Khan, Safi U.

Abstract Aims Anticoagulants are the mainstay treatment for stroke prevention in patients with non-valvular atrial fibrillation (NVAF), and the CHA2DS2-VASc score is widely used to guide anticoagulation therapy in this cohort. However, utility of CHA2DS2-VASc in NVAF patients is debated, primarily because it is a vascular scoring system, which does not incorporate atrial fibrillation related parameters. Therefore, we conducted a meta-analysis to estimate the discrimination ability of CHA2DS2-VASc in predicting ischaemic stroke overall, and in subgroups of patients with or without NVAF. Methods and results PubMed and Embase databases were searched till June 2020 for published articles that assessed the discrimination ability of CHA2DS2-VASc, as measured by C-statistics, during mid-term (2–5 years) and long-term (>5 years) follow-up. Summary estimates were reported as random effects C-statistics with 95% confidence intervals (CIs). Seventeen articles were included in the analysis. Nine studies (n = 453 747 patients) reported the discrimination ability of CHA2DS2-VASc in NVAF patients, and 10 studies (n = 138 262 patients) in patients without NVAF. During mid-term follow-up, CHA2DS2-VASc predicted stroke with modest discrimination in the overall cohort [0.67 (0.65–0.69)], with similar discrimination ability in patients with NVAF [0.65 (0.63–0.68)] and in those without NVAF [0.69 (0.68–0.71)] (P-interaction = 0.08). Similarly, at long-term follow-up, CHA2DS2-VASc had modest discrimination [0.66 (0.63–0.69)], which was consistent among patients with NVAF [0.63 (0.54–0.71)] and those without NVAF [0.67 (0.64–0.70)] (P-interaction = 0.39). Conclusion This meta-analysis suggests that the discrimination power of the CHA2DS2-VASc score in predicting ischaemic stroke is modest, and is similar in the presence or absence of NVAF. More accurate stroke prediction models are thus needed for the NVAF population.

Abstract Aim The 2018 American Heart Association/American College of Cardiology/Multi-Society Cholesterol Guidelines recommended the addition of non-statins to statin therapy for high-risk secondary prevention patients above a low-density lipoprotein cholesterol (LDL-C) threshold of ≥70 mg/dL (1.8 mmol/L). We compared effectiveness and safety of treatment to achieve lower (<70) vs. higher (≥70 mg/dL) LDL-C among patients receiving intensive lipid-lowering therapy (statins alone or plus ezetimibe or proprotein convertase subtilisin/kexin type 9 inhibitors). Methods and results Eleven randomized controlled trials (130 070 patients), comparing intensive vs. less-intensive lipid-lowering therapy, with follow-up ≥6 months and sample size ≥1000 patients were selected. Meta-analysis was reported as random effects risk ratios (RRs) [95% confidence intervals] and absolute risk differences (ARDs) as incident cases per 1000 person-years. The median LDL-C levels achieved in lower LDL-C vs. higher LDL-C groups were 62 and 103 mg/dL, respectively. At median follow-up of 2 years, the lower LDL-C vs. higher LDL-C group was associated with significant reduction in all-cause mortality [ARD −1.56; RR 0.94 (0.89–1.00)], cardiovascular mortality [ARD −1.49; RR 0.90 (0.81–1.00)], and reduced risk of myocardial infarction, cerebrovascular events, revascularization, and major adverse cardiovascular events (MACE). These benefits were achieved without increasing the risk of incident cancer, diabetes mellitus, or haemorrhagic stroke. All-cause mortality benefit in lower LDL-C group was limited to statin therapy and those with higher baseline LDL-C (≥100 mg/dL). However, the RR reduction in ischaemic and safety endpoints was independent of baseline LDL-C or drug therapy. Conclusion This meta-analysis showed that treatment to achieve LDL-C levels below 70 mg/dL using intensive lipid-lowering therapy can safely reduce the risk of mortality and MACE.

