Spironolactone in HFpEF: the early eGFR dip was prognostic, but the drug still helped

Design

Post hoc analysis of a randomised trial (TOPCAT Americas)

Population

1,648 patients with heart failure with preserved ejection fraction

Primary outcome

CV death, HF hospitalisation or aborted cardiac arrest by early eGFR dip

Effect

Dip 33% vs 20% (OR 1.97); spironolactone HR 0.75 with dip vs 0.80 without (P interaction 0.81)

This post hoc analysis of 1,648 patients in the Americas cohort of TOPCAT examined an eGFR fall of 15% or more between baseline and week 4 after starting spironolactone or placebo for heart failure with preserved ejection fraction.

A dip occurred in 33% on spironolactone and 20% on placebo (OR 1.97, 95% CI 1.58–2.47). A dip was associated with a higher risk of later cardiovascular events in both arms. But spironolactone's effect on cardiovascular death, heart failure hospitalisation or aborted arrest was similar with a dip (HR 0.75, 0.53–1.08) and without (HR 0.80, 0.64–1.00; P for interaction 0.81), and was consistently lower at every magnitude of eGFR decline.

The pattern mirrors what is known for RAAS inhibitors and SGLT2 inhibitors: an early haemodynamic dip does not cancel benefit. For nephrologists co-managing HFpEF, the message is not to stop an MRA reflexively when eGFR falls in the first month — check potassium, volume status and interacting drugs instead.

• Do not stop spironolactone automatically when eGFR falls in the first four weeks.
• Recheck potassium and creatinine at 1 and 4 weeks after starting.
• Look for volume depletion, NSAIDs or excessive diuresis when eGFR falls.
• Stop or reduce for hyperkalaemia, not for an isolated moderate eGFR dip.
• An early dip marks a higher-risk patient — follow them more closely, not less treated.

Why it matters

It extends the 'acceptable dip' principle to MRAs, where clinicians most often stop too early.

Don't overread it

A post hoc analysis of one regional cohort; the subgroup hazard ratios have wide intervals that touch 1.

The statistics, in plain English

A P for interaction of 0.81 means there was no evidence that the eGFR dip changed spironolactone's effect; the individual HRs are imprecise because each is estimated in a subgroup.

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