Medicare Bundled Payment Policy on Anemia Care, Major Adverse Cardiovascular Events, and Mortality among Adults Undergoing Hemodialysis

Background and objectives In 2011, the Centers forMedicare & Medicaid Services implemented bundling of all services for patients receiving dialysis, including erythropoietin-stimulating agents use, and the Food and Drug Administration recommended conservative erythropoietin-stimulating agent dosing. Design, setting, participants, & measurements This retrospective cohort study investigated anemia care and clinical outcomes before and after the Centers for Medicare & Medicaid Services bundled payment and the revised Food and Drug Administration–recommended erythropoietin-stimulating agent labeling for Medicareinsured adults receiving hemodialysis using data from the United States Renal Data System from January 1, 2006 to December 31, 2016. Clinical outcomes included major adverse cardiovascular event (stroke, acute myocardial infarction, and all-cause mortality), cardiovascular mortality, and heart failure. Measurements were compared between prepolicy (2006–2010) and postpolicy (2012–2016) implementation using interrupted time series and Cox proportional hazards regression models. Results Of 481,564 patients, erythropoietin-stimulating agent use immediately decreased by 84.8 per 1000 persons (P11 g/dl decreased from 68% in January 2006 to 28% in December 2016, whereas those with hemoglobin >9 g/dl increased from 5% to 9%. Overall major adverse cardiovascular event (adjusted hazard ratio, 0.95; 95% confidence interval, 0.94 to 0.96), stroke (adjusted hazard ratio, 0.83; 95% confidence interval, 0.80 to 0.86), all-cause mortality (adjusted hazard ratio, 0.87; 95% confidence interval, 0.86 to 0.89), cardiovascular mortality (adjusted hazard ratio, 0.81; 95% confidence interval, 0.79 to 0.83), and heart failure (adjusted hazard ratio, 0.86; 95% confidence interval, 0.84 to 0.88) risks were lower. Acute myocardial infarction risk (adjusted hazard ratio, 1.04; 95% confidence interval, 1.01 to 1.06) was higher after policies changed. Conclusions The Medicare reimbursement policy and Food and Drug Administration–recommended erythropoietin-stimulating agent dosing changes were associated with lower erythropoietin-stimulating agent use and lower hemoglobin levels. These changes in anemia care were associated with lower risks of major adverse cardiovascular event, stroke, mortality, and heart failure but higher risk of acute myocardial infarction among adults receiving hemodialysis

Adverse Cardiovascular Outcomes and Antihypertensive Treatment: A Genome-Wide Interaction Meta-Analysis in the International Consortium for Antihypertensive Pharmacogenomics Studies

We sought to identify genome-wide variants influencing antihypertensive drug response and adverse cardiovascular outcomes, utilizing data from four randomized controlled trials in the International Consortium for Antihypertensive Pharmacogenomics Studies (ICAPS). Genome-wide antihypertensive drug-single nucleotide polymorphism (SNP) interaction tests for four drug classes (β-blockers, n = 9,195; calcium channel blockers (CCBs), n = 10,511; thiazide/thiazide-like diuretics, n = 3,516; ACE-inhibitors/ARBs, n = 2,559) and cardiovascular outcomes (incident myocardial infarction, stroke, or death) were analyzed among patients with hypertension of European ancestry. Top SNPs from the meta-analyses were tested for replication of cardiovascular outcomes in an independent Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) study (n = 21,267), blood pressure (BP) response in independent ICAPS studies (n = 1,552), and ethnic validation in African Americans from the Genetics of Hypertension Associated Treatment study (GenHAT; n = 5,115). One signal reached genome-wide significance in the β-blocker-SNP interaction analysis (rs139945292, Interaction P = 1.56 × 10−8). rs139945292 was validated through BP response to β-blockers, with the T-allele associated with less BP reduction (systolic BP response P = 6 × 10−4, Beta = 3.09, diastolic BP response P = 5 × 10−3, Beta = 1.53). The T-allele was also associated with increased adverse cardiovascular risk within the β-blocker treated patients’ subgroup (P = 2.35 × 10−4, odds ratio = 1.57, 95% confidence interval = 1.23–1.99). The locus showed nominal replication in CHARGE, and consistent directional trends in β-blocker treated African Americans. rs139945292 is an expression quantitative trait locus for the 50 kb upstream gene NTM (neurotrimin). No SNPs attained genome-wide significance for any other drugs classes. Top SNPs were located near CALB1 (CCB), FLJ367777 (ACE-inhibitor), and CES5AP1 (thiazide). The NTM region is associated with increased risk for adverse cardiovascular outcomes and less BP reduction in β-blocker treated patients. Further investigation into this region is warranted

Gender in cardiovascular medicine: chest pain and coronary artery disease

Contains fulltext : 215443.pdf (Publisher’s version ) (Closed access)Ischaemic heart disease (IHD) remains the leading cause of morbidity and mortality among women and men yet women are more often underdiagnosed, have a delay in diagnosis, and/or receive suboptimal treatment. An implicit gender-bias with regard to lack of recognition of sex-related differences in presentation of IHD may, in part, explain these differences in women compared with men. Indeed, existing knowledge demonstrates that angina does not commonly relate to obstructive coronary artery disease (CAD). Emerging knowledge supports an inclusive approach to chest pain symptoms in women, as well as a more thoughtful consideration of percutaneous coronary intervention for angina in stable obstructive CAD, to avoid chasing our tails. Emerging knowledge regarding the cardiac autonomic nervous system and visceral pain pathways in patients with and without obstructive CAD offers explanatory mechanisms for angina. Interdisciplinary investigation approaches that involve cardiologists, biobehavioural specialists, and anaesthesia/pain specialists to improve angina treatment should be pursued

Pharmacogenomic association of nonsynonymous SNPs in SIGLEC12, A1BG, and the selectin region and cardiovascular outcomes

We sought to identify novel pharmacogenetic markers associated with cardiovascular outcomes in patients with hypertension on antihypertensive therapy. We genotyped a 1:4 case:control cohort (n=1345) on the Illumina HumanCVD Beadchip from the INternational VErapamil SR–Trandolapril STudy (INVEST), where participants were randomized to a β-blocker strategy or a calcium channel blocker strategy. Genome-spanning single nucleotide polymorphism (SNP)×treatment interaction analyses of nonsynonymous SNPs were conducted in white and Hispanic race/ethnic groups. Top hits from whites were tested in Hispanics for consistency. A genetic risk score was constructed from the top 3 signals and tested in the Nordic Diltiazem study. SIGLEC12 rs16982743 and A1BG rs893184 had a significant interaction with treatment strategy for adverse cardiovascular outcomes (INVEST whites and Hispanics combined interaction P=0.0038 and 0.0036, respectively). A genetic risk score, including rs16982743, rs893184, and rs4525 in F5, was significantly associated with treatment-related adverse cardiovascular outcomes in whites and Hispanics from the INVEST study and in the Nordic Diltiazem study (meta-analysis interaction P=2.39×10−5). In patients with a genetic risk score of 0 or 1, calcium channel blocker treatment was associated with lower risk (odds ratio [95% confidence interval]=0.60 [0.42–0.86]), and in those with a genetic risk score of 2 to 3, calcium channel blocker treatment was associated with higher risk (odds ratio [95% confidence interval]=1.31 [1.08–1.59]). These results suggest that cardiovascular outcomes may differ based on SIGLEC12, A1BG, F5 genotypes, and antihypertensive treatment strategy. These specific genetic associations and our risk score provide insight into a potential approach to personalized antihypertensive treatment selection