scholarly journals Colchicine as an Adjuvant Therapy for Coronary Artery Disease: A Systematic Review

Author(s):  
Nobian Andre ◽  
Patricia Renata ◽  
Muhamad Hafiz Mahruzza ◽  
Rony Marethianto Santoso

Background:Inflammation plays a significant role in atherosclerosis at all phases. Colchicine is a pleiotropic anti-inflammatory agent that may be beneficial in various stages of coronary artery disease (CAD). Methods:We searched for literatures in PubMed, Cochrane Library, ScienceDirect, and Proquest regarding the use of colchicine on top of current optimal medical therapy for CAD. Results: Twelve studies were identified: three studies in stable CAD patients and the remaining nine assessed in acute coronary syndrome (ACS) and post-ACS patients. The majority of studies used a colchicine dose of 0.5 mg/day. Adjuvant colchicine of 0.5 mg daily reduced the risk of developing ACS, cardiac arrest, or ischemic stroke in stable CAD: HR (hazard risk) 0.33 (95% CI 0.18-0.59), p<0.001. Patients admitted with ACS who received a 2 mg loading dose of colchicine pre-percutaneous coronary intervention (PCI) showed smaller infarct size than control: 18.3 (IQR 7.6-29.9) ml/1.73 m2vs 23.2 (18.5-33.4) ml/1.73 m2(p=0.019).In post-ACS patients, adjuvant colchicine of 0.5 mg daily significantly reduced the rate of ischemic cardiovascular events: HR 0.77 (95% CI 0.61-0.96), p=0.02. Conclusion: Stable CAD patients benefit from 0.5 mg daily dose of adjuvant colchicine to reduce the incidence of future cardiovascular events. For patients presenting with ACS, a loading dose of 2 mg of colchicine pre-PCI followed by a week of 0.5 mg colchicine twice daily on top of optimal medical care can reduce infarct size. This should be followed by consumption of 0.5 mg daily dose of adjuvant colchicine post-ACS for at least 20 months to prevent future reinfarctions.

2019 ◽  
Vol 46 (04) ◽  
pp. 446-456
Author(s):  
Mads Lamm Larsen ◽  
Erik Lerkevang Grove ◽  
Steen Dalby Kristensen ◽  
Anne-Mette Hvas

AbstractThe trade-off between the benefits and harm of long-term (> 12 months) treatment with P2Y12 inhibitors in patients with coronary artery disease (CAD) after percutaneous coronary intervention (PCI) remains controversial. This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. PubMed and Embase were searched without time restrictions to identify randomized controlled trials comparing > 12-month P2Y12 inhibition versus ≤ 12-month treatment in patients with acute coronary syndrome (ACS) or stable CAD undergoing PCI. A qualitative assessment was performed using the assessment tool from the National Heart, Lung, and Blood Institute of the National Institutes of Health. We performed a meta-analysis of the following endpoints: primary outcome (primarily major cardiovascular events), all-cause death, and major bleeding. Eight trials, comprising 40,218 patients, were included. Five studies were rated “good,” two studies “fair,” and one study “poor.” The meta-analysis showed that > 12-month P2Y12 inhibition significantly reduced the primary outcomes compared with ≤ 12-month treatment (hazard ratio [HR]: 0.85; 95% confidence interval (CI): 0.75–0.97; p = 0.01). No significant difference was demonstrated between groups in all-cause death (HR: 1.02; 95% CI: 0.76–1.36; p = 0.91) or major bleedings (HR: 1.26; 95% CI: 0.93–1.70; p = 0.14). I 2 test showed low to moderate heterogeneity among the included studies (21.6–62.3%). This systematic review and meta-analysis therefore demonstrates a reduction in major cardiovascular events during extended P2Y12-inhibitor treatment beyond 12 months compared with ≤ 12 months in patients with ACS or stable CAD undergoing PCI. There was no significant difference in all-cause death or major bleedings.


2019 ◽  
Vol 116 (6) ◽  
pp. 1113-1124 ◽  
Author(s):  
Amanpreet Kaur ◽  
Sharon T Mackin ◽  
Kenny Schlosser ◽  
Fui Lin Wong ◽  
Malik Elharram ◽  
...  

