Khan, Safi

Background Despite improvements in the management and prevention of stroke, increasing hospitalizations for stroke and stagnant mortality rates have been described in young adults. However, there is a paucity of contemporary national mortality estimates in young adults. Methods and Results Trends in mortality related to stroke in young adults (aged 25–64 years) were assessed using the Centers for Disease Control and Prevention Wide‐Ranging Online Data for Epidemiologic Research database. Age‐adjusted mortality rates per 100 000 people with associated annual percentage change were calculated. Joinpoint regression was used to assess the trends in the overall sample and different demographic (sex, race and ethnicity, and age) and geographical (state, urban‐rural, and regional) subgroups. Between 1999 and 2019, a total of 566 916 stroke‐related deaths occurred among young adults. After the initial decline in mortality in the overall population, age‐adjusted mortality rate increased from 2013 to 2019 with an associated annual percentage change of 1.5 (95% CI, 1.1–2.0). Mortality rates were higher in men versus women and in non‐Hispanic Black people versus individuals of other races and ethnicities. Non‐Hispanic American Indian or Alaskan Native people had a marked increase in stroke‐related mortality (annual percentage change 2010–2019: 3.3). Furthermore, rural (nonmetropolitan) counties experienced the greatest increase in mortality (annual percentage change 2012–2019: 3.1) compared with urban (metropolitan) counties. Conclusions Following the initial decline in stroke‐related mortality, young adults have experienced increasing mortality rates from 2013 to 2019, with considerable differences across demographic groups and regions.

Abstract 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.

BACKGROUND The United States (US)‐Mexico border is a socioeconomically underserved area. We sought to investigate whether stroke‐related mortality varies between the US border and nonborder counties. METHODS AND RESULTS We used death certificates from the Centers for Disease Control and Prevention Wide‐Ranging Online Data for Epidemiologic Research database to examine stroke‐related mortality in border versus nonborder counties in California, Texas, New Mexico, and Arizona. We measured average annual percent changes (AAPCs) in age‐adjusted mortality rates (AAMRs) per 100 000 between 1999 and 2018. Overall, AAMRs were higher for nonborder counties, older adults, men, and non‐Hispanic Black adults than their counterparts. Between 1999 and 2018, AAMRs reduced from 55.8 per 100 000 to 34.4 per 100 000 in the border counties (AAPC, −2.70) and 64.5 per 100 000 to 37.6 per 100 000 in nonborder counties (AAPC, −2.92). The annual percent change in AAMR initially decreased, followed by stagnation in both border and nonborder counties since 2012. The AAPC in AAMR decreased in all 4 states; however, AAMR increased in California’s border counties since 2012 (annual percent change, 3.9). The annual percent change in AAMR decreased for older adults between 1999 and 2012 for the border (−5.10) and nonborder counties (−5.01), followed by a rise in border counties and stalling in nonborder counties. Although the AAPC in AAMR decreased for both sexes, the AAPC in AAMR differed significantly for non‐Hispanic White adults in border (−2.69) and nonborder counties (−2.86). The mortality decreased consistently for all other ethnicities/races in both border and nonborder counties. CONCLUSIONS Stroke‐related mortality varied between the border and nonborder counties. Given the substantial public health implications, targeted interventions aimed at vulnerable populations are required to improve stroke‐related outcomes in the US‐Mexico border area.

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 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.

Abstract Aims To compare early de-escalation of dual antiplatelet therapy (DAPT) (1–3 months) to monotherapy with either P2Y12 inhibitor or aspirin vs. 12 months DAPT after percutaneous coronary intervention (PCI) with drug-eluting stent (DES). Methods and results Electronic databases of Medline, Embase, and Cochrane library were searched through February 2020 to identify randomized controlled trials. A Bayesian network meta-analysis was conducted with random effects model. The main endpoints of interest were cardiovascular mortality and total bleeding events. Among seven trials (35 821 patients), 52.6% patients were presented with acute coronary syndrome. A total of 3359 patients and 14 530 patients were de-escalated to aspirin and P2Y12 inhibitor monotherapy, respectively. At a median follow-up of 12 months, compared with 12 months of DAPT, there was no significant difference in cardiovascular mortality between 1-month DAPT followed by P2Y12 inhibitor monotherapy [hazard ratio (HR) 0.84 (95% credible interval 0.29–2.43)], 3 months of DAPT followed by P2Y12 inhibitor monotherapy [HR 0.74 (0.39–1.46)], or 3 months of DAPT [HR 1.00 (0.54–1.86)] followed by aspirin monotherapy. Except for de-escalation of DAPT to aspirin monotherapy after 3 months [HR 0.75 (0.43–1.20)], de-escalation to P2Y12 inhibitor monotherapy after 1 month [HR 0.28 (0.10–0.83)], or 3 months [HR 0.57 (0.33–0.98)] were associated with significant decrease in total bleeding events. There were no significant differences in terms of ischaemic endpoints among different DAPT strategies. Conclusion Early de-escalation of DAPT (1–3 months) to monotherapy with a P2Y12 inhibitor instead of aspirin might be a safer and equally effective approach compared with 12 months of DAPT in patients with PCI and DES.

AbstractBackgroundHypertrophic cardiomyopathy (HCM) accounts for significant morbidity and mortality worldwide. Arrhythmias are considered the main cause of mortality, however, there is paucity of data relating to trends of arrhythmia and associated outcomes in HCM patients.MethodsNationwide Inpatient Sample from 2003 to 2014 was analyzed. HCM related hospitalizations were identified using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD9‐CM) code 425.1 and 425.11 in all diagnosis fields.ResultsOverall, there was an increase in number of hospitalizations related to arrhythmias among HCM patients from 7784 in 2003 to 8380 in 2014 (relative increase 10.5%, P < 0.001). The increase was most significant in patients ≥ 80 years and those with higher comorbidity burden. Atrial fibrillation (AF) was the most frequently occurring arrhythmia however atrial flutter (AFL) witnessed the highest rise during the study period. In general, there was a down trend in mortality with the greatest reduction occurring in patients with ventricular fibrillation/flutter (VF/VFL). The mean length of stay was higher if patients had arrhythmia, which led to increased cost of care from $16105 in 2003 to $19310 in 2014 (relative increase 22.9%, P < 0.001).ConclusionThere is overall decline in HCM related hospitalizations but rise in hospitalization among HCM patients with arrhythmias. HCM with arrhythmia accounts for significant inpatient mortality coupled with prolonged hospital stay and increased cost of care. However, there is an encouraging downtrend in the mortality most likely because of improved clinical practice, cardiac screening and primary and secondary prevention strategies.