Aggressive treatment of LDL-cholesterol and patients undergoing CABG: news from IMPROVE-IT

Abstract

taking S + Ez compared with those assigned to S + Pl (incidence-rate ratio, RR, 0.70: 0.59–0.84).[1] The corresponding RR for the group without prior CABG was 0.96 (0.89–1.03). Overall, there were 4231 additional primary endpoint events; 1050 in the prior CABG group (9% of the IMPROVE-IT population) and 3181 additional events in the non-prior CABG group (91% of the IMPROVE-IT population) (p < 0.001). The IMPROVE-IT trial “prior CABG” analysis [1] has several limitations. For example, patients with prior CABG represented only 9% of the participants; this limited the power to carry out any further detailed analysis within this population. Also, the time elapsed from the CABG was not available and there are no details regarding the type of grafts. Despite several limitations, IMPROVE-IT provides credible evidence that patients with prior CABG who develop an ACS are a high-risk subset with a substantial increased risk of recurrent CV ischemic events (56% at 7 years). These patients benefit more from adding ezetimibe to simvastatin (so as to achieve lower LDL-C levels) than patients without prior CABG. Future guidelines will need to consider this finding. Also, prior CABG + ACS patients may constitute an ideal population for assessing the effect of new potent LDL-C lowering drugs (e.g. proprotein convertase subtilisin/kexin nine inhibitors). The role of lipid lowering therapy for patients undergoing CABG was recognised several decades ago.[5–19] Also, of interest is that this literature includes evidence that high-density lipoprotein cholesterol (HDL-C), triglyceride and non-HDL-C levels may be relevant in terms of predicting disease progression in patients who underwent CABG. A meta-analysis also considered statin loading for CABG although it seems that the increased dose of statins was administered after CABG to achieve lower LDL-C levels long term; more aggressive statin treatment was superior.[20] It is of interest that even a recent study showed that post-CABG patients were undertreated with statins and aspirin. [21] In contrast, in IMPROVE-IT, at randomisation, 94.8% of those with prior CABG and 97.3% of those without prior CABG were on aspirin.[1] In addition, the corresponding % of patients on a thienopyridine was 79.0 and 87.2%, respectively.[1] There is evidence from IMPROVE-IT that more patients achieved the dual target of LDL-C (<70 mg/dl; 1.8 mmol/l) and high sensitivity C-reactive protein (<2 mg/l) with combination therapy than with monotherapy.[22] In turn, those achieving this dual target had fewer events than those not achieving this goal.[22] A dual target analysis was not carried out to the IMPROVE-IT CABG subgroup analysis probably because of the smaller number of participants in the CABG group.[1] OPEN ACCESS