Abstract The aim of this systematic review was to assess dysregulated miRNA biomarkers in coronary artery disease (CAD). Dysregulated microRNA (miRNAs) have been shown to be linked to cardiovascular pathologies including CAD and may have utility as diagnostic and prognostic biomarkers. We compared miRNAs identified in acute coronary syndrome (ACS) compared with stable CAD and control populations. We conducted a systematic search of controlled vocabulary and free text terms related to ACS, stable CAD and miRNA in Biosis Previews (OvidSP), The Cochrane Library (Wiley), Embase (OvidSP), Global Health (OvidSP), Medline (PubMed and OvidSP), Web of Science (Clarivate Analytics), and ClinicalTrials.gov which yielded 7370 articles. Of these, 140 original articles were appropriate for data extraction. The most frequently reported miRNAs in any CAD (miR-1, miR-133a, miR-208a/b, and miR-499) are expressed abundantly in the heart and play crucial roles in cardiac physiology. In studies comparing ACS cases with stable CAD patients, miR-21, miR-208a/b, miR-133a/b, miR-30 family, miR-19, and miR-20 were most frequently reported to be dysregulated in ACS. While a number of miRNAs feature consistently across studies in their expression in both ACS and stable CAD, when compared with controls, certain miRNAs were reported as biomarkers specifically in ACS (miR-499, miR-1, miR-133a/b, and miR-208a/b) and stable CAD (miR-215, miR-487a, and miR-502). Thus, miR-21, miR-133, and miR-499 appear to have the most potential as biomarkers to differentiate the diagnosis of ACS from stable CAD, especially miR-499 which showed a correlation between the level of their concentration gradient and myocardial damage. Although these miRNAs are potential diagnostic biomarkers, these findings should be interpreted with caution as the majority of studies conducted predefined candidate-driven assessments of a limited number of miRNAs (PROSPERO registration: CRD42017079744).


Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Paulo V Camargo ◽  
Raquel M Roman ◽  
Ana Paula W Rossini ◽  
Anderson Dedonelli ◽  
Steffan F Stella ◽  
...  

Background: The balance between pro-inflammatory cytokine IL-18 and anti-inflammatory cytokine IL-10 has been suggested to play a role in atherogenesis and in the prognosis of acute coronary syndrome (ACS). We hypothesized that stable coronary artery disease (CAD) patients have a pro-inflammatory profile prior to an acute event. Methods : A case-control study nested in a cohort of stable CAD patients was performed. Patients were consecutively included and blood samples collected at 3-months intervals. Cases were patients who presented any vascular event (death, ACS, ischemic stroke, peripheral arterial occlusion and revascularization) and controls were retrieved from a sequential list, in a 1:2 ratio, after 22 ± 9 months of follow-up. Serum hs-CRP, interleukin (IL)-10, IL-18 were measured in two serial samples, collected before the events. Results : Among 176 CAD patients, 42 developed a vascular event (cases) and 76 were selected to the control group. Serum levels of IL-18 were significantly higher among cases (411 ± 185 vs. 340 ± 133pg/ml; p = 0.037). Hs-CRP levels (5.4 vs. 5.1mg/l), IL-10 (7.4 vs. 7.2pg/ml), and IL-18/IL-10 ratio (66 vs. 61) were not different between cases and controls in both samples. Cox regression analysis showed that IL-18 levels (HR 1.75 (0.89 –3.5;p = 0.11) and IL-18/IL-10 ratio (HR 1.97; 1.0 –3.8) were predictors of worse prognosis (Figure ). Conclusion: In this study, IL-18 and IL-18/IL-10 ratio were associated with clinical outcomes and support the hypothesis that the balance between pro-inflammatory and anti-inflammatory cytokines may be an important determinant of vascular events in stable CAD patients.


2012 ◽  
Vol 58 (6) ◽  
pp. 1055-1058 ◽  
Author(s):  
Georg Goliasch ◽  
Arvand Haschemi ◽  
Rodrig Marculescu ◽  
Georg Endler ◽  
Gerald Maurer ◽  
...  

Abstract BACKGROUND Low serum butyrylcholinesterase activity was associated with all-cause and cardiovascular mortality in a community-based study; however, there are no data from investigations of the long-term effects of butyrylcholinesterase on mortality in patients with diagnosed coronary artery disease (CAD). We therefore assessed the effect of butyrylcholinesterase activity on the outcomes of patients with CAD. METHODS AND RESULTS We prospectively included 720 patients in our study: 293 patients with stable CAD and 427 patients with acute coronary syndrome. During a median follow-up of 11.3 years corresponding to 6469 overall person-years, 278 deaths (38.6%) were recorded. We detected a significant and independent protective effect of butyrylcholinesterase on all-cause mortality [adjusted hazard ratio (HR) for a 1-SD increase, 0.62; 95% CI, 0.54–0.71; P &lt; 0.001] and cardiovascular mortality (adjusted HR, 0.64; 95% CI, 0.54–0.76; P &lt; 0.001) in a Cox proportional hazards regression analysis. The 10-year survival rates were 42%, 74%, and 87% in the first, second, and third tertiles of butyrylcholinesterase activity. The presentation of CAD affected the effect of butyrylcholinesterase on mortality (P for interaction = 0.012), with a stronger association found in patients with stable CAD (adjusted HR, 0.56; 95% CI, 0.45–0.70; P &lt; 0.001). CONCLUSIONS Our study demonstrates a strong inverse association between butyrylcholinesterase activity and long-term outcome in patients with known CAD. Because butyrylcholinesterase added predictive information after adjustment for established cardiovascular risk factors, additional underlying pathophysiological mechanisms and the potential applicability of butyrylcholinesterase activity for secondary risk prediction needs to be addressed in future studies.


