Can Generic Medications Be a Safe and Effective Alternative to Brand-Name Drugs for Cardiovascular Disease Treatment? A Systematic Review and Meta-Analysis.

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

The prospero registration: CRD42023481597, https://www.crd.york.ac.uk/PROSPERO/view/CRD42023481597.