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Candesartan and hydrochlorothiazide: a NEW HOPE for blood pressure reduction in hypertensive patients?

A new analysis of 2016’s HOPE-3 trial has found no benefit to the aggressive lowering of systolic blood pressure (SBP) below 120mmHg. However, hypertensive patients may reduce the risk of major cardiovascular events (MACE) by using a combination of antihypertensive and lipid-lowering therapies. The data were presented by Doctor Eva Lonn (Population Health Research Institute, Hamilton, Canada) during yesterday’s Clinical Trials Update session.

Cardiovascular Pharmacotherapy

Lonn.jpg“The Heart Outcomes-3 trial (HOPE-3) evaluated blood pressure lowering with a daily fixed dose of both candesartan 16mg and hydrochlorothiazide 12.5mg versus placebo in an intermediate-risk population (n=12,705),” Dr. Lonn explained. The two-by-two factorial study design included co-randomisation to daily rosuvastatin 10mg or placebo, and followed patients out to 5.6 years median follow-up. 

The intermediate-risk population was made up of participants without cardiovascular disease, including men ≥55 and women ≥60 years old with risk factors such as smoking, early renal dysfunction and low LDL cholesterol levels. 

The risk of cardiovascular death, non-fatal myocardial infarction or non-fatal stroke was 4.1% at a median of 5.6 years for those patients by medical therapy, versus the control group’s 4.4% (p=0.4). A composite secondary endpoint including risk of heart failure also failed to reveal a significant difference between the groups (p=0.51). 

The new post-hoc analysis has re-examined the data to investigate associations between baseline and time-averaged in-trial achieved blood pressure and MACE. The team used multivariate adjusted Cox models and multivariate adjusted restriction cubic spline analyses to evaluate the original HOPE-3 results, stratifying the data according to blood pressure level. 

For patients with baseline SBP ≥150mmHg, the percentage of patients experiencing cardiovascular death, stroke or myocardial infarction was significantly lower among the treatment group (4.8%) than the control group (7.2%, p=0.024). There was no difference in the event rate with or without treatment in those patients with a SBP <150mmHg. This was also the case when secondary endpoints were included in the analysis (5.7% vs. 8%, p=0.03). 

In this population, HOPE-3 data demonstrated a link between baseline SBP >120mmHg and an increase in risk for MACE, cardiovascular death and stroke. This risk was “substantially higher” for participants with a baseline SBP ≥160mmHg. Baseline diastolic blood pressure, in comparison, was not linked to higher major cardiovascular events between <70 and ≥90mmHg. 

Over a follow-up period of 5.6 years, the team observed a mean reduction in blood pressure of 6/3mmHg (systolic/ diastolic) for therapy patients, with the largest reductions seen in higher blood pressure patients. In addition, “Fixed dose combination [therapy] reduced major cardiovascular events in the upper third of baseline SBP (≥143.5mmHg), with the largest effect in those with baseline SBP ≥150mmHg,” Dr. Lonn told the audience. 

“Optimal blood pressure during the trial appeared to be about 130/80mmHg,” Dr. Lonn added, “But no benefit was found with aggressive SBP lowering below 120mmHg.” 

This second analysis of the HOPE-3 data revealed that, whilst the overall impact of lowering blood pressure with the use of combined candesartan and hydrochlorothiazide therapy in an intermediate group of patients was not significant, patients with a higher baseline blood pressure do experience a reduction of risk in line with falling blood pressure. 

Click here to read other scientific highlights in the full edition of the Congress news.