2019 ◽  
Vol 32 (12) ◽  
pp. 1199-1205 ◽  
Author(s):  
Eugenia Gkaliagkousi ◽  
Eleni Gavriilaki ◽  
Ioannis Vasileiadis ◽  
Barbara Nikolaidou ◽  
Efthalia Yiannaki ◽  
...  

Abstract BACKGROUND Endothelial microvesicles (EMVs) have emerged as markers of endothelial injury. However, little is known about their levels in the coronary circulation of acute coronary syndrome (ACS) and stable coronary artery disease (CAD). We hypothesized that ACS patients exhibit a more pronounced increase of EMVs both in the peripheral and coronary circulation when compared with CAD. We also investigated possible associations of EMVs with markers preclinical target organ damage. METHODS We enrolled consecutive eligible patients undergoing coronary angiography. Blood samples were collected from the stem of the left coronary artery and the femoral artery. ΕMVs were measured by a standardized flow cytometry protocol. Central systolic blood pressure (cSBP) was measured invasively and patients’ history was recorded. RESULTS CAD patients exhibited increased levels of EMVs compared with controls. When patients with ACS and stable CAD were compared, the former had significantly increased EMVs in both coronary and peripheral circulation. Importantly, both ACS and CAD patients exhibited increased levels of EMVs in the coronary circulation compared with periphery. In addition, EMVs were associated with cSBP. CONCLUSIONS EMVs emerge as novel markers of ongoing underlying vascular damage, further augmenting the vicious cycle of inflammation and thrombosis mainly in ACS but also in stable CAD.


Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Hirofumi Hioki ◽  
Takashi Miura ◽  
Yusuke Miyashita ◽  
Souichirou Ebisawa ◽  
Hirohiko Motoki ◽  
...  

Background: Until now, Omega-3/Omega-6 polyunsaturated fatty acid (PUFA) ratio, particularly in ratio of eicosapentaenoic acid (EPA) to arachnidonic acid (AA), has been reported to associate with the incidence of cardiovascular events. However, the clinical impact of monounsaturated fatty acid (MUFA) on cardiovascular events has not been well understood. Objective: In this study, we evaluate whether ratio of MUFA to PUFA, especially EPA/Oleic acid (OA), could predict clinical outcome in patients with coronary artery disease (CAD) who underwent percutaneous coronary intervention (PCI). Methods: SHINANO registry was prospective, observational, multicenter cohort study, enrolling 1,923 consecutive patients with CAD. From this registry, we identified 182 patients who measured fatty acid on admission. We stratified according to median of EPA/OA ratio. The primary endpoint was net adverse clinical events (NACE) including cardiac death, nonfatal myocardial infarction, ischemic stroke, PCI for ACS, heart failure, and major bleeding (Bleeding Academic Research Consortium II-IV) for 1-years. Results: Mean age was 72±10 years, 24% female, and 27% was acute coronary syndrome. One-years follow-up was completed in 181 patients (99.5%). Cumulative incidence of NACE was 22 cases. In Kaplan-Meier analysis, incidence of NACE was significantly higher in patients with EPA/OA of 0.03 to 0.12 compared to 0.13 to 0.54 (16.6% vs. 6.6%, Log-rank p=0.025). After adjusting for the calculated propensity score for EPA/OA ≥ 0.13 or not, EPA/OA ≥ 0.13 was remained an independent predictor of NACE (hazard ratio, 0.36; 95% confidence interval [CI], 0.14-0.96; p-value 0.042). The ROC curve of EPA/OA for NACE demonstrated that the area under the ROC curve (ACU) was 0.73 (95% CI; 0.61-0.85). Conclusions: This study firstly demonstrated that the patients with high EPA/OA ratio would have low incidence of NACE in patients with CAD who underwent PCI.


2008 ◽  
Vol 99 (01) ◽  
pp. 142-149 ◽  
Author(s):  
Anetta Undas ◽  
Matthew T Gissel ◽  
Konstanty Szuldrzynski ◽  
Krzysztof Zmudka ◽  
Kenneth G Mann ◽  
...  

