Kidney, Cardiac, and Safety Outcomes Associated With α-Blockers in Patients With CKD: A Population-Based Cohort Study.

Alpha-blockers (ABs) are commonly prescribed for control of resistant or refractory hypertension in patients with and without chronic kidney disease (CKD). The association between AB use and kidney, cardiac, mortality, and safety-related outcomes in CKD remains unknown. Population-based retrospective cohort study. Ontario (Canada) residents 66 years and older treated for hypertension in 2007 to 2015 without a prior prescription for an AB. New use of an AB versus new use of a non-AB blood pressure (BP)-lowering medication. 30% or greater estimated glomerular filtration rate (eGFR) decline; dialysis initiation or kidney transplantation (kidney replacement therapy); composite of acute myocardial infarction, coronary revascularization, congestive heart failure, or atrial fibrillation; safety (hypotension, syncope, falls, and fractures) events; and mortality. New users of ABs (doxazosin, terazosin, and prazosin) were matched to new users of non-ABs by a high dimensional propensity score. Cox proportional hazards and Fine and Gray models were used to examine the association of AB use with kidney, cardiac, mortality, and safety outcomes. Interactions by eGFR categories (≥90, 60-89, 30-59, and<30mL/min/1.73m2) were explored. Among 381,120 eligible individuals, 16,088 were dispensed ABs and matched 1:1 to non-AB users. AB use was associated with higher risk for≥30% eGFR decline (HR, 1.14; 95% CI, 1.08-1.21) and need for kidney replacement therapy (HR, 1.28; 95% CI, 1.13-1.44). eGFR level did not modify these associations, P interaction=0.3and 0.3, respectively. Conversely, AB use was associated with lower risk for cardiac events, which was also consistent across eGFR categories (HR, 0.92; 95% CI, 0.89-0.95; P interaction=0.1). AB use was also associated with lower mortality risk, but only among those with eGFR<60mL/min/1.73m2 (P interaction<0.001): HRs were 0.85 (95% CI, 0.78-0.93) and 0.71 (95% CI, 0.64-0.80) for eGFR of 30 to 59 and<30mL/min/1.73m2, respectively. Observational design, BP measurement data unavailable. AB use in CKD is associated with higher risk for kidney disease progression but lower risk for cardiac events and mortality compared with alternative BP-lowering medications.

Hundemer GL ，Knoll GA ，Petrcich W ，Hiremath S ，Ruzicka M ，Burns KD ，Edwards C ，Bugeja A ，Rhodes E ，Sood MM ... -  《-》

Comparative Effectiveness of Renin-Angiotensin System Inhibitors and Calcium Channel Blockers in Individuals With Advanced CKD: A Nationwide Observational Cohort Study.

It is unknown whether initiating renin-angiotensin system (RAS) inhibitor therapy in patients with advanced chronic kidney disease (CKD) is superior to alternative antihypertensive agents such as calcium channel blockers (CCBs). We compared the risks for kidney replacement therapy (KRT), mortality, and major adverse cardiovascular events (MACE) in patients with advanced CKD in routine nephrology practice who were initiating either RAS inhibitor or CCB therapy. Observational study in the Swedish Renal Registry, 2007 to 2017. 2,458 new users of RAS inhibitors and 2,345 CCB users with estimated glomerular filtration rates<30mL/min/1.73m2 (CKD G4-G5 without KRT) who were being followed up by a nephrologist. As a positive control cohort, new users of the same drugs with CKD G3 (estimated glomerular filtration rate, 30-60mL/min/1.73m2) were evaluated. RAS inhibitor versus CCB therapy initiation. Initiation of KRT (maintenance dialysis or transplantation), all-cause mortality, and MACE (composite of cardiovascular death, myocardial infarction, or stroke). HRs with 95% CIs were estimated using propensity score-weighted Cox proportional hazards regression adjusting for demographic, clinical, and laboratory covariates. Median age was 74 years, 38% were women, and median follow-up was 4.1 years. After propensity score weighting, there was significantly lower risk for KRT after new use of RAS inhibitors compared with new use of CCBs (adjusted HR, 0.79 [95% CI, 0.69-0.89]) but similar risks for mortality (adjusted HR, 0.97 [95% CI, 0.88-1.07]) and MACE (adjusted HR, 1.00 [95% CI, 0.88-1.15]). Results were consistent across subgroups and in as-treated analyses. The positive control cohort of patients with CKD G3 showed similar KRT risk reduction (adjusted HR, 0.67 [95% CI, 0.56-0.80]) with RAS inhibitor therapy compared with CCBs. Potential confounding by indication. Our findings provide evidence from real-world clinical practice that initiation of RAS inhibitor therapy compared with CCBs may confer kidney benefits among patients with advanced CKD, with similar cardiovascular protection.

Fu EL ，Clase CM ，Evans M ，Lindholm B ，Rotmans JI ，Dekker FW ，van Diepen M ，Carrero JJ ... -  《-》

Alpha-Blocker Use and the Risk of Hypotension and Hypotension-Related Clinical Events in Women of Advanced Age.

