HOPE-3 Trial: Lasting Effect of Rosuvastatin Prevents Major Cardiovascular Events

Compared with placebo, the cardiovascular (CV) benefits of rosuvastatin continued to accrue for at least 3 years after the cessation of randomized treatment in patients without CV disease, which indicates the treatment has a legacy effect, according to authors of a study published in the European Heart Journal.

The Heart Outcomes Prevention Evaluation (HOPE)-3 study (ClinicalTrials.gov identifier: NCT00468923) was designed to assess if reducing blood pressure (BP) or low-density lipoprotein cholesterol (LDL-C), either alone or in combination, would reduce CV events in 12,705 study participants at intermediate risk who had no prior CV events. Compared with placebo, rosuvastatin 10 mg daily reduced major adverse CV events by 24% after 5.6 years.

Although there was no BP lowering benefit overall in the group, participants with the highest third of baseline systolic blood pressure (>143 mmHg; mean, 154 mmHg) did experience a significant reduction in CV disease. Once the trial medications were ceased, investigators assessed whether the benefits observed were enhanced, sustained, or attenuated.

Participants were asked to participate in a median of 3.1 more years of follow-up, for a total of 8.7 years. Coprimary outcomes include a composite of stroke, myocardial infarction, or CV death (major adverse CV event, designated MACE-1), and MACE-1 plus heart failure, resuscitated cardiac arrest, or coronary revascularization (MACE-2). To avoid biases that could be introduced by selective participation in the observation phase of this study, the investigators performed a sensitivity analysis using data from study centers where at least 80% of patients continued through follow-up. To determine any impact of non-CV deaths as competing risks for the MACE-1 outcome, the investigators also performed a cumulative incidence function analysis.

Overall 78% (n=9326/11,994) of surviving HOPE-3 study patients participated in the extended follow-up. There were no significant differences between participants and nonparticipants. During the 3.1 years of post-trial observation, those participants originally randomly assigned to rosuvastatin had a 20% additional reduction in risk of MACE-1, with 146 CV events in the rosuvastatin group compared with 181 in the placebo group (hazard ratio [HR], 0.80; 95% CI, 0.64-0.99). A similar reduction was seen for risk of MACE-2, with 173 CV events (3.7%) in the rosuvastatin group compared with 207 (4.5%) in the placebo group (HR, 0.83; 95% CI, 0.68-1.01).

Over the total 8.7 years of follow-up, patients randomized to rosuvastatin experienced a 21% reduction in MACE-1, with 378 CV events (5.9%) reported among those treated with rosuvastatin compared with 472 (7.4%) events among those who received placebo (HR, 0.79; 95% CI, 0.69-0.90; P =.0005) and a 21% reduction in MACE-2 (HR,0.79; 95% CI, 0.69-0.89; P =.0002). There was no benefit of BP lowering observed, either during the active trial or post-trial observation period. However, a 24% reduction in MACE-1 (95% CI, 0.62-0.96) was seen for participants with the highest baseline systolic BP, with no benefit observed for those with baseline systolic BP ≤143 mmHg (P =.009).

In conclusion, the investigators wrote, “Following the end of randomized statin treatment, in patients without prior CVD and at intermediate risk [for] CV events who were treated with rosuvastatin for a median of 5.6 years, the benefits of treatment continue to accrue for at least several years after it is discontinued. Similar results were observed for BP-lowering treatment in those with elevated BP, but not for those with systolic BP <140 mmHg. These data underscore the importance of early treatment of risk factors and suggest that the benefits of primary prevention may be underestimated in primary prevention trials that do not follow patients beyond the period of active intervention.”

Disclosure: This clinical trial was supported by AstraZeneca. Please see the original reference for a full list of authors’ disclosures.

Reference

Bosch J, Lonn EM, Jung H, et al; on behalf of the Heart Outcomes Prevention Evaluation (HOPE)-3 Investigators. 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. Eur Heart J. Published online May 8, 2021. doi:10.1093/eurheartj/ehab225