SummaryIt has been established that inflammation and enhanced procoagulant activity are associated with the pathogenesis of atherosclerotic vascular disease. We evaluated and compared the contributions of the factor (F)XIa and tissue factor (TF) activity in plasma of patients with coronary artery disease (CAD). Citrate plasma was obtained prior to therapy from 53 patients with stable angina (29 with a history of previous myocardial infarction; CAD-MI) and 30 with acute coronary syndrome (ACS) within 12 hours from pain onset. Four ACS patients treated with heparin were excluded. FXIa andTF activity were determined in clotting assays based upon the prolongation of clotting time by inhibitory monoclonal antibodies. Twenty-five of 26ACS patients (96%) and 22 of 29 CAD-MI patients (76%) had quantifiable FXIa (50 ± 33 and 42 ± 45pM, respectively).Ten of 26 (38%) ACS patients and only three of 53 (6%) stable CAD patients showedTF activity (<0.4pM). No FXIa or TF activity was observed in agematched healthy controls (n=12).For both CAD-MI andACS patients, there were correlations (p<0.05) between FXIa and interleukin-6 (R2= 0.59 and 0.39, respectively) and between FXIa and TAT (R2= 0.64 and 0.63, respectively). In conclusion, the majority of ACS and CAD-MI patients have circulating FXIa that correlates with markers of coagulation and inflammation.


2007 ◽  
Vol 98 (08) ◽  
pp. 413-419 ◽  
Author(s):  
Pal Soltesz ◽  
Katalin Veres ◽  
Renata Laczik ◽  
Henrietta Der ◽  
Istvan Csipo ◽  
...  

SummaryThe aim was to measure the level of antibodies to oxidized LDL (oxLDL) and C-reactive protein (CRP) in the serum of patients with acute coronary syndrome (ACS). The results were correlated with data obtained from patients with stable coronary artery disease (stable CAD) and healthy controls.Thirty-three patients with ACS and 62 stable CAD patients were enrolled in the study. Fifty healthy individuals served as controls.The evaluation of anti-oxLDL autoantibodies was performed by ELISA, while CRP levels were measured by turbidimetry. The level of antibodies to oxLDL was significantly higher in both groups of patients with ACS and stable CAD compared to controls.The comparison between the acute and stable groups showed that anti-oxLDL levels were higher in the acute group,but because of high SD, the difference was not significant. By performing group analysis, anti-oxLDL levels were found to be significantly higher in ACS patients with unstable clinical state (circulatory insufficiency, malignant arrhythmias, recurring ischemic pain, need for urgent coronary intervention and death). CRP level in patients with ACS was significantly higher than in those with stable CAD. A positive correlation was found between anti-oxLDL antibodies and CRP levels both in patients with ACS and stable CAD. The association between the two biomarkers was stronger in the ACS group. In conclusion, our findings support the notion that the presence of antibodies to oxLDL, a plaquespecific antigen, plays a major role as a predictor of complicated manifestations of ACS.


2016 ◽  
Vol 22 (2) ◽  
pp. 142-152 ◽  
Author(s):  
Qiang Niu ◽  
Zhongsu Wang ◽  
Yong Zhang ◽  
Jiangrong Wang ◽  
Pei Zhang ◽  
...  

Background: Published data indicated that combination use of clopidogrel and proton pump inhibitors (PPIs) may increase the incidence of major adverse cardiovascular events (MACEs). This has been a highly controversial topic for years. Design: The present study was performed to evaluate whether combination therapy of clopidogrel and PPIs is associated with increased risk of MACEs than with clopidogrel alone in patients with coronary artery disease. Methods: A systematic search of MEDLINE, EMBASE, and the Cochrane Library was conducted for studies recording the occurrence of MACEs in patients with exposure to concomitant use of clopidogrel and PPIs up to February 2015. Odds ratios (ORs) were combined using a random-effects model. Results: Patients receiving combination therapy with PPIs and clopidogrel were at significantly increased risk of MACEs (OR: 1.42; 95% confidence interval [CI]: 1.30-1.55). Adding a PPI to clopidogrel treatment was associated with a higher rate of MACE occurrence in rapid metabolizers (RMs, *1/*1) of CYP2C19 (OR: 1.42; 95% CI: 1.12-1.81), but there was no obviously increased rate (OR: 1.43; 95% CI: 0.89-2.28) in decreased metabolizers (with 1 or 2 loss-of-function allele). The increased risk of MACEs was similar in 4 classes of PPIs (omeprazole, lansoprazole, esomeprazole, and pantoprazole), but rabeprazole (OR: 1.03; 95% CI: 0.55-1.95) wasn’t. Conclusion: The combination use of clopidogrel and certain types of PPIs (omeprazole, lansoprazole, esomeprazole, pantoprazole) increases the risk of MACE in patients with coronary artery disease. Only in the RMs of CYP2C19, PPIs were associated with significantly increased MACE in patients coadministered with clopidogrel.


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