Faculty Bibliography

OBJECTIVE: To compare the efficacy and safety of biodegradable polymer drug eluting stents with those of bare metal stents and durable polymer drug eluting stents. DESIGN: Mixed treatment comparison meta-analysis of 258 544 patient years of follow-up from randomized trials. DATA SOURCES AND STUDY SELECTION: PubMed, Embase, and Central were searched for randomized trials comparing any of the Food and Drug Administration approved durable polymer drug eluting stents (sirolimus eluting, paclitaxel eluting, cobalt chromium everolimus eluting, platinum chromium everolimus eluting, zotarolimus eluting-Endeavor, and zotarolimus eluting-Resolute) or biodegradable polymer drug eluting stents, with each other or against bare metal stents. OUTCOMES: Long term efficacy (target vessel revascularization, target lesion revascularization) and safety (death, myocardial infarction, stent thrombosis). Landmark analysis at more than one year was evaluated to assess the potential late benefit of biodegradable polymer drug eluting stents. RESULTS: From 126 randomized trials and 258 544 patient years of follow-up, for long term efficacy (target vessel revascularization), biodegradable polymer drug eluting stents were superior to paclitaxel eluting stents (rate ratio 0.66, 95% credibility interval 0.57 to 0.78) and zotarolimus eluting stent-Endeavor (0.69, 0.56 to 0.84) but not to newer generation durable polymer drug eluting stents (for example: 1.03, 0.89 to 1.21 versus cobalt chromium everolimus eluting stents). Similarly, biodegradable polymer drug eluting stents were superior to paclitaxel eluting stents (rate ratio 0.61, 0.37 to 0.89) but inferior to cobalt chromium everolimus eluting stents (2.04, 1.27 to 3.35) for long term safety (definite stent thrombosis). In the landmark analysis after one year, biodegradable polymer drug eluting stents were superior to sirolimus eluting stents for definite stent thrombosis (rate ratio 0.29, 0.10 to 0.82) but were associated with increased mortality compared with cobalt chromium everolimus eluting stents (1.52, 1.02 to 2.22). Overall, among all stent types, the newer generation durable polymer drug eluting stents (zotarolimus eluting stent-Resolute, cobalt chromium everolimus eluting stents, and platinum chromium everolimus eluting stents) were the most efficacious (lowest target vessel revascularization rate) stents, and cobalt chromium everolimus eluting stents were the safest with significant reductions in definite stent thrombosis (rate ratio 0.35, 0.21 to 0.53), myocardial infarction (0.65, 0.55 to 0.75), and death (0.72, 0.58 to 0.90) compared with bare metal stents. CONCLUSIONS: Biodegradable polymer drug eluting stents are superior to first generation durable polymer drug eluting stents but not to newer generation durable polymer stents in reducing target vessel revascularization. Newer generation durable polymer stents, and especially cobalt chromium everolimus eluting stents, have the best combination of efficacy and safety. The utility of biodegradable polymer stents in the context of excellent clinical outcomes with newer generation durable polymer stents needs to be proven.

BACKGROUND: A variety of claims about possible associations between gun ownership rates, mental illness burden, and the risk of firearm-related deaths have been put forward. However, systematic data on this issue among various countries remain scant. Our objective was to assess whether the popular notion "guns make a nation safer" has any merits. METHODS: Data on gun ownership were obtained from the Small Arms Survey, and for firearm-related deaths from a European detailed mortality database (World Health Organization), the National Center for Health Statistics, and others. Crime rate was used as an indicator of safety of the nation and was obtained from the United Nations Surveys of Crime Trends. Age-standardized disability-adjusted life-year rates due to major depressive disorder per 100,000 inhabitants with data obtained from the World Health Organization database were used as a putative indicator for mental illness burden in a given country. RESULTS: Among the 27 developed countries, there was a significant positive correlation between guns per capita per country and the rate of firearm-related deaths (r = 0.80; P <.0001). In addition, there was a positive correlation (r = 0.52; P = .005) between mental illness burden in a country and firearm-related deaths. However, there was no significant correlation (P = .10) between guns per capita per country and crime rate (r = .33), or between mental illness and crime rate (r = 0.32; P = .11). In a linear regression model with firearm-related deaths as the dependent variable with gun ownership and mental illness as independent covariates, gun ownership was a significant predictor (P <.0001) of firearm-related deaths, whereas mental illness was of borderline significance (P = .05) only. CONCLUSION: The number of guns per capita per country was a strong and independent predictor of firearm-related death in a given country, whereas the predictive power of the mental illness burden was of borderline significance in a multivariable model. Regardless of exact cause and effect, however, the current study debunks the widely quoted hypothesis that guns make a nation safer.

