Transposition of cardiovascular outcome trial effects to the real-world population of patients with type 2 diabetes

Veronica Sciannameo ,Angelo Avogaro ,Paola Berchialla ,Gian Paolo Fadini

doi:10.1186/s12933-021-01300-y

Veronica Sciannameo , Angelo Avogaro + Show 2 more

Open Access

https://doi.org/10.1186/s12933-021-01300-y

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Abstract

BackgroundTransferring results obtained in cardiovascular outcome trials (CVOTs) to the real-world setting is challenging. We herein transposed CVOT results to the population of patients with type 2 diabetes (T2D) seen in routine clinical practice and who may receive the medications tested in CVOTs.MethodsWe implemented the post-stratification approach based on aggregate data of CVOTs and individual data of a target population of diabetic outpatients. We used stratum-specific estimates available from CVOTs to calculate expected effect size for the target population by weighting the average of the stratum-specific treatment effects according to proportions of a given characteristic in the target population. Data are presented as hazard ratio (HR) and 95% confidence intervals.ResultsCompared to the target population (n = 139,708), the CVOT population (n = 95,816) was younger and had a two to threefold greater prevalence of cardiovascular disease. EMPA-REG was the CVOT with the largest variety of details on stratum-specific effects, followed by TECOS, whereas DECLARE and PIONEER-6 had more limited stratum-specific information. The post-stratification HR estimate for 3 point major adverse cardiovascular event (MACE) based on EMPA-REG was 0.88 (0.74–1.03) in the target population, compared to 0.86 (0.74–0.99) in the trial. The HR estimate based on LEADER was 0.88 (0.77–0.99) in the target population compared to 0.87 (0.78–0.97) in the trial. Consistent results were obtained for SUSTAIN-6, EXSCEL, PIONEER-6 and DECLARE. The effect of DPP-4 inhibitors observed in CVOTs remained neutral in the target population.ConclusionsBased on CVOT stratum-specific effects, cardiovascular protective actions of glucose lowering medications tested in CVOTs are transferrable to a much different real-world population of patients with T2D.

Highlights

Transferring results obtained in cardiovascular outcome trials (CVOTs) to the real-world setting is challenging
Selection of CVOTs Since the method for transposing trial effects to the target population relies on the availability of stratum-specific information of effect [16], we selected CVOTs reporting the hazard ratio for the primary outcome in various subgroups of patients based on clinical characteristics of the trial population
Transposition could not be performed for the Canagliflozin Cardiovascular Assessment Study (CANVAS) study because reporting of stratum-specific effects was not accompanied by numbers of patients in each stratum [26]

Summary

Introduction

Transferring results obtained in cardiovascular outcome trials (CVOTs) to the real-world setting is challenging. Small proportions of patients with T2D would satisfy enrolment criteria of CVOTs on GLP-1RA or SGLT2i and even smaller proportions have CVOT-like characteristics [12, 13] For these reasons, there has been an intense debate on whether results of CVOTs can be transferred to the general real-world population of patients with T2D, irrespective of their cardiovascular risk profile [14, 15]. There has been an intense debate on whether results of CVOTs can be transferred to the general real-world population of patients with T2D, irrespective of their cardiovascular risk profile [14, 15] This is a clinically-relevant question informing on which and how many patients would benefit from GLM with CVOTproven cardiovascular protective effect in routine care. Though prior studies have addressed the generalizability of trial populations, no study so far has explored whether CVOT findings, i.e. the drug’s effect on the outcome(s), can be transferred to a target population with different characteristics from that of the trial

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