Epidemiologic Evaluation of Cardiovascular Risk in Patients Receiving Milnacipran, Venlafaxine, or Amitriptyline: Evidence from French Health Data
Bibliographic record
Abstract
BACKGROUND: Milnacipran, a selective serotonin and norepinephrine reuptake inhibitor, is approved by the Food and Drug Administration for the management of fibromyalgia. It has been available for many years in several countries outside the US for the treatment of depression. OBJECTIVE: To conduct population-based analyses comparing the risk of serious cardiovascular (CV) events (eg, acute myocardial infarction, stroke, congestive heart failure) associated with treatment with milnacipran compared with venlafaxine and amitriptyline, 2 other commonly prescribed drugs that also inhibit reuptake of norepinephrine and serotonin. METHODS: Information from the French Thales electronic health record database from 2001 to 2007 was used. Patients with 1 or more prescriptions for milnacipran, venlafaxine, or amitriptyline; 180 or more days of continuous eligibility prior to the first prescription; and no prior CV event diagnoses during the 180-day baseline period were included. A retrospective, matched-cohort design was employed. The incidence rates of CV events between cohorts receiving milnacipran, venlafaxine, and amitriptyline were compared using unadjusted incidence rate ratio (IRR) and adjusted conditional IRR based on Poisson regression. RESULTS: We identified 4452 milnacipran-venlafaxine and 3761 milnacipran-amitriptyline matched pairs. The matched cohorts had similar baseline characteristics. The unadjusted IRRs of any CV events, comparing milnacipran with venlafaxine or amitriptyline, were 1.02 (95% CI 0.73 to 1.44) and 1.30 (95% CI 0.90 to 1.89), respectively. Adjusted IRRs confirmed the statistical similarity in the CV event risk between milnacipran and venlafaxine (adjusted IRR = 1.29, 95% CI 0.76 to 2.17) or amitriptyline (adjusted IRR = 1.06, 95% CI 0.59 to 1.89). CONCLUSIONS: This French population-based study found that the risk of CV events was not significantly different for patients receiving milnacipran versus those receiving venlafaxine or amitriptyline.
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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 | 0.010 | 0.021 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.003 |
| Bibliometrics | 0.003 | 0.004 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 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".