scholarly journals Cholesteryl Ester Transfer Protein Inhibitors and Cardiovascular Outcomes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Cardiology ◽  
2020 ◽  
Vol 145 (4) ◽  
pp. 236-250 ◽  
Author(s):  
Hossein Taheri ◽  
Kristian B. Filion ◽  
Sarah B. Windle ◽  
Pauline Reynier ◽  
Mark J. Eisenberg
Keyword(s):  
Systematic Review ◽  
Cholesteryl Ester Transfer Protein ◽  
Cardiovascular Events ◽  
Density Lipoprotein ◽  
Cardiovascular Death ◽  
Controlled Trials ◽  
Transfer Protein ◽  
Randomized Controlled ◽  
Cetp Inhibitors ◽  
All Cause Mortality

Background: Cholesteryl ester transfer protein (CETP) inhibitors increase serum high-density lipoprotein cholesterol (HDL-c) concentration; however, their impact on cardiovascular outcomes is not clear. This systematic review examines the effect of CETP inhibitors on serum lipid profiles, cardiovascular events, and all-cause mortality. Methods: We searched MEDLINE, Embase, and the Cochrane Library of Clinical Trials for placebo-controlled randomized controlled trials (RCTs) that examined the effect of a CETP inhibitor (dalcetrapib, anacetrapib, evacetrapib, or TA-8995) on all-cause mortality, major adverse cardiovascular events (MACE), or the components of MACE at ≥6 months. Data were pooled using random-effects models. Results: A total of 11 RCTs (n = 62,431) were included in our systematic review; 4 examined dalcetrapib (n = 16,612), 6 anacetrapib (n = 33,682), and 1 evacetrapib (n = 12,092). Compared to dalcetrapib, ana­cetrapib and evacetrapib were more efficacious at raising HDL-c levels (∼100–130 vs. ∼30%). Anacetrapib and evacetrapib also decreased low-density lipoprotein cholesterol (LDL-c) by approximately 30% while dalcetrapib did not affect the LDL-c level. Overall, CETP inhibitors were not associated with the incidence of MACE (pooled relative risk [RR]: 0.97; 95% confidence interval [CI]: 0.91–1.04). CETP inhibitors may decrease the risks of nonfatal myocardial infarction (MI) (RR: 0.93; 95% CI: 0.87–1.00) and cardiovascular death (RR: 0.92; 95% CI: 0.83–1.01), though these trends did not reach statistical significance. Conclusions: CETP inhibitors are not associated with an increased risk of MACE or all-cause mortality. There is a trend towards small reductions in nonfatal MI and cardiovascular death, though the clinical im­portance of such reductions is likely modest.

Adenosine diphosphate receptor inhibitor monotherapy with ticagrelor or clopidogrel following percutaneous coronary intervention: a systematic review and meta-analysis of randomized controlled trials

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
H Haghbayan ◽  
D.P Durocher ◽  
E.A Coomes ◽  
S Lavi
Keyword(s):  
Systematic Review ◽  
Percutaneous Coronary Intervention ◽  
Meta Analysis ◽  
Adenosine Diphosphate ◽  
Coronary Intervention ◽  
Controlled Trials ◽  
Randomized Controlled ◽  
Percutaneous Coronary ◽  
All Cause Mortality ◽  
Receptor Inhibitor

Abstract Background and purpose In patients undergoing percutaneous coronary intervention (PCI) with implantation of coronary stents, the risk of stent thrombosis is mitigated with antiplatelet therapy. While current clinical practice is to treat patients with dual antiplatelet therapy (DAPT) combining aspirin with an adenosine diphosphate receptor inhibitor (ADPri), prolonged therapy is associated with heightened bleeding risk. Limiting DAPT to a shorter period after PCI, followed by ADPri monotherapy, may be an attractive strategy for optimizing the balance between thrombotic and bleeding risks. While several randomized controlled trials (RCTs) have been published examining this strategy, the optimal duration of abbreviated DAPT run-in and the ideal choice of ADPri remain uncertain. Methods We undertook a systematic review and meta-analysis of RCTs assessing abbreviated DAPT followed by ADPri monotherapy post coronary stenting. Our primary outcomes were defined as clinically important bleeding, major adverse cardiovascular events (MACE), and all-cause mortality. We searched Ovid MEDLINE and EMBASE from their inceptions to November 2019 with study selection and data extraction performed in duplicate. We pooled data at one year using random effects models; relative risks (RRs) with 95% confidence intervals (95% CIs) were generated using the inverse variance method. Pre-specified sub-group analyses were undertaken according to duration of DAPT and the primary ADPri employed. Results Four trials (n=29084) were eligible for inclusion. Mean age was 65 years and 51.5% of patients were recruited in the context of acute coronary syndrome. Following meta-analysis, the occurrence of clinically significant bleeding events was significantly lower in patients receiving ADPri monotherapy (4 studies; n=29084; RR=0.60; 95% CI, 0.43–0.83; I2=73%; Figure-A), with no significant difference in the rates of all-cause mortality (4 studies; n=29084; RR=0.87; 95% CI, 0.71–1.06; I2=0%; Figure-B) or MACE (4 studies; n=29084; RR=0.90; 95% CI, 0.79–1.03; I2=1%; Figure-C). In subgroup analysis, trends toward lower rates of both all-cause mortality (2 studies; n=23082 participants; RR=0.81; 95% CI, 0.65–1.01; I2=0%; Figure-B) and MACE (2 studies; n=23082 participants; RR=0.90; 95% CI, 0.79–1.03; I2=25%; Figure-C) were seen in the studies employing ticagrelor as opposed to clopidogrel; however, neither analysis reached statistical significance (p-values=0.06 and 0.19, respectively). There was no differential treatment effect based on the duration of abbreviated DAPT prior to ADPri monotherapy in sub-group analysis. Conclusions Following PCI in patients with coronary disease, an abbreviated course of DAPT followed by ADPri monotherapy significantly reduces rates of bleeding with no difference in rates of MACE or all-cause mortality. Future studies are required to conclusively determine whether the use of ticagrelor in this setting may also reduce rates of all-cause mortality. Meta-analysis of included studies Funding Acknowledgement Type of funding source: None

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