Hypertension is a chronic condition characterized by high blood pressure. It represents one of the main risk factors leading to cardiovascular diseases. In England, hypertension affects approximately 30% of men and 26% of women. Clinical guidelines for hypertension first recommend changing some lifestyle factors that could have an impact on blood pressure. These changes may be followed by the prescription of medications for hypertension.
Perindopril and indapamide Sustained Released (SR) are two medications commonly used to treat hypertension. Combining both treatments may help decreasing high blood pressure and reaching the blood pressure level targeted to prevent the risk of cardiovascular diseases. Efficacy of such antihypertensive drugs is usually demonstrated in clinical studies following a strictly defined protocol with multiple and frequent measures of blood pressure, which is quite different to what happens in real life. This study aims at seeing whether a comparable efficacy to what is observed in controlled clinical studies could be observed using blood pressure information collected in routine clinical care. To do this, the study will measure the effect on blood pressure of perindopril and indapamide, when prescribed and followed in real life using the Clinical Research Practice Datalink (CPRD) database. This study will appraise whether there is a suitable methodology to evaluate the efficacy of antihypertensive drugs using blood pressure measures recorded by general practitioners in their usual practice.
Hypertension is a chronic condition characterized by high blood pressure (BP) that affects 30% of men and 26% of women in England. It is a major contributing factor to cardiovascular outcome and reduction of elevated BP can decrease cardiovascular mortality. Perindopril (tert-butylamine 4mg or arginine 5mg) and indapamide Sustained Released (SR) 1.5mg are common hypertensive treatments.
Antihypertensive treatments efficacy is demonstrated in Randomized Controlled Trials (RCT) based on frequent, iterative BP measures while these measurements are sparse in real life setting. The aim of this study is to assess whether this efficacy can be objectivised using BP records collected in routine practice.
In a main approach, this study will emulate, using Clinical Research Practice Datalink, a planned phase III RCT comparing the BP changes when adding indapamide SR on top of perindopril 4/5mg versus staying on perindopril 4/5mg alone, in patients who have uncontrolled hypertension.
Adults patients with 145 ≤ Systolic BP < 160 mmHg, treated with perindopril 4/5mg at stable dose for at least 4 weeks and who either initiate indapamide SR on top of perindopril or renew their prescription for perindopril 5mg/4mg (without adding other therapies) between 2000 and 2020, will be followed for 1 year. Patients in both groups will be matched using a propensity score. The primary outcome that will be SBP change between baseline and week 8, will be assessed using a linear regression model. Missing data will be handled using multiple imputation and return-to-baseline approaches according to missing pattern.
The secondary objective will further assess how BP effect of antihypertensive drugs can be measured considering real life context (less selected population, sparse BP measures). Thus, different methods like alternative definitions of population, alternative definitions of outcomes (e.g., BP control), and complementary statistical approaches (Standardized Mortality Ratio and Inverse probability censoring weighting) will be used.
Blood pressure Change, Blood pressure control.
CELINE DARRICARRERE - Chief Investigator - IRIS - Institut de Recherches Internationales Servier
CELINE DARRICARRERE - Corresponding Applicant - IRIS - Institut de Recherches Internationales Servier
dominique Procureur - Collaborator - IRIS - Institut de Recherches Internationales Servier
Emmanuelle Jacquot - Collaborator - IRIS - Institut de Recherches Internationales Servier
Jaume Aguado - Collaborator - RTI Health Solutions ( USA )
MANEL PLADEVALL - Collaborator - RTI Health Solutions ( USA )
Marie MANGIN - Collaborator - IRIS - Institut de Recherches Internationales Servier
Morgane Ballon - Collaborator - IRIS - Institut de Recherches Internationales Servier
Stéphanie HENNEL - Collaborator - IRIS - Institut de Recherches Internationales Servier
Virginie SIMON - Collaborator - IRIS - Institut de Recherches Internationales Servier
Xabier Garcia de Albeniz - Collaborator - RTI Health Solutions ( USA )
HES Admitted Patient Care;Patient Level Index of Multiple Deprivation