Faculty Bibliography

BACKGROUND: Studies demonstrate that lowering low-density lipoprotein cholesterol (LDL-C) using a statin is associated with significant reduction in cardiovascular events. Whether visit-to-visit variability in LDL-C levels affects cardiovascular outcomes is unknown. OBJECTIVES: This study sought to evaluate the role of visit-to-visit variability in LDL-C levels on cardiovascular outcomes. METHODS: We evaluated patients with coronary artery disease and LDL-C <130 mg/dl enrolled in the TNT (Treating to New Targets) trial, randomly assigned to receive atorvastatin 80 mg/day versus 10 mg/day and with at least one post-baseline measurement of LDL-C. Visit-to-visit LDL-C variability was evaluated from 3 months into random assignment through the use of various measurements of LDL-C variability: SD, average successive variability (ASV), coefficient of variation, and variation independent of mean, with the first 2 measurements used as the primary measurements. Primary outcome was any coronary event, and secondary outcomes were any cardiovascular event, death, myocardial infarction, or stroke. RESULTS: Among 9,572 patients, SD and ASV were significantly lower with atorvastatin 80 mg/day versus 10 mg/day (SD: 12.03 +/- 9.70 vs. 12.52 +/- 7.43; p = 0.005; ASV: 12.84 +/- 10.48 vs. 13.76 +/- 8.69; p < 0.0001). In the adjusted model, each 1-SD increase in LDL-C variability (by ASV) increased the risk of any coronary event by 16% (hazard ratio [HR]: 1.16; 95% confidence interval [CI]: 1.10 to 1.23; p < 0.0001), any cardiovascular event by 11% (HR: 1.11; 95% CI: 1.07 to 1.15; p < 0.0001), death by 23% (HR: 1.23; 95% CI: 1.14 to 1.34; p < 0.0001), myocardial infarction by 10% (HR: 1.10; 95% CI: 1.02 to 1.19; p = 0.02), and stroke by 17% (HR: 1.17; 95% CI: 1.04 to 1.31; p = 0.01), independent of treatment effect and achieved LDL-C levels. Results were largely consistent when adjusted for medication adherence. CONCLUSIONS: In subjects with coronary artery disease, visit-to-visit LDL-C variability is an independent predictor of cardiovascular events.

BACKGROUND: The 2013 American College of Cardiology Foundation/American Heart Association guidelines for patients with ST-segment-elevation myocardial infarction gives a class III indication for nonculprit artery percutaneous coronary intervention at the time of primary percutaneous coronary intervention, driven by data from observational studies. However, more recent trials suggest otherwise. METHODS AND RESULTS: We conducted PUBMED, EMBASE, and CENTRAL searches for randomized trials comparing complete versus culprit-only revascularization in patients with ST-segment-elevation myocardial infarction. Efficacy outcomes were major adverse cardiovascular events, as well as death, cardiovascular death, myocardial infarction, and repeat revascularization. Safety outcomes were contrast-induced nephropathy, contrast volume used, and procedure time. Five trials with 1165 patients fulfilled the inclusion criteria. Complete revascularization (68% during index percutaneous coronary intervention) was associated with significant reduction in major adverse cardiovascular events (rate ratio =0.48; 95% confidence interval =0.37-0.61), death (rate ratio =0.60; 95% confidence interval =0.38-0.97), cardiovascular death (rate ratio =0.38, 95% confidence interval =0.20-0.73), and repeat revascularization (rate ratio =0.42; 95% confidence interval =0.31-0.57) when compared with culprit-only revascularization. However, trial sequential analyses (similar to interim analysis of a randomized trial) powered for a 25% relative reduction showed firm evidence (cumulative z-curve crossed the monitoring boundary) only for major adverse cardiovascular events driven by a decrease in repeat revascularization with no firm evidence for reduction in death and myocardial infarction. Moreover, there was a significant increase in contrast volume use (mean difference 85.12 [70.41-83.00] ml) and procedure time (mean difference 16.42 [13.22-19.63] mins) with complete revascularization without increase in contrast-induced nephropathy. CONCLUSIONS: In patients with ST-segment-elevation myocardial infarction, immediate or staged complete revascularization results in significant reduction in major adverse cardiovascular events driven largely by reduction in repeat revascularization with no firm evidence for the reduction in death or myocardial infarction when compared with culprit-only revascularization.

Various scientific societies have recently published practice guidelines for the diagnosis and management of arterial hypertension with no clear consensus on a blood pressure target. This article reviews those recommendations and critically examines if they are based on sound evidence.

