Xiao-Min Jiang

Stenting strategy for coronary artery bifurcation with drug-eluting stents: a meta-analysis of nine randomised trials and systematic review.

AIMS The present study sought to compare angiographic and clinical outcomes of a simple strategy versus a complex strategy in patients with coronary bifurcation lesions undergoing drug-eluting stent implantation. METHODS AND RESULTS Medline, the Cochrane Library, and other internet sources were searched for randomised trials comparing simple strategy versus complex strategy for treating patients with bifurcation lesions. Nine eligible randomised trials including 2,569 patients were identified. The meta-analysis showed that cardiac death (odds ratio [OR]: 0.99, 95% confidence interval [CI]: 0.40- 2.41, p=0.98) and stent thrombosis (OR: 0.64, 95% CI: 0.31-1.34, p=0.24) were similar in the simple and the complex strategy. Compared with the complex strategy, the simple strategy was associated with a reduced risk of either early or follow-up myocardial infarction (OR: 0.53, 95% CI: 0.36-0.79, p=0.002; OR: 0.60, 95% CI: 0.43-0.86, p=0.01, respectively). The overall risks of side branch restenosis (OR: 1.44, 95% CI: 0.73-2.87, p=0.30), target lesion (OR: 1.72, 95% CI: 0.95-3.12, p=0.07) and target vessel revascularisation (OR: 1.59, 95% CI: 0.94-2.69, p=0.09) were comparable between the two groups. In the true bifurcation, with large side branches, and DK-crush subgroups, there were higher rates of reintervention seen in the simple strategy than in the complex strategy. CONCLUSIONS A complex strategy remains an optional treatment for patients with coronary bifurcation lesions without severe safety concerns. A complex strategy may be an optimal treatment for true bifurcation lesions with large side branches.

Antithrombotic Regimens for Patients Taking Oral Anticoagulation After Coronary Intervention: A Meta‐analysis of 16 Clinical Trials and 9185 Patients

The optimal antithrombotic regimen remains controversial in patients taking oral anticoagulation (OAC) undergoing coronary stenting. This study sought to compare efficacy and safety outcomes of triple therapy (OAC, aspirin, and clopidogrel) vs dual therapy (clopidogrel with aspirin or OAC) in these patients. We hypothesize OAC plus clopidogrel could be the optimal regimen for patients with indications for OAC receiving stent implantation. Medline, the Cochrane Library, and other Internet sources were searched for clinical trials comparing the efficacy and safety of triple vs dual therapy for patients taking OAC after coronary stenting. Sixteen eligible trials including 9185 patients were identified. The risks of major adverse cardiac events (odds ratio [OR]: 1.06, 95% confidence interval [CI]: 0.82‐1.39, P = 0.65), all‐cause mortality (OR: 0.98, 95% CI: 0.76‐1.27, P = 0.89), myocardial infarction (OR: 1.01, 95% CI: 0.77‐1.31, P = 0.97), and stent thrombosis (OR: 0.91, 95% CI: 0.49‐1.69, P = 0.75) were similar between triple and dual therapy. Compared with dual therapy, triple therapy was associated with a reduced risk of ischemic stroke (OR: 0.57, 95% CI: 0.35‐0.94, P = 0.03) but with higher major bleeding (OR: 1.52, 95% CI: 1.11‐2.10, P = 0.01) and minor bleeding (OR: 1.59, 95% CI: 1.05‐2.42, P = 0.03). Subgroup analysis indicated there were similar ischemic stroke and major bleeding outcomes between triple therapy and therapy with OAC plus clopidogrel. Treatment with OAC and clopidogrel was associated with similar efficacy and safety outcomes compared with triple therapy. Triple therapy could be replaced by OAC plus clopidogrel without any concern about additional risk of thrombotic events.

Pulmonary Artery Denervation Attenuates Pulmonary Arterial Remodeling in Dogs With Pulmonary Arterial Hypertension Induced by Dehydrogenized Monocrotaline.

OBJECTIVES This study aimed to investigate sympathetic nerve (SN) ultrastructural changes and hemodynamic and pulmonary artery (PA) pathological improvements by pulmonary arterial denervation (PADN) in animals with pulmonary arterial hypertension (PAH), as well as the underlying mechanisms. BACKGROUND SN overactivity plays a role in PAH. Previous studies have reported short-term improvements in pulmonary arterial pressure (PAP) and cardiac function by PADN, but PA remodeling and the associated mechanisms remain unclear. METHODS Forty dogs were randomly (ratio of 1:3) assigned to the control (intra-atrial injection of N-dimethylacetamide, 3 mg/kg) and test (intra-atrial injection of dehydrogenized-monocrotaline, 3 mg/kg) groups. After 8 weeks, the animals in the test group with a mean PAP >25 mm Hg (n = 20) were randomized (ratio of 1:1) into the sham and PADN groups. At 14 weeks, the hemodynamics, medial wall thickness and PA muscularization, and messenger ribonucleic acid expression of genes in lung tissues were measured. Another 35 PAH dogs were used to measure the SN conduction velocity, electron microscopic assessment, and nerve distribution. RESULTS PADN induced significant SN demyelination and axon loss and slowed SN conduction velocity over time, with resulting profound reductions in the mean PAP (23.5 ± 2.3 mm Hg vs. 33.7 ± 5.8 mm Hg), pulmonary vessel resistance (3.5 ± 2.3 Wood units vs. 7.7 ± 1.7 Wood units), medial wall thickness (22.3 ± 3.3% vs. 30.4 ± 4.1%), and full muscularization (40.3 ± 9.3% vs. 57.1 ± 5.7%) and increased nonmuscularization (29.8 ± 6.1% vs. 12.9 ± 4.9%) compared with the Sham group (all p < 0.001). PADN inhibited the messenger ribonucleic acid expression of genes correlated with inflammation, proliferation, and vasoconstriction. CONCLUSIONS PADN induces permanent SN injury and subsequent improvements in hemodynamics and PA remodeling in animals with PAH through mechanisms that may be experimentally and clinically beneficial.

Obstructive sleep apnea affects the clinical outcomes of patients undergoing percutaneous coronary intervention

Background There is a paucity of evidence regarding the association between obstructive sleep apnea (OSA) and patients undergoing percutaneous coronary intervention (PCI) for coronary artery disease. We sought to investigate whether OSA affects the clinical outcomes of patients undergoing PCI. Patients and methods All enrolled individuals treated with PCI were evaluated for OSA by polysomnography. The primary end point was defined as major adverse cardiac events (MACEs) at 2 years, including cardiac death, myocardial infarction (MI), and/or target vessel revascularization. Results A total of 340 consecutive patients undergoing PCI were assigned to the OSA (n=152, apnea–hypopnea index ≥15) and non-OSA (n=188, apnea–hypopnea index <15) groups. The incidence of OSA in patients with coronary artery disease undergoing PCI was 44.7%. Patients in the OSA group had more three-vessel disease (34.9%), increased number of total implanted stents (3.3±2.0), and longer total stent length (83.8±53.1 mm) when compared to the non-OSA group (23.4%, P=0.020; 2.8±1.9, P=0.007; 68.7±48.4, P=0.010). After a median follow-up of 2 years, the incidence of MACEs was significantly higher in patients with OSA (25.0% vs 16.0%, P=0.038), mainly driven by the increased periprocedural MI (19.2% vs 11.2%, P=0.038) in the OSA group. By Cox regression multivariable analysis, the independent predictor of MACEs was OSA (hazard ratio: 1.962, 95% confidence interval: 1.036–3.717, P=0.039). Conclusion There was a high prevalence of moderate-to-severe OSA in patients undergoing PCI, and OSA was associated with significantly increased MACE rate, mainly due to the increase in periprocedural MI rate.

Obstructive Sleep Apnea Affecting Platelet Reactivity in Patients Undergoing Percutaneous Coronary Intervention

Background: The relationship between obstructive sleep apnea (OSA) and platelet reactivity in patients undergoing percutaneous coronary intervention (PCI) has not been defined. The present prospective, single-center study explored the relationship between platelet reactivity and OSA in patients with PCI. Methods: A total of 242 patients were finally included in the study. OSA was screened overnight by polysomnography. Platelet reactivity was assessed with a sequential platelet counting method, and the platelet maximum aggregation ratio (MAR) and average aggregation ratio were calculated. All patients were assigned per apnea-hypopnea index (AHI) to non-OSA (n = 128) and OSA (n = 114) groups. The receiver operating characteristic curve analysis was used to evaluate the accuracy of AHI for high platelet reactivity (HPR) on aspirin and clopidogrel, and multivariable logistic regression was used to determine the independent predictors of HPR on aspirin and clopidogrel. Results: Median AHI was significantly higher in the OSA group than in the non-OSA group (34.5 events/h vs. 8.1 events/h, Z = −13.422, P < 0.001). Likewise, median arachidonic acid- and adenosine diphosphate-induced maximum aggregation rate (MAR) in the OSA group was significantly higher than those in the non-OSA group (21.1% vs. 17.7%, Z = −3.525, P < 0.001 and 45.8% vs. 32.2%, Z = −5.708, P < 0.001, respectively). Multivariable logistic regression showed that OSA was the only independent predictor for HPR on aspirin (odds ratio [OR]: 1.055, 95% confidence interval [CI]: 1.033–1.077, P < 0.001) and clopidogrel (OR: 1.036, 95% CI: 1.017–1.056, P < 0.001). The cutoff value of AHI for HPR on aspirin was 45.2 events/h (sensitivity 47.1% and specificity 91.3%), whereas cutoff value of AHI for HPR on clopidogrel was 21.3 events/h (sensitivity 68.3% and specificity 67.7%). Conclusion: Platelet reactivity appeared to be higher in OSA patients with PCI despite having received a loading dose of aspirin and clopidogrel, and OSA might be an independent predictor of HPR on aspirin and clopidogrel.

Targeted drugs for pulmonary arterial hypertension: a network meta-analysis of 32 randomized clinical trials

Background Pulmonary arterial hypertension (PAH) is a devastating disease and ultimately leads to right heart failure and premature death. A total of four classical targeted drugs, prostanoids, endothelin receptor antagonists (ERAs), phosphodiesterase 5 inhibitors (PDE-5Is), and soluble guanylate cyclase stimulator (sGCS), have been proved to improve exercise capacity and hemodynamics compared to placebo; however, direct head-to-head comparisons of these drugs are lacking. This network meta-analysis was conducted to comprehensively compare the efficacy of these targeted drugs for PAH. Methods Medline, the Cochrane Library, and other Internet sources were searched for randomized clinical trials exploring the efficacy of targeted drugs for patients with PAH. The primary effective end point of this network meta-analysis was a 6-minute walk distance (6MWD). Results Thirty-two eligible trials including 6,758 patients were identified. There was a statistically significant improvement in 6MWD, mean pulmonary arterial pressure, pulmonary vascular resistance, and clinical worsening events associated with each of the four targeted drugs compared with placebo. Combination therapy improved 6MWD by 20.94 m (95% confidence interval [CI]: 6.94, 34.94; P=0.003) vs prostanoids, and 16.94 m (95% CI: 4.41, 29.47; P=0.008) vs ERAs. PDE-5Is improved 6MWD by 17.28 m (95% CI: 1.91, 32.65; P=0.028) vs prostanoids, with a similar result with combination therapy. In addition, combination therapy reduced mean pulmonary artery pressure by 3.97 mmHg (95% CI: −6.06, −1.88; P<0.001) vs prostanoids, 8.24 mmHg (95% CI: −10.71, −5.76; P<0.001) vs ERAs, 3.38 mmHg (95% CI: −6.30, −0.47; P=0.023) vs PDE-5Is, and 3.94 mmHg (95% CI: −6.99, −0.88; P=0.012) vs sGCS. There were no significant differences in all-cause mortality and severe adverse events between prostanoids, ERAs, PDE-5Is, sGCS, combination therapy, and placebo. Conclusion All targeted drugs for PAH are associated with improved clinical outcomes, especially combination therapy. However, all these drugs seem to show less favorable effects on survival in the short-term follow-up, suggesting further clinical trials are required.

Efficacy and safety of oral targeted therapies in pulmonary arterial hypertension: a meta-analysis of randomized clinical trials

Oral targeted therapies play an important role in the treatment of pulmonary arterial hypertension (PAH). Several new oral agents have emerged for PAH in recent years. However, whether they provide a survival advantage is still not clear. This meta-analysis aimed to assess the efficacy and safety of oral targeted therapies, especially on predefined clinical worsening events. Trials were searched in the Cochrane Library, EMBASE, and PUBMED databases through June 2018. We calculated risk ratios for dichotomous data and weighted mean differences with 95% confidence intervals (CI) for continuous data. Twenty-five trials with a total of 6847 participants were included in the meta-analysis. Oral targeted therapies were associated with significant risk reduction in clinical worsening compared with placebo (relative risk [RR] 0.64; 95% CI = 0.58–0.70; P < 0.001). This reduction in risk was driven by reduction in non-fatal endpoints, including PAH-related admissions to hospital (RR = 0.66; 95% CI = 0.56–0.76; P < 0.001), treatment escalation (RR = 0.43; 95% CI = 0.28–0.66; P < 0.001), and symptomatic progression (RR = 0.55; 95% CI = 0.48–0.64; P < 0.001), but not by reduction of mortality (RR = 0.87; 95% CI = 0.68–1.12; P = 0.215). Oral targeted therapies were also associated with improvement in 6-min walk distance (26.62 m; 95% CI = 20.54–32.71; P < 0.001) and World Health Organization functional class (RR = 1.36; 95% CI = 1.20–1.54; P < 0.001). The results of this meta-analysis showed the benefits of oral treatments on clinical worsening events in PAH. However, these oral agents did not show any survival benefit in the short-term follow-up.

Berberine attenuates pulmonary arterial hypertension via protein phosphatase 2A signaling pathway both in vivo and in vitro: LUO et al.

Excessive proliferation, migration, and antiapoptosis of pulmonary artery (PA) smooth muscle cells (PASMCs) underlies the development of pulmonary vascular remodeling. The innervation of the PA is predominantly sympathetic, and increased levels of circulating catecholamines have been detected in pulmonary arterial hypertension (PAH), suggesting that neurotransmitters released by sympathetic overactivation may play an essential role in PAH. However, the responsible mechanism remains unclear. Here, to investigate the effects of norepinephrine (NE) on PASMCs and the related mechanism, we used 3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyl‐2‐H‐tetrazolium bromide, the proliferating cell nuclear antigen and the cell counting kit‐8 assay to evaluate the proliferation of PASMCs, Boyden chamber migration, and wound‐healing assays to assess migration and western blot analysis to investigate protein expression. We demonstrated that the phosphorylation level of the protein phosphatase 2A (PP2A) catalytic subunit (Y307) was higher in PAH patients and PAH models than in controls, both in vivo and in vitro. In addition, NE induced the proliferation and migration of PASMCs, which was attenuated by berberine (BBR), a Chinese herbal medicine, and/or PP2A overexpression. PP2A inhibition worsened NE‐induced PAH and could not be reversed by BBR. Thus, PP2A is critical in driving PAH, and BBR may alleviate PAH via PP2A signaling pathways, thereby offering a potential therapeutic option for PAH.