HOPE-3: Blood Pressure, Cholesterol Lowering Evaluated in Intermediate-Risk Patients

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In patients with intermediate risk for CVD, statin therapy appeared to have a more significant effect on outcomes vs antihypertensive therapy.
In patients with intermediate risk for CVD, statin therapy appeared to have a more significant effect on outcomes vs antihypertensive therapy.

Blood pressure and cholesterol-lowering effects were studied in patients without the presence of cardiovascular (CV) disease but who were considered “immediate risk” for disease in the HOPE-3 (Heart Outcomes Prevention Evaluation) clinical trial.

The findings were presented by study investigators Eva Lonn, MD, MSc, FRCPC, FACC; Jackie Bosch, MD; and Salim Yusuf, MD, DPhil at the American College of Cardiology's (ACC) Scientific Sessions and simultaneously published in the New England Journal of Medicine.

A total of 12 705 patients were enrolled in the trial with a 2-by-2 factorial design. Patients were recruited from 228 centers in 21 countries and were followed-up for a median of 5.6 years. Dr Eva Lonn, professor of medicine at McMaster University in Hamilton, Canada, pointed out that the ethnically diverse population allowed the research team to conduct multiple subanalyses, including stroke risk, LDL cholesterol levels, and systolic blood pressure values at baseline.


The first coprimary outcome was composite death from CV causes, nonfatal myocardial infarction (MI), or nonfatal stroke.  The second coprimary outcome included resuscitated cardiac arrest, heart failure, and revascularization.

The mean blood pressure was 138.1/81.9 mm Hg at baseline. In addition, the mean systolic blood pressure was 138.2 ± 14.7 mm Hg in the active-treatment group and 137.9 ± 14.8 mm Hg in the placebo group. The decrease was 6.0/3.0 mm Hg greater in the treatment group vs the placebo group.

Antihypertensive therapy with candesartan (16 mg/day) plus hydrochlorothiazide (HCTZ; 12.5 mg/day) was not associated with lower rates of major CV events compared with placebo. However, researchers did observe significantly lower rates of the first and second coprimary outcomes in the upper third SBP group (>143.5 mm Hg). In the middle and lower thirds, the effects were neutral (P=.02 and P=.009, respectively, for trend in the 2 outcomes).

“The pattern for stroke differed, with no heterogeneity in the 3 subgroups that were defined according to baseline systolic blood pressure,” the researchers wrote in 1 of their published reports. “Blood-pressure differences between the trial groups were similar across the 3 subgroups of baseline systolic blood pressure. Therefore, the observed subgroup findings are not related to differences in the magnitude of blood-pressuring lowering but rather to a differential effect in participants at different baseline blood-pressure levels.”

At the ACC press conference, Dr Lonn commented that both the JNC-8 and European guidelines still debate over the BP entry level for patients with “uncomplicated hypertension,” but the results from HOPE-3 may help better define those values.

By studying the effects of rosuvastatin (10 mg/day) on LDL cholesterol, researchers found that the agent resulted in a significantly lower risk of CV events. The first coprimary outcome occurred in 235 patients (3.7%) of the treatment group and 304 patients (4.8%) in the placebo group (hazard ratio=0.76; 95% CI, 0.64-0.91; P=.002). Interestingly, results were consistent regardless of race or ethnic group, lipid level, C-reactive protein level, blood pressure, or CV risk at baseline.

Dr Salim Yusuf, president of the World Heart Federation, was careful to note that trials lasting 5 to 6 years, such as HOPE-3, often underestimate the benefits of prevention. Over longer periods of time, combining treatments will lead to better risk reduction and more cost-effective health care. “If you don't have to bring [patients] back to re-titrate drugs over and over again, you're saving money,” Dr Yusuf said. “You're also saving [the patient] in indirect ways — time, travel, etc.”

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