No reduction of MACE with PCSK9i in patients with a history of HF
Alirocumab after acute coronary syndrome in patients with a history of heart failure
Literature - White HD, Schwarz GG, Szarek M et al., - Eur Heart J 2021; https://doi.org/10.1093/eurheartj/ehab804Introduction and methods
Background
There was no CV benefit of statins in patients with a history of heart failure (HF) in the GISSI-HF trial [1] and the CORONA trial [2], although these trials enrolled a high proportion of patients with ischemic HF.
The ODYSSEY OUTCOMES [3,4] and the FOURIER trial [5], in which the effect of PCSK9 inhibitors on CV events were evaluated, showed no effect of PCKS9 inhibitors on hospitalization for HF.
In this analysis was examined whether the PCKS9 inhibitor alirocumab reduced major adverse cardiovascular events (MACE) or reduced hospitalizations for HF in patients with a history of HF using data from the ODYSSEY OUTCOMES trial.
Study design
18,924Patients enrolled in the ODYSSEY OUTCOMES trial had been hospitalized with an ACS 1-12 months before randomization and elevated LDL-c or non-HDL-c, or ApoB after ≥2 weeks of statin treatment. Patients with NYHA class III or IV for HF and LVEF <25% were excluded. Patients were randomized to alirocumab or matching placebo. Median follow-up was 2.8 (Q1, Q3: 2.3, 3,4).
There were 2815 patients (14.9%) with a history of HF and 16,109 patients (85.1%) without a history of HF.
Main outcomes
In this analysis, the effect of alirocumab on MACE, components of MACE including types of MI, hospitalization for HF and death were evaluated.
Main results
Effects on lipids
- Alirocumab treatment resulted in a similar decrease in LDL-c in patients with vs. without a history of HF: -1.4 (-1.9 to -0.9) vs. -1.4 (-1.8 to -0.9).
Effects on (components of) MACE
- In the group of patients with no history of HF, there was a reduction of MACE with alirocumab compared to placebo (HR 0.78, 95%CI: 0.70-0.86, P<0.0001). In contrast, in patients with a history of HF, there was no reduction of MACE with alirocumab compared to placebo (Pinteraction between randomized treatment and history of HF on MACE was 0.0001).
- In patients without a history of HF, alirocumab reduced non-fatal MIs compared to placebo (HR 0.78, 95%CI: 0.69-0.88, P<0.0001). There was an excess of non-fatal MIs with alirocumab compared to placebo in patients with a history of HF (HR 1.30, 95%CI: 1.02-1.64, P=0.032) (Pinteraction=0.0002).
Effects on hospitalization for heart failure
- There was no effect of treatment on HF hospitalization in patients without a history of HF or in patients with HF.
Effects on death
- Treatment with alirocumab reduced all-cause death compared to placebo in patients without a history of HF (HR 0.80, 95%CI: 0.67-0.95, P=0.0135), but not in patients with a history of HF.
Conclusion
In this analysis of ODYSSEY OUTCOMES, treatment with alirocumab resulted in a similar reduction of LDL-c in patients with or without a history of HF. However, in patients on alirocumab, there was a reduction of MACE in those without a history of HF and there was no reduction of MACE in those with a history of HF. Furthermore, alirocumab had no effect on hospitalizations for HF either in patients with or without HF.
References
1. Tavazzi L, Maggioni AP, Marchioli R et al.; GISSI-HF Investigators. Effect of rosuvastatin in patients with chronic heart failure (the GISSI-HF trial): a randomised, double-blind, placebo-controlled trial. Lancet 2008;372: 1231–1239.
2. Kjekshus J, Apetrei E, Barrios V et al.; CORONA Group. Rosuvastatin in older patients with systolic heart failure. N Engl J Med 2007;357:2248–2261.
3. Schwartz GG, Steg PG, Szarek M et al.; ODYSSEY OUTCOMES Committees and Investigators. Alirocumab and cardiovascular outcomes after acute coronary syndrome. N Engl J Med 2018;379:2097–2107.
4. Steg PG, Szarek M, Bhatt DL et al.; For the ODYSSEY OUTCOMES Committees and Investigators. Effect of alirocumab on mortality after acute coronary syn dromes. Circulation 2019;140:103–112.
5. Sabatine MS, Giugliano RP, Keech AC et al.; FOURIER Steering Committee and Investigators. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med 2017;376:1713–1722.
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