Physicians' Academy for Cardiovascular Education

High benefit from dual lipid-lowering therapy for ACS patients with a prior CABG

The benefit of adding ezetimibe to statin therapy in patients with prior coronary artery bypass graft surgery and acute coronary syndrome in the IMPROVE-IT trial

Eisen A, Cannon CP, Blazing MA, et al. - Eur Heart J 2016; 37:3576–3584

Background

Patients with a history of coronary artery bypass graft surgery (CABG) are at increased risk for recurrent CV events, and when they present with an ACS, they are at a particularly high risk [1–3].

Ezetimibe leads to reduced intestinal cholesterol absorption. In the IMPROVE-IT study, it led to a 24% additional reduction of LDL-C levels and to a 2.0% absolute reduction of the composite endpoint of CV death, major coronary event, or stroke in patients stabilized within 10 days after an ACS, compared with placebo [4,5].

In current analysis of the IMPROVE-IT study, the effect of adding ezetimibe to statin therapy was evaluated in 18 134 patients after ACS with (9%) or without (91%) a history of CABG.

Main results

Conclusion

In an analysis of the IMPROVE-IT study, ACS patients with a history of CABG had a greater clinical benefit of ezetimibe therapy on top of statin versus placebo, compared with patients without CABG. These findings support the hypothesis that intensive, dual lipid-lowering therapy is more effective in CABG patients at increased risk for recurrent events.

Editorial comment

In their editorial article, Jacoby and Rader state that the current report by the TIMI group published in the European Heart Journal provides the strongest evidence yet that treating the highest risk patients more aggressively confers greater benefit. They argue that the results might be reasonably applied to other very high-risk patients, despite the study limitations that include:

  • The lack of subgroup analyses based on the comorbidities of CABG patients, including prior MI, HF, DM, hypertension and PAD.
  • The lack of similar data on stable CABG patients, or high-risk patients with other co-morbidities but without ACS.

Finally they reach five conclusions:

‘(1) CABG patients, especially those who experience a subsequent event, have very high-residual risk, even on ‘optimal’ medical therapy; (2) Implementation of current guidelines in clinical practice focused on high-intensity statin therapy has not resulted in achievement of the aggressive LDL-C goals or elimination of recurrent CV events; (3) The addition of ezetimibe in CABG patients with subsequent ACS to lower the LDL-C from >70 mg/dL to ~55 mg/dL resulted in an 8% absolute risk reduction, with a highly favourable number needed to treat of 11; (4) An LDL-C goal of ~50 mg/dL should be considered for CABG patients who have progression to an ACS event (and potentially for very high-risk patients in general); (5) Whether different pharmacologic classes that lower LDL-C provide similar benefits remains uncertain, but is increasingly likely given the positive results for both statins and now ezetimibe. For now, statins remain first line agents for LDL-C reduction, and ezetimibe serves as the second line agent for high-risk patients and those who require additional LDL-C reduction.’

References

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Find this article online at Eur Heart J