Effects of canagliflozin on cardiovascular and kidney outcomes and mortality in primary and secondary cardiovascular prevention: pooled analysis from the CANVAS program and CREDENCE trial
Bibliographic record
Abstract
Abstract Background/Introduction Individuals with type 2 diabetes mellitus (T2DM) are at a greater risk for experiencing cardiovascular (CV) and kidney events. Canagliflozin is a sodium glucose co-transporter 2 inhibitor that has demonstrated reduction of these events in participants with T2DM with or without a history of CV disease (CVD) in both the CANVAS Program and CREDENCE trial. Purpose To determine the pooled effects of canagliflozin on CV outcomes, kidney outcomes, and all-cause mortality in trial participants with and without a history of CVD (secondary and primary prevention, respectively). Methods This post hoc analysis pooled individual participant data from the CANVAS Program and CREDENCE trial. The effects of canagliflozin versus placebo on time to first event for CV outcomes (major adverse cardiovascular events [MACE], which was defined as CV death, myocardial infarction [MI] or stroke; CV death; hospitalization for heart failure [HHF], and the composite of CV death or HHF), kidney outcomes (end-stage kidney disease [ESKD], doubling of serum creatinine [dSCr], and the composite of ESKD or dSCr), and all-cause mortality were assessed in participants with T2DM with or without a history of CVD. Results Among the 14,543 participants from the pooled CANVAS Program (N=10,142) and CREDENCE trial (N=4401), 5667 (39%; canagliflozin, n=3128; placebo, n=2539) were in the primary prevention group and 8876 (61%; canagliflozin, n=4869; placebo, n=4007) were in the secondary prevention group. Baseline characteristics of participants in each group were generally similar. Across both primary and secondary prevention participants, no heterogeneity in the relative risk reduction of CV outcomes, kidney outcomes, and all-cause mortality with canagliflozin versus placebo was observed (all P interaction >0.624; Figures 1 and 2). The benefits of canagliflozin on MACE and the composite of CV death or HHF were observed as early as 6 months into treatment in both subgroups of participants and were sustained throughout the study. Conclusions In this pooled analysis of patient-level data from the CANVAS Program and CREDENCE trial, treatment with canagliflozin demonstrated early benefits and was associated with reduced risk of CV outcomes, kidney outcomes, and all-cause mortality, with similar results across primary and secondary prevention participants with T2DM. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Janssen, Inc.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.018 | 0.020 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.010 | 0.019 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".