European Primary Care Cardiovascular Society

Comprehensive disease-modifying pharmacological therapies reduce CV events in HFrEF

Estimating lifetime benefits of comprehensive disease-modifying pharmacological therapies in patients with heart failure with reduced ejection fraction: a comparative analysis of three randomised controlled trials

Literature - Vaduganathan M, Claggett BL, Jhund PS et al., - The Lancet. 2020. doi: 10.1016/S0140-6736(20)30748-0.

Introduction and methods

Randomized controlled trials (RCTs) have shown that three drug classes (mineralocorticoid receptor antagonists [MRAs], angiotensin receptor–neprilysin inhibitors [ARNIs], and sodium/glucose cotransporter 2 [SGLT2] inhibitors) reduce mortality due to heart failure with reduced ejection fraction (HFrEF) beyond conventional therapy [1-3]. Treatment with MRAs and SGLT2 inhibitors showed clinical superiority when tested against placebo in addition to standard care inclusive of renin-angiotensin-system inhibitors and beta blockers [1,2]. Treatment with ARNI was superior in improving clinical outcomes when directly tested against an ACE inhibitor [3]. Despite the benefits, real-world data have shown that MRAs, ARNIs and SGLT2 inhibitors are infrequently prescribed, even among HFrEF patients who are clinically eligible without known contraindication or intolerance [4-8].

This cross-trial analysis used overall trial-level estimates from pivotal RCTs that assessed the efficacy and safety of MRA (EMPHASIS-HF, n=27377) [1], ARNI (PARADIGM-HF, n=10,521) [2], and a SGLT2 inhibitor (DAPA-HF, n=4744) [3] to estimate treatment effects of comprehensive disease-modifying pharmacological therapy (ARNI, beta blocker, MRA and SGLT2 inhibitor) vs. conventional therapy (ACE inhibitor or ARB and beta blocker) in patients with chronic HFrEF.

The primary composite endpoint was CV death or first hospital admission for HF. Other endpoints were the individual components of the composite outcome and all-cause mortality. Furthermore, event-free survival (survival free from the primary composite endpoint) and overall survival were estimated.

Main results

Conclusion

This cross-trial analysis used data from EMPHASIS-HF, PARADIGM-HF and DAPA-HF to estimate the aggregate benefits of comprehensive disease-modifying pharmacological therapy (ARNI, beta blocker, MRA and SGLT2 inhibitor) vs. conventional therapy (ACE inhibitor or ARB and beta blocker) in patients with chronic HFrEF. Comprehensive disease-modifying pharmacological therapy was estimated to reduce the hazard of the primary composite endpoint of CV death or hospital admission for HF, compared with conventional therapy. This also resulted in estimated benefit in event-free and overall survival among HFrEF patients aged 55 to 80 years. The largest survival gain was found in patients aged 55 years.

References

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