Safety and Effectiveness of Direct Oral Anticoagulants Versus Vitamin K Antagonists: Pilot Implementation of a Near‐Real‐Time Monitoring Program in Italy

Abstract

BackgroundReal‐time monitoring is used to the ends of postmarketing observational research on newly marketed drugs. We implemented a pilot near‐real‐time monitoring program on the test case of oral anticoagulants. Specifically, we evaluated the safety and effectiveness of direct oral anticoagulants compared to vitamin K antagonists in nonvalvular atrial fibrillation secondary prevention during 2013‐2015 in the Lazio Region, Italy.Methods and ResultsA cohort study was conducted using a sequential propensity‐score–matched new user parallel‐cohort design. Sequential analyses were performed using Cox models. Overall, 10 742 patients contributed to the analyses. Compared with vitamin K antagonists, direct oral anticoagulant use was associated with a reduction of all‐cause mortality (0.81; 95% confidence interval [CI] 0.66‐0.99), cardiovascular mortality (0.71; 95% CI 0.54‐0.93), myocardial infarction (0.67; 95% CI 0.43‐1.04), ischemic stroke (0.87; 95% CI 0.52‐1.45), hemorrhagic stroke (0.25; 95% CI 0.07‐0.88), and with a nonsignificant increase of gastrointestinal bleeding (1.26; 95% CI 0.69‐2.30).ConclusionsThe present pilot study is a cornerstone to develop real‐time monitoring for new drugs in our region.

Cardiovascular safety of linagliptin compared with other oral glucose‐lowering agents in patients with type 2 diabetes: A sequential monitoring programme in routine care

“…18,43,44 In conclusion, in a prespecified analysis from a 5-year monitoring programme, involving >100 000 commercially insured patients with T2D, linagliptin had similar CV safety compared to other DPP-4 inhibitors and pioglitazone, and was associated with a reduced CV risk compared to sulphonylureas. Together with other recent examples, 18,43,44 this monitoring programme demonstrates the value of routinely collected healthcare data in a framework of principled epidemiological analyses to monitor prospectively the effectiveness and safety of approved medical products.…”

“…Unlike a clinical trial, non-experimental studies based on large utilization databases cannot prevent people from receiving substandard treatment once the treatment effects in routine care have been established; thus, the periodic analyses in database studies are not performed to evaluate potential earlier study termination, nor any other time-dependent actions, such as regulatory decisions, but rather to provide the most timely and accurate information when treating individual patients. 18,43,44 In conclusion, in a prespecified analysis from a 5-year monitoring programme, involving >100 000 commercially insured patients with T2D, linagliptin had similar CV safety compared to other DPP-4 inhibitors and pioglitazone, and was associated with a reduced CV risk compared to sulphonylureas. Together with other recent examples, 18,43,44 this monitoring programme demonstrates the value of routinely collected healthcare data in a framework of principled epidemiological analyses to monitor prospectively the effectiveness and safety of approved medical products.…”

“…The monitoring system was set up to inform the medical community in a timely manner of the best available effect estimate as the data accumulated over time. Unlike a clinical trial, non‐experimental studies based on large utilization databases cannot prevent people from receiving substandard treatment once the treatment effects in routine care have been established; thus, the periodic analyses in database studies are not performed to evaluate potential earlier study termination, nor any other time‐dependent actions, such as regulatory decisions, but rather to provide the most timely and accurate information when treating individual patients …”

The EMPagliflozin compaRative effectIveness and SafEty (EMPRISE) study programme: Design and exposure accrual for an evaluation of empagliflozin in routine clinical care

“…Studies based on real‐world data sources offer a tremendous opportunity to fill these gaps and guide decision‐making . Over the past 20 years, tremendous advances have been made and new design and analytic standards are emerging to limit avoidable design flaws, for example, time‐related biases, in which this monitoring programme incorporates to achieve high validity findings …”

Healthcare Database Networks for Drug Regulatory Policies: International Workshop on the Canadian, US and Spanish Experience and Future Steps for Italy

“…This is particularly important since Italian observational data could be leveraged much more effectively for public health purposes than it currently is. All speakers agreed that the use of EHRs/claims collected through these data networks is very useful for a better understanding of treatment safety and effectiveness in Italy, as in other countries [7,8].…”