COMPARATIVE EFFECTIVENESS OF HYDROCHLOROTHIAZIDE VERSUS CHLORTHALIDONE ON CARDIAC, RENAL AND ELECTROLYTE EVENTS BY EGFR STAGE
Bibliographic record
Abstract
Objective: Thiazide diuretics are recommended as first line blood pressure lowering therapy. Previously conducted trials demonstrating cardiovascular benefit (like ALLHAT and SHEP), used Chlorthalidone and not Hydrochlorothiazide as the diuretic. Despite this, Hydrochlorothiazide is commonly prescribed and is available in many combination preparations. Little is known about the comparative effectiveness of the 2 drugs, as estimated glomerular filtration rate (eGFR) declines. We set out to examine the association of hydrochlorothiazide and cardiac, kidney and electrolyte-related adverse events compared to chlorthalidone by eGFR level. Design and method: Population-based, retrospective cohort study of adults of advanced age (> or = 66 years) with a diagnosis of hypertension in Ontario, Canada (2009–2016). Fine and Grey sub-distribution hazards models examining the association of matched hydrochlorothiazide vs. chlorthalidone pairs and outcome events in an intention to treat analysis. Study outcomes were a cardiac event, kidney (egfr decline> 30%) event, electrolyte disorder (hypo- or hyperkalemia, hyponatremia) or all-cause mortality. We examined the effect of eGFR groups (> 60, 45–59, < 45 ml/min/1.73m2) on outcomes using an interaction term. Results: A total of 9,786 hydrochlorothiazide users were matched 4:1 to 2,936 chlorthalidone users (mean age 73.6, 55% female, 41.6% diabetes). Baseline eGFR distributions were 73.4, 17.4 and 9.2% for > 60, 45–59, and <45 ml/min, respectively. In individuals with an eGFR > 60 ml/min, hydrochlorothiazide was associated with a lower risk of eGFR decline (HR 0.78 95%CI 0.70–0.88), CV events (HR 0.83 95%CI 0.76–0.92), hypokalemia (HR 0.54 95CI 0.48–0.60) and all-cause mortality (HR 0.79 95%CI 0.63–0.98) compared to chlorthalidone. These effects attenuated with lower eGFR levels and no differences were observed in hyperkalemia or hyponatremia. Conclusions: Among individuals with an eGFR > 60 ml/min, hydrochlorothiazide use was associated with a lower risk of eGFR decline, CV events, hypokalemia and all-cause mortality. These differential effects were not observed at lower eGFR levels.
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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 | 0.002 | 0.004 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.002 |
| 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 | 0.001 | 0.001 |
| 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".