Hypertension (high blood pressure) is a condition that affects approximately 1 in 3 people in the UK. People may not know they have hypertension until their blood pressure is measured but the condition is associated with a range of complications including heart attacks and strokes. Whilst blood pressure can be lowered by dietary changes such as reducing salt intake, stopping smoking and increasing exercise, some patients may require blood pressure lowering medications. Different types of medications exist and some patients may take multiple tablets if their blood pressure is not controlled by one type of tablet alone. There is evidence that minimizing the number of tables a patient takes may improve outcomes. Therefore, different types of blood pressure therapies can be combined into one tablet. We want to examine the efficacy and safety of taking two blood pressure drugs, valsartan and indapamide, together. We will select patients diagnosed with hypertension in the Clinical Practice Research Datalink who are initially prescribed one of these drugs and then have the other added to their therapy. We will then compare their blood pressure before they have the second drug added to measurements recorded at between 30–150 days and 90–270 days after the second drug was started. We will also compare any side effects that might have occurred to other patients with hypertension treated with one of the drugs who have a different drug added. This will provide useful data, which may improve patient outcomes by increasing the effectiveness of blood pressure lowering therapies.
Hypertension, affecting one in three of the UK population, is associated with increased vascular complications. Hypertensive patients whose blood pressure remains uncontrolled with one anti-hypertensive therapy may benefit from an additional anti-hypertensive added to their regimen. This study aims to evaluate the efficacy and safety of concomitant valsartan and indapamide therapy within the Clinical Practice Research Datalink Aurum and GOLD databases using a retrospective cohort design. Patients with essential arterial hypertension prescribed valsartan or indapamide at a stable dose augmented with the other monocomponent will be selected. Patients with secondary hypertension or those whose other antihypertensive agents change within one month before the index date will be excluded. The combination of valsartan in two different strengths and indapamide will be presented separately and compared. Index date will be the date that valsartan and indapamide are prescribed in combination. Systolic (SBP) and diastolic (DBP) blood pressure measurements at baseline and checkpoints 1 (30–150 days post-index) and 2 (90–270 days post-index) will be compared using the dependent t test or paired sample Wilcoxon signed ranks test depending on the distribution. Between groups comparisons for different strengths of valsartan will use the independent t-tests (or Mann-Whitney U test). The proportion of patients reaching targets (DBP <90 mmHg, SBP <140 mmHg, DBP reduction of ≥10 mmHg or SBP reduction of ≥20 mmHg) will be reported and compared to the baseline using the Chi2 test. The incidence of safety events will be reported in the year post index and incidence rate ratios compared (mid-p test) to a reference group whose antihypertensive therapy (valsartan or indapamide) is augmented with a different antihypertensive agent. This study will provide valuable data that will assist in the potential development of a fixed dosed combination therapy and inform the impact on outcomes with ultimate efficiencies for health services.
Systolic blood pressure change, diastolic blood pressure change, adverse events (agranulocytosis, abnormal hepatic function, acute angle-closure glaucoma, agranulocytosis, angioedema, aplastic anaemia, arrhythmia, arthralgia, back pain, blood glucose increased , blood uric acid increased , blurred vision, choroidal effusion, constipation, cough, diarrhoea, dizziness/vertigo, dry mouth, electrocardiogram qt prolonged , elevated liver enzyme levels, erectile dysfunction, fatigue, haemolytic anaemia, headache, hepatitis, hypercalcaemia, hyperkalaemia, hypersensitivity reactions, hypochloraemia, hypokalaemia, hypomagnesaemia, hyponatraemia, hyponatraemia, hypotension, increased liver enzymes, leukopenia, maculopapular rashes, muscle spasms, muscular weakness, myalgia, myopia, nausea, neutropenia, pancreatitis, paraesthesia, photosensitivity reaction, hepatic encephalopathy in case of hepatic insufficiency, worsening of pre-existing acute disseminated lupus erythematosus, pruritis, purpura, rash, renal failure, renal impairment, including renal failure in susceptible patients, rhabdomyolysis, Stevens-Johnson syndrome, syncope, thrombocytopenia, torsade de pointes), toxic epidermal necrolysis, urticaria, vertigo, visual impairment, vomiting).
Christopher Morgan - Chief Investigator - Pharmatelligence Limited t/a Human Data Sciences
Christopher Morgan - Corresponding Applicant - Pharmatelligence Limited t/a Human Data Sciences
Elgan Mathias - Collaborator - Pharmatelligence Limited t/a Human Data Sciences
Irena Orel - Collaborator - Krka - Slovenia
Sara Redenšek Trampuž - Collaborator - Krka - Slovenia
Sarah Holden - Collaborator - Pharmatelligence Limited t/a Human Data Sciences