Primary Prevention With Statin Therapy in the Elderly
T he use of statin therapy for secondary prevention is established in all age groups. 1 However, in primary prevention, current cardiovascular guidelines in the United States and Canada describe the role for statin therapy in the elderly as uncertain.To examine this question, we performed a meta-analysis of age-specific outcome data from 2 recent primary prevention statin trials, JUPITER (Justification for Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin) 2 and HOPE-3 (Heart Outcomes Prevention Evaluation). 3We combined new subgroup data from these contemporary trials using a fixed-effect meta-analysis with inverse variance weighting of the log hazard ratios by age group (<65, 65-<70, and ≥70 years) using the meta package in R (R version 3.2.3).The pooled treatment effect within each subgroup was estimated, as was the between-subgroup heterogeneity statistic, Q.The JUPITER trial, published in 2008, evaluated rosuvastatin 20 mg daily among 17 802 men and women free of cardiovascular disease with low-density lipoprotein cholesterol levels <130 mg/dL and high-sensitivity C-reactive protein levels >2 mg/L. 2 For the end point of hard atherosclerotic cardiovascular events (nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death), the JUPITER trial overall reported a 47% reduction in risk (hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.40-0.69;P<0.0001), as well as a 20% reduction in all-cause mortality (HR, 0.80; 95% CI, 0.67-0.97;P=0.02).As shown in the Figure (top), for the 5695 JUPITER participants ≥70 years of age, a comparable 39% reduction in risk was found for this combined cardiovascular end point (HR, 0.61; 95% CI, 0.43-0.86;P=0.004); a nonsignificant 20% reduction in all-cause mortality in this age strata (HR, 0.80; 95% CI, 0.62-1.0;P=0.09) was previously reported. 4These elderly participants, representing 32% of the total JUPITER population, suffered 55% of all the hard atherosclerotic cardiovascular events occurring in the trial.In JUPITER, effects were consistent across age groups, and a formal test for heterogeneity was nonsignificant.Rates of drug withdrawal in the rosuvastatin groups were 14.3%, 17.0%, and 21.6% among those <65, 65 to <70, and ≥70 years of age, respectively.The HOPE-3 trial, published in 2016, evaluated rosuvastatin 10 mg daily among 12 705 men and women free of cardiovascular disease who were at intermediate risk. 3For the identical end point of hard atherosclerotic cardiovascular events, the HOPE-3 trial overall reported a 24% reduction in risk (HR, 0.76; 95% CI, 0.64-0.91;P=0.002) and a 7% nonsignificant reduction in all-cause mortality (HR, 0.93; 95% CI, 0.80-1.08;P=0.32).As also shown in the Figure (top), for the 3086 HOPE-3 participants ≥70 years of age, a comparable nonsignificant 17% reduction in risk was found for the combined cardiovascular end point (HR, 0.83; 95% CI, 0.64-1.07;P=0.16), as well as a comparable nonsignificant 9% reduction in all-cause mortality (HR, 0.91; 95% CI, 0.73-1.13;P=0.38).In HOPE-3, those ≥70 years of age represented 24% of the total trial population yet suffered 43% of all the hard atherosclerotic cardiovascular events.