Higher quality scaled-up evidence on pulmonary arterial hypertension (PAH), a rare and life-threatening disease, is needed to support informed decision-making. We aimed to map the current knowledge of PAH treatments and evaluate the methodological quality of published systematic reviews.
An overview with literature searches in PubMed and Embase (May 2025) was performed (CRD42023414469). The methodological and reporting quality of the eligible records was assessed using A Measurement Tool to Assess Systematic Reviews (AMSTAR 2) and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 checklist, respectively. Association analyses between tools’ scores with key variables (article publication date, journal impact factor, country/region) were performed (SPSS v.28). An evidence map summarizing the most reported treatments and outcomes was also built.
Overall, 57 systematic reviews (n = 52; 91.2% with meta-analysis) published between 1997 and 2025 (median year 2017), authored mostly by countries from Asia (n = 35; 61.4%) and North America (n = 12; 21.1%), were included. The classes of phosphodiesterase type-5 inhibitors, endothelin receptor antagonists, and prostanoids and combination therapies were each assessed in one-third of the studies each. Over 20 different outcomes were reported, with the most common surrogate endpoints being 6-min walking distance (n = 42; 73.7%) and mean pulmonary arterial pressure (n = 33; 57.9%). Most studies were classified as having critically low methodological quality (n = 48; 84.2%), with only three presenting high-quality methodology according to AMSTAR 2. The mean PRISMA score was 21.3 ± 2.9, indicating an adherence rate of 78.9% to the checklist among authors. Although there was an improvement over time in the quality of the reviews (p = 0.016 for AMSTAR; p = 0.002 for PRISMA), no correlations were found based on country nor journal impact factor.
Methodological weaknesses remain common in systematic reviews of PAH; therefore, enforcing compliance with guidelines and standardizing outcome measurements through a core outcome set is crucial for improving data comparability and clinical application.
PROSPERO identifier no. CRD42023414469.
Cholinesterase inhibitors (ChEIs) are widely prescribed for dementia, but their effects on cardiovascular outcomes in high-risk populations remain unclear.
Our objective was to evaluate the association between ChEI use and the risk of major adverse cardiovascular events (MACE) and all-cause mortality among individuals with high cardiovascular risk.
We conducted a retrospective cohort study using data from the Chang Gung Research Database in Taiwan from 2001 to 2022. Individuals aged ≥ 50 years with cardiovascular risk factors who received ChEIs were matched 1:1 with non-users based on birth year, sex, history of dementia, and cardiovascular comorbidities. The primary outcome was time to first MACE, defined as hospitalization for acute ischemic stroke, acute myocardial infarction, or cardiovascular death. Secondary outcomes included individual cardiovascular events, heart failure, and all-cause mortality. Competing risk and survival analyses were performed using Fine and Gray subdistribution hazard models and Cox proportional hazards models, respectively.
Among 21,598 matched patients (mean age 77.7 years; 61.1% female), ChEI use was associated with a significantly reduced risk of MACE (adjusted subdistribution hazard ratio 0.79; 95% confidence interval 0.74–0.84; P < 0.001) and acute myocardial infarction (adjusted subdistribution hazard ratio 0.70; 95% confidence interval 0.55–0.90; P = 0.006). ChEI users also had significantly improved overall survival (log-rank P < 0.001).
ChEI use is associated with a lower risk of major cardiovascular events and improved survival in patients at high cardiovascular risk. These findings suggest potential cardiovascular benefits of ChEIs beyond cognitive symptom management.
The cardiovascular safety of testosterone-replacement therapy (TRT) for middle-aged and older men with low to low-normal levels of testosterone remains unclear.
We systematically searched PubMed, Embase, Cochrane Library, and ClinicalTrials.gov for randomized controlled trials (RCTs) comparing TRT versus placebo for men aged ≥ 40 years old with hypogonadism or low to low-normal testosterone levels (≤ 14 nmol/L), and at least 12 months of follow-up. We pooled risk ratios (RRs) with 95% confidence intervals (CIs) applying a random-effects model and using R version 4.3.1 for statistical analyses.
