BackgroundAtrial fibrillation is associated with higher mortality. Identification of causes of death and contemporary risk factors for all‐cause mortality may guide interventions.Methods and ResultsIn the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) study, patients with nonvalvular atrial fibrillation were randomized to rivaroxaban or dose‐adjusted warfarin. Cox proportional hazards regression with backward elimination identified factors at randomization that were independently associated with all‐cause mortality in the 14 171 participants in the intention‐to‐treat population. The median age was 73 years, and the mean CHADS 2 score was 3.5. Over 1.9 years of median follow‐up, 1214 (8.6%) patients died. Kaplan–Meier mortality rates were 4.2% at 1 year and 8.9% at 2 years. The majority of classified deaths (1081) were cardiovascular (72%), whereas only 6% were nonhemorrhagic stroke or systemic embolism. No significant difference in all‐cause mortality was observed between the rivaroxaban and warfarin arms (P=0.15). Heart failure (hazard ratio 1.51, 95% CI 1.33–1.70, P<0.0001) and age ≥75 years (hazard ratio 1.69, 95% CI 1.51–1.90, P<0.0001) were associated with higher all‐cause mortality. Multiple additional characteristics were independently associated with higher mortality, with decreasing creatinine clearance, chronic obstructive pulmonary disease, male sex, peripheral vascular disease, and diabetes being among the most strongly associated (model C‐index 0.677).ConclusionsIn a large population of patients anticoagulated for nonvalvular atrial fibrillation, ≈7 in 10 deaths were cardiovascular, whereas <1 in 10 deaths were caused by nonhemorrhagic stroke or systemic embolism. Optimal prevention and treatment of heart failure, renal impairment, chronic obstructive pulmonary disease, and diabetes may improve survival.Clinical Trial Registration URL: https://www.clinicaltrials.gov/. Unique identifier: NCT00403767.
IMPORTANCE Atrial fibrillation (AF) is the most common cardiac arrhythmia, and multiple studies have reported increasing AF incidence rates over time, although the underlying explanations remain unclear. OBJECTIVESTo estimate AF incidence rates from 2006 to 2018 in a community-based setting and to investigate possible explanations for increasing AF by evaluating the changing features of incident AF cases and the pool of patients at risk for AF over time. DESIGN, SETTING, AND PARTICIPANTS This cohort study included 500 684 patients who received primary care and other health care services for more than 2 years through a single integrated health care delivery network in Pennsylvania. Data collection was conducted from January 2003 to December 2018. The base study population had no documentation of AF in the electronic medical record for at least 2 years prior to baseline. Data analysis was conducted from May to December 2019. MAIN OUTCOMES AND MEASURES Incident AF cases were identified through diagnostic codes recorded at inpatient or outpatient encounters. Age-and sex-adjusted AF incidence rates were estimated by calendar year from 2006 to 2018 both overall and across subgroups, including according to diagnostic setting (inpatient vs outpatient) and priority (primary vs secondary diagnosis). RESULTSAmong 514 293 patients meeting criteria for the base study population, the mean (SD) age at baseline was 47 (18) years and 282 103 (54.9%) were women; 13 609 (2.6%) met AF diagnostic criteria on or prior to the baseline date and were excluded. Among 500 684 patients free of AF at baseline, standardized AF incidence rates from 2006 to 2018 increased from 4.74 (95% CI, 4.58-4.90) to 6.82 (95% CI, 6.65-7.00) cases per 1000 person-years, increasing significantly over time (P < .001). Incidence rates increased in all age and sex subgroups, although absolute rate increases were largest among those aged 85 years or older. The fraction of incident AF cases among individuals aged 85 years or older increased from 135 of 1075 (12.6%) in 2006 to 451 of 2427 (18.6%) in 2017. Patients with incident AF were more likely over time to have high body mass index (1351 of 3389 patients [39.
BACKGROUND Guidelines recommend nonstatin lipid-lowering agents in patients at very high risk for major adverse cardiovascular events (MACE) if low-density lipoprotein cholesterol (LDL-C) remains ≥70 mg/dL on maximum tolerated statin treatment. It is uncertain if this approach benefits patients with LDL-C near 70 mg/dL. Lipoprotein(a) levels may influence residual risk. OBJECTIVES In a post hoc analysis of the ODYSSEY Outcomes (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) trial, the authors evaluated the benefit of adding the proprotein subtilisin/kexin type 9 inhibitor alirocumab to optimized statin treatment in patients with LDL-C levels near 70 mg/dL. Effects were evaluated according to concurrent lipoprotein(a) levels. METHODS ODYSSEY Outcomes compared alirocumab with placebo in 18,924 patients with recent acute coronary syndromes receiving optimized statin treatment. In 4,351 patients (23.0%), screening or randomization LDL-C was <70 mg/dL (median 69.4 mg/dL; interquartile range: 64.3–74.0 mg/dL); in 14,573 patients (77.0%), both determinations were ≥70 mg/dL (median 94.0 mg/dL; interquartile range: 83.2–111.0 mg/dL). RESULTS In the lower LDL-C subgroup, MACE rates were 4.2 and 3.1 per 100 patient-years among placebo-treated patients with baseline lipoprotein(a) greater than or less than or equal to the median (13.7 mg/dL). Corresponding adjusted treatment hazard ratios were 0.68 (95% confidence interval [Cl]: 0.52–0.90) and 1.11 (95% Cl: 0.83–1.49), with treatment-lipoprotein(a) interaction on MACE ( P interaction = 0.017). In the higher LDL-C subgroup, MACE rates were 4.7 and 3.8 per 100 patient-years among placebo-treated patients with lipoprotein(a) >13.7 mg/dL or ≤13.7 mg/dL; corresponding adjusted treatment hazard ratios were 0.82 (95% Cl: 0.72–0.92) and 0.89 (95% Cl: 0.75–1.06), with P interaction = 0.43. CONCLUSIONS In patients with recent acute coronary syndromes and LDL-C near 70 mg/dL on optimized statin therapy, proprotein subtilisin/kexin type 9 inhibition provides incremental clinical benefit only when lipoprotein(a) concentration is at least mildly elevated. (ODYSSEY Outcomes: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; NCT01663402 )
We report a significant decrease of 39% in the number of inappropriate discharge prescriptions for PPIs during the study period; however, the percentage of inappropriate use of PPIs remains high. There is room for improvement in cost-effective use of PPIs.
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