Chlorthalidone vs Hydrochlorothiazide for Hypertension-CV Events: Did the Design Influence the Outcome?

The Diuretic Comparison Project (DCP)1 was a real world study planned to evaluate in a pragmatic manner whether Chlorthalidone (CTD), as compared with Hydrochlorothiazide (HCTZ), would reduce the risk of major nonfatal cardiovascular disease outcomes in elderly hypertensive participants (≥65 years) who were receiving HCTZ (25 or 50 mg) at baseline. This study being a real world study lacks the robustness of a randomized controlled trial. The principle limitation being unequal exposure of the two diuretics, prolonged unknown duration of exposure to HCTZ vs a short exposure to CTD (Median 2.4 years). In the high risk population with history of MI/Stroke, CTD conferred a lower risk of primary outcome as compared to low risk population where no significant difference in outcome was seen in both diuretics. Other factors included, lack of established dose equivalency of the two diuretics and absence of use of 12.5 mg HCTZ in older hypertensives. How to cite this article: Pareek A, Messerli FH, Ram CVS. Chlorthalidone vs Hydrochlorothiazide for Hypertension-CV Events: Did the Design Influence the Outcome? J Assoc Physicians India 2023;71(10):93-93.

Interamerican Society of Cardiology (IASC) position statement: Chlorthalidone vs. thiazide-type diuretics.

The Interamerican Society of Cardiology (IASC) Position Statement for hypertension management in Latin America is a practical and useful review of five different hypertension guidelines. Though, thiazide diuretics have been recommended as firstline option, the position statement needs to highlight differences within the thiazide class. Chlorthalidone is structurally and pharmacokinetically distinct from thiazide-type iuretics like hydrochlorothiazide with a longer half-life and 24-h anti-hypertensive effect. It has been shown to reduce cardiovascular morbidity and mortality in several landmark studies evaluating anti-hypertensives.

Compelling therapy of LVH: straight (and not-so-straight) inferences from evidence.

We have read with interest the Korean Society of Hypertension guidelines for the management of hypertension and congratulate the Society for an extensive review of literature while drafting the guidelines. The guidelines indicate preferring ACE-I and CCB over diuretics in patients with left ventricle hypertrophy. However, in landmark head-to-head comparison trials, the thiazide-like diuretic chlorthalidone has been shown to be superior to ACE-I and CCB in decreasing left ventricle mass and preventing heart failure in hypertensive patients. Also, we put forth the paradoxical finding that mere regression of LVH may not always translate into reduction in risk of HF; and that the pleiotropic effects of chlorthalidone may be the explanation behind its beneficial action in HF.

Chlorthalidone, not hydrochlorothiazide, is the right diuretic for comparison.

We have read the study design "Comparison of effects between calcium channel blocker and diuretics in combination with angiotensin II receptor blocker on 24-h central blood pressure and vascular hemodynamic parameters in hypertensive patients: study design for a multicenter, double-blinded, active controlled, phase 4, randomized trial" by Oh GC, et al. with interest. The authors aim to compare the efficacy of amlodipine or hydrochlorothiazide (HCTZ) with an ARB. However, we wish to highlight that chlorthalidone (CTD) is the evidence-based and recommended anti-hypertensive diuretic, and should replace HCTZ in the trial to effectively compare efficacy against the CCB amlodipine.

Aceclofenac cocrystal nanoliposomes for rheumatoid arthritis with better dermatokinetic attributes: a preclinical study.

AIM: The aim of present research was to complex aceclofenac with lysine (LYS) and the developed aceclofenac-LYS cocrystal was encapsulated in lipid bilayers of liposomes by employing dual carrier approach for the treatment of pain-related disorders in rheumatoid arthritis (RA). MATERIALS & METHODS: The developed carriers were characterized for particle size, drug release, ex vivo and in vivo studies, dermatokinetic modeling, complete freund's adjuvant (CFA)-induced RA rat model, radiant heat tail-flick method, formalin-induced paw-licking model, paw edema model and xylene-induced ear edema model in mice. RESULTS: The developed nanoliposomes offered nanometric size, controlled drug release and enhanced drug permeation. Further, hydrogel incorporated nanoproduct was found to be rheologically acceptable and substantially compatible with rodent skin. CONCLUSION: The studies indicated the superiority of LYS-conjugated liposome-entrapped nanocarriers for improved management of conditions like RA over the marketed product.