We included 23 RCTs comprising 9280 men with testosterone deficiency, of whom 4800 (51.7%) were randomized to TRT. The mean age was 64.6 years, and the baseline total testosterone was 9.17 nmol/L. Placebo and TRT had similar rates of all-cause mortality (RR 0.85; 95% CI 0.60–1.19; p = 0.33). There was a significant increase in the incidence of cardiac arrhythmias (RR 1.53; 95% CI 1.20–1.97; p < 0.01). There was no significant difference between groups in cardiovascular mortality (RR 0.85; 95% CI 0.65–1.12; p = 0.25), stroke (RR 1.00; 95% CI 0.67–1.50; p = 0.99), and myocardial infarction (RR 0.94; 95% CI 0.69–1.28; p = 0.70).
In men with low to low-normal testosterone, aged 40 and above, TRT did not increase all-cause mortality, cardiovascular mortality, stroke, or myocardial infarction, but increased the incidence of cardiac arrhythmias.
PROSPERO identifier number CRD42024502421.
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have shown efficacy in reducing cardiovascular events in patients with diabetes mellitus (DM), but conflicting evidence exists regarding their impact on cardiac arrhythmias. Whereas some studies associated GLP-1RAs with arrhythmogenesis, other studies suggested a decreased association with atrial fibrillation (AF).
The aim was to compare the risk of incident AF after initiation of GLP-1RAs versus dipeptidyl peptidase-4 inhibitors (DPP4is), as active comparators, in patients with DM.
A retrospective propensity score-matched cohort study was conducted.
The national data of Veterans Health Administration during fiscal years 2006–2021 were used for the study.
Adults who initiated either GLP-1RA or DPP4i medications were included.
The primary outcome was a composite outcome of AF (diagnosis of AF/flutter or undergoing an AF procedure).
Out of 116,235 GLP-1RA users and 217,668 DPP4i users, we propensity score-matched 80,948 pairs, on 88 characteristics. The composite outcome of AF was similar in the GLP-1RA group (4.1%) and DPP4i group (4.3%); odds ratio (OR) 0.96, 95% confidence interval (CI) 0.92–1.01. Secondary analyses stratified by medication use duration showed no significant differences in composite AF risk (p > 0.05). Individuals achieving 5% weight loss from baseline body weight had significantly lower AF incidence (OR 0.83, 95% CI 0.78–0.89), whereas no significant differences were observed in those with no weight loss or weight gain (OR 1.05, 95% CI 0.97–1.12).
GLP-1RA use was not associated with a decreased or increased risk of AF compared to DPP4i use. In subgroup analysis, lower AF risk was seen in GLP-1RA versus DPP4i users who achieved weight loss, which suggests weight loss as a potential modifier of response to GLP-1RAs.
Chronic total occlusion (CTO) affects 15–25% of patients undergoing coronary angiography, and successful percutaneous coronary intervention (PCI) can improve ischemia, angina symptoms, and overall quality of life. However, CTO-PCI is a complex procedure with higher risks of acute thrombosis, restenosis, and long-term thrombosis due to factors such as longer lesion length, calcification, and the need for more stents. Dual antiplatelet therapy (DAPT) is essential after PCI, but the optimal regimen for CTO, particularly in patients with chronic coronary syndrome, remains under debate. Although more potent P2Y12 inhibitors such as ticagrelor may offer benefits in some cases, recent studies have shown mixed results.
This study aimed to assess the effect of potent DAPT on long-term outcomes in patients with CTO undergoing retrograde PCI.
We conducted a retrospective analysis of 836 consecutive patients who underwent elective retrograde CTO-PCI at a single center between January 2011 and April 2023. We compared patient and lesion characteristics, procedural details and results, and long-term outcomes between patients who received ticagrelor and those who received clopidogrel after retrograde CTO-PCI.
Clinical follow-up was available in 767 (91.2%) patients, with a median follow-up of 1041 days (range 531–1511). The risk of major adverse cardiovascular events was significantly lower in patients receiving ticagrelor than in those receiving clopidogrel (8.8% vs. 18.5%, p = 0.005), primarily due to reductions in all-cause mortality (1.9% vs. 8.1%, p = 0.009) and cardiac death (0.6% vs. 5.8%, p = 0.012).
DAPT with ticagrelor may represent a safe and efficient management strategy for patients undergoing retrograde CTO-PCI.
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