UK supply of chlortalidone for hypertension must be restored

Morrison, Emma; Turtle, Emma; Webb, David J.

doi:10.1136/bmj.f3076

Cited by 3 publications

(2 citation statements)

References 3 publications

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“…Third, we identified only a small number of thiazide-like diuretic users in the cohort, which limited our evaluation to their duration-exposure relationship. This might result from the fact that many patients had started HCTZ when a thiazide diuretic was first indicated or that thiazide-like diuretics were in limited supply (41). Fourth, accurate dosage information was unavailable, precluding analysis of the dose-response relationship.…”

Section: Strengths and Limitationsmentioning

confidence: 99%

The Risk of Cutaneous Squamous Cell Carcinoma Among Patients with Type 2 Diabetes Receiving Hydrochlorothiazide: A Cohort Study

Landman

Groenier²,

Vissers

et al. 2021

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background: Because of continuous hyperglycemia and hyperinsulinemia and the use of photosensitizing drug, hydrochlorothiazide (HCTZ), the risk of cutaneous squamous cell carcinoma (cSCC) might be increased among patients with diabetes. This study aimed to estimate the risk of cSCC among HCTZ users with type 2 diabetes, and to determine whether thiazide-like diuretics, another drug in the same class with HCTZ, would be safer.Methods: We linked the benchmarking database in Dutch primary care, the Netherlands Cancer Registry, and the Dutch Personal Records Database (1998-2019). All 71,648 patients were included, except for those who had a history of skin cancer prior to cohort entry. We used Cox modeling to estimate the HRs and 95% confidence intervals for cSCC. The model was adjusted by cumulative exposure to each antihypertensive, age, sex, smoking, body mass index, blood pressure, serum creatinine, other confounding drug use at cohort entry, and cohort entry year.Results: There were 1,409 cSCC events (23 among thiazide-like diuretics users), during a follow-up of 679,789 person-years. Compared with no HCTZ use, the adjusted HRs for HCTZ use were 1.18 (1.00-1.40) for ≤2 years, 1.57 (1.32-1.88) for 2 to 4 years, and 2.09 (1.73-2.52) for >4 years. The HR was 0.90 (0.79-1.03) for an additional year of thiazide-like diuretic use.Conclusions: In patients with diabetes, exposure to HCTZ for >2 years is associated with an increased risk of cSCC, whereas no increased risk associated with thiazide-like diuretics was observed.Impact: The potential increased risk of cSCC should be a consideration when prescribing HCTZ, with thiazide-like diuretics offering a safer alternative.

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Section: Strengths and Limitationsmentioning

confidence: 99%

The Risk of Cutaneous Squamous Cell Carcinoma Among Patients with Type 2 Diabetes Receiving Hydrochlorothiazide: A Cohort Study

Landman

Groenier²,

Vissers

et al. 2021

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…The hypertension community remains in equipoise about diuretic choice, and many local prescribing policies did not take up the NICE recommendation. This situation is likely to have also been influenced by chlortalidone not being readily available in the UK and indapamide being significantly more expensive than bendroflumethiazide [21].…”

Section: Rationale For Evidencementioning

confidence: 99%

Evaluating Diuretics in Normal Care (EVIDENCE): Protocol of a cluster randomised controlled equivalence trial of prescribing policy to compare the effectiveness of thiazide-type diuretics in hypertension

