High-Maintenance-Dose Clopidogrel in Patients Undergoing Percutaneous Coronary Intervention: A Systematic Review and Meta-Analysis

<div><p>Background</p><p>Despite routine use of clopidogrel, adverse cardiovascular events recur among some patients undergoing percutaneous coronary intervention (PCI). To optimize antiplatelet therapies, we performed a meta-analysis to quantify the efficacy of high versus standard-maintenance-dose clopidogrel in these patients.</p> <p>Methods</p><p>Randomized controlled trials (RCTs) comparing high (>75 mg) and standard maintenance doses of clopidogrel in patients undergoing PCI were included. The primary efficacy and safety end-points were major adverse cardiovascular/cerebrovascular events (MACE/MACCE) and major bleeding. The secondary end-points were other ischemic and bleeding adverse effects. The pooled odds ratio (OR) for each outcome was estimated.</p> <p>Results</p><p>14 RCTs with 4424 patients were included. Compared with standard-maintenance-dose clopidogrel, high-maintenance-dose clopidogrel significantly reduced the incidence of MACE/MACCE (OR 0.60; 95% CI 0.43 to 0.83), stent thrombosis (OR 0.56; 95% CI 0.32 to 0.99) and target vessel revascularization (OR 0.38; 95% CI 0.20 to 0.74), without significant decrease of the risk of cardiovascular death (OR 0.92; 95% CI 0.74 to 1.13) and myocardial infarction (OR 0.83; 95% CI 0.51 to 1.33). For safety outcomes, it did not significantly increase the risk of major bleeding (OR 0.73; 95% CI 0.41 to 1.32), minor bleeding (OR 1.29; 95% CI 1.00 to 1.66) and any bleeding (OR 1.14; 95% CI 0.91 to 1.43).</p> <p>Conclusion</p><p>High-maintenance-dose clopidogrel reduces the recurrence of most ischemic events in patients post-PCI without increasing the risk of bleeding complications.</p> </div

Comparisons of high versus standard maintenance-dose clopidogrel on MACE/MACCE, ST and TVR.

<p>A: MACE/MACCE; B: ST; C: TVR. MACE: major adverse cardiac events; MACCE, major adverse cardiac and cerebrovascular events; ST: stent thrombosis; TVR: target vessel revascularization.</p

Funnel plots of MACE/MACCE for the comparison of high versus standard maintenance-dose clopidogrel.

<p>MACE: major adverse cardiac events; MACCE, major adverse cardiac and cerebrovascular events.</p

Comparisons of high versus standard maintenance-dose clopidogrel on bleeding complications.

<p>A: major bleeding; B: minor bleeding; C: any bleeding.</p

Flow chart of study selection.

<p>Flow chart of study selection.</p

Risk of bias graph.

<p>Risk of bias graph.</p

The quality of life of patients with chronic fanigue syndrome

<p>The blank group has no nutrients. The control groups have no PM_2.5. A&B, representative IL-6 detection; C&D, TNF-α detection. Significant difference **<i>p</i>< 0.01, *<i>p</i>< 0.05 vs. blank group; ^#<i>p</i> < 0.05, ^##<i>p</i> < 0.05 vs. previous group in the bar graph.</p

Combined action of vitamin E (Ve) and Ω-3 fatty acids (Ω-3 FA) (n = 3 per group).

<p>The blank group has no nutrients. The control groups have no PM_2.5. A1&A2, representative cell membrane integrity; B1-D2, oxidative stress of HUVECs; E1-F2, the level of inflammatory cytokines. Significant difference **<i>p</i>< 0.01, *<i>p</i>< 0.05 vs. blank group; ^#<i>p</i> < 0.05, ^##<i>p</i> < 0.05 vs. previous group in the bar graph.</p

In Vivo Delivery of Adenoviral Vector Containing Interleukin-17 Receptor A Reduces Cardiac Remodeling and Improves Myocardial Function in Viral Myocarditis Leading to Dilated Cardiomyopathy

<div><p>Th17 cells have been implicated in the pathogenesis of myocarditis. Interleukin (IL)-17A produced by Th17 cells is dispensable for viral myocarditis but essential for the progression to dilated cardiomyopathy (DCM). This study investigated whether the adenoviral transfer of the IL-17 receptor A reduces myocardial remodeling and dysfunction in viral myocarditis leading to DCM. In a mouse model of Coxsackievirus B3 (CVB3)-induced chronic myocarditis, the delivery of the adenovirus-containing IL-17 receptor A (Ad-IL17RA:Fc) reduced IL-17A production and decreased the number of Th17 cells in the spleen and heart, leading to the down-regulation of systemic TNF-α and IL-6 production. Cardiac function improved significantly in the Ad-IL17R:Fc- compared with the Ad-null-treated mice 3 months after the first CVB3 infection. Ad-IL17R:Fc reduced the left ventricle dilation and decreased the mortality in viral myocarditis, leading to DCM (56% in the Ad-IL17R:Fc versus 76% in the Ad-null group). The protective effects of Ad-IL17R-Fc on remodeling correlated with the attenuation of myocardial collagen deposition and the reduction of fibroblasts in CVB3-infected hearts, which was accompanied by the down-regulation of A distintegrin and metalloprotease with thrombospondin type 1 motifs (ADAMTS-1), Matrix metalloproteinase-2(MMP-2), and collagen subtypes I and III in the heart. Moreover, in cultured cardiac fibroblasts, IL-17A induced the expression of ADAMTS-1, MMP-2, and collagen subtypes I and III and increased the proliferation of fibroblasts. We determined that the delivery of IL-17-RA:Fc reduces cardiac remodeling, improves function, and decreases mortality in viral myocarditis leading to DCM, possibly by suppressing fibrosis. Therefore, the adenoviral transfer of the IL-17 receptor A may represent an alternative therapy for chronic viral myocarditis and its progression to DCM.</p></div

The levels of IL-6 and TNF-α in the supernatants of cardiac fibroblast cultures treated with IL-17.

<p>The IL-17 (10 ng/ml)-treated group produced higher levels of IL-6 and TNF-α cytokines than the control- and IL-17 (5 ng/ml)-treated groups. Moreover, IL-6 in the IL-17 (5 ng/ml)-treated group was highly expressed in the supernatants of the heart homogenates (ELISA). The values in the IL-17-treated CFs were normalized to the values in the control cells (n = 5 per group). The data represent the mean ± SEM. **<i>P</i><0.01 vs control group, ^##<i>P</i><0.01 vs control group.</p