertensive medications on the observed mortality and morbidity benefits.

Risk of hospitalized and non-hospitalized gastrointestinal bleeding in ALLHAT trial participants receiving diuretic, ACE-inhibitor, or calcium-channel blocker.

Objectives: This post-trial data linkage analysis was to utilize the data of Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) participants linked with their Medicare data to examine the risk of hospitalized and non-hospitalized gastrointestinal (GI) bleeding associated with antihypertensives.

Settings: ALLHAT was a multicenter, randomized, double-blind, active-controlled trial conducted in a total of 42,418 participants aged ≥55 years with hypertension in 623 North American centers. Data for ALLHAT participants who were aged at ≥65 have been linked with their Medicare claims data.

Blood pressure lowering and risk of new-onset type 2 diabetes: an individual participant data meta-analysis.

Background: Blood pressure lowering is an established strategy for preventing microvascular and macrovascular complications of diabetes, but its role in the prevention of diabetes itself is unclear. We aimed to examine this question using individual participant data from major randomised controlled trials.

Methods: We performed a one-stage individual participant data meta-analysis, in which data were pooled to investigate the effect of blood pressure lowering per se on the risk of new-onset type 2 diabetes.

Statistical reanalysis of vascular event outcomes in primary and secondary vascular prevention trials.

Background: Vascular prevention trials typically use dichotomous event outcomes although this may be inefficient statistically and gives no indication of event severity. We assessed whether ordinal outcomes would be more efficient and how to best analyse them.

Methods: Chief investigators of vascular prevention randomised controlled trials that showed evidence of either benefit or harm, or were included in a systematic review that overall showed benefit or harm, shared individual participant data from their trials.

Sustained SBP control and long-term nursing home admission among Medicare beneficiaries.

Objectives: Sustaining SBP control reduces the risk for cardiovascular events that impair function but its association with nursing home admission has not been well studied.

Methods: We conducted an analysis of sustained SBP control and long-term nursing home admissions using data from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) linked to Medicare claims restricted to participants with fee-for-service coverage, at least eight study visits with SBP measurements, who were not living in a nursing home during a 48-month baseline BP assessment period (n = 6557). Sustained SBP control was defined as less than 140 mmHg at less than 50%, 50% to less than 75%, 75% to less than 100%, and 100% of visits.

Blood pressure-lowering treatment for the prevention of cardiovascular events in patients with atrial fibrillation: An individual participant data meta-analysis.

Background: Randomised evidence on the efficacy of blood pressure (BP)-lowering treatment to reduce cardiovascular risk in patients with atrial fibrillation (AF) is limited. Therefore, this study aimed to compare the effects of BP-lowering drugs in patients with and without AF at baseline.

Methods And Findings: The study was based on the resource provided by the Blood Pressure Lowering Treatment Trialists' Collaboration (BPLTTC), in which individual participant data (IPD) were extracted from trials with over 1,000 patient-years of follow-up in each arm, and that had randomly assigned patients to different classes of BP-lowering drugs, BP-lowering drugs versus placebo, or more versus less intensive BP-lowering regimens.

A Phase II study of autologous mesenchymal stromal cells and c-kit positive cardiac cells, alone or in combination, in patients with ischaemic heart failure: the CCTRN CONCERT-HF trial.

Aims: CONCERT-HF is an NHLBI-sponsored, double-blind, placebo-controlled, Phase II trial designed to determine whether treatment with autologous bone marrow-derived mesenchymal stromal cells (MSCs) and c-kit positive cardiac cells (CPCs), given alone or in combination, is feasible, safe, and beneficial in patients with heart failure (HF) caused by ischaemic cardiomyopathy.

Methods And Results: Patients were randomized (1:1:1:1) to transendocardial injection of MSCs combined with CPCs, MSCs alone, CPCs alone, or placebo, and followed for 12 months. Seven centres enrolled 125 participants with left ventricular ejection fraction of 28.

Antihypertensive treatment and risk of cancer: an individual participant data meta-analysis.

Background: Some studies have suggested a link between antihypertensive medication and cancer, but the evidence is so far inconclusive. Thus, we aimed to investigate this association in a large individual patient data meta-analysis of randomised clinical trials.

Methods: We searched PubMed, MEDLINE, The Cochrane Central Register of Controlled Trials, and ClinicalTrials.

Association of Sustained Blood Pressure Control with Lower Risk for High-Cost Multimorbidities Among Medicare Beneficiaries in ALLHAT.

Background: Clustering of chronic conditions is associated with high healthcare costs. Sustaining blood pressure (BP) control could be a strategy to prevent high-cost multimorbidity clusters.

Objective: To determine the association between sustained systolic BP (SBP) control and incident multimorbidity cluster dyads and triads.