1.
Stents and statins: history, clinical outcomes and mechanisms.
Nair, PK, Mulukutla, SR, Marroquin, OC
Expert review of cardiovascular therapy. 2010;(9):1283-95
Abstract
The 1980s witnessed the inception of both stents and 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitors (statins). While they evolved separately, it was soon realized that they each offered a unique and powerful mechanism for targeting the major offender in cardiovascular disease, namely atherosclerosis. Coincidentally, the first statin was approved by the US FDA in 1987, the same year that the coronary stent was conceived. Since that time, stents and statins have revolutionized the field of cardiovascular medicine and their paths have been intertwined. Several pivotal randomized clinical trials have established statins as an effective therapy for improving clinical outcomes after percutaneous coronary intervention (PCI) among patients presenting with stable coronary artery disease and acute coronary syndromes. In addition, chronic statin therapy and acute loading of statins prior to PCI has consistently been shown to limit periprocedural myocardial necrosis. The mechanism for improved clinical outcomes with statins has clearly been associated with statin-induced reductions in LDL. In addition, statins may also exert 'pleiotropic' effects, independent of LDL lowering, that might counteract the inflammatory and prothrombotic mileu created with PCI. This article provides a brief historical perspective of the evolution of the use of statins and stents in patients with coronary artery disease, an evaluation of the available clinical data supporting the use of statins in patients undergoing PCI across a wide spectrum of clinical scenarios, and a discussion of the potential mechanisms of the benefit of statins in these patients.
2.
History and development of plant sterol and stanol esters for cholesterol-lowering purposes.
Thompson, GR, Grundy, SM
The American journal of cardiology. 2005;(1A):3D-9D
Abstract
Plant stanol esters provide a novel approach to lowering plasma low-density lipoprotein (LDL) cholesterol by dietary means. Their development was preceded by a long period of research into the cholesterol-lowering properties of plant sterols and, recently, plant stanols. Both classes of compound competitively inhibit the absorption of cholesterol and thus lower its level in plasma. Initial impressions were that stanols were more effective and safer than sterols, but the negative outcome of a study led to the recognition that the lipid solubility of free stanols was very limited. This was overcome by esterifying them with fatty acids, with the resultant stanol esters being freely soluble in fat spreads. This led to the launch of Benecol (margarine; Raisio Group, Raisio, Finland) in 1995. The coincident publication of the year-long North Karelia study conclusively demonstrated the long-term LDL-lowering efficacy of plant stanol esters. Variables that might influence the efficacy of stanol esters include dose, frequency of administration, food vehicle in which the stanol ester is incorporated, and background diet. The effective dose is 1 to 3 g/day, expressed as free stanol, which, in placebo-controlled studies, decreased LDL cholesterol by 6% to 15%. This effect is maintained, appears to be similar with once-daily or divided dosage, and is independent of the fat content of the food vehicle. Short-term studies suggest that equivalent amounts of plant sterol and stanol esters are similarly effective in lowering LDL, the main difference being that plasma plant sterol levels increase on plant sterols and decrease on plant stanols. The clinical significance of these changes remains to be determined.