School of Cardiovascular Medicine and Sciences, James Black Centre, King's College London BHF Centre of Excellence, 125 Coldharbour Lane, London, SE5 9NU, UK.
Institute of Cardiovascular Science, University College London, London, UK.
Basic Res Cardiol. 2019 Oct 31;114(6):48. doi: 10.1007/s00395-019-0754-x.
Current myocarditis guidelines do not advocate treatment to prevent myocardial injury and scar deposition in patients with myocarditis and normal left ventricular ejection fraction. We aimed to ascertain the utility of beta blockers, calcium channel blockers and antagonists of the renin-angiotensin system in ameliorating myocardial injury, scar formation and calcification in animal in vivo models of myocarditis. The project was prospectively registered with the PROSPERO database of systematic reviews (CRD42018089336). Primary outcomes (necrosis, fibrosis and calcification) were meta-analysed with random-effects modelling. 52 studies were systematically reviewed. Meta-analysis was performed compared with untreated controls. In each study, we identified all independent comparisons of treatment versus control groups. The pooled weighted mean difference (WMD) indicated treatment reduced necrosis by 16.9% (71 controlled analyses, 95% CI 13.2-20.7%; P < 0.001), however there was less evidence of an effect after accounting for publication bias. Treatment led to a 12.8% reduction in fibrosis (73 controlled analyses, 95% CI 7.6-18.0%; P < 0.001). After accounting for publication bias this was attenuated to 7.8% but remained significant. Treatment reduced calcification by 4.1% (28 controlled analyses, 95% CI 0.2-8.0%; P < 0.0395). We observed significant heterogeneity in effect size in all primary endpoints, which was predominantly driven by differences between drug categories. Beta blockers and angiotensin-converting enzyme (ACE) inhibitors were the only agents that were effective for both necrosis and fibrosis, while only ACE inhibitors had a significant effect on calcification. This study provides evidence for a role for ACE inhibitors and beta blockers to prevent myocardial injury and scar deposition in in vivo models of myocarditis. There is a need for further well-designed studies to assess the translational application of these treatments.
现行心肌炎指南不主张对射血分数正常的心肌炎患者进行治疗以预防心肌损伤和瘢痕形成。我们旨在确定β受体阻滞剂、钙通道阻滞剂和肾素-血管紧张素系统拮抗剂在改善心肌炎动物模型中的心肌损伤、瘢痕形成和钙化中的作用。该项目已在 PROSPERO 系统评价数据库（CRD42018089336）中进行了前瞻性注册。采用随机效应模型对主要结局（坏死、纤维化和钙化）进行荟萃分析。系统评价了 52 项研究。进行荟萃分析以比较与未治疗对照组的差异。在每项研究中，我们确定了治疗组与对照组所有独立比较的结果。汇总的加权均数差（WMD）表明，治疗组可使坏死减少 16.9%（71 项对照分析，95%CI 13.2-20.7%；P<0.001），但在考虑到发表偏倚后，疗效证据减少。治疗组可使纤维化减少 12.8%（73 项对照分析，95%CI 7.6-18.0%；P<0.001）。在考虑到发表偏倚后，这一数值降低至 7.8%，但仍有统计学意义。治疗组可使钙化减少 4.1%（28 项对照分析，95%CI 0.2-8.0%；P<0.0395）。我们观察到所有主要结局的效应大小存在显著的异质性，主要是由于药物类别之间的差异所致。β受体阻滞剂和血管紧张素转换酶（ACE）抑制剂是对坏死和纤维化均有效的唯一药物，而只有 ACE 抑制剂对钙化有显著影响。本研究为 ACE 抑制剂和β受体阻滞剂在心肌炎动物模型中预防心肌损伤和瘢痕形成提供了证据。需要进一步设计良好的研究来评估这些治疗方法的转化应用。
Zotero 插件