TY - JOUR
T1 - REPORTING OF CARDIOVASCULAR EVENTS IN CLINICAL TRIALS SUPPORTING FDA-APPROVAL OF CONTEMPORARY CANCER DRUGS
AU - Addison, Daniel
AU - Bonsu, Janice
AU - Charles, Lawrence
AU - Guha, Avirup
AU - Baker, Brandee
AU - Woyach, Jennifer
AU - Awan, Farrukh
AU - Rogers, Kerry
AU - Lustberg, Maryam
AU - Reinbolt, Raquel
AU - Brammer, Jonathan
AU - Miller, Eric
AU - Jneid, Hani
AU - Paskett, Electra
PY - 2019/3
Y1 - 2019/3
N2 - Background: Cardiovascular disease (CVD) is a leading cause of morbidity and mortality among patients treated with anticancer therapies. In the US, novel cancer therapy trials are required to report concerning adverse events prior to Food and Drug Administration (FDA) approval. Yet, the pattern and reported incidence of CVD events in these pivotal clinical trials is unknown. Method(s): From the Drugs@FDA database, MEDLINE, clinicaltrial.gov, and publicly available FDA reviews we identified all pivotal (phase II and III) clinical trials tied to anticancer drug approvals from 1998-2018. The primary outcome was the report of major adverse cardiovascular events (MACE), defined as incident myocardial infarction (MI), stroke, heart failure (HF), coronary or peripheral revascularization, atrial fibrillation (AF) and CVD death, irrespective of treatment arm. Pooled reported annualized incidence-rates of MACE were compared to reported rates in a large contemporary similar-aged general population using relative risks (RR). Population risk difference (RD) for MACE was estimated. Differences in drug efficacy using pooled binary endpoint hazard ratios (HR), based on the presence or absence of reported MACE events were also assessed. Result(s): Overall, there were 189 trials, linked to 123 drugs, enrolling 97,365 participants (58.5+/-5 years, 46.0% female, 80.4% on biologic, targeted or immune-based therapies) with 148,138 person-years of follow-up. Over a median follow-up of 18 months, 954 cases of incident MACE (370 HF, 65 MI, 179 stroke, 29 revascularizations, 65 AF and 246 CVD deaths; 680 in the intervention vs 274 control arm; P
AB - Background: Cardiovascular disease (CVD) is a leading cause of morbidity and mortality among patients treated with anticancer therapies. In the US, novel cancer therapy trials are required to report concerning adverse events prior to Food and Drug Administration (FDA) approval. Yet, the pattern and reported incidence of CVD events in these pivotal clinical trials is unknown. Method(s): From the Drugs@FDA database, MEDLINE, clinicaltrial.gov, and publicly available FDA reviews we identified all pivotal (phase II and III) clinical trials tied to anticancer drug approvals from 1998-2018. The primary outcome was the report of major adverse cardiovascular events (MACE), defined as incident myocardial infarction (MI), stroke, heart failure (HF), coronary or peripheral revascularization, atrial fibrillation (AF) and CVD death, irrespective of treatment arm. Pooled reported annualized incidence-rates of MACE were compared to reported rates in a large contemporary similar-aged general population using relative risks (RR). Population risk difference (RD) for MACE was estimated. Differences in drug efficacy using pooled binary endpoint hazard ratios (HR), based on the presence or absence of reported MACE events were also assessed. Result(s): Overall, there were 189 trials, linked to 123 drugs, enrolling 97,365 participants (58.5+/-5 years, 46.0% female, 80.4% on biologic, targeted or immune-based therapies) with 148,138 person-years of follow-up. Over a median follow-up of 18 months, 954 cases of incident MACE (370 HF, 65 MI, 179 stroke, 29 revascularizations, 65 AF and 246 CVD deaths; 680 in the intervention vs 274 control arm; P
UR - https://www.mendeley.com/catalogue/f9fa127a-84fe-308a-bab7-a6d0ad0d24cc/
U2 - 10.1016/s0735-1097(19)32485-4
DO - 10.1016/s0735-1097(19)32485-4
M3 - Article
SN - 0735-1097
VL - 73
SP - 1879
JO - Journal of the American College of Cardiology
JF - Journal of the American College of Cardiology
IS - 9
ER -