Background Results of trials and registry studies have shown lower long-term mortality after coronary-artery bypass grafting (CABG) than after percutaneous coronary intervention (PCI) among patients with multivessel disease. These previous analyses did not evaluate PCI with second-generation drug-eluting stents. Methods In an observational registry study, we compared the outcomes in patients with multivessel disease who underwent CABG with the outcomes in those who underwent PCI with the use of everolimus-eluting stents. The primary outcome was all-cause mortality. Secondary outcomes were the rates of myocardial infarction, stroke, and repeat revascularization. Propensity-score matching was used to assemble a cohort of patients with similar baseline characteristics. Results Among 34,819 eligible patients, 9223 patients who underwent PCI with everolimus-eluting stents and 9223 who underwent CABG had similar propensity scores and were included in the analyses. At a mean follow-up of 2.9 years, PCI with everolimus-eluting stents, as compared with CABG, was associated with a similar risk of death (3.1% per year and 2.9% per year, respectively; hazard ratio, 1.04; 95% confidence interval [CI], 0.93 to 1.17; P=0.50), higher risks of myocardial infarction (1.9% per year vs. 1.1% per year; hazard ratio, 1.51; 95% CI, 1.29 to 1.77; P<0.001) and repeat revascularization (7.2% per year vs. 3.1% per year; hazard ratio, 2.35; 95% CI, 2.14 to 2.58; P<0.001), and a lower risk of stroke (0.7% per year vs. 1.0% per year; hazard ratio, 0.62; 95% CI, 0.50 to 0.76; P<0.001). The higher risk of myocardial infarction with PCI than with CABG was not significant among patients with complete revascularization but was significant among those with incomplete revascularization (P=0.02 for interaction). Conclusions In a contemporary clinical-practice registry study, the risk of death associated with PCI with everolimus-eluting stents was similar to that associated with CABG. PCI was associated with a higher risk of myocardial infarction (among patients with incomplete revascularization) and repeat revascularization but a lower risk of stroke. (Funded by Abbott Vascular.).

BACKGROUND: COURAGE and BARI-2D have questioned the utility of routine revascularization for the prevention of cardiovascular events in patients with stable ischemic heart disease (SIHD). On the other end of the spectrum, a routine invasive strategy in patients with acute coronary syndrome (ACS) is superior to a conservative strategy. The impact of the above trials on the trend in percutaneous coronary intervention (PCI) volume for SIHD and ACS is not known. METHODS: Data from the 2001-2011 Nationwide Inpatient Sample for discharges with PCI were used. The trend in PCI volume over time was analyzed, especially in relation to the COURAGE (2007) and the BARI-2D (2009) trials. Age and gender adjusted PCI rates were calculated using direct standardization method. RESULTS: Among the 8,150,764 PCI procedures, there was a steady increase in PCI volumes until the publication of the COURAGE/BARI-2D trials after which the volume decreased. Compared to the peak volume of 909,331 in 2006, PCI volume declined by 38% to 562,036 in 2011 (P<0.0001); driven by a 60% decrease in PCI for SIHD from 409,199 in 2006 to 160,707 in 2011 (P<0.0001). Moreover, there was a 20% decrease in PCI for ACS from 500,132 in 2006 to 401,330 in 2011 (P<0.0001) driven by a significant decrease in PCI for unstable angina. Results were similar in diabetics with a decline in the volume after BARI-2D trial, although the decline was less dramatic. CONCLUSION: The 11-year trend indicates a substantial impact of COURAGE/BARI-2D on SIHD PCI volumes with an unintended consequence of lower PCI volumes for ACS.

Background: The safety of drug eluting stents (DES) vs. bare metal stents (BMS) in the perioperative setting, a heightened state of inflammation and thrombosis is not well defined. Methods: All adults undergoing NCS within 1 year following percutaneous coronary intervention (PCI) in Massachusetts between April 1, 2004 and September 30, 2007 were identified from an administrative claims database. Patient were divided into those who received BMS vs. DES at index PCI. Primary net clinical outcome was death, myocardial infarction (MI) or bleeding within 30-days of NCS. Primary clinical outcome was 30-day death or MI. Results: Among 8415 (22% BMS) patients that satisfied our inclusion criteria, 1838 BMS patients were matched with 3565 DES patients with similar propensity scores. In the DES cohort, the 30-day primary net clinical outcome rate was lower with longer time from PCI to NCS (P=0.02) with lowest rates if NCS was performed after 90 days from PCI (Event rate 8.57% 7.53%, 5.21%, 5.75% for 1-30, 31-90, 91-180 and 181-365 days from PCI to NCS). However, in the BMS cohort, the event rate was uniformly high regardless of the time from PCI to NCS (P=0.60) (Event rate 8.20%, 6.58%, 8.05%, 8.82% for 1-30, 31-90, 91-180 and 181-365 days from PCI to NCS). There was no significant difference between DES and the BMS group for 30-day primary net clinical outcome (6.64% vs. 7.89%; P=0.10), but there was a 26% lower odds of primary clinical outcome (OR=0.74, 95% CI 0.58-0.94) with DES when compared with BMS, driven mainly by differences in event rates when NCS was performed >90 days post PCI. Conclusion: DES implantation was not associated with higher adverse events after NCS. Moreover, the incidence of adverse events following NCS was lower when NCS was performed >90 days post DES implantation suggesting that it may not be necessary to wait until 12 months post PCI with DES before NCS. (c) 2014 Wiley Periodicals, Inc.