Ha JT, Neuen BL, Cheng LP, et al. Benefits and Harms of Oral Anticoagulant Therapy in Chronic Kidney Disease: A Systematic Review and Meta-analysis. Ann Intern Med. 2019 Jul 16. pii: 2738158. doi: 10.7326/M19-0087. (Systematic review)

Background: Effects of oral anticoagulation in chronic kidney disease (CKD) are uncertain.

Purpose: To evaluate the benefits and harms of vitamin K antagonists (VKAs) and non-vitamin K oral anticoagulants (NOACs) in adults with CKD stages 3 to 5, including those with dialysis-dependent end-stage kidney disease (ESKD).

Data Sources: English-language searches of MEDLINE, EMBASE, and Cochrane databases (inception to February 2019); review bibliographies; and ClinicalTrials.gov (25 February 2019).

Study Selection: Randomized controlled trials evaluating VKAs or NOACs for any indication in patients with CKD that reported efficacy or bleeding outcomes.

Data Extraction: Two authors independently extracted data, assessed risk of bias, and rated certainty of evidence.

Data Synthesis: Forty-five trials involving 34 082 participants who received anticoagulation for atrial fibrillation (AF) (11 trials), venous thromboembolism (VTE) (11 trials), thromboprophylaxis (6 trials), prevention of dialysis access thrombosis (8 trials), and cardiovascular disease other than AF (9 trials) were included. All but the 8 trials involving patients with ESKD excluded participants with creatinine clearance less than 20 mL/min or estimated glomerular filtration rate less than 15 mL/min/1.73 m2. In AF, compared with VKAs, NOACs reduced risks for stroke or systemic embolism (risk ratio [RR], 0.79 [95% CI, 0.66 to 0.93]; high-certainty evidence) and hemorrhagic stroke (RR, 0.48 [CI, 0.30 to 0.76]; moderate-certainty evidence). Compared with VKAs, the effects of NOACs on recurrent VTE or VTE-related death were uncertain (RR, 0.72 [CI, 0.44 to 1.17]; low-certainty evidence). In all trials combined, NOACs seemingly reduced major bleeding risk compared with VKAs (RR, 0.75 [CI, 0.56 to 1.01]; low-certainty evidence).

Limitation: Scant evidence for advanced CKD or ESKD; data mostly from subgroups of large trials.

Conclusion: In early-stage CKD, NOACs had a benefit-risk profile superior to that of VKAs. For advanced CKD or ESKD, there was insufficient evidence to establish benefits or harms of VKAs or NOACs.

Primary Funding Source: None. (PROSPERO: CRD42017079709).

Discipline Area Score
Nephrology 6 / 7
Hemostasis and Thrombosis 6 / 7
Cardiology 6 / 7
Internal Medicine 6 / 7
Comments from MORE raters

Cardiology rater

The paper clearly provides guidance in specific patient settings while raising new questions in other clinical scenarios. It will directly impact the clinical management of these patients.

Hemostasis and Thrombosis rater

This review highlights the lack of evidence in this area; however, the conclusions seem somewhat misleading based on the available data.

Internal Medicine rater

Mostly not very helpful. The question was too broad in my view. For example, they shouldn`t have included thomboprophylaxis and clotted HD access; they didn`t focus on the subgroups of most concern (e.g., GFR <40 or so); they didn`t point out major differences in renal excretion among the NOACs. One interesting finding that was not highlighted at all was that there was nothing to support lower bleeding with aspirin vs OACs in this group. The main message I got was to await the results of ongoing trials.

Nephrology rater

Good systematic review of the evidence comparing NOACs to vitamin K antagonists across a range of indications. Unfortunately, there remains a paucity of data in ESKD, but practice should change in earlier stages of CKD.
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