Long-term outcomes of patients receiving drug-eluting stents.

BACKGROUND: We sought to establish the long-term safety of drug-eluting stents compared with bare-metal stents in a usual care setting. METHODS: Using data from a prospective multicentre registry, we compared rates of death and of death or repeat revascularization during 3 years of follow-up of 6440 consecutive patients who underwent angioplasty with either drug-eluting or bare-metal stents between Apr. 1, 2003, and Mar. 31, 2006. RESULTS: Drug-eluting stents were inserted in 1120 patients and bare-metal stents in 5320. The drug-eluting stents were selected for patients who had a greater burden of comorbid illness, including diabetes mellitus (32.8% v. 20.8% in the bare-metal group, p < 0.001) and renal disease (7.4% v. 5.0%, p = 0.001). At 1-year follow-up, the drug-eluting stents were associated with a mortality of 3.0%, as compared with 3.7% with the bare-metal stents (adjusted odds ratio [OR] 0.62, 95% confidence interval [CI] 0.46-0.83). The rate of the composite outcome of death or repeat revascularization was 12.0% for the drug-eluting stents and 15.8% for the bare-metal stents (adjusted OR 0.40, 95% CI 0.33-0.49). In the subgroup of patients who had acute coronary syndromes, the adjusted OR for this composite outcome was 0.46 (95% CI 0.35-0.61). During the 3 years of observation, the relative risks for death and repeat revascularization varied over time. In year 1, there was an initial period of lower risk in the group with drug-eluting stents than in the group with bare-metal stents; this was followed by a shift toward outcome rates favouring bare-metal stents in years 2 and 3. The adjusted relative risk of the composite outcome of death or repeat revascularization associated with drug-eluting stents relative to bare-metal stents was 0.73 early in the first year of follow-up; it then rose gradually over time, to a peak of 2.24 at 3 years. INTERPRETATION: Drug-eluting stents are safe and effective in the first year following insertion. Thereafter, the possibility of longer term adverse events cannot be ruled out.

Aldehyde dehydrogenase, nitric oxide synthase and superoxide in ex vivo nitrate tolerance in rat aorta.

The role of aldehyde dehydrogenase (ALDH) in ex vivo tolerance to transdermal glyceryl trinitrate was explored in rat aorta. ALDH activity, measured by aldehyde-induced NADH formation, was strongly depressed in the tolerant arteries. ALDH inhibitors, chloral hydrate (0.3 mM) and cyanamide (0.1-1 mM) inhibited relaxation to glyceryl trinitrate in non-tolerant and tolerant arteries. The inhibition differed from tolerance in that (a) the glyceryl trinitrate concentration-response curve was sigmoidal cf. biphasic in tolerance, (b) the potentiating effect of nitric oxide synthase (eNOS) inhibition was unchanged cf. increased in tolerance and (c) superoxide inhibited the response cf. no significant effect in tolerant or non-tolerant arteries. Hence, reduced ALDH activity does not account fully for ex vivo tolerance. The discrepancies are consistent with evidence that (a) organic nitrates, unlike chloral and cyanamide, irreversibly inactivate ALDH (hence reduced enzyme saturability can explain the biphasic curve) and (b) eNOS contributes to tolerance by a mechanism independent of glyceryl trinitrate metabolism.

Niacin improves lipid profile but not endothelial function in patients with coronary artery disease on high dose statin therapy.

