Toyota, Toshiaki, Morimoto, Takeshi, Yamashita, Yugo, Shiomi, Hiroki, Kato, Takao, Makiyama, Takeru, Nakagawa, Yasuaki, Saito, Naritatsu, Shizuta, Satoshi, Ono, Koh, and Kimura, Takeshi
Introduction: It has not been yet adequately addressed whether the addition of the non-statin low-density lipoprotein cholesterol (LDL-C) lowering agents on top of statins has the same magnitude of risk reduction in the cardiovascular events as compared with more intensive statin therapy. Methods: We performed a systematic review and meta-analysis of randomized controlled trials comparing the more- versus less-intensive lipid-lowering therapy (LLT) on clinical outcomes in patients with atherosclerotic cardiovascular risk. The primary outcome measure was major adverse cardiovascular events (MACE), which was equivalent to the composite of coronary heart death, non-fatal myocardial infarction, stroke, or coronary revascularization. Results: We included 23 studies involving 133,037 patients (more-intensive LLT: 67,691 patients, and less-intensive LLT: 65,346 patients). We evaluated 3 types of more- versus less-intensive LLT, including more- versus less-statins (12 studies, 57,672 patients), combination therapy of ezetimibe versus statins alone (4 studies, 20,688 patients) or a proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors with statins versus statins alone (7 studies, 54,677 patients). The risk for MACE was significantly lower in the more-intensive LLT group compared with the less-intensive LLT group in the entire study population (odds ratio [OR] 0.84, 95% confidence interval [CI] [0.79-0.88], P<0.001), and in all the 3 categories of more intensive LLT strategies (more-intensive statin therapy: OR 0.83, 95%CI [0.76-0.90], P<0.001, ezetimibe: OR 0.90, 95%CI [0.85-0.96], P<0.001, and PCSK9 inhibitors: OR 0.81, 95%CI [0.73-0.90], P<0.001) with numerically greater relative risk reduction by more-intensive statin therapy and PCSK9 inhibitors than by ezetimibe. Relative risk reduction for MACE per 20mg/dl LDL-C reduction was also different across the 3 types of more-intensive LLT (more-intensive statin therapy: 17.4%, ezetimibe: 11.0%, and PCSK9 inhibitors: 6.6%). Conclusions: In this meta-analysis of 23 randomized controlled trials, more-intensive LLT as compared with less-intensive LLT was associated with significant risk reduction for MACE in the entire study population and in all the 3 categories of more-intensive LLT such as more-intensive statin therapy, ezetimibe, and PCSK9 inhibitors. However, overall relative risk reduction for MACE, as well as relative risk reduction for MACE per 20mg/dl LDL-C reduction were different across the 3 types of more-intensive LLT. [ABSTRACT FROM AUTHOR]