A systematic review of a series of trials investigating the effect of cholesterol-lowering drugs (statins, ezetimibe and PCSK9 inhibitors) in patients at increased risk of cardiovascular events shows very inconsistent outcomes. Robert DuBroff et al. Publish the results of the review in The BMJ.
Guidance for the researchers was the guidelines from the American Heart Association / American College of Cardiology, which recommend a 30 to more than 50 percent reduction in LDL cholesterol, depending on the risk. Most of the studies in the review were of good quality, with little bias, according to DuBroff et al., But some were nevertheless negatively attributed to fewer than a thousand participants or the lack of a placebo control group.
No positive effect
Key results: First, more than three-quarters of all studies reported no positive effect on the risk of death, and nearly half found no positive effect on the risk of future cardiovascular disease. Second, DuBroff et al. Found no linear relationship between the degree of LDL cholesterol reduction and the absolute risk of cardiovascular disease. Example: In one of the included trials, reduction in the risk of cardiovascular events was associated with an LDL cholesterol reduction of only 11 to 15 percent, while in another trial no cardiovascular benefit was seen with LDL reductions of 50 percent or more. Also the number needed to treat varied enormously, reports DuBroff et al. For example, in a Scandinavian trial only 30 patients had to take simvastatin for 5.4 years to prevent one death, while in another trial 250 patients needed treatment with alirocumab (PCSK9 inhibitor) for 2.8 years. had to prevent one death.
Different classes of medicines
The DuBroff et al. Study has its limitations. In the first place, they consciously chose a systematic review, and not a meta-analysis. Reason: It concerned three different classes of drugs, applied in quite different patient populations. In addition, all studies varied widely on other points, such as study duration, degree of LDL reduction, and definition of cardiovascular endpoints. They also had to exclude a few known trials, such as the PROSPER trial due to an average age of over 75 years and the Heart Protection Study because it did not report the percentage change in LDL cholesterol.
Nevertheless, DuBroff et al. Come to a critical conclusion: ‘In most fields of science, the existence of conflicting evidence usually leads to a paradigm shift or modification of the theory in question, but in this case the conflicting evidence is largely ignored simply because it does not fit the prevailing paradigm. ”