There have been many meta-analyses for statins, ezetimibe and proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) to evaluate clinical outcomes, but the efficacy and safety of different intensity of these three drugs on clinical outcomes was absent. PCSK9i, ezetimibe, and statins were divided into seven interventions as follows: including PCSK9i + high-intensity statins (P9i+HT), PCSK9i + moderate-intensity statins (P9i+MT), ezetimibe + high-intensity statins (Eze+HT), ezetimibe + moderate-intensity statins (Eze+MT), high-intensity statins (HT), moderate-intensity statins (MT), and low-intensity statins (LT). The risk ratios (RR) and 95% confidence intervals (CI) were calculated to evaluate the clinical outcomes in all randomized controlled trials included. In traditional meta-analysis, the more intensive treatment had a lower risk of all-cause mortality (RR 0.91, 95% CI 0.88–0.95), cardiovascular mortality (RR 0.89, 95% CI 0.86–0.92), myocardial infarction (RR 0.79, 95% CI 0.77–0.81), coronary revascularization (RR 0.80, 95% CI 0.76-0.84), and cerebrovascular events (RR 0.84, 95% CI 0.80–0.88) compared with the less intensive treatment. However, the more intensive treatment had a higher risk of new-onset diabetes (RR 1.08, 95% CI 1.04-1.12). The network meta-analysis demonstrated that P9i+HT, P9i+MT, HT, and MT were significantly associated with a risk reduction in coronary revascularization and cerebrovascular events compared with PLBO. LT could effectively reduce the risk of cardiovascular mortality (RR 0.71, 95% CI 0.54–0.92), MI (RR 0.67, 95% CI 0.54-0.82), and coronary revascularization (RR 0.77, 95% CI 0.65–0.91) compared with PLBO. P9i+HT was superior to HT in reducing the risk of MI (RR 0.78, 95% CI 0.68–0.90), coronary revascularization (RR 0.84, 95% CI 0.73–0.96), and cerebrovascular events (RR 0.78, 95% CI 0.64–0.95). However, compared with PLBO, P9i+HT, HT, and MT could increase the risk of new-onset diabetes (RR 1.23, 95% CI 1.11–1.37; RR 1.23, 95% CI 1.14–1.33; RR 1.09, 95% CI 1.02–1.15, respectively). In conclusion, PCSK9i added to background statins may be recommended as preferred lipid-lowering therapy, and did not increase the additional risk of new-onset diabetes. The safety and efficacy of ezetimibe was not superior to that of statins. LT can be recommended as the initial therapy.
BackgroundAt present, effective clinical therapies for myocardial ischemia-reperfusion injury (MIRI) are lacking. We investigated if luteolin conferred cardioprotective effects against MIRI and elucidated the potential underlying mechanisms.MethodFour databases were searched for preclinical studies of luteolin for the treatment of MIRI. The primary outcomes were myocardial infarct size (IS) and intracardiac hemodynamics. The second outcomes were representative indicators of apoptosis, oxidative stress, and inflammatory. The Stata and RevMan software packages were utilized for data analysis.ResultsLuteolin administration was confirmed to reduce IS and ameliorate hemodynamics as compared to the control groups (p < 0.01). IS had decreased by 2.50%, 2.14%, 2.54% in three subgroups. Amelioration of hemodynamics was apparent in two different myocardial infarct models (model of left anterior descending branch ligation and model of global heart ischemia), as left ventricular systolic pressure improved by 21.62 and 35.40 mmHg respectively, left ventricular end-diastolic pressure decreased by 7.79 and 4.73 mmHg respectively, maximum rate of left ventricular pressure rise increased by 737.48 and 750.47 mmHg/s respectively, and maximum rate of left ventricular pressure decrease increased by 605.66 and 790.64 mmHg/s respectively. Apoptosis of cardiomyocytes also significantly decreased, as indicated by thelevels of MDA, an oxidative stress product, and expression of the inflammatory factor TNF-α (p < 0.001).ConclusionPooling of the data demonstrated that luteolin exerts cardioprotective effects against MIRI through different signaling pathways. As possible mechanisms, luteolin exerts anti-apoptosis, anti-oxidation, and anti-inflammation effects against MIRI.
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