Can we identify response markers to antihypertensive drugs? First results from the Ideal Trial

Current antihypertensive strategies do not take into account that individual characteristics may influence the magnitude of blood pressure (BP) reduction. Guidelines promote trial-and-error approaches with many different drugs. We conducted the Identification of the Determinants of the Efficacy of Arterial blood pressure Lowering drugs (IDEAL) Trial to identify factors associated with BP responses to perindopril and indapamide. IDEAL was a cross-over, double-blind, placebo-controlled trial, involving four 4-week periods: indapamide, perindopril and two placebo. Eligible patients were untreated, hypertensive and aged 25-70 years. The main outcome was systolic BP (SBP) response to drugs. The 112 participants with good compliance had a mean age of 52. One in every three participants was a woman. In middle-aged women, the SBP reduction from drugs was -11.5 mm Hg (indapamide) and -8.3 mm Hg (perindopril). In men, the response was significantly smaller: -4.8 mm Hg (indapamide) and -4.3 (perindopril) (P for sex differences 0.001 and 0.015, respectively). SBP response to perindopril decreased by 2 mm Hg every 10 years of age in both sexes (P=0.01). The response to indapamide increased by 3 mm Hg every 10 years of age gradient in women (P=0.02). Age and sex were important determinants of BP response for antihypertensive drugs in the IDEAL population. This should be taken into account when choosing drugs a priori.Journal of Human Hypertension advance online publication, 17 April 2014; doi:10.1038/jhh.2014.29

Association between difference in blood pressure reduction and risk of cardiovascular events in a type 2 diabetes population: A meta-regression analysis

International audienceAIM: Recent US recommendations indicate a target blood pressure (BP) of 130/80mmHg for patients with type 2 diabetes (T2D). Our aim was to characterize the association between risk of cardiovascular events and differences in BP decreases in randomized trials of a T2D population. METHODS: A systematic search was made for randomized clinical trials assessing the effects of antihypertensive treatments in T2D patients on mortality, and fatal and non-fatal cardiovascular events, using a meta-regression technique to explore the influence of BP decreases on treatment effects. RESULTS: A total of 88,503 patients from 44 randomized trials were included. There was no significant association between BP decreases and risk of all-cause or cardiovascular mortality, cardiovascular events or myocardial infarction. However, stroke risk was influenced by BP decreases: compared with no reduction, a 10-mmHg reduction in systolic BP was associated with a relative odds ratio (OR) decrease of 33% (OR: 0.67, 95% CI: 0.54-0.82), and a 5-mmHg diastolic BP reduction was associated with a relative OR decrease of 38% (OR: 0.62, 95% CI: 0.50-0.76). Restricting the analysis to double-blind studies did not change the results for diastolic BP. CONCLUSION: A reduction in BP lowers the risk of stroke, but does not appear to affect the risk of other cardiovascular events in a T2D population

Efficacy and safety of insulin in type 2 diabetes: meta-analysis of randomised controlled trials

International audienc

CO-05: The first risk score for sudden death prediction in primary prevention patients.

BACKGROUND: Sudden death defined as a death within 1h from the onset of symptom, is a common cardiovascular accident, even more frequent than fatal myocardial infarction. Up to now, DUKE is the only sudden death risk predictor and it was designed specifically for patients of high coronary risk. We constructed here the first sudden death risk score for primary prevention, developed in patients with hypertension and type 2 diabetes. METHODS: We used the Cox model to build this risk score on R (version 3.2.2) based on 30 560 individual data from seven randomized controlled trials (six of INDANA database in hypertension & one in type 2 diabetes Diahhycab). RESULTS: There was no treatment effect and no interaction between treatment and other covariates on the risk of sudden death. This allowed us to develop the model on both treatment/placebo groups. We identified seven risk factors of sudden death : age, sex (male), smoking, cholesterolemia, systolic blood pressure, baseline of type 2 diabetes and history of myocardial infarction. The discrimination performance of the tool was fair (area under the receiver operating characteristic curve (AUC) was about 70%). CONCLUSIONS: Our work provides the first risk score for sudden death prediction in primary prevention patients. This risk score, in particular in hypertension and type 2 diabetes could help stratify patients in order to optimize preventive therapeutic strategies in primary prevention. Further research on sudden death is required to better prevent this highly frequent form of death

P-136: Do sudden death & fatal myocardial infarction have the same risk factors in primary prevention?

Objectifs : Sudden death, defined as a death which happens within 1 hour from the first symptom, is classified commonly as a coronary accident. Myocardial infarction is proposed as principal cause of sudden death. The frequency of sudden death is higher than that of fatal myocardial infarction. A recent overview showed that blood pressure lowering drugs did not decrease sudden death risk, whereas they decrease the risk of fatal myocardial infarction. We analyzed here the risk factors of sudden death and fatal myocardial infarction to provide more insight of the relation between these two accidents. Méthodes : We used Cox model to build the risk scores for two studied accidents on R (version 3.2.2), based on 15279 individual data in placebo group from seven randomized controlled trials (six of INDANA database in hypertension & one in type 2 diabetes Diahhycab)

Can we identify response markers to antihypertensive drugs? First results from the Ideal Trial.

International audienceCurrent antihypertensive strategies do not take into account that individual characteristics may influence the magnitude of blood pressure (BP) reduction. Guidelines promote trial-and-error approaches with many different drugs. We conducted the Identification of the Determinants of the Efficacy of Arterial blood pressure Lowering drugs (IDEAL) Trial to identify factors associated with BP responses to perindopril and indapamide. IDEAL was a cross-over, double-blind, placebo-controlled trial, involving four 4-week periods: indapamide, perindopril and two placebo. Eligible patients were untreated, hypertensive and aged 25-70 years. The main outcome was systolic BP (SBP) response to drugs. The 112 participants with good compliance had a mean age of 52. One in every three participants was a woman. In middle-aged women, the SBP reduction from drugs was -11.5 mm Hg (indapamide) and -8.3 mm Hg (perindopril). In men, the response was significantly smaller: -4.8 mm Hg (indapamide) and -4.3 (perindopril) (P for sex differences 0.001 and 0.015, respectively). SBP response to perindopril decreased by 2 mm Hg every 10 years of age in both sexes (P=0.01). The response to indapamide increased by 3 mm Hg every 10 years of age gradient in women (P=0.02). Age and sex were important determinants of BP response for antihypertensive drugs in the IDEAL population. This should be taken into account when choosing drugs a priori