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Indian guidelines on hypertension-IV (2019): need to differentiate thiazide-like diuretics

Journal of Human Hypertension volume 34, pages 841–842 (2020)Cite this article

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We have read with interest the 4th edition of the Indian Guidelines on Hypertension [1]. The authors have offered balanced information to clinicians in a precise format. We wish to discuss few points.

  • In “What is New” section, β-blockers are not considered as first-line agents; while under ‘Principles of drug treatment’, newer β-blockers are enlisted as first-line option for stage 1–2 hypertension. We believe it is a typographical error and new-generation β-blockers must be considered as first-line option for specific profiles like young hypertensives.

  • The authors rightly highlight that “Like white-coat hypertension, masked hypertension should also be recognized” and that ambulatory blood pressure monitoring (ABPM) is useful to identify these patterns and nocturnal hypertension (nondippers). In this regard, differences between chlorthalidone (CTD) and hydrochlorothiazide (HCTZ) are noteworthy, especially the long half-life of CTD (40–60 h vs. 3.2–13.1 h of HCTZ) [2]. A double-blind RCT in Indian patients compared CTD (6.25 mg) with HCTZ (12.5 mg) by 24-h ABPM and found that HCTZ merely converted sustained hypertension into masked hypertension. CTD significantly reduced mean 24-h ABP as well as nocturnal BP [3]. The recent American and Canadian hypertension guidelines also have clarified upon the differences between thiazide-type and thiazide-like diuretics with long-acting thiazide-like diuretics like CTD being preferred [4, 5]. Indian guidelines too must clearly state this difference while recommending ‘thiazide diuretics’ in management of hypertension.

  • The authors recommend that ACEI+CCB is better than a diuretic-based combination based on the ACCOMPLISH trial. However, in ACCOMPLISH – a sponsored trial, a weaker thiazide-type diuretic HCTZ was used for comparison (and not CTD which has been used in all NIH-funded studies). CTD is structurally and pharmacokinetically distinct from HCTZ with a much longer duration of action; and against amlodipine, CTD is the appropriate diuretic to be evaluated, as done by major trials funded by National Institutes of Health [6].

  • Another major concern with preferring CCBs over thiazide-like diuretics is the stark difference between these two classes on the incidence of heart failure (HF) in hypertensive patients. In ALLHAT, the largest hypertension trial, substantially higher risk of HF was found with amlodipine than with CTD; risk being even higher in diabetes. Remarkably, Kaplan–Meier curves for hospitalizations or HF-death begin to separate immediately after randomization (RR 2.22; 95% CI: 1.69–2.91; p < 0.001 for amlodipine vs. CTD in first year) [7]. Furthermore, amlodipine-based therapy was not associated with reduction in HF-related outcomes in ACCOMPLISH (HR 1.04; 95% CI: 0.79–1.38, p = 0.77). Thus, use of amlodipine as initial therapy in hypertensive patients, particularly with diastolic dysfunction, is of clinical concern [8] and thiazide-like diuretics must be preferred in these patients.

In “What is New” section, β-blockers are not considered as first-line agents; while under ‘Principles of drug treatment’, newer β-blockers are enlisted as first-line option for stage 1–2 hypertension. We believe it is a typographical error and new-generation β-blockers must be considered as first-line option for specific profiles like young hypertensives.

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References

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Authors and Affiliations

  1. Medical Affairs, Ipca Laboratories Ltd, Mumbai, India

    Anil Pareek & Ravi Tejraj Mehta

  2. Texas Blood Pressure Institute, University of Texas Southwestern Medical School, Dallas, TX, USA

    C. Venkata S. Ram

  3. Consultant Cardiologist, Jaswant Rai Speciality Hospital, Merrut, India

    Rajeev Agarwala

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  1. Anil Pareek
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  2. C. Venkata S. Ram
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Correspondence to Anil Pareek.

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AP and RTM are employees of Ipca Laboratories Ltd., India and are involved in clinical research on chlorthalidone. CVSR, and RA declare no relevant conflicts in relation to this manuscript.

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Pareek, A., Ram, C.V.S., Agarwala, R. et al. Indian guidelines on hypertension-IV (2019): need to differentiate thiazide-like diuretics. J Hum Hypertens 34, 841–842 (2020). https://doi.org/10.1038/s41371-020-00412-4

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