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How does SMuRF status impact long-term outcomes in coronary artery disease?

Patients with stable coronary artery disease (CAD) but without standard modifiable cardiovascular risk factors (SMuRFs) have a substantial but significantly lower risk of long-term cardiovascular events than people with risk factors, an observational study has found.

Previous research found patients without SMuRFs presenting with first myocardial infarction (MI) had a higher in-hospital mortality than patients with risk factors, researchers wrote in the European Heart Journal.

They said the term ‘SMuRF-less’ was recently coined to stress the need for further research on cardiovascular outcomes in this group who did not have the standard risk factors of diabetes, dyslipidaemia, hypertension, and smoking.

To explore the long-term outcomes of SMuRF-less patients with stable CAD, the researchers analysed data from CLARIFY, an observational study of 32,703 patients with stable CAD enrolled between 2009 and 2010 in 45 countries in Europe, Asia, America, the Middle East, Australia, and South Africa.

Among 22,132 patients with complete risk factor and outcome information, 977 (4.4%) were classed as SMuRF-less.

Age, sex, and time since CAD diagnosis were similar across groups, the researchers reported.

SMuRF-less patients had a lower five-year rate of cardiovascular death or non-fatal MI than patients with risk factors (5.43% vs 7.68%), researchers reported.

All-cause mortality and major adverse cardiovascular events (cardiovascular death, non-fatal MI, or non-fatal stroke) were also lower in SMuRF-less patients, they found.

Senior author Professor Phillipe Gabriel Steg, professor of cardiology at the University of Paris, France, and colleagues said the risk of adverse cardiovascular outcomes increased steadily with the number of risk factors.

‘Standard modifiable cardiovascular risk factor-less status appeared more protective in women than in men,’ Professor Steg and co-authors noted.

However, they stressed the study did not question the need for SMuRF-less patients with stable CAD to receive guideline-based therapy, adding that SMuRF-less patients remained at a substantial risk of cardiovascular events.

‘While the risk was lower in SMuRF-less patients, they still experience a substantial risk of cardiovascular events; thus efforts should be made to achieve higher rates of implementation of evidence-based therapies,’ Professor Steg and colleagues wrote.

The study found SMuRF-less patients were less likely to be prescribed statins, angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers, and beta-blockers.

‘It remains crucial to improve the visibility of the SMuRF-less population in future clinical trials and guidelines,’ Professor Steg and colleagues concluded.

The previous body of research of SMuRF-less patients had focused on in-hospital mortality after first-presentation MI, with the paradoxical finding that SMuRF-less patients might experience more adverse outcomes after first-presentation MI.

However, the causes of the poor prognosis of SMuRF-less patients in the immediate post-infarction period as reported in previous research were not explored in the present study, the study authors noted.

‘SMuRF-less patients may have specific causes of MI (dissection, embolism, spasms, and the use of toxic substances), which can be difficult to manage during the acute phase but are associated with fewer comorbidities,’ the researchers suggested.

‘Future research efforts should focus on the early post-MI period, when the vulnerability of SMuRF-less patients seems to be at stake.’

The study was funded by pharmaceutical firm Servier, but the authors said the sponsor had no role in the study design or management.