Did all thiazides take undue credit of good work of chlorthalidone?

Diuretics have been used as antihypertensive agents since the advent of mercurial diuretics. However, resurrection of thiazides in treatment of hypertension began after the Antihypertensive and Lipid‑Lowering Treatment to Prevent Heart Attack (ALLHAT) trial [1] which brought back diuretics to the forefront in Joint National Committee 7 (JNC 7) recommendations for hypertension. ALLHAT showed that chlorthalidone as an antihypertensive drug was associated with fewer incidents of heart failure (HF) than amlodipine and fewer strokes than lisinopril. The secondary outcomes for amlodipine versus chlorthalidone were similar except for a higher 6‑year rate of HF with amlodipine (10.2% vs. Diuretics were back with a bang! Barring the alpha‑blocker doxazosin which had failed in the ALLHAT trial, diuretics were here to claim their justified place as antihypertensive drugs at par with the more fancied angiotensin‑converting enzyme (ACE) inhibitors and calcium channel blockers and hitherto revered beta blockers. Prologue to this was a dwindling interest in diuretics due to robust and scientific data that had started emerging for newer generation antihypertensive agents, suchs the data from the Heart Outcomes Prevention Evaluation (HOPE) trial supporting ramipril. The potent calcium channel blocker amlodipine, without reflex tachycardia, was the new heartthrob among calcium channel blockers. [4] Prescriptions for good old diuretics were dwindling the world all over. However, diuretics were never evaluated before the ALLHAT era, unlike the newer molecules whose efficacy and safety were proven in well‑designed randomized controlled trials such as HOPE. Diuretics needed a similar head on comparison data for their revival. The Anglo‑Scandinavian Cardiac Outcomes Trial (ASCOT) and the Hypertension in the Very Elderly Trial (HYVET) were like the long needed breather for diuretics though in a different perspective. ASCOT showed that the combination of ACE inhibitors with calcium channel blockers did better than a combination of a diuretic with atenolol. The study was stopped prematurely after 5.5 years' median follow‑up and accumulated a total 106,153 patient‑years of data and evidence. Although not statistically significant, compared with the atenolol‑based regimen, fewer individuals on the amlodipine‑based regimen had a primary endpoint (unadjusted hazard ratio [HR] 0.90, Many ascribed the difference to a lower reduction in the latter combination but the " pro‑diuretic " lobby realized that benefits of diuretics may be nullified by adding a beta blocker! It also made us ponder why what worked for chlorthalidone in ALLHAT did not work for bendroflumethiazide in ASCOT. Was there any difference among different molecules in …