Candesartan/hydrochlorothiazide/rosuvastatin combo reduces stroke risk in patients with intermediate CV risk
A combination of the cholesterol-lowering drug rosuvastatin and blood pressure-lowering drugs candesartan and hydrochlorothiazide led to a significant 44 percent reduction in the risk of first strokes among individuals with an intermediate risk of cardiovascular (CV) disease, results from the HOPE-3* study showed.
“These results indicate that to prevent stroke in those at moderate risk, blood pressure lowering plus cholesterol lowering should be considered in those with elevated blood pressure,” said lead author Dr Jackie Bosch from McMaster University and Hamilton Health Sciences in Hamilton, Ontario, Canada who presented the findings at the recent International Stroke Conference 2018 (ISC 2018) in Los Angeles, California, US.
In this multinational study (21 countries), 12,705 participants (mean age 66 years, 46 percent female, mean baseline blood pressure 138/82 mm Hg) with an intermediate risk of CV disease but without overt vascular disease were randomized to receive daily fixed-dose candesartan (16 mg) plus hydrochlorothiazide (12.5 mg) or placebo, rosuvastatin (10 mg) or placebo, or a candesartan/hydrochlorothiazide/rosuvastatin combination or double placebo. One hundred and sixty-six strokes occurred over a median 5.6-year follow-up period.
When compared with placebo, the candesartan plus hydrochlorothiazide combination resulted in a nonsignificant 20 percent reduction in the risk of stroke (hazard ratio [HR], 0.80, 95 percent confidence interval [CI], 0.59–1.08; p=0.14) and a nonsignificant 7 percent reduction in the risk of a composite of myocardial infarction (MI), stroke, and CV death (HR, 0.93, 95 percent CI, 0.79–1.10; p=0.40). [ISC 2018, presentation 104-session A19]
Rosuvastatin alone was associated with a 30 percent decrease in stroke risk (HR, 0.70, 95 percent CI, 0.52–0.95; p=0.02) and a 24 percent decrease in the risk of MI/stroke/CV death (HR, 0.76, 95 percent CI, 0.64–0.91; p=0.002) compared with placebo.
The reduction in stroke risk was most evident among participants on candesartan plus hydrochlorothiazide plus rosuvastatin with the triple combo associated with a 44 percent risk reduction (HR, 0.56, 95 percent CI, 0.36–0.87; p=0.02). Participants on this combination also experienced a significant reduction in the risk of MI/stroke/CV death (HR, 0.71, 95 percent CI, 0.56–0.90; p=0.005).
While the effect of candesartan plus hydrochlorothiazide on stroke risk was not significant, there was a trend towards fewer ischaemic and haemorrhagic strokes with this combination. The 30 percent reduction in strokes with rosuvastatin was a larger effect than expected, primarily through a greater reduction in ischaemic stroke, said Bosch.
According to Bosch, 76 percent of strokes are first strokes that often result in permanent disability or death; therefore, the focus should be on primary prevention to reduce this burden of disease.
“Use of these well tolerated, simple to implement therapies has the potential to prevent 44 percent of first strokes. These are existing drugs that are well-tolerated, have strong safety profiles, and it is easy for patients to stick with them,” she said.
“[However], implementation into practice depends on systems issues, availability, and individual patient situations. The public health implications will require debate and consideration by guideline writers,” said Bosch, highlighting that the next step is to assess if a single tablet containing blood pressure and cholesterol medications will encourage medication adherence in this population, which is at the centre of the ongoing TIPS-3**study.
She also cautioned that these results do not pre-empt the need for lifestyle modifications such as diet, exercise, and smoking cessation as the first line of therapy, but rather present new options for individuals who may have a risk of strokes such as those with a family history of CV disease.