Abstract Aims Primary percutaneous coronary intervention (pPCI) is the gold standard, guideline-recommended revascularization strategy in patients presenting with ST-elevation myocardial infarction (STEMI). However, there are limited data on its use and effectiveness among patients with active cancer presenting with STEMI. Methods and results All STEMI hospitalizations between 2004 and 2015 from the National Inpatient Sample were retrospectively analysed, stratified by cancer type. Propensity score matching was performed to estimate the average treatment effect of pPCI in each cancer on in-hospital adverse events, including major adverse cardiovascular and cerebrovascular events (MACCE) and its individual components, and compare treatment effect between cancer and non-cancer patients. Out of 1 870 815 patients with STEMI, 38 932 (2.1%) had a current cancer diagnosis [haematological: 11 251 (28.9% of all cancers); breast: 4675 (12.0%); lung: 9538 (24.5%); colon: 3749 (9.6%); prostate: 9719 (25.0%)]. Patients with cancer received pPCI less commonly than those without cancer (from 54.2% for lung cancer to 70.6% for haematological vs. 82.3% in no cancer). Performance of pPCI was strongly associated with lower adjusted probabilities of MACCE and all-cause mortality in the cancer groups compared with the no cancer group. There was no significant difference in estimated average pPCI treatment effect between the cancer groups and non-cancer group. Conclusion Primary percutaneous coronary intervention is underutilized in STEMI patients with current cancer despite its significantly lower associated rates of in-hospital all-cause mortality and MACCE that is comparable to patients without cancer. Further work is required to assess the long-term benefit and safety of pPCI in this high-risk group.

Background: Assessment of heterogeneity in meta-analyses is critical to ensure the consistency of pooled results. Therefore, we sought to assess the evaluation and reporting of heterogeneity in heart failure (HF) meta-analyses. Methods: Study level meta-analyses pertaining to HF were selected from January 2009 to July 2019, published in 11 high impact factor journals. We tabulated the overall proportion of the meta-analyses reporting statistical heterogeneity and specific metrics and methods employed to quantify and explore heterogeneity. Results: Of 126 HF meta-analyses (612 outcomes), heterogeneity was reported for 422 outcomes (68.9 %) in 108 meta-analyses. Out of the 422 outcomes reporting statistical heterogeneity, 137 outcomes (32.5%) had no observable heterogeneity: ( I 2 =0%), 40 outcomes (9.5%) had low heterogeneity ( I 2 <25%), 76 outcomes (18%) had moderate heterogeneity ( I 2 =25%–50%), and 169 outcomes (40%) had high heterogeneity ( I 2 >50%). Reporting of statistical heterogeneity was not significantly associated with year of publication, funding source, disclosure information, or the type of studies pooled. Sensitivity analysis (n=68) was the most common statistical technique employed to evaluate the source of heterogeneity followed by subgroup analyses (n=59) and meta-regression (n=40). Conclusions: Despite being an essential component of meta-analyses, heterogeneity was not reported for nearly 30% of outcomes and variably handled in contemporary HF meta-analyses. As meta-analyses increase across HF science, interpreting and handling of heterogeneity should be standardized.

Background Aortic stenosis–related mortality might vary across demographic subsets, regions, and states in the United States. Methods and Results We reviewed the death certificate data from the Centers for Disease Control and Prevention Wide‐Ranging OnLine Data for Epidemiologic Research database to examine aortic stenosis–related mortality trends from 2008 to 2018. Crude and age‐adjusted mortality rates (AAMRs) per 100 000 people and annual percentage change with 95% CIs were calculated. Between 2008 and 2018, AAMR reduced from 12.7 to 11.5 (average annual percentage change, −1.0 [95% CI, −1.5 to −0.5]), because of an accelerated decline between 2015 and 2018 (annual percentage change, −4.4 [95% CI, −6.0 to −2.7]). Older (aged >85 years), male, and White patients had higher death rates than younger, female, and non‐White patients, respectively. Although mortality reduction was similar across sexes, significant mortality reduction was limited to White patients only. The AAMRs were higher in rural than urban areas. States with AAMRs >90th percentile were distributed in the West and the Northeast, and <10th percentile in the South. The AAMRs for sex and race were highest in the West and lowest in the South. None of the states located in the Midwest showed a significant reduction in mortality. Mortality remained stable for hospital setting and nursing home/long‐term care facility, except that the number of deaths increased at home and hospice facility since 2014. Conclusions The reduction in mortality in patients with aortic stenosis was not consistent among demographic subsets and states. The substantial public health and economic implications call for determination of underlying clinical and socioeconomic factors to narrow the gap.

Background: Representation trends of women, older adults, and ethnic/racial minorities in randomized controlled trials (RCTs) of atrial fibrillation (AF) are uncertain. Methods: We systematically reviewed 134 AF related RCTs (phase II and III) encompassing 149,162 participants using Medline and ClinicalTrials.gov through April 2019 to determine representation trends of women, older patients (≥ 75 years), and ethnic/racial minorities. Weighted data on the prevalence of AF from epidemiological studies were used to compare the representation of the studied groups of interest in AF RCTs to their expected burden of the disease. Results: Only 18.7% of the RCTs reported proportion of older patients, and 12.7% RCTs reported ethnic/racial minorities. In RCTs, proportions of women, Hispanics, Blacks, American Indian/Alaskan patients, Asians, native Hawaiian/Pacific Islanders and non-Whites were 35.2%, 11.9%, 1.2%, 0.2%, 14.2%, 0.05%, and 19.5%, respectively. The corresponding proportions in general population were 35.1%, 5.2%, 5.7%, 0.2%, 2.4%, 0.1%, and 22.5%, respectively. The weighted mean age (SD) across the trials was 65.3 (3.2) years which was less than the corresponding weighted mean age of 71.1 (4.5) years in the comparative epidemiological data. Conclusion: The reporting of older patients and ethnic/racial minorities was poor in RCTs of AF. The representation of women and American Indian/Alaskan natives matched their expected population share of disease burden. Hispanics and Asians were over-represented and Blacks, native Hawaiian/Pacific Islanders and non-Whites were under-represented in RCTs of AF. In nearly all studied RCTs, the reporting of racial demographics did not start until later part of last decade.

Background Heart failure (HF) imparts a significant clinical and economic burden on the health system in the United States. Methods and Results We used the National Inpatient Sample database between September 2002 and December 2016. We examined trends of comorbidities, inpatient mortality, and healthcare resource use in patients admitted with acute HF. Outcomes were adjusted for demographic variables, comorbidities, and inflation. A total of 11 806 679 cases of acute HF hospitalization were identified. The burden of coronary artery disease, peripheral vascular disease, valvular heart disease, diabetes mellitus, hypertension, anemia, cancer, depression, and chronic kidney disease among patients admitted with acute HF increased over time. The adjusted mortality decreased from 6.8% in 2002 to 4.9% in 2016 ( P‐ trend<0.001; average annual decline, 1.99%), which was consistent across age, sex, and race. The adjusted mean length of stay decreased from 8.6 to 6.5 days ( P <0.001), but discharge disposition to a long‐term care facility increased from 20.8% to 25.6% ( P <0.001). The inflation adjusted mean cost of stay increased from $14 301 to $17 925 ( P <0.001) (average annual increase, 1.52%), which was partially explained by the higher proportion of procedures (echocardiogram, right heart catheterization, use of ventricular assist devices, coronary artery bypass grafting) and the higher incidence of HF complications (cardiogenic shock, respiratory failure, ventilator, and renal failure requiring dialysis). Conclusions This national data set showed that despite increasing medical complexities, there was significant reduction in inpatient mortality and length of stay. However, these measures were counterbalanced by a higher proportion of discharge disposition to long‐term care facilities and expensive cost of care.