Low-dose neuroleptic therapy and relapse in schizophrenia: meta-analysis of randomized controlled trials

Abstract Introduction Coronary Artery Disease (CAD) is the single greatest cause of mortality and loss of disability adjusted life years (DALYs) worldwide. Inflammation plays a central role in the pathogenesis of atherosclerosis, with numerous evidence from prospective studies indicating that increasing C-reactive protein levels (hs-CRP) are independently associated with increasing risk of cardiovascular events. Colchicine, is an inexpensive, potent anti-inflammatory drug considered as a staple therapy for gout. Recent studies have shown that colchicine use may prove to be useful in the prevention of cardiovascular events. Purpose In patients with coronary artery disease (CAD) does administration of low dose colchicine lead to reduced all-cause mortality, cardiovascular risk and morbidity. Methods A meta-analysis was performed based on randomized controlled trials obtained from Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, Medline and Medline ahead of print published between 2000 and 2020. Main outcome measures include all-cause mortality, cardiovascular events, CRP levels and prevalence of CRP levels less than 2.0 mg/L. Data synthesis and analysis was done using RevMan 5.3 using a random effects model. Results A total of 5 randomized controlled trials, representing 5,430 patients were included in this meta-analysis. Three trials administered colchicine 1 mg/day while the rest were assigned colchicine. 5 mg/day. Administration of colchicine in CAD patients was found to reduce all-cause mortality (RR=0.66, 95% CI: 0.30 to 1.46, p=0.31) and major adverse cardiovascular events (MACE) (RR=0.61, 95% CI: 0.25 to 1.47, p=0.27), although results were non-significant. Reduced CRP levels (Mean difference = −0.88, 95% CI: −1.76 to 0.01, p=0.05) compared to control group as well as a higher prevalence of patients with CRP levels <2.0 mg/L were found (RR=2.27, 95% CI: 0.45 to 11.33, p=0.32), although results were non-significant. Discussion Few studies are available evaluating the benefits of low dose colchicine in CAD patients. The beneficial effects of colchicine has been proposed due to its ability to inhibit neutrophil chemotaxis which may reduce the risk of plaque instability. The use of colchicine for secondary prevention of CAD will require long-term use, which will require the need for preparations that address its intolerance (mostly gastrointestinal) to prevent early discontinuation of the medication. Conclusion There's limited evidence on the benefit of low dose colchicine in CAD patients. Further large scale randomized-controlled trials are needed, and its dose-response relationship ascertained before consideration of its use could be given in CAD patients. Funding Acknowledgement Type of funding source: None

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Platelet inhibition and clinical outcomes of low dose ticagrelor in patients with coronary artery disease: a meta-analysis of randomized controlled trials

10.21203/rs.3.rs-418616/v1 ◽

2021 ◽

Author(s):

Cheng Xie ◽

Xiaoliang Ding ◽

Qiong Qin ◽

Jia Lin ◽

Yuzhen Zhang

Keyword(s):

Randomized Controlled Trials ◽

Clinical Outcomes ◽

Fixed Effects ◽

Low Dose ◽

Platelet Reactivity ◽

Standard Dose ◽

Meta Analysis ◽

Platelet Inhibition ◽

Controlled Trials ◽

Randomized Controlled

Abstract Background Although current guidelines recommend ticagrelor 90 mg twice daily in ACS patients for 12 months and 60 mg twice daily in stable patients 1 to 3 years after MI with additional high-risk features, the bleeding complication was actually higher than clopidogrel. This meta-analysis was performed to assess the platelet inhibition and clinical outcomes of low dose ticagrelor in patients with CAD. Methods Medline, EMBASE and Cochrane Databases were systematically searched from inception to March, 2021 for randomized controlled trials (RCTs) comparing low dose ticagrelor with standard dose clopidogrel or standard dose ticagrelor in patients with CAD. Pooled estimates were calculated using fixed-effects or random-effects model as appropriate. Results 15 RCTs that included 15357 patients were identified. Low dose ticagrelor had no statistical differences of the risks of MACE and major bleeding compared with standard dose ticagrelor and standard dose clopidogrel (RR 0.98, 95%CI 0.87 − 1.11, P = 0.80; RR 1.35, 95%CI 0.46 − 4.00, P = 0.59; RR 0.86, 95%CI 0.68 − 1.10, P = 0.23; RR 1.46, 95%CI 0.45 − 4.76, P = 0.53, respectively). Compared with standard dose clopidogrel, low dose ticagrelor showed significantly lower platelet reaction units (PRU) (MD -118.48, 95%CI -144.33−-92.63, P ༜0.00001), rates of high on-treatment platelet reactivity (HTPR) (RR 0.10, 95%CI 0.04 − 0.21, P ༜ 0.00001) and minor or minimal bleeding (RR 0.73, 95%CI 0.55 − 0.96, P = 0.03), but increased the incidence of dyspnea (RR 6.48, 95%CI 1.78 − 23.54, P = 0.005). Compared with standard dose ticagrelor, low dose ticagrelor showed significantly higher PRU (MD 15.45, 95%CI 5.45 − 25.44, P = 0.002) and risk of dyspnea (RR 0.81, 95%CI 0.75 − 0.88, P ༜ 0.00001), but similar rates of HTPR (RR 1.63, 95%CI 0.40 − 6.70, P = 0.50) and minor or minimal bleeding (RR 1.36, 95%CI 0.78 − 2.38, P = 0.28). Conclusion Low dose ticagrelor may provide an additional choice for secondary prevention in CAD patients. However, the specific dose of ticagrelor should be selected according to the patients’ clinical characteristics.

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