No CLEAR Advantage for Spironolactone in STEMI Patients

Mineralocorticoid receptor antagonists (MRA) have proven beneficial in lowering cardiovascular (CV) risk for many conditions. The first data showing that these agents reduced mortality rates in heart failure was published in 1999, and eplerenone has demonstrated benefit in patients with heart failure after STEMI or NSTEMI. More recently, the fully synthetic MRA finerenone has been found to improve outcomes in patients with diabetic kidney disease.

Prior studies have failed to demonstrate a benefit for spironolactone in a broad cohort of patients with acute coronary syndrome (ACS) without heart failure. However, data evaluating the effects of spironolactone in a pure STEMI cohort are lacking. In this installment of Talking Therapeutics, we discuss an important study addressing this key gap in the evidence.

Talking Point: A CLEARLY Neutral Trial

The CLEAR study enrolled over 7000 patients with myocardial infarction who had undergone percutaneous coronary intervention to receive either spironolactone or placebo. The 2 primary outcomes were a composite of death from cardiovascular causes or new or worsening heart failure, evaluated as the total number of events, and a composite of the first occurrence of myocardial infarction, stroke, new or worsening heart failure, or death from cardiovascular causes.

For the first primary outcome, there were 183 events (1.7 per 100 patient-years) in the spironolactone group compared with 220 events (2.1 per 100 patient-years) in the placebo group over a median follow-up period of 3 years (HR 0.91; 95% CI, 0.69-1.21; P = 0.51). For the second primary outcome, the event rate was 7.9% in the spironolactone group and 8.3% in the placebo group (HR, 0.96; 95% CI, 0.81-1.13; P = 0.60). Adverse drug events were similar between groups.

Talking Point: CLEARLY Important Data

Data like this, while disappointing, are still very informative. Polypharmacy is rampant among patients with cardiovascular diseases, as these conditions often overlap. Polypharmacy is very dangerous, as each new drug added to a patient’s regimen can reduce adherence to existing medication.

Based on the results of this trial, we can confidently withhold MRAs in patients with STEMI without concomitant heart failure. Pharmacists can instead focus on medications essential after STEMI, such as P2Y12 receptor antagonists and statins.