Superintendent Pharmacist University of Dundee Dundee, United Kingdom
Background: Hypertension remains an important public health problem. Effective treatment reduces cardiovascular complications such as stroke, myocardial infarction (MI), heart failure and early death. In the United Kingdom, National Institute for Health and Clinical Excellence (NICE) guidelines for the management of hypertension have, since 2011, suggested using indapamide (a thiazide-like diuretic) in preference to bendroflumethiazide (a thiazide diuretic), in patients where a diuretic is to be initiated or changed. A recent systematic review highlighted a lack of studies on comparative efficacy of bendroflumethiazide versus indapamide.
Objectives: To compare the effects of prescribing indapamide with bendroflumethiazide as the first-line diuretic in the treatment of hypertension in primary care
Methods: We conducted a cohort study among all patients aged 18 years and over with first diagnosis of hypertension after 1987 in the Clinical Practice Research Datalink (CPRD). We identified two groups with a first-ever prescription of indapamide or bendroflumethiazide and followed them up until the date of last prescription, medication switch, additional hypertension medication, outcome, de-registration, or last data collection. Our primary outcome measure was a composite of non-fatal MI, acute coronary syndrome, stroke, acute decompensated heart failure or death from cardiovascular causes. We use data on age, sex, medical practice, co-morbidities, co-prescribed medication, smoking, weight and alcohol consumption to generate propensity-score matched cohorts. We calculated event rates for each and used descriptive analysis and Cox regression survival models.
Results: We identified 684,331 adults aged 18 years and older diagnosed with hypertension, of whom 5,747 were prescribed indapamide and 125,248 bendroflumethiazide at least twice as first-line therapy for hypertension. After matching, there were 5,747 and 22,988 patients respectively. In the primary per-protocol analysis, there were 118 events in 10,618 PYs for indapamide versus 612 primary outcome events in 45,827 patient years (PYs) for bendroflumethiazide. Indapamide was associated with significantly lower risk of such events: HR 0.79 (95% CI 0.65, 0.96). Indapamide users were less likely to switch to other antihypertensive treatment or have additional antihypertensive medications prescribed.
Conclusions: Patients prescribed indapamide as first-line antihypertensive monotherapy were less likely than those prescribed bendroflumethiazide to experience non-fatal MI, acute coronary syndrome, stroke, acute decompensated heart failure or death from cardiovascular causes. The possibility of residual confounding means these finding need to be confirmed in a randomised study.
