Quadruple therapy should be 'new therapeutic standard' for heart failure, say researchers

Treatment with a four-drug regimen incorporating newer classes of treatment can meaningfully extend the lives of patients with heart failure with reduced ejection fraction (HFrEF), a new analysis published in The Lancet suggests.

Newer drug therapies are known to individually improve outcomes in patients with chronic HFrEF, but their aggregate benefits have not previously been explored. | SCIENCE PHOTO LIBRARY
Newer drug therapies are known to individually improve outcomes in patients with chronic HFrEF, but their aggregate benefits have not previously been explored. | SCIENCE PHOTO LIBRARY

Analysing data from three randomised controlled trials in patients with HFrEF (n=15,880), researchers from France, the UK and the US found significant gains in life expectancy associated with a 'comprehensive contemporary regimen' comprising an angiotensin II receptor antagonist/neprilysin inhibitor (ARNI), beta-blocker, aldosterone antagonist and SGLT2 inhibitor, compared with conventional therapy.  

The trials included in the analysis evaluated the three newer classes of therapy (aldosterone antagonists, ARNI and SGLT2 inhibitors) individually. The researchers conducted an actuarial analysis to estimate the lifetime benefit of taking all three drugs in addition to a conventional regimen composed of an ACE inhibitor or angiotensin II receptor antagonist plus a beta-blocker.

They found that over a lifetime of use, assuming consistent treatment effects, the comprehensive regimen could add up to 8 years of survival free from cardiovascular events and hospitalisation due to heart failure.

The survival benefits were particularly pronounced in younger patients with HFrEF, but gains in life expectancy were seen for all the age groups analysed.

'There's been some resistance to adopting comprehensive therapy for heart failure patients,' said corresponding author Scott Solomon, MD, from the Brigham and Women's Hospital in Boston, USA. 'What we did here was to say, "What might the benefit be over a patient's lifetime?" And the benefit we're seeing is pretty dramatic.'

Survival gain

In the researchers' analysis, use of a comprehensive regimen reduced the hazard of cardiovascular death or admission to hospital for heart failure (primary endpoint) with a hazard ratio (HR) of 0.38 [95% CI 0.30–0.47]). There were also favourable effects on cardiovascular death alone (HR 0.50 [95% CI 0.37–0.67]), hospitalisation for heart failure alone (HR 0.32 [0.24–0.43]), and all-cause mortality (HR 0.53 [0.40–0.70]).

The comprehensive approach was estimated to afford an additional 2.7 to 8.3 years of event-free survival and 1.4 to 6.3 years of survival overall, depending on the age at which treatment is initiated.

The authors also found that switching to an ARNI from an ACE inhibitor or angiotensin receptor antagonist and adding an SGLT2 inhibitor to a beta-blocker and aldosterone antagonist reduced the risk of cardiovascular death or hospital admission for heart failure (HR 0.64 [95% CI 0.52–0.78]) and might lengthen life by 0.8–3.1 years.

"Across a broad range of ages, these therapies, when implemented in combination, may meaningfully improve life expectancy and help patients remain out of the hospital,' said lead author Muthiah Vaduganathan, MD, MPH, also from the Brigham and Women's Hospital.

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