OBJECTIVES: To conduct an updated meta-analysis on clinical outcomes with thrombectomy prior to primary percutaneous coronary intervention (PPCI) compared with conventional PPCI alone. BACKGROUND: The clinical efficacy of thrombectomy in acute myocardial infarction (AMI) remains uncertain. METHODS: Clinical trials that randomized AMI patients to aspiration or mechanical thrombectomy prior to PPCI compared with conventional PPCI alone were included. RESULTS: The weighted mean duration of clinical follow-up was 6 months. Aspiration thrombectomy vs. conventional PPCI (18 trials, n=3,936): Major adverse cardiac events (MACE) (Risk ratio [RR]=0.76; 95% CI 0.63-0.92; p=0.006) and all-cause mortality (RR=0.71, 95% CI 0.51-0.99; p=0.049) were significantly reduced with aspiration thrombectomy. Beneficial trends were noted for MI (p=0.11) and target vessel revascularization (p=0.06). Final infarct size (p=0.64) and ejection fraction (p=0.32) at 1 month were similar. ST-segment resolution (STR) at 60 minutes (RR=1.31; 95% CI 1.16-1.48; p<0.0001) and TIMI blush grade (TBG) 3 post-procedure (RR=1.37; 95% CI 1.19-1.59; p<0.0001) were both improved with aspiration thrombectomy. Mechanical thrombectomy vs. conventional PPCI (7 trials, n=1,598): There was no difference between the thrombectomy and conventional PPCI arms in the incidence of MACE (RR=1.10; 95% CI 0.59-2.05; p=0.77), mortality (p=0.57), MI (p=0.32), target vessel revascularization (p=0.19), or final infarct size (p=0.47). A benefit in STR at 60 minutes (RR=1.25; 95% CI 1.06-1.47; p=0.007), but not TBG 3 (RR=1.09; 95% CI 0.86-1.38; p=0.48) was noted. CONCLUSIONS: Thrombectomy during AMI by manual catheter aspiration, but not mechanically, is beneficial in reducing MACE, including mortality, at 6 to 12 months compared with conventional PCI alone.

BACKGROUND: The efficacy and safety of drug-eluting stents (DES) in patients with ST-segment-elevation myocardial infarction (STEMI) is controversial. Consequently, DES implantation has a class IIa indication in the American College of Cardiology/American Heart Association and the European Society of Cardiology STEMI guidelines. METHODS AND RESULTS: PUBMED, EMBASE, and CENTRAL were searched for randomized clinical trials, until March 2013, comparing any of the 5 Food and Drug Administration-approved durable stent and polymer DES (sirolimus eluting stent, paclitaxel eluting stent, everolimus-eluting stent [EES], zotarolimus-eluting stent, and zotarolimus-eluting stent resolute), against each other or bare metal stents (BMS), and enrolling >/=50 patients with STEMI. Efficacy (target vessel revascularization) and safety (death, myocardial infarction, and stent thrombosis) outcomes at the longest reported follow-up times were evaluated. Twenty-eight randomized clinical trials with 34 068 patient-years of follow-up on subjects with STEMI fulfilled the inclusion criteria. When compared with BMS (reference rate ratio [RR] of 1), sirolimus eluting stent (RR, 0.46; 95% credibility interval [CrI], 0.36-0.56), paclitaxel eluting stent (RR, 0.69; 95% CrI, 0.53-0.87), and EES (RR, 0.42; 95% CrI, 0.26-0.62) were associated with a statistically significant reduction in rate of target vessel revascularization, with the point estimate for zotarolimus-eluting stent resolute trending in a similar direction. There was no increase in the risk of death, myocardial infarction, or stent thrombosis with any DES compared with BMS. Moreover, EES was associated with a statistically significant reduction in the rate of stent thrombosis when compared with sirolimus eluting stent (RR, 0.38; 95% CrI, 0.21-0.74), paclitaxel eluting stent (RR, 0.39; 95% CrI, 0.21-0.73), and even BMS (RR, 0.42; 95% CrI, 0.23-0.76). There was a 74% probability that EES had the lowest rate of any stent thrombosis when compared with all other stent types (no data on zotarolimus-eluting stent resolute). There was no increase in very late stent thrombosis with EES versus BMS (RR, 0.89; 95% CrI, 0.09-8.67). CONCLUSIONS: In patients with STEMI, DES versus BMS was associated with substantial decrease in the risk of target vessel revascularization without compromising safety. EES had the added advantage of substantial reduction in the risk of stent thrombosis when compared with first-generation DES and BMS with no increase in very late stent thrombosis.

Aspirin is the most widely prescribed antiplatelet agent for the secondary prevention of stroke. Cilostazol, an antiplatