Abstract P251: Substitution to Generic Angiotensin II Receptor Blockers: Impact on Risk of Hospitalizations, Emergency Room Consultations and Mortality
Bibliographic record
Abstract
Background: Substitution from brand-name to generic drugs is one way to reduce costs of pharmacological treatments. Generic drugs licensing is obtained through comparative bioavailability studies for which a variation of up to 20% is generally accepted. However, “real-life” efficacy and tolerance of generic drugs are not studied prior to commercialization. We aimed to evaluate the impact of brand-name to generic losartan, valsartan or candesartan substitution on serious adverse events (hospitalizations, emergency room consultations [ER] or mortality). Method: Three cohorts of persistent angiotensin II receptor blockers (ARB) users (losartan [brand-name and 8 generics], valsartan [brand-name and 5 generics] and candesartan [brand-name and 3 generics])aged ≥ 66 years were constituted using data from the Quebec Integrated Chronic Disease Surveillance System. Generic exposition was determined by substitution time-distribution matching. Time free of adverse events up to 365 days after the onset of generic exposition was compared between groups by survival analysis using Cox regression models adjusted for age, sex, comorbidities, concomitant treatments, socioeconomic status, previous brand-name drug, healthcare resources utilization and prescriber’s speciality, to provide hazard ratio (HR). Sensitivity analysis including non-persistent users was also conducted. Results: Within cohorts (losartan, n = 15,469; valsartan, n = 17,205; and candesartan, n = 25,008), proportions of exposed to generic substitution vs. unexposed who had at least one adverse event were respectively: 35% vs. 25%, 34% vs. 28% and 31% vs. 27% (all, p <0.0001). When adjusted for potential confounders, risk of hospitalizations and ER were higher for those exposed to generic substitution. Specifically, HR for exposed to generic substitution are the following for losartan, valsartan and candesartan: hospitalizations (HR: 1.23 [ p < 0.0001]; 1.22 [ p < 0.0001] and 1.08 [ p = 0.0317]) and ER (HR: 1.55; 1.20 and 1.16, all = p < 0.0001). Regarding mortality, HR were respectively: 0.63 [ p = 0.1456]; 0.95 [ p = 0.8487] and 0.43 [ p < 0.0001]). Survival was not significantly different for exposed to generic losartan and valsartan substitution. However, even if the time free of hospitalizations and ER was 8% and 16% shorter for patients exposed to generic candesartan substitution, their survival was 2.3 times better when compared to patients who remained on brand-name candesartan (unexposed). Sensitivity analysis yield similar results. Conclusion: Substitution to generic antihypertensive drugs is associated with a significantly reduced delay before hospitalizations and ER for the three ARBs but a better survival for patients exposed to generic candesartan substitution only. Better bioavailability of generics versions of candesartan or differences in health cares between users could explain these differences.
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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 | 0.001 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.002 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.006 | 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".