Statins slash long-term death risk in men without CVD
Primary-prevention statins were associated with a 28 percent reduction in long-term risk of death from coronary heart disease (CHD) in men with very high LDL-C levels (≥190 mg/dL) and without established heart disease at baseline, according to a post hoc analysis of the WOSCOPS* trial.
“The present analysis provides novel supporting evidence from a randomized trial to reinforce current recommendations of initiation of lipid-lowering therapy in the primary prevention of individuals with primary elevations of LDL-C ≥190 mg/dL without the need for risk estimation,” wrote the investigators.
The post hoc analysis on WOSCOPS includes data collected during the randomized-trial phase and observational post-trial follow-up of 5,529 men (aged 45–64 years) without pre-existing vascular disease at baseline. During the randomized-trial phase, participants received either pravastatin 40 mg/day or placebo for 4.9 years. [Circulation 2017;doi:10.1161/CIRCULATIONAHA.117.027966]
At the end of the randomized-trial phase, participants with LDL-C levels ≥190 mg/dL who received pravastatin had a 27 percent reduced risk of CHD (p=0.033) and a 25 percent reduced risk in major adverse cardiovascular events (MACE; p=0.037) compared with those receiving placebo.
Over 20 years of follow-up (15 years post-trial), the risk of CHD death was significantly reduced by 28 percent (p=0.020), risk of cardiovascular (CV) death by 25 percent (p=0.009), and risk of all-cause mortality by 18 percent (p=0.004) among participants with LDL-C ≥190 mg/dL in the pravastatin vs the placebo arms.
Compared with pravastatin-treated participants with LDL-C <190 mg/dL, those with LDL-C ≥190 mg/dL derived more than twice the benefit of pravastatin in terms of an absolute risk reduction (ARR) in deaths from CHD, CV causes, or any cause (ARR, 2.34, 3.25, and 5.39 percent, respectively).
Diving deeper into long-term data
Among participants with LDL-C ≥190 mg/dL, achieving a >30 percent (39 mg/dL) reduction in LDL-C with pravastatin was associated with lower risks of developing CHD and MACE than those in the placebo group. Participants whose LDL-C reduction with pravastatin was <30 percent did not differ from placebo controls in their risks of CHD and MACE.
Based on a CV disease risk calculator, a majority (67 percent) of the trial participants with LDL-C ≥190 mg/dL who were free from diabetes had a 10-year predicted MACE risk of <7.5 percent at baseline, who would usually be ineligible for statins.
“Among placebo-treated patients with LDL-C ≥190 mg/dL the observed risk of MACE at 5 years was already 7.5 percent, ie, double what would have been predicted using a risk calculator,” observed the researchers. However, this risk was reduced to 4.8 percent in those receiving pravastatin, corresponding to a 38 percent risk reduction (p=0.018).
“These data reinforce the notion that among patients with a LDL-C ≥190 mg/dL the observed risk is much greater than would be predicted through a risk calculator, and thus global risk estimation is not necessary,” they added.
Nonetheless, the researchers acknowledged that the 15 years post-trial follow-up was observational and subjected to residual confounding, including the lack of continuing information on medication use. Also, the study population comprised a large proportion of smokers (at least 40 percent in each group), which according to the investigators “might mean that a similar study today might not show as strong an effect with a statin regimen of similar potency.”
Added value for clinical practice
While the ACC/AHA** cholesterol guidelines recommend that individuals with LDL-C ≥190 mg/dL be treated with high-intensity statin therapy, randomized trial evidence for statins were lacking for those with very high LDL-C but without pre-existing vascular disease.
“[W]e show that statins reduce the risk of death in this specific group of people who appear largely healthy except for very high LDL levels. This legitimizes current guidelines which recommend treating this population with statins,” said study principal investigator Professor Kaushik Ray of the School of Public Health at Imperial College London in London, UK.
“Nowadays it would be unethical to perform a placebo-controlled trial in the population with LDL-C ≥190 mg/dL … Our findings provide the first trial-based evidence to support the guidelines for treating patients with LDL above 190 mg/dL and no signs of heart disease,” said Ray and co-authors. “Our analysis firmly establishes that controlling LDL over time translates to fewer deaths in this population.”