(107) Association of The Swissmedic Safety Alert Regarding Skin Cancer and The Use of Hydrochlorothiazide and Other Antihypertensives in Switzerland

Sunday, August 28, 2022

8:00 AM – 1:45 PM CEST

Location: Hall C

Publication Number: 1152

Presenting Author(s)

Tamino Zappalà
– University of Basel, University of Basel, Basel, Basel-Stadt, Switzerland

Co-Author(s)

Anton Pottegård, PhD, MSc
– University of Southern Denmark, Odense C, Denmark
Carola A Huber
– Department of Health Sciences, Helsana Insurance Group, Zürich, Switzerland, Switzerland
Christoph Meier, Prof Dr
– Basel Pharmacoepidemiology Unit, Division of Clinical Pharmacy and Epidemiology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland, Switzerland
Julia Spoendlin
– Basel Pharmacoepidemiology Unit, Division of Clinical Pharmacy and Epidemiology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland, Switzerland

Background: Over the past five years, studies consistently revealed an increased risk of non-melanoma skin cancer in association with hydrochlorothiazide (HCT). Swissmedic issued a direct healthcare professional communication (DHPC) on November 18th 2018.

Objectives: To evaluate the association between the DHPC and the use of HCT and other first-line antihypertensives in Switzerland.

Methods: We performed an interrupted time series analysis using claims data from the Swiss health insurance ‘Helsana’ between January 1st 2014 and February 28th 2020. Within monthly intervals (30 days), we quantified the total dispensed defined daily doses (DDD) per 10’000 insured individuals of preparations containing 1) HCT, 2) ACE-inhibitors and angiotensin-receptor blockers (ACEI / ARB), 3) calcium-channel blockers (dihydropyridine-type, CCB) and 4) thiazide-like diuretics (bendroflumethiazide not on Swiss market). We conducted segmented linear regression (adjusted for seasonality) to quantify the average number and the trend of monthly dispensed DDD per 10’000 individuals prior to the DHPC, as well as the immediate change (four months lag period) and the slope change over time after the DHPC.

Results: We identified a yearly average of 1’121’043 insured individuals during the study period. We observed an average number of dispensed DDD of HCT of 11’713 / 10’000 prior to the DHPC, which was already declining (trend = - 26.6 DDD/10’000 per month, p< 0.0001). The DHPC was associated with an immediate 5.9% decline in the number of dispensed DDD of HCT (- 692.5 DDD/10’000, p=0.007) and a slope change of - 79.8 DDD/10’000 per month (p=0.0046). The average number of dispensed DDD (60’822/10’000) of ACEI / ARB increased prior to the DHPC (104.8 DDD/10’000 per month, p< 0.0001), but the DHPC was not associated with a significant immediate effect (-2’324, p=0.0962) or slope change (-101.8, p=0.5019). The same was the case for CCB (average = 18’366 DDD/10’000 per month before DHPC; trend = 61.4, p< 0.0001; immediate effect = -193, p=0.7187; slope change = -2.3, p=0.9681). Thiazide-like diuretics were not frequently used (1’546 DDD/10’000 per month before DHPC; trend = 6.7, p< 0.0001; immediate effect = -63.3 DDD/10’000, p=0.1839; slope change = 12.5 DDD/10’000, p=0.0173).

Conclusions: Between 2014 and end of February 2020, the use of HCT (in DDD) decreased by 31%. The DHPC was associated with a moderate immediate and prolonged accelerated decline in the use of HCT in Switzerland. Due to the lack of bendroflumethiazide, this decrease appears to be mainly compensated by a 6.6% increase in ACEI / ARB, the most frequently used antihypertensives. Use of CCB increased by 22%, although at a third of the use volume of ACEI / ARB. The DHPC per se was not associated with a change in trend of the use of ACEI / ARB and CCB.