Background: The effects of allopurinol in patients with cardiovascular disease are not well defined; therefore, the latest evidence is summarized in this study. Methods: PubMed, Embase, Cochrane Library, and ClinicalTrials.gov databases were searched for randomized controlled trials (RCTs) of allopurinol in patients with cardiovascular disease published up to 11 February 2023. The primary outcome was cardiovascular death. Results: We combined the results of 21 RCTs that included 22,806 patients. Compared to placebo/usual care, allopurinol treatment was not associated with a significant reduction in cardiovascular death (RR 0.60; 95% CI 0.33–1.11) or all-cause death (RR 0.90; 95% CI 0.72–1.12). However, evidence from earlier trials and studies with small sample sizes indicated that allopurinol might confer a protective effect in decreasing cardiovascular death (RR 0.34; 95% CI 0.15–0.76) across patients undergoing coronary artery bypass grafting (CABG) or having acute coronary syndrome (ACS). In comparisons between allopurinol and febuxostat, we observed no difference in cardiovascular death (RR 0.92; 95% CI 0.69–1.24) or all-cause death (RR 1.02; 95% CI 0.75–1.38). Conclusion: Allopurinol could not reduce cardiovascular (CV) death or major adverse CV outcomes significantly in patients with existing cardiovascular diseases. Given the limitations of the original studies, the potential advantages of allopurinol observed in patients undergoing CABG or presenting with ACS necessitate further confirmation through subsequent RCTs. In the comparisons between allopurinol and febuxostat, our analysis failed to uncover any marked superiority of allopurinol in reducing the risk of adverse cardiovascular incidents.

Introduction: Sleep disturbances are prevalent among patients with heart failure (HF) and may trigger acute exacerbations of the condition. However, the causal relationship between sleep disturbances and HF remains uncertain. This study aims to explore the association and potential causal relationship between sleep disturbances and HF.Material and methods: Observational Study: NHANES data (2005-2008) involving 10,432 participants. Sleep disturbances defined as insomnia, sleep disorders, difficulty falling asleep, trouble sleeping, and waking up during the night. Mendelian randomization (MR) Study: Genetic variants linked to sleeplessness were obtained from GWAS datasets. MR Two-sample analysis was conducted using summary statistics from sleeplessness and HF GWASs.Results: After full adjustment, the association between insomnia and HF remained significant, with an OR of 5.10 (1.81–14.33, P = 0.003). After full adjustment, the association between sleep disorder and HF remained significant, with an OR of 3.51 (1.67–7.39; P = 0.002). The IVW method provided evidence supporting a causal association between sleeplessness and HF (OR = 1.535, SE = 0.177, P = 0.016).MR-Egger analysis demonstrated a causal association between sleeplessness and HF (OR = 3.333, SE = 0.493, p =0.023). Our observational study may be influenced by unaddressed confounding factors; however, Mendelian randomization helps mitigate the bias and confounding commonly found in non-genetic observational research.Conclusions: Our study identified a correlation between sleep disturbances and HF, potentially suggesting a causal relationship. Addressing sleep disturbances may be a key strategy in reducing the risk of HF.