AIMS: To determine the effect of extended release (ER) niacin on endothelial and vascular function assessed by brachial flow-mediated dilatation (FMD), peak hyperemic velocity (VTiRH) and pulse arterial tonometry (PAT) in patients with established coronary artery disease (CAD), already treated with high dose statins. Endothelial dysfunction is common in patients with established coronary artery disease (CAD) and has prognostic implications. Niacin has proven clinical benefit in patients with CAD, but its additive effect in patients on statin therapy is being evaluated. The effect of niacin on endothelial function, in the presence of optimal LDL cholesterol is unclear. METHODS AND RESULTS: Sixty-six patients with CAD (mean age 57.9 ± 8.5 yrs) received ER niacin (1500 mg per day) and placebo in a randomized crossover fashion for 3 months of each therapy. All patients received atorvastatin 80 mg per day. FMD, VTiRH and PAT measurements were performed at baseline and after each treatment period. Treatment with niacin improved dyslipidemia parameters (LDL placebo 1.52 ± 0.51 vs. niacin 1.30 ± 0.43; p = 0.004; HDL placebo 0.95 ± 0.16 vs. niacin 1.11 ± 0.22; p < 0.001). However, there was no observed improvement in endothelial function as assessed by FMD (placebo 6.1 ± 4.9 vs. niacin 6.6 ± 4.8%; p = 0.48), VTiRH (placebo 75 ± 28 vs. niacin 78 ± 26 cm; p = 0.23) or PAT (placebo 1.8 ± 0.42 vs. niacin 1.79 ± 0.5; p = 0.43). CONCLUSION: Niacin as add-on treatment to high dose statins in patients with established CAD significantly improves lipid profile. However, these changes were not associated with improved endothelial or microvascular function. Registered clinical trial with clinicaltrials.gov: NCT00150722.

Time dependency of outcomes for drug-eluting vs bare-metal stents.

BACKGROUND: Previous research suggests that the early benefit from revascularization with drug-eluting stents might diminish over time. METHODS: We performed an extended analysis of a previously identified cohort of 6440 patients who underwent percutaneous coronary intervention between April 1, 2003 and March 31, 2005 using a prospective provincial clinical registry in Alberta, Canada. We compared rates of death, and of death or repeat revascularization among the 6440 patients receiving either drug-eluting (sirolimus- and paclitaxel) stents or bare-metal stents. We determined risk-adjusted hazard ratios at moments in time with a spline analysis using Cox proportional hazards modelling. RESULTS: During the 8 years of observation, the relative risks for death or the composite outcome of death or repeat revascularization varied over time. There was an early finding of better outcomes associated with drug-eluting stents in the first year after implantation. Thereafter, there was no significant benefit associated with drug-eluting stents compared with bare-metal stents with 8 years of follow-up. At 30 days, the adjusted hazard ratio was 0.38 (95% confidence interval [CI], 0.18-0.81) for death and 0.27 (95% CI, 0.14-0.54) for the composite outcome of death or repeat revascularization. By 8 years, the adjusted hazard ratio of death or the composite outcome was 1.15 (95% CI, 0.97-1.36) and 1.01 (95% CI, 0.87-1.17), respectively. CONCLUSIONS: Revascularization with first-generation drug-eluting stents is associated with better outcomes within the first year only. Thereafter, the risk of death or repeat revascularization is similar between drug-eluting stents and bare-metal stents.

Comparison of new measures of vascular function to flow mediated dilatation as a measure of cardiovascular risk factors.

Although flow-mediated dilatation (FMD) is widely used, the ideal vascular parameter for the measurement of cardiovascular risk is not clear. Recently, it has been proposed that shear stress and blood velocity during hyperemia (VRH) may provide stronger correlations with cardiovascular risk factors than FMD. The aim of this study was to evaluate the relations of VRH and shear stress during reactive hyperemia (SSRH) to FMD and the association of these measures to cardiovascular risk factors in 1,477 men without cardiovascular disease. SSRH and VRH showed weak correlations with FMD in bivariate analysis (r = 0.239, p <0.001, and r = 0.108, p <0.001, respectively). The only cardiovascular risk factor independently associated with FMD was systolic blood pressure (beta = -0.073, p <0.01). In contrast, as the dependent variable, SSRH (R2 for model = 0.107) was independently associated with age, systolic blood pressure, low-density lipoprotein cholesterol, and body mass index. As the dependent variable, VRH was associated with the same risk factors with a slightly weaker R2 value of 0.095. In conclusion, SSRH and simply calculated VRH have stronger associations with cardiovascular risk factors than FMD. This may reflect greater sensitivity of these measures to detect early abnormalities associated with risk factors in a relatively young and healthy population.