Time to Say Goodbye to the DRE for Prostate Cancer Screening

Data Support Upfront RAS Inhibitors for Advanced CKD

Kidney replacement therapy risk lower vs starting with CCB treatment

BY JOHN SCHIESZER INITIATION OF antihypertensive therapy with a renin-angiotensinsystem inhibitor (RASi) in patients with advanced chronic kidney disease (CKD) may confer additional renal bene ts compared with starting patients on a calcium channel blocker (CCB), according to new evidence from administrative databases in Sweden.

Investigators examined the risks for kidney replacement therapy (KRT), mortality, and major adverse cardiovascular events (MACE) in patients with advanced CKD by using 2007 to 2017 data from the Swedish Renal Registry. The study included 2458 and 2345 new users of RASi and CCB, respectively, who had an estimated glomerular ltration rate (eGFR) less than 30 mL/min/1.73m2 . Patients had a median age of 74 years, and 38% were women. “We chose this comparison because it mirrors a common clinical scenario, that of starting a rst or subsequent antihypertensive medication and choosing between these 2 drug classes,” said study investigator Catherine Clase, MB, MSc, an associate professor at McMaster University in Ontario, Canada.

Decreased KRT Risk The RAS inhibitor group had a signi cant 21% decreased risk for KRT compared with the CCB group, the investigators reported in the American Journal of Kidney Diseases. The RAS inhibitor and CCB groups, however, had similar risks for mortality and MACE. The absolute 5-year mortality risk was 48.3% among RAS inhibitor users and 49.5% among CCB users. The absolute 5-year risk of MACE was 25.0% among RAS inhibitor users and 25.1% among CCB users. Overall results were consistent across subgroups and in as-treated analyses, according to the investigators.

“This evidence may potentially inform clinical decisions on the choice of antihypertensive therapy for this patient group, minimally included in pivotal trials,” the investigators concluded.

The investigators de ned new users as individuals receiving a RAS inhibitor or CCB without dispensation of either drug in the previous 6 months. They excluded prevalent users of these agents, individuals with a history of kidney transplantation, individuals with an eGFR greater than 30 mL/min/1.73 m2 , or those initiating both drugs simultaneously. The majority of patients initiating RASi therapy received enalapril (37.2%), candesartan (23.4%), losartan (21.4%) or ramipril (9.6%). Among these patients, 249 individuals (10.1%) experienced a cardiovascular hospitalization in the 6 months prior to

initiation. Of the patients initiating a CCB, 97.7% received a dihydropyridine, which was primarily amlodipine (55.4%) or felodipine (36.9%). Among these patients, 231 (9.9%) had a cardiovascular hospitalization in the 6 months prior to initiation.

Study Limitations The authors acknowledged a number of study limitations. They noted, for example, despite adjusting for a wide range of potential confounders, residual confounding-by-indication bias cannot be excluded in observational studies. In addition, the reasons why patients were started on these drugs are unknown.

“The strength of the current study is the number of patients analyzed and the relatively long median follow-up, but the study carries the limitations associated with the observational study design, as well as studying Swedish registry with probably uniformly Caucasian individuals, limiting generalization of results,” commented Emaad Abdel-Rahman, MBBS, PhD, professor of nephrology at the University of Virginia in Charlottesville.

Dr Abdel-Rahman cited a recent observational study of 678 patients with stage 4-5 CKD who participated in the Chronic Renal Insuf ciency Cohort (CRIC) study that demonstrated no difference in the rate of progression to end-stage kidney disease or death between participants treated continuously with RASi or not treated at all for the duration of the study.

Clinically Useful Information Kausik Umanath, MD, MS, section head of clinical research in the division of nephrology and hypertension at Henry Ford Hospital in Detroit, Michigan, praised the new study as providing clinically useful information. “It is surprising to note that despite published guidelines for many years, a substantial portion of patients reach CKD stage 4/5 and are not already on a renin-angiotensin system inhibitor,” Dr Umanath said. “I am not surprised that initiating therapy later in the course of CKD still provides bene t in terms of forestalling kidney disease progression. Comparative effectiveness studies like this are particularly valuable when they come out of Europe due to the centralization of healthcare systems, which allows for fairly clean long-term epidemiologic data.”

Julia Breyer Lewis, MD, professor of medicine, nephrology, and hypertension at Vanderbilt University Medical Center in Nashville, Tennessee, said the new ndings support the well-established bene t of RAS inhibitors in slowing progression of CKD. Issues related to starting or discontinuing RAS inhibitors in patients with advanced CKD are important to address in more heterogeneous populations and ideally in prospective studies, Dr Breyer Lewis said. ■

RAS inhibitors and CCBs are associated with similar risks for MACE, mortality.

Apixaban May Offer an Edge Over Warfarin

PATIENTS WITH chronic kidney disease (CKD) who also have nonvalvular atrial brillation may have a lower risk for progression to a more advanced CKD stage when treated with apixaban instead of warfarin, a new study suggests.

Using Medicare claims data from 2013-2017, investigators identi ed 12,816 patients (mean age 80 years; 51% female; 88% White) with stage 3 to 5 CKD and nonvalvular atrial brillation. Of these patients, 50.3% were newly prescribed apixaban, a direct oral anticoagulant, and 49.7% were newly prescribed warfarin, a vitamin K antagonist.

Apixaban was associated with a 10% lower risk for CKD stage progression compared with warfarin, James B. Wetmore, MD, MS, of Hennepin Healthcare Research Institute in Minneapolis, Minnesota, and colleagues reported in the American Journal of Kidney Diseases. At baseline, 84% of patients had stage 3, 15% stage 4, and 1% stage 5 CKD.

The rate of CKD progression in events per 100 patients per year was 11.4 for apixaban users compared with 12.0 for warfarin users, according to the investigators. Compared with warfarin, apixaban was signi cantly associated with a 10% decreased risk for CKD progression.

Apixaban was not associated with a lower risk for kidney failure compared with warfarin.

Combined with the results of other studies, Dr Wetmore’s team noted, “our results suggest that apixaban may be associated with superior long-term renal outcomes relative to warfarin in this population, but this cannot be de nitively determined in the absence of data from clinical trials.” ■