Randomized cardiovascular trials aimed to reduce the excessive residual risk in high-risk patients through a more aggressive LDL-cholesterol control or targeting triglycerides or HDL-cholesterol levels have shown a null or, at best, limited incremental benefit. In some cases, the treatment produced meaningful effects only in study subgroups. As a consequence, some compounds were withdrawn (e.g. nicotinic acid derivatives and CETP inhibitors), whereas others (fibrates) are utilized with reluctance due to the low level of evidence-based data. By reviewing these trials analytically, we identified a common feature that might explain their meagre results: most of them involved patients generically at high cardiovascular risk with normal or near normal lipid levels and not patients with "true" dyslipidemia, who would receive the treatment if it were part of usual care. These observations may warrant reexamining a central criterion of pragmatism, eligibility, in the outline of forthcoming cardiovascular trials with novel lipid-modifying drugs.
Werba JP, Vigo LM, Veglia F, Marenzi G, Tremoli E, Baldassarre D. Trials in "true" dyslipidemic patients are urged to reconsider comprehensive lipid management as a means to reduce residual cardiovascular risk. Clin Pharmacol Ther 2019 Mar 27. doi: 10.1002/cpt.1436. [Epub ahead of print]