Hiremath S ，Ruzicka M ，Petrcich W ，McCallum MK ，Hundemer GL ，Tanuseputro P ，Manuel D ，Burns K ，Edwards C ，Bugeja A ，Magner P ，McCormick B ，Garg AX ，Rhodes E ，Sood MM ... -  《-》

Risk of Cardiovascular Events and Mortality Among Elderly Patients With Reduced GFR Receiving Direct Oral Anticoagulants.

Evidence for the efficacy of direct oral anticoagulants (DOACs) to prevent cardiovascular (CV) events and mortality in older individuals with a low estimated glomerular filtration rate (eGFR) is lacking. We sought to characterize the association of oral anticoagulant use with CV morbidity in elderly patients with or without reductions in eGFRs, comparing DOACs with vitamin K antagonists (VKAs). Population-based retrospective cohort study. All individuals 66 years or older with an initial prescription for oral anticoagulants dispensed in Ontario, Canada, from 2009 to 2016. DOACs (apixaban, dabigatran, and rivaroxaban) compared with VKAs by eGFR group (≥60, 30-59, and<30mL/min/1.73m2). The primary outcome was a composite of a CV event (myocardial infarction, revascularization, or ischemic stroke) or mortality. Secondary outcomes were CV events alone, mortality, and hemorrhage requiring hospitalization. High-dimensional propensity score matching of DOAC to VKA users and Cox proportional hazards regression. 27,552 new DOAC users were matched to 27,552 new VKA users (median age, 78 years; 49% women). There was significantly lower risk for CV events or mortality among DOAC users compared with VKA users (event rates of 79.78 vs 99.77 per 1,000 person-years, respectively; HR, 0.82 [95% CI, 0.75-0.90]) and lower risk for hemorrhage (event rates of 10.35 vs 16.77 per 1,000 person-years, respectively; HR, 0.73 [95% CI, 0.58-0.91]). There was an interaction between eGFR and the association of anticoagulant class with the primary composite outcome (P<0.02): HRs of 1.01 [95% CI, 0.92-1.12], 0.83 [95% CI, 0.75-0.93], and 0.75 [95% CI, 0.51-1.10] for eGFRs of≥60, 30 to 59, and<30mL/min/1.73m2. No interaction was detected for the outcome of hemorrhage. Retrospective observational study design limits causal inference; dosages of DOACs and international normalized ratio values were not available; low event rates in some subgroups limited statistical power. DOACs compared with VKAs were associated with lower risk for the composite of CV events or mortality, an association for which the strength was most apparent among those with reduced eGFRs. The therapeutic implications of these findings await further study.

Ashley J ，McArthur E ，Bota S ，Harel Z ，Battistella M ，Molnar AO ，Jun M ，Badve SV ，Garg AX ，Manuel D ，Tanuseputro P ，Wells P ，Mavrakanas T ，Rhodes E ，Sood MM ... -  《-》

Incident Atrial Fibrillation and the Risk of Congestive Heart Failure, Myocardial Infarction, End-Stage Kidney Disease, and Mortality Among Patients With a Decreased Estimated GFR.

The association of atrial fibrillation (AF), estimated glomerular filtration rate (eGFR), and adverse events remains unknown. Population-based retrospective cohort study from Ontario, Canada. 1,422,978 adult residents with eGFRs < 90mL/min/1.73m2 from April 1, 2006, through March 31, 2015. A diagnosis of AF at hospitalization. Congestive heart failure (CHF), myocardial infarction (MI), end-stage kidney disease, all-cause mortality. All adverse events were more frequent in individuals with AF (93,414 propensity score matched) compared to no AF, and this difference was more pronounced within the first 6 months of the index date (CHF: 3.04% [AF] vs 0.28% [no AF], subdistribution HR [sHR] of 11.57 [95% CI, 10.26-13.05]; MI: 0.97% [AF] vs 0.21% [no AF], sHR of 4.76 [95% CI, 4.17-5.43]; end-stage kidney disease: 0.16% [AF] vs 0.03% [no AF], sHR of 5.84 [95% CI, 3.82-8.93]; and all-cause mortality: 6.11% [AF] vs 2.50% [no AF], HR of 2.62 [95% CI, 2.50-2.76]) than in the period more than 6 months after the index date (CHF: 6.87% [AF] vs 2.87% [no AF], sHR of 2.64 [95% CI, 2.55-2.74]; MI: 2.21% [AF] vs 1.81% [no AF], sHR of 1.24 [95% CI, 1.18-1.30]; end-stage kidney disease: 0.52% [AF] vs 0.32% [no AF], sHR of 1.75 [95% CI, 1.57-1.95]; and all-cause mortality: 15.55% [AF] vs 15.10% [no AF], HR of 1.07 [95% CI, 1.04-1.10]). The results accounted for the competing risk for mortality. eGFR level modified the effect of AF on CHF (P for interaction < 0.05). Observational study design does not permit determination of causality; only a single outpatient eGFR measure was used; medication data were not included. Incident AF is associated with a high risk for adverse outcomes in patients with eGFRs < 90mL/min/1.73m2. Because the risk is exceedingly high within the first 6 months after AF diagnosis, therapeutic interventions and monitoring may improve outcomes.

Massicotte-Azarniouch D ，Kuwornu JP ，Carrero JJ ，Lam NN ，Molnar AO ，Zimmerman D ，McCallum MK ，Garg AX ，Sood MM ... -  《-》