The cardioprotective mechanisms of colchicine in patients with stable ischemic heart disease remain uncertain. We tested varying concentrations of colchicine on platelet activity in vitro, and a clinically relevant 1.8 mg oral loading dose administered over one hour in 10 healthy subjects. Data are shown as median [interquartile range]. Colchicine addition in vitro decreased light transmission platelet aggregation only at supratherapeutic concentrations, but decreased monocyte- (MPA) and neutrophil-platelet aggregation (NPA) at therapeutic concentrations. Administration of 1.8 mg colchicine to healthy subjects had no significant effect on light transmission platelet aggregation but decreased the extent of MPA (28% [22–57] to 22% [19–31], p=0.05) and NPA (19% [16–59] to 15% [11–30], p=0.01), platelet surface expression of PAC-1 (370 mean fluorescence intensity (MFI) [328–555] to 333 MFI [232–407], p=0.02) and P-selectin (351 MFI [269–492] to 279 [226–364], p=0.03), and platelet adhesion to collagen (10.2% [2.5–32.6] to 2.0% [0.2–9.5], p=0.09) 2 hours post-administration. Thus, in clinically relevant concentrations, colchicine decreases expression of surface markers of platelet activity and inhibits leukocyte-platelet aggregation, but does not inhibit homotypic platelet aggregation.

Since the advent of percutaneous coronary intervention, enormous advances have been made in the treatment of coronary artery disease. Angioplasty and bare metal stents were plagued by high rates of restenosis leading to repeat revascularization procedures. Examination of the underlying pathophysiology of restenosis led to the development of drug-eluting stents to reduce neointimal hyperplasia. However, as restenosis rates declined, length of dual antiplatelet therapy use and risk of long-term stent thrombosis associated with drug-eluting stents increased. Subsequent generations have improved each facet of stent design. Novel alloys maintain durability and reduce strut thickness to increase deliverability, biocompatible polymers decrease the inflammatory response and improve drug elution kinetics, and new generations of drugs predictably inhibit restenosis. Developments on the horizon include stents with bioabsorbable polymers and platforms. The purpose of this review is to assess the evolution of stent design and the evidence behind each generation and to peer into the future of stent technology.

Summary Introduction: Blood donation has been proposed as a potential therapy to reduce risk of cardiovascular disease, but the effects of phlebotomy on vascular function in human subjects have not been well characterized. Aims: We conducted a prospective randomized double-blind study to determine the effects of serial phlebotomy on vascular endothelial function in the brachial artery. Eighty-four iron-replete, non-anemic subjects were randomly assigned to one of three study treatment groups: (a) four serial phlebotomy procedures each followed by intravenous infusion of placebo normal saline; (b) four serial phlebotomy procedures each followed by intravenous infusion to replete lost iron; and (c) four serial sham phlebotomy procedures each followed by intravenous infusion of placebo normal saline. Assigned phlebotomy procedures were conducted at 56-day intervals. We measured brachial artery reactivity (BAR, %) in response to transient oxidative stress induced by oral methionine with high-resolution duplex ultrasound imaging before and one week after the fourth study phlebotomy. Results: Before phlebotomy, oral methionine decreased BAR by −2.04% (95% CI −2.58%, −1.50%), P < 0.001) with no significant difference between groups (P = 0.42). After phlebotomy, the BAR response to oral methionine did not significantly change between groups (P = 0.53). Brachial artery nitroglycerin-mediated dilation did not change in response to phlebotomy. Conclusions: Four serial phlebotomy procedures over six months with or without intravenous iron supplementation did not alter vascular endothelial function in the brachial artery when compared with sham phlebotomy.

In the original publication the initial sentences of the legends for Figs. 4 and 5 were inadvertently reversed. They should read as follows: Figure 4. Effect of a 1.8 mg load of colchicine on extent of monocyte-and neutrophil-platelet aggregate. Extent of monocyte-platelet aggregate (Panel A) and neutrophil-platelet aggregate (Panel B) were assessed before and 2 and 24 h after completion of the 1.8 mg load of colchicine in healthy subjects (n=10). Medians shown via dashed line.Figure 5. Effect of a 1.8 mg load of colchicine on platelet surface expression of PAC-1 and P-selectin. Platelet surface expression of PAC-1 in response to 0.4 μM epinephrine (Panel A) and P-selectin in response to 0.025 U thrombin (Panel B) were assessed before and 2 and 24 h after completion of the 1.8 mg load of colchicine in healthy subjects (n=10). Medians shown via dashed line.The online version of the original article can be found at http://dx.

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