Clinical implications of the IMPROVE-IT trial in the light of current and future lipid-lowering treatment options

Abstract

The results from IMPROVE-IT revalidated the concept that low-density lipoprotein cholesterol (LDL-C) levels are a clinically relevant treatment goal. This trial also suggested that further decrease of LDL-C levels (53 vs. 70 mg/dl; 1.4 vs. 1.8 mmol/l) was more beneficial in lowering CV events. This "even lower is even better" evidence for LDL-C levels may influence future guidelines and the use of new drugs. Furthermore, these findings make ezetimibe a more realistic option to treat patients with statin intolerance or those who cannot achieve LDL-C targets with statin monotherapy.

Lipids, blood pressure and kidney update 2014

“…Similar results were obtained in the Open-Label Study of Long-Term Evaluation Against LDL-C (OSLER) trial with evolocumab [7]. However, the data concerning the safety of preserving very low LDL-C levels on long term are still limited [6].…”

“…Beside IMPROVE-IT trial, another important trial ODYSSEY LONG-TERM (NCT01507831) with proprotein convertase subtilisin/ kexin type 9 (PCSK9) inhibitor -alirocumab, supported the hypothesis 'even lower is even better' for LDL-C levels [4], generating more arguments for lower LDL-C targets <50 mg/dl (1.3 mmol/l), in contrast with the current targets <70 mg/dl (1.8 mmol/l) for patients at the highest risk [5]. The same trial also confirmed that LDL-C goals below <25 mg/dl and even <15 mg/dl were not connected with the increase of any adverse events [5,6]. Similar results were obtained in the Open-Label Study of Long-Term Evaluation Against LDL-C (OSLER) trial with evolocumab [7].…”

Evaluating bempedoic acid for the treatment of hyperlipidaemia

“…inhibitors (however it is worth mentioning that these studies were neither designed nor powered to investigate CV outcomes) and confirmed the safety of LDL-C reduction, to levels even below 25 mg/dL [6,7]. The results of the cardiovascular outcomes trials (CVOT) with these agents (FOURIER, ODYSSEY OUTCOMES) are expected in 2017 and 2018 [11,12].…”

“…The combination led to lower LDL-C levels (53.7 vs 69.5 mg/dL) than simvastatin monotherapy, and importantly this translated to reduced risk of the primary endpoint, which was a composite of cardiac events (hazard ratio [HR] 0.936 [0.89 to 0.99]) [5]. However, surprisingly, despite these positive and significant results the US Food and Drug Administration (FDA) did not approve ezetimibe for use as an addition to statin therapy for reduction of CV events in patients with coronary heart disease (CHD) [6,7].…”

“…However, the effectiveness of LDL-C lowering therapy in clinical practice has been limited by a number of factors, including poor adherence to statin therapy, statin discontinuation [13] and statin intolerance [14] and residual risk despite achieving therapeutic LDL-C targets [6,15]. Statin monotherapy or combinations of currently available drugs are unlikely to achieve optimal concentrations of LDL-C in all patients, especially those who are at high CV risk [16].…”