Impact of Lifestyle on the Benefit of Pharmacotherapy for Hypertension and Dyslipidemia

Introduction

HOPE-3 was an international double-blind, placebo-controlled clinical trial involving 12,705 patients at moderate cardiovascular risk without CV diseases. Patients were randomized to therapy with rosuvastatin at a dose of 10 mg, or a fixed combination of candesartan/hydrochlorothiazide at a dose of 16/12.5 mg, or their combination, or to placebo. The median follow-up was 5.6 years. The primary endpoint was the incidence of CV events.

Rosuvastatin showed a reduction in the risk of the composite CV endpoint by 23% compared to placebo, and combination therapy by 29%. The benefit of antihypertensive therapy in reducing the risk of CV events was observed only in patients with systolic blood pressure in the highest tertile (≥ 143.5 mmHg), with relative risk reduced by 28% in this group.

Methodology of Analysis

For the purpose of analysis, patients were divided into groups according to adherence to healthy lifestyle principles. Four lifestyle factors were considered: smoking (non-smokers and former smokers who have not smoked for > 1 year vs. active smokers and former smokers who have not smoked for ≤ 1 year), physical activity (moderate to high vs. low), optimal waist-to-hip ratio (≤ 0.89 for men and ≤ 0.84 for women vs. higher values), and quality of nutrition (healthy vs. unhealthy diet). The endpoint was the incidence of cardiovascular events: death from CV causes, non-fatal myocardial infarction, stroke, heart failure, revascularization, resuscitated cardiac failure, or angina pectoris with documented myocardial ischemia.

Health data necessary for the analysis were available for 12,521 participants in the HOPE-3 study. Patients were divided into two groups: with ≥ 2 healthy lifestyle factors (n = 8329, 66.5%) and with < 2 healthy lifestyle factors (n = 4192; 33.5%). No significant difference in therapy adherence was observed between the groups.

Results

Patients with ≥ 2 healthy lifestyle factors had a lower risk of CV events compared to patients with < 2 healthy lifestyle factors (hazard ratio [HR] 0.85, 95% confidence interval [CI] 0.73–1.00).

Combined antihypertensive and hypolipidemic therapy reduced the risk of CV events compared to placebo in both the healthier living group (HR 0.74; 95% CI 0.57–0.97) and the less healthy living group (HR 0.61; 95% CI 0.43–0.88). Similar results were observed with rosuvastatin treatment. In patients with ≥ 2 healthy lifestyle factors, the risk of CV events was reduced by 26% compared to placebo (HR 0.74; 95% CI 0.62–0.90) and by 21% in patients with < 2 healthy lifestyle factors (HR 0.79; 95% CI 0.61–1.01).

The benefit of candesartan/hydrochlorothiazide monotherapy in reducing the risk of CV events compared to placebo was observed in the less healthy living group (HR 0.78; 95% CI 0.61–1.00), but not in the group with ≥ 2 healthy lifestyle factors. In patients with systolic blood pressure in the highest tertile (≥ 143.5 mmHg), candesartan/hydrochlorothiazide led to a significant reduction in the risk of CV events compared to placebo in both groups (healthier living group: HR 0.76; 95% CI 0.58–1.01; less healthy living group: HR 0.65; 95% CI 0.44–0.97).

Conclusion

The analysis results showed that combined therapy with candesartan/hydrochlorothiazide and rosuvastatin and monotherapy with this statin reduce the risk of CV events in both healthier and less healthy living patients. Monotherapy with candesartan/hydrochlorothiazide demonstrated a significant reduction in the risk of CV events in patients with < 2 healthy lifestyle factors and in patients with systolic blood pressure ≥ 143.5 mmHg regardless of evaluated lifestyle factors.

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Source: Dagenais G. R., Jung H., Lonn E. Effects of lipid-lowering and antihypertensive treatments in addition to healthy lifestyles in primary prevention: an analysis of the HOPE-3 trial. J Am Heart Assoc 2018; 7 (15), pii: e008918, doi: 10.1161/JAHA.118.008918.