Background Influenza infection causes considerable morbidity and mortality in patients with cardiovascular disease. We assessed the effects of the influenza vaccine on mortality and cardiovascular outcomes in patients with cardiovascular disease. Methods and Results We searched PubMed, Embase, and the Cochrane Library through January 2020 for randomized controlled trials and observational studies assessing the effects of influenza vaccine on mortality and cardiovascular outcomes in patients with cardiovascular disease. Estimates were reported as random effects risk ratios (RRs) with 95% CIs. Analyses were stratified by study design into randomized controlled trials and observational studies. A total of 16 studies (n=237 058), including 4 randomized controlled trials (n=1667) and 12 observational studies (n=235 391), were identified. Participants' mean age was 69.2±7.01 years, 36.6% were women, 65.1% had hypertension, 31.1% had diabetes mellitus, and 23.4% were smokers. At a median follow‐up duration of 19.5 months, influenza vaccine was associated with a lower risk of all‐cause mortality (RR, 0.75; 95% CI, 0.60–0.93 [ P =0.01]), cardiovascular mortality (RR, 0.82; 95% CI, 0.80–0.84 [ P <0.001]), and major adverse cardiovascular events (RR, 0.87; 95% CI, 0.80–0.94 [ P <0.001]) compared with control. The use of the influenza vaccine was not associated with a statistically significant reduction of myocardial infarction (RR, 0.73; 95% CI, 0.49–1.09 [ P =0.12]) compared with control. Conclusions Data from both randomized controlled trials and observational studies support the use of the influenza vaccine in adults with cardiovascular disease to reduce mortality and cardiovascular events, as currently supported by clinical guidelines. Clinicians and health systems should continue to promote the influenza vaccine as part of comprehensive secondary prevention.

Objective To compare the impact of ezetimibe and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors on cardiovascular outcomes in adults taking maximally tolerated statin therapy or who are statin intolerant. Design Network meta-analysis. Data sources Medline, EMBASE, and Cochrane Library up to 31 December 2020. Eligibility criteria for selecting studies Randomised controlled trials of ezetimibe and PCSK9 inhibitors with ≥500 patients and follow-up of ≥6 months. Main outcome measures We performed frequentist fixed-effects network meta-analysis and GRADE (grading of recommendations, assessment, development, and evaluation) to assess certainty of evidence. Results included relative risks (RR) and absolute risks per 1000 patients treated for five years for non-fatal myocardial infarction (MI), non-fatal stroke, all-cause mortality, and cardiovascular mortality. We estimated absolute risk differences assuming constant RR (estimated from network meta-analysis) across different baseline therapies and cardiovascular risk thresholds; the PREDICT risk calculator estimated cardiovascular risk in primary and secondary prevention. Patients were categorised at low to very high cardiovascular risk. A guideline panel and systematic review authors established the minimal important differences (MID) of 12 per 1000 for MI and 10 per 1000 for stroke. Results We identified 14 trials assessing ezetimibe and PCSK9 inhibitors among 83 660 adults using statins. Adding ezetimibe to statins reduced MI (RR 0.87 (95% confidence interval 0.80 to 0.94)) and stroke (RR 0.82 (0.71 to 0.96)) but not all-cause mortality (RR 0.99 (0.92 to 1.06)) or cardiovascular mortality (RR 0.97 (0.87 to 1.09)). Similarly, adding PCSK9 inhibitor to statins reduced MI (0.81 (0.76 to 0.87)) and stroke (0.74 (0.64 to 0.85)) but not all-cause (0.95 (0.87 to 1.03)) or cardiovascular mortality (0.95 (0.87 to 1.03)). Among adults with very high cardiovascular risk, adding PCSK9 inhibitor was likely to reduce MI (16 per 1000) and stroke (21 per 1000) (moderate to high certainty); whereas adding ezetimibe was likely to reduce stroke (14 per 1000), but the reduction of MI (11 per 1000) (moderate certainty) did not reach MID. Adding ezetimibe to PCSK9 inhibitor and statin may reduce stroke (11 per 1000), but the reduction of MI (9 per 1000) (low certainty) did not reach MID. Adding PCSK9 inhibitors to statins and ezetimibe may reduce MI (14 per 1000) and stroke (17 per 1000) (low certainty). Among adults with high cardiovascular risk, adding PCSK9 inhibitor probably reduced MI (12 per 1000) and stroke (16 per 1000) (moderate certainty); adding ezetimibe probably reduced stroke (11 per 1000), but the reduction in MI did not achieve MID (8 per 1000) (moderate certainty). Adding ezetimibe to PCSK9 inhibitor and statins did not reduce outcomes beyond MID, while adding PCSK9 inhibitor to ezetimibe and statins may reduce stroke (13 per 1000). These effects were consistent in statin-intolerant patients. Among moderate and low cardiovascular risk groups, adding PCSK9 inhibitor or ezetimibe to statins yielded little or no benefit for MI and stroke. Conclusions Ezetimibe or PCSK9 inhibitors may reduce non-fatal MI and stroke in adults at very high or high cardiovascular risk who are receiving maximally tolerated statin therapy or are statin-intolerant, but not in those with moderate and low cardiovascular risk.

AW readmission within 30 days and multiple readmissions during the year were common and were particularly predicted by AMA discharge and comorbid psychotic disorder. While these and other factors can help identify high-risk patients, further study to determine causal mechanisms may aid efforts to improve both the outcomes and costs associated with acute AW treatment.

Aims To compare premature heart disease- and cancer-related deaths in women in the USA. Methods and results We analysed the US national database of death certificates of women aged &lt;65 from the Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research database between 1999 and 2018. We measured annual percentage changes (APCs) in age-adjusted mortality rates (AAMRs) and years of potential life lost per 100 000 persons due to heart disease and cancer. Overall, cancer was a more prevalent cause of premature death compared with heart disease. Between 1999 and 2018, the AAMRs decreased for both cancer (61.9/100 000 to 45.6/100 000) and heart disease (29.2/100 000 to 22.6/100 000). However, while APC in AAMR for cancer declined consistently over time, after an initial decline, APC in AAMR for heart disease increased between 2010 and 2018 [0.53 95% confidence interval (0.18–0.89)], with a significant rise in Midwest, medium/small metros, and rural areas after 2008. Compared with cancer, APC in AAMR for heart disease increased in women aged 25–34 years [2.24 (0.30–4.22); 2013–18) and 55–64 years [0.46 (0.13–0.80); 2009–13], as well as Non-Hispanic (NH) Whites [APC, 0.79 (0.46–1.13); 2009–18] and NH American Indian/Alaskan Native [2.71 (0.59–4.87); 2011–2018]. Consequently, the mortality gap between cancer and heart disease has narrowed from an AAMR of 32.7/100 000 to 23.0/100 000. Conclusions The mortality gap between cancer and heart disease is decreasing among women &lt;65 years. Intensive cardiovascular health interventions are required focusing on vulnerable young demographic subgroups and underserved regional areas to meet the American Heart Association’s Impact Goal and Million Hearts Initiative.

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