title: Generic versus brand-name drugs used in cardiovascular diseases.
abstract: This meta-analysis aimed to compare the efficacy and adverse events, either serious or mild/moderate, of all generic versus brand-name cardiovascular medicines. We searched randomized trials in MEDLINE, Scopus, EMBASE, Cochrane Controlled Clinical Trial Register, and ClinicalTrials.gov (last update December 1, 2014). Attempts were made to contact the investigators of all potentially eligible trials. Two investigators independently extracted and analyzed soft (including systolic blood pressure, LDL cholesterol, and others) and hard efficacy outcomes (including major cardiovascular adverse events and death), minor/moderate and serious adverse events. We included 74 randomized trials; 53 reported ≥1 efficacy outcome (overall sample 3051), 32 measured mild/moderate adverse events (n = 2407), and 51 evaluated serious adverse events (n = 2892). We included trials assessing ACE inhibitors (n = 12), anticoagulants (n = 5), antiplatelet agents (n = 17), beta-blockers (n = 11), calcium channel blockers (n = 7); diuretics (n = 13); statins (n = 6); and others (n = 3). For both soft and hard efficacy outcomes, 100 % of the trials showed non-significant differences between generic and brand-name drugs. The aggregate effect size was 0.01 (95 % CI -0.05; 0.08) for soft outcomes; -0.06 (-0.71; 0.59) for hard outcomes. All but two trials showed non-significant differences in mild/moderate adverse events, and aggregate effect size was 0.07 (-0.06; 0.20). Comparable results were observed for each drug class and in each stratified meta-analysis. Overall, 8 serious possibly drug-related adverse events were reported: 5/2074 subjects on generics; 3/2076 subjects on brand-name drugs (OR 1.69; 95 % CI 0.40-7.20). This meta-analysis strengthens the evidence for clinical equivalence between brand-name and generic cardiovascular drugs. Physicians could be reassured about prescribing generic cardiovascular drugs, and health care organization about endorsing their wider use.
authors.affiliation: Department of Medicine and Aging Sciences, University of Chieti, Via dei Vestini 5, 66013, Chieti, Italy. lmanzoli@post.harvard.edu.|Regional Health Care Agency of Abruzzo, Via Attilio Monti 9, Pescara, Italy. lmanzoli@post.harvard.edu.
authors.forename: Lamberto
authors.identifier: 0000-0002-8129-9344
authors.initials: L
authors.lastname: Manzoli
authors.affiliation: Department of Medicine and Aging Sciences, University of Chieti, Via dei Vestini 5, 66013, Chieti, Italy.|Regional Health Care Agency of Abruzzo, Via Attilio Monti 9, Pescara, Italy.
authors.forename: Maria Elena
authors.initials: ME
authors.lastname: Flacco
authors.affiliation: Institute of Public Health, Catholic University of Rome, Largo Francesco Vito, 1, 00168, Rome, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Boccia
authors.affiliation: Department of Public Health and Infectious Diseases, Sapienza University of Rome, Viale Regina Elena 324, 00161, Rome, Italy.
authors.forename: Elvira
authors.initials: E
authors.lastname: D'Andrea
authors.affiliation: Institute of Public Health, Catholic University of Rome, Largo Francesco Vito, 1, 00168, Rome, Italy.
authors.forename: Nikola
authors.initials: N
authors.lastname: Panic
authors.affiliation: Department of Public Health and Infectious Diseases, Sapienza University of Rome, Viale Regina Elena 324, 00161, Rome, Italy.
authors.forename: Carolina
authors.initials: C
authors.lastname: Marzuillo
authors.affiliation: Department of Public Health Sciences, University of Turin, Via Santena 5bis, 10126, Turin, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Siliquini
authors.affiliation: Institute of Public Health, Catholic University of Rome, Largo Francesco Vito, 1, 00168, Rome, Italy.|Italian National Institute of Health, Via Regina Elena 299, 00161, Rome, Italy.
authors.forename: Walter
authors.initials: W
authors.lastname: Ricciardi
authors.affiliation: Department of Public Health and Infectious Diseases, Sapienza University of Rome, Viale Regina Elena 324, 00161, Rome, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Villari
authors.affiliation: Stanford Prevention Research Center, Department of Medicine and Department of Health Research and Policy, Stanford University School of Medicine, Stanford, CA, USA.|Department of Statistics, Stanford University School of Humanities and Sciences, Stanford, CA, USA.|Meta-Research Innovation Center at Stanford (METRICS), Stanford, CA, USA.
authors.forename: John P A
authors.initials: JP
authors.lastname: Ioannidis
mesh_terms: D002317:Cardiovascular Agents / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000188:drug therapy*; D064420:Drug-Related Side Effects and Adverse Reactions; D016568:Drugs, Generic / Q000627:therapeutic use*; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D013810:Therapeutic Equivalency
chemical_list: D002317:Cardiovascular Agents; D016568:Drugs, Generic
keywords: Brand-name drug; Cardiovascular diseases; Efficacy; Generic drug; Meta-analysis; Safety