Luo Bing, Yu Feng, Ge Weihong, Yang Xian
Department of Pharmacy, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, 210008 Nanjing, Jiangsu, China.
School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, 210009 Nanjing, Jiangsu, China.
Rev Cardiovasc Med. 2025 Mar 7;26(3):26116. doi: 10.31083/RCM26116. eCollection 2025 Mar.
Cardiovascular disease is the leading cause of death in most of the world. Previous meta-analyses of generic drugs for the treatment of cardiovascular disease have not provided sufficient evidence to demonstrate the true efficacy and safety of the drugs. Subsequently, concern exists regarding whether the use of generic drugs can fully substitute brand-name drugs in clinical treatment. To enhance the evidence for generic drugs, this meta-analysis compares the actual effectiveness of generic drugs with brand-name drugs in preventing and treating cardiovascular diseases. This study aimed to resolve the controversy over whether generic drugs in cardiovascular disease can replace brand-name drugs, fully evaluating the best evidence on the clinical equivalence of generic drugs.
The PubMed, Embase, The Cochrane Library, and Clinicaltrials.gov databases were searched. The search period included articles published before December 2023. Studies on generic and branded cardiovascular drugs were collected, and two independent reviewers screened eligibility, extracted study data, and assessed the risk of bias. Safety outcomes included major adverse cardiovascular events and other adverse events. Efficacy outcomes included relevant vital signs (e.g., blood pressure, heart rate, urine volume) and laboratory measures (e.g., international normalized ratio, low-density lipoprotein cholesterol, platelet aggregation inhibition). A meta-analysis and subgroup analysis were conducted using the Rev Man software.
A total of 4238 studies were retrieved, and 87 studies (n = 2,303,818) were included in the qualitative analysis. There were 57 quantitatively assessed studies (n = 560,553), including angiotensin II receptor blockers, beta-blockers, calcium channel blockers, antithrombotic drugs (anticoagulants or antiplatelet agents), diuretics, statins, and other classes of cardiovascular medications. Regarding clinical safety, 19 studies assessed the occurrence of major adverse cardiovascular events (MACEs) (n = 384,640), and 35 reported secondary adverse events (n = 580,125). In addition to the MACEs for statins (risk ratio (RR) 1.13 [1.05, 1.21]) and adverse events (AEs) for calcium channel blockers (RR 0.90 [0.88, 0.91]), there were no significant differences in the overall risk of MACEs (RR = 1.02 [0.90, 1.15]) and minor adverse events (RR = 0.98 [0.91, 1.05]) between generic and brand-name cardiovascular drugs. In terms of effectiveness, there were no significant differences observed between the two groups in blood pressure (BP), platelet aggregation inhibition (PAI), international normalized ratio (INR), low-density lipoprotein (LDL), and urinary sodium levels. Subgroup analyses for the region, study design, duration of follow-up, and grant funding revealed no significant differences in the risk of MACEs. However, the risk of AE was significantly higher in the Asian region for brand-name cardiovascular drugs than for generics. There was no statistically significant difference in risk between generic and brand-name drugs in the remaining subgroup analyses.
Cardiovascular drugs encompass many types; a minority of generic and brand-name drugs have discrepancies. Given the overall development trend of multi-manufacturer generic drugs in the future, this study provides a strong basis for the global application of generic drugs. The feasibility of generic drugs in terms of efficacy and safety in cardiovascular diseases is clarified. However, some drugs still need to be improved to replace the original drugs used in clinical practice completely. Therefore, large-sample, multicenter, high-quality studies are still required to guide the clinical use of cardiovascular drugs.
CRD42023481597, https://www.crd.york.ac.uk/PROSPERO/view/CRD42023481597.
心血管疾病是世界上大多数地区的主要死因。先前对治疗心血管疾病的仿制药进行的荟萃分析未能提供充分证据来证明这些药物的真正疗效和安全性。随后，人们担心在临床治疗中使用仿制药是否能完全替代品牌药。为了加强对仿制药的证据支持，本荟萃分析比较了仿制药与品牌药在预防和治疗心血管疾病方面的实际效果。本研究旨在解决心血管疾病仿制药能否替代品牌药的争议，全面评估关于仿制药临床等效性的最佳证据。
检索了PubMed、Embase、Cochrane图书馆和Clinicaltrials.gov数据库。检索期包括2023年12月之前发表的文章。收集了关于心血管仿制药和品牌药的研究，两名独立评审员筛选了纳入标准、提取了研究数据并评估了偏倚风险。安全结局包括主要心血管不良事件和其他不良事件。疗效结局包括相关生命体征（如血压、心率、尿量）和实验室指标（如国际标准化比值、低密度脂蛋白胆固醇、血小板聚集抑制）。使用Rev Man软件进行荟萃分析和亚组分析。
共检索到4238项研究，87项研究（n = 2,303,818）纳入定性分析。有57项进行定量评估的研究（n = 560,553），包括血管紧张素II受体阻滞剂、β受体阻滞剂、钙通道阻滞剂、抗血栓药物（抗凝剂或抗血小板药物）、利尿剂、他汀类药物和其他类心血管药物。关于临床安全性，19项研究评估了主要心血管不良事件（MACE）的发生情况（n = 384,640），35项报告了次要不良事件（n = 580,125）。除了他汀类药物的MACE（风险比（RR）1.13 [1.05, 1.21]）和钙通道阻滞剂的不良事件（AE）（RR 0.90 [0.88, 0.91]）外，心血管仿制药和品牌药在MACE的总体风险（RR = 1.02 [
