Physicians' Academy for Cardiovascular Education

Sustained CV benefits of statin treatment after discontinuation

Lowering cholesterol, blood pressure, or both to prevent cardiovascular events: results of 8.7 years of follow-up of Heart Outcomes Evaluation Prevention (HOPE)-3 study participants

Literature - Bosch J, Lonn EM, Jung H et al. - Eur Heart J. 2021 May 8;ehab225. doi: 10.1093/eurheartj/ehab225.

Introduction and methods

The Heart Outcomes Evaluation Prevention (HOPE)-3 study investigated whether LDL-c reduction or BP reduction, either alone or in combination, reduced CV events in participants without a history of CVD [1-3]. The study enrolled men aged ≥55 years and women aged ≥65 years with one CV risk factor (elevated waist-to-hip ratio, current smoking, impaired fasting glucose, impaired glucose tolerance, diabetes requiring only diet control, eGFR 45-60 mL/min/1.73m², or a family history with premature CVD in first-degree relatives). Women aged between 60-65 years were enrolled when they had 2 risk factors. A total of 12 705 participants were randomized to receive rosuvastatin 10 mg daily or placebo and candesartan 16 mg daily plus hydrochlorothiazide 12.5 mg daily or placebo.

After an active treatment period of 5.6 years, it was found that rosuvastatin reduced MACE by 24%, compared to placebo. Treatment with candesartan plus hydrochlorothiazide led to a reduction in SBP of 6 mmHg. However, this treatment did not reduce MACE in the overall trial population. Only in those in the upper third of baseline BP, a significant reduction in MACE was observed with candesartan plus hydrochlorothiazide, compared to placebo. To study possible longer-term effects of treatments, participants were asked after the active intervention phase of the study of 5.6 years to enroll in the passive extended follow-up of 3.1 further years in which they no longer received study drug. 9326 participants consented to participate in the passive follow-up. The aims of this passive extended follow-up were to determine whether 1) the benefits observed during the active phase with rosuvastatin were sustained, enhanced, or attenuated during the passive phase and 2) delayed benefits would emerge in those receiving candesartan plus hydrochlorothiazide during the active phase compared with placebo.

The two co-primary outcomes in both the active and extended passive phase were MACE-1 (MI, stroke or CV death) and MACE-2 (MACE-1 plus resuscitated cardiac arrest, HF, or coronary revascularization). A secondary endpoint was MACE-2 plus angina, and coronary ischemic events were analyzed in a post hoc analysis. Median length of total follow-up (active treatment period plus post-trial passive observation period) was 8.7 years (IQR 8.1-9.3 years).

Main results


The results of this study suggest that the CV benefits of treatment with rosuvastatin for a median of 5.6 years, compared with placebo, are sustained or enhanced for at least 3 years after stopping therapy in individuals without CVD but at intermediate risk for CV events. Similar results were observed for BP-lowering treatment in individuals with elevated systolic BP (>143 mmHg), but not for those with lower systolic BP.

The authors noted: ‘our data should not be interpreted that statins should be discontinued after 5 or 6 years of treatment, but instead indicate that sustained and enhanced benefits occur even after stopping statin therapy.’


Show references

Find this article online at Eur Heart J.

Share this page with your colleagues and friends: