An early eGFR dip on spironolactone did not cancel its cardiovascular benefit in HFpEF

The edition in brief

In 1,648 patients with heart failure with preserved ejection fraction from TOPCAT Americas, a 15% or greater eGFR fall within 4 weeks occurred in 33% on spironolactone and 20% on placebo. An early dip was associated with worse cardiovascular outcomes in both arms, but spironolactone's effect on cardiovascular death, heart failure admission or aborted arrest was similar whether a dip occurred (HR 0.75) or not (HR 0.80), with no interaction. A meta-analysis of 20 placebo-controlled trials (83,004 people with type 2 diabetes) found GLP-1 receptor agonists reduced a composite kidney outcome by 20% (RR 0.80) and MACE by 13%. A meta-analysis of 8 SGLT2 inhibitor trials (57,356 patients) found cardiovascular death or heart failure admission fell by 20% both below and above a BMI of 30, with no effect modification. In 441 patients with biopsy-proven IgA nephropathy, dipstick haemoglobinuria was associated with active histological lesions (composite OR 2.28), more strongly than microscopic haematuria or proteinuria. A UK Biobank genetic study found variants that shift creatinine and cystatin C independent of kidney function, biasing eGFR by up to several mL/min for an individual.