Effects antihypertensive and lipid-lowering therapy on CV risk not influenced by lifestyle
Effects of Lipid-Lowering and Antihypertensive Treatments in Addition to Healthy Lifestyles in Primary Prevention: An Analysis of the HOPE3 Trial
Literature - Dagenais GR, Jung H, Lonn E et al. - J Am Heart Assoc. 2018;7: e008918. DOI: 10.1161/JAHA.118.008918Introduction and methods
Statins and antihypertensive therapy reduce CVD risk, but it remains unknown whether this effect differs between patient with and without a healthy lifestyle. This post hoc analysis of the Heart Outcomes Prevention Evaluation (HOPE-3) trial [1-4], therefore investigated the relationship between the number of healthy lifestyle factors and the advantages of lipid-lowering and antihypertensive medication in CVD risk.
This post hoc analysis of the HOPE-3 trial investigated whether the lifestyle factors non-smoking, physical activity, optimal waist/hip ratio and healthy diet modify the effect of rosuvastatin and the antihypertensive medications candestartan/hydrochlorothiazide on CVD risk.
The double-blind, randomized, placebo-controlled HOPE-3 trial included 12,705 men ≥55 years and women ≥65 years with one CVD risk factor, or women ≥60 years with two CVD risk factors. Participants were randomly assigned to 10 mg rosuvastatin or placebo, 16/2.5 mg candestartan/hydrochlorothiazide or placebo, or the combination of rosuvastatin with candestartan/hydrochlorothiazide or placebo, and were followed for 5.6 years. The physician or nurse assessed the number of healthy lifestyle factors based on a standardized questionnaire.
The primary outcome was a composite of CVD death, non-fatal myocardial infarction, stroke, heart failure, revascularization, resuscitated cardiac arrest or ischemic angina.
Main results
- Patients with ≥2 healthy lifestyle factors had 15% lower CVD risk, compared to patients with <2 healthy lifestyle factors (HR: 0.85, 95%CI: 0.73-1.00).
- Rosuvastatin was associated with decreased number of CV events in both patients with ≥2 healthy lifestyle factors (HR: 0.74, 95%CI: 0.62-0.90) and patients with <2 healthy lifestyle factors (HR: 0.79, 95%CI: 0.61-1.01), compared to placebo (P-interaction=0.749).
- The number of CV events was lowered with rosuvastatin in combination with candestartan/hydrochlorothiazide in both patients with ≥2 healthy lifestyle factors (HR: 0.74, 95%CI: 0.57-0.97) and patients with <2 healthy lifestyle factors (HR: 0.61, 95%CI: 0.43-0.88), compared to placebo.
- Candestartan/hydrochlorothiazide was associated with reduced CVD risk in patients with <2 healthy lifestyle risk factors (HR: 0.78, 95%CI: 0.61-1.00) but not in patients with ≥2 healthy lifestyle factors (HR: 1.00, 95%CI: 0.83-1.20), compared to placebo (P-interaction=0.126).
- Patients with elevated systolic pressure (≥143.5 mmHg) showed lower risk of CV events with candestartan/hydrochlorothiazide (≥2 healthy lifestyle factors HR: 0.76, 95%CI: 0.58-1.01, <2 healthy lifestyle factors HR: 0.65, 95%CI: 0.44-0.97), compared to placebo (P-interaction=0.546).
- Rosuvastatin was associated with reduced CVD risk in both lifestyle groups with elevated systolic pressure (≥2 HR: 0.77, 95%CI: 0.58-1.02 and <2 HR: 0.73, 95%CI: 0.50-1.08), compared to placebo (P-interaction=0.787).
- Combined therapy showed reduced outcomes in both lifestyle groups with elevated systolic pressure (≥2 HR: 0.55, 95%CI: 0.36-0.84 and <2 HR: 0.48, 95%CI: 0.27-0.83), compared to placebo (P-interaction=0.654).
Conclusion
Healthy lifestyle factors are associated with reduced CVD risk. The effect of statins, with or without antihypertensive therapies, on CVD risk is not affected by the extent to which participants have a healthy lifestyle. In contrast, treatment with only candestartan/hydrochlorothiazide did not have any effect on CVD risk in patients with a healthy lifestyle.
References
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