The role of heart rate may differ according to pathophysiological setting: from SHIFT to SIGNIFY
Bibliographic record
Abstract
The results of the SIGNIFY (study assessing the morbidity–mortality benefits of the If inhibitor ivabradine in patients with coronary artery disease) trial, which were recently published in the New England Journal of Medicine,1 raise an important pathophysiological question regarding the relationship between elevated heart rate and outcomes in cardiovascular disease. Why did heart rate reduction with ivabradine improve prognosis in patients with chronic heart failure and left ventricular (LV) systolic dysfunction in the SHIFT (systolic heart failure treatment with the If inhibitor ivabradine trial) study,2 but not in patients with stable coronary artery disease (CAD) without heart failure and LV systolic dysfunction in SIGNIFY? The 19 102 patients recruited in SIGNIFY presented with stable CAD plus additional cardiovascular risk factors and resting heart rate ≥70 bpm.1 The SIGNIFY investigators deliberately recruited patients with no symptoms of heart failure or LV systolic dysfunction: the population had a mean left ventricular ejection fraction (LVEF) at baseline of 56.5 ± 8.6%.3 All were receiving guideline-based background therapy for their condition. In this stable CAD population, ivabradine had no effect on the primary endpoint, a composite of cardiovascular death or non-fatal myocardial infarction (MI), with annual event rates of 3.0% with ivabradine and 2.8% with placebo (hazard ratio [HR] 1.08, 95% confidence interval [CI], 0.96–1.20, P = 0.20).1 There were no significant differences between the groups in terms of any of the secondary endpoints including cardiovascular death (HR 1.10, P = 0.25), non-fatal MI (HR 1.04, P = 0.60), or all-cause death (HR 1.06, P = 0.35). Treatment with ivabradine was associated with an increase in primary composite endpoint in a sub-group of 12 049 patients with angina Canadian Cardiovascular Society (CCS) 2 and higher (63% of the whole population) vs. those on placebo (HR 1.18, P = 0.018, in patient with CCS class 2 angina or higher; P = 0.02 for interaction). There was no significant effect of ivabradine on the components of the primary endpoint or the main secondary endpoints in this angina population. There was no interaction between the use of ivabradine and outcomes in seven other pre-specified sub-groups, which were defined according to age, β-blocker use at baseline, sex, heart rate at baseline, history of diabetes, previous MI, or previous coronary revascularization.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.009 | 0.029 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.002 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.002 |
| Scholarly communication | 0.002 | 0.002 |
| Open science | 0.002 | 0.003 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.007 | 0.001 |
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".