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Background The comparative effects of statins, ezetimibe with or without statins and proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors remain unassessed. Design Bayesian network meta-analysis was conducted to compare treatment groups. Methods Thirty-nine randomized controlled trials were selected using MEDLINE, EMBASE, and CENTRAL (inception - September 2017). Results In network meta-analysis of 189,116 patients, PCSK9 inhibitors were ranked as the best treatment for prevention of major adverse cardiovascular events (Surface Under Cumulative Ranking Curve (SUCRA), 85%), myocardial infarction (SUCRA, 84%) and stroke (SUCRA, 80%). PCSK9 inhibitors reduced the risk of major adverse cardiovascular events compared with ezetimibe + statin (odds ratio (OR): 0.72; 95% credible interval (CrI), 0.55-0.95; Grading of Recommendation Assessment, Development and Evaluation (GRADE) criteria: moderate), statin (OR: 0.78; 95% CrI: 0.62-0.97; GRADE: moderate) and placebo (OR: 0.63; 95% CrI: 0.49-0.79; GRADE: high). The PCSK9 inhibitors were consistently superior to groups for major adverse cardiovascular event reduction in secondary prevention trials (SUCRA, 95%). Statins had the highest probability of having lowest rates of all-cause mortality (SUCRA, 82%) and cardiovascular mortality (SUCRA, 84%). Compared with placebo, statins reduced the risk of all-cause mortality (OR: 0.88; 95% CrI: 0.83-0.94; GRADE: moderate) and cardiovascular mortality (OR: 0.84; 95% CrI: 0.77-0.90; GRADE: high). For cardiovascular mortality, PCSK9 inhibitors were ranked as the second best treatment (SUCRA, 78%) followed by ezetimibe + statin (SUCRA, 50%). Conclusion PCSK9 inhibitors were ranked as the most effective treatment for reducing major adverse cardiovascular events, myocardial infarction and stroke, without having major safety concerns. Statins were ranked as the most effective therapy for reducing mortality.

Background The relationship between lowering LDL (low‐density lipoprotein) cholesterol with contemporary lipid‐lowering therapies and incident diabetes mellitus ( DM ) remains uncertain. Methods and Results Thirty‐three randomized controlled trials (21 of statins, 12 of PCSK9 [proprotein convertase subtilisin/kexin type 9] inhibitors, and 0 of ezetimibe) were selected using Medline , Embase, and the Cochrane Central Register of Controlled Trials (inception through November 15, 2018). A total of 163 688 nondiabetic patients were randomly assigned to more intensive (83 123 patients) or less intensive (80 565 patients) lipid‐lowering therapy. More intensive lipid‐lowering therapy was defined as the more potent pharmacological strategy ( PCSK 9 inhibitors, higher intensity statins, or statins), whereas less intensive therapy corresponded to active control group or placebo/usual care of the trial. Metaregression and meta‐analyses were conducted using a random‐effects model. No significant association was noted between 1‐mmol/L reduction in LDL cholesterol and incident DM for more intensive lipid‐lowering therapy (risk ratio: 0.95; 95% CI , 0.87–1.04; P =0.30; R 2 =14%) or for statins or PCSK 9 inhibitors. More intensive lipid‐lowering therapy was associated with a higher risk of incident DM compared with less intensive therapy (risk ratio: 1.07; 95% CI , 1.03–1.11; P <0.001; I 2 =0%). These results were driven by higher risk of incident DM with statins (risk ratio: 1.10; 95% CI , 1.05–1.15; P <0.001; I 2 =0%), whereas PCSK 9 inhibitors were not associated with incident DM (risk ratio: 1.00; 95% CI , 0.93–1.07; P =0.96; I 2 =0%; P =0.02 for interaction). Conclusions Among intensive lipid‐lowering therapies, there was no independent association between reduction in LDL cholesterol and incident DM . The risk of incident DM was higher with statins, whereas PCSK 9 inhibitors had no association with risk of incident DM .

Background: Although the consequences of bleeding after percutaneous coronary intervention (PCI) are well documented, there are no data on the impact of post-PCI anemia (PPA) on clinical outcomes. Methods: We evaluated the incidence, predictors, and prognostic implications of PPA on clinical outcomes in 1415 PCI procedures. We compared clinical outcomes of patients with PPA (ie, nadir post-PCI hemoglobin <10 gm/dL) vs without PPA. In patients with PPA, we assessed the influence of thrombolysis in myocardial infarction (TIMI; major or minor) bleeding, drop in hemoglobin by ≥3 gm/dL, and use of blood transfusions on outcomes.Results: Post-PCI anemia developed in 124 (8.8%) patients. Of these, 50 (40%) suffered TIMI (major or minor) bleeding, 68 (55%) had a hemoglobin drop of ≥3 gm/dL, and 39 (32%) patients received blood transfusions. Compared to patients without PPA, those with PPA had greater incidence of 6 month death (6.5% vs 1.7 %, p = 0.003), 6 month major adverse cardiovascular event (MACE; death, reinfarction, or target vessel revascularization; 27.3% vs 14.5%, p = 0.0006), and long-term mortality (25.8% vs 8.7 %, p≤0.0001). After adjustment for baseline differences, PPA showed an independent association with 6 month MACE (odds ratio [OR]: 2.4, 95% confidence interval [CI]: 1.5-3.9) and long-term mortality (hazard ratio [HR]: 1.3, 95% CI: 1.0-1.6). In patients who developed PPA, the occurrence of TIMI (major or minor) bleeding, hemoglobin drop of ≥3 gm/dL, and use of blood transfusions did not impact outcomes. conclusion: We found that PPA is common, occurs frequently in the absence of bleeding or significant drop in hemoglobin, and connotes poor long-term outcomes. IntroductionIn patients undergoing percutaneous coronary intervention (PCI) for stable or unstable coronary syndromes, antiplatelet and anticoagulant agents are frequently utilized to minimize ischemic complications. These agents are associated with significant risk of bleeding complications and anemia.