Rogers

Flynn

Mackenzie

et al. 2020

Preprint

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IntroductionHealthcare systems must use treatments that are effective and safe. Regulators licensed many currently used older medications before introducing the stringent evidential requirements imposed on modern treatments. Also, there has been little encouragement to carry out within-class, head-to-head comparisons of licensed medicines. For commonly prescribed drugs, even small differences in effectiveness or safety could have significant public health implications. However, conventional clinical trials that randomise individual subjects are costly and unwieldy. Such trials are also often criticised as having low external validity. We describe an approach to rapidly generate externally valid evidence of comparative safety and effectiveness using the example of two widely used diuretics for the management of hypertension.Methods and AnalysisThe EVIDENCE (Evaluating Diuretics in Normal Care) study has a prospective, cluster-randomised, open-label, blinded end-point design. By randomising prescribing policy in primary care practices, the study compares the safety and effectiveness of commonly used diuretics in treating hypertension. Participating practices are randomised 1:1 to a policy of prescribing either indapamide or bendroflumethiazide when clinically indicated. Suitable patients who are not already taking the policy diuretic are switched accordingly. All patients taking the study medications are written to explaining the rationale for changing the prescribing policy and notifying them they can opt-out of any switch. The prescribing policies’ effectiveness and safety will be compared using rates of major adverse cardiovascular events (hospitalisation with myocardial infarction, heart failure or stroke or cardiovascular death), routinely collected in national healthcare administrative datasets. The study will seek to recruit 250 practices to provide a study population of approximately 50,000 individuals with a mean follow-up time of 2 years. The primary analysis will test for equivalence with a 30% margin in a per-protocol cohort.Ethics and DisseminationEVIDENCE has been approved by the East of Scotland Research Ethics Service (17/ES/0016, current approved protocol version 4, 28th September 2019). The results will be disseminated widely in peer review journals, guideline committees, National Health Service (NHS) organisations and patient groups.Trial registration numberISRCTN 46635087; registered pre-results, 11/08/2017.Strengths and limitations of this study designA cluster randomisation design maximises generalisability of results to UK NHS primary care.Study interventions with minimal impact on existing NHS workflows should encourage recruitment.Development of electronic study search tools and routinely collected data facilitates participation by remote and rural practices.One-off policy interventions may have a limited long-term effect on prescribing behaviour.

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Evaluating Diuretics in Normal Care (EVIDENCE): protocol of a cluster randomised controlled equivalence trial of prescribing policy to compare the effectiveness of thiazide-type diuretics in hypertension

Rogers

Flynn

Mackenzie

et al. 2021

Trials

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Introduction Healthcare systems must use treatments that are effective and safe. Regulators licensed many currently used older medications before introducing the stringent evidential requirements imposed on modern treatments. Also, there has been little encouragement to carry out within-class, head-to-head comparisons of licensed medicines. For commonly prescribed drugs, even small differences in effectiveness or safety could have significant public health implications. However, conventional clinical trials that randomise individual subjects are costly and unwieldy. Such trials are also often criticised as having low external validity. We describe an approach to rapidly generate externally valid evidence of comparative safety and effectiveness using the example of two widely used diuretics for the management of hypertension. Methods and analysis The EVIDENCE (Evaluating Diuretics in Normal Care) study has a prospective, cluster-randomised, open-label, blinded end-point design. By randomising prescribing policy in primary care practices, the study compares the safety and effectiveness of commonly used diuretics in treating hypertension. Participating practices are randomised 1:1 to a policy of prescribing either indapamide or bendroflumethiazide when clinically indicated. Suitable patients who are not already taking the policy diuretic are switched accordingly. All patients taking the study medications are written to explaining the rationale for changing the prescribing policy and notifying them they can opt-out of any switch. The prescribing policies’ effectiveness and safety will be compared using rates of major adverse cardiovascular events (hospitalisation with myocardial infarction, heart failure or stroke or cardiovascular death), routinely collected in national healthcare administrative datasets. The study will seek to recruit 250 practices to provide a study population of approximately 50,000 individuals with a mean follow-up time of two years. A primary intention-to-treat time-to-event analysis will be used to estimate the relative effect of the two policies. Ethics and dissemination EVIDENCE has been approved by the East of Scotland Research Ethics Service (17/ES/0016, current approved protocol version 5, 26 August 2021). The results will be disseminated widely in peer reviewed journals, guideline committees, National Health Service (NHS) organisations and patient groups. Trial registration ISRCTN46635087. Registered on 11 August 2017 (pre-recruitment).

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UK supply of chlortalidone for hypertension must be restored

Abstract: specialist trainee year 3, clinical pharmacology, Emma J Turtle McKenzie lecturer in clinical pharmacology, David J Webb Christison professor of therapeutics and clinical pharmacology Pharmacology, Toxicology and Therapeutics,

Cited by 3 publications

References 3 publications

The Risk of Cutaneous Squamous Cell Carcinoma Among Patients with Type 2 Diabetes Receiving Hydrochlorothiazide: A Cohort Study

The Risk of Cutaneous Squamous Cell Carcinoma Among Patients with Type 2 Diabetes Receiving Hydrochlorothiazide: A Cohort Study

Evaluating Diuretics in Normal Care (EVIDENCE): Protocol of a cluster randomised controlled equivalence trial of prescribing policy to compare the effectiveness of thiazide-type diuretics in hypertension

Evaluating Diuretics in Normal Care (EVIDENCE): protocol of a cluster randomised controlled equivalence trial of prescribing policy to compare the effectiveness of thiazide-type diuretics in hypertension

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