Time Gained to Cardiovascular Disease by Intensive Lipid-Lowering Therapy: Results of Individual Placebo-Controlled Trials and Pooled Effects

IntroductionDespite the effect on blood lipid levels, the clinical benefits of intensive versus standard pharmacological lipid-lowering therapy remain unclear. Previous reviews have presented relative effects on the risk of clinical outcomes, but not the absolute risk reductions (ARRs) and the time gained to a clinical outcome, also called outcome postponement (OP). The aim of this study was to estimate the effect of intensive versus standard lipid-lowering therapy in terms of ARR and OP of major adverse cardiovascular events (MACE), myocardial infarction (MI), stroke, and all-cause mortality.MethodsWe searched PubMed, Embase, and prior reviews to identify trials comparing intensive versus standard lipid-lowering therapy for the risk of cardiovascular disease. We extracted the number of patients with MACE, MI, stroke, and all-cause mortality. Risk of bias was assessed according to the five domains of the Cochrane Risk of Bias Tool 2.0. We calculated ARRs and OPs to assess the clinical benefits of intensive versus standard therapy for each outcome. We conducted meta-analyses standardizing the results to 2 and 5 years of follow-up.ResultsWe identified 11 double-blind, randomized, controlled trials (n = 101,357). The follow-up period ranged from 1.5 to 7.0 years, with an average follow-up duration of 3.7 years. Risk of bias was generally high. During an estimated 2 years of intensive versus standard lipid-lowering therapy, 1.1% (95% confidence interval [CI] 0.7-1.5) fewer patients had MACE and the OP of MACE was 4.1 days (95% CI 2.6-5.6). The effects were 0.7% (95% CI 0.4-0.8) and 2.5 days (95% CI 1.6-3.3) for MI, 0.2% (95% CI 0.1-0.3) and 0.9 days (95% CI 0.5-1.2) for stroke, and 0.2% (95% CI - 0.1 to 0.4) and 0.6 days (95% CI - 0.4 to 1.5) for all-cause death. During on average 5 years of intensive versus standard lipid-lowering therapy, 2.4% (95% CI 1.5-3.3) fewer patients had MACE and the time gained to MACE was 23.5 days (95% CI 14.9-32.0). The effects were 1.5% (95% CI 1.0-2.1) and 14.6 days (95% CI 9.3-20.0) for MI, 0.6% (95% CI 0.4-0.8) and 5.3 days (95% CI 3.3-7.4) for stroke, and 0.4% (95% CI -0.2 to 0.1) and 3.6 days (95% CI - 2.1 to 9.2) for all-cause death.ConclusionIntensive lipid-lowering therapy during 2 or 5 years did not lead to fewer deaths or lifetime gained, and the effects on MI and stroke were negligible. The largest effect was that MACE did not occur in two of 100 patients and was postponed 3-4 weeks after 5 years of intensive treatment. Given the small effect, patients should receive this information as part of shared decision making. Cholesterol-lowering therapy is effective in reducing the risk of heart disease and stroke. Over time, low-density lipoprotein (LDL) cholesterol targets have been progressively lowered to further minimize this risk. This study aimed to compare the effectiveness of intensive versus standard cholesterol-lowering medications for heart disease and stroke benefits. Unlike previous research, this study focused on the absolute difference in risk and the average delay of heart attacks and strokes associated with these treatments. This study analysed data from 11 clinical trials involving over 100,000 participants. It found that intensive cholesterol-lowering medications for 2 or 5 years had a very small impact on heart attacks and strokes and did not lead to fewer deaths or longer lives. The biggest benefit seen was that overall heart disease and strokes did not happen in two out of every 100 patients, and it was delayed by about 3-4 weeks after 5 years of intense treatment. Given the modest effect found in this study, patients should think carefully about this information when making treatment decisions with their doctors.