Dapagliflozin and Cardiovascular Outcomes in Patients With Type 2 Diabetes Mellitus and Previous Myocardial Infarction
Bibliographic record
Abstract
BACKGROUND: Sodium glucose transporter-2 inhibitors reduce the risk of major adverse cardiovascular events (MACE) in patients with type 2 diabetes mellitus and a history of atherosclerotic cardiovascular disease. Because of their baseline risk, patients with previous myocardial infarction (MI) may derive even greater benefit from sodium glucose transporter-2 inhibitor therapy. METHODS: DECLARE-TIMI 58 (Dapagliflozin Effect on Cardiovascular Events-Thrombolysis in Myocardial Infarction 58) randomized 17 160 patients with type 2 diabetes mellitus and either established atherosclerotic cardiovascular disease (n=6974) or multiple risk factors (n=10 186) to dapagliflozin versus placebo. The 2 primary end points were composite of MACE (cardiovascular death, MI, or ischemic stroke) and the composite of cardiovascular death or hospitalization for heart failure. Those with previous MI (n=3584) made up a prespecified subgroup of interest. RESULTS: In patients with previous MI (n=3584), dapagliflozin reduced the relative risk of MACE by 16% and the absolute risk by 2.6% (15.2% versus 17.8%; hazard ratio [HR], 0.84; 95% CI, 0.72-0.99; P=0.039), whereas there was no effect in patients without previous MI (7.1% versus 7.1%; HR, 1.00; 95% CI, 0.88-1.13; P=0.97; P for interaction for relative difference=0.11; P for interaction for absolute risk difference=0.048), including in patients with established atherosclerotic cardiovascular disease but no history of MI (12.6% versus 12.8%; HR, 0.98; 95% CI, 0.81-1.19). There seemed to be a greater benefit for MACE within 2 years after the last acute event ( P for interaction trend=0.007). The relative risk reductions in cardiovascular death/hospitalization for heart failure were more similar, but the absolute risk reductions tended to be greater: 1.9% (8.6% versus 10.5%; HR, 0.81; 95% CI, 0.65-1.00; P=0.046) and 0.6% (3.9% versus 4.5%; HR, 0.85; 95% CI, 0.72-1.00; P=0.055) in patients with and without previous MI, respectively ( P interaction for relative difference=0.69; P interaction for absolute risk difference=0.010). CONCLUSIONS: Patients with type 2 diabetes mellitus and previous MI are at high risk of MACE and cardiovascular death/hospitalization for heart failure. Dapagliflozin appears to robustly reduce the risk of both composite outcomes in these patients. Future studies should aim to confirm the large clinical benefits with sodium glucose transporter-2 inhibitors we observed in patients with previous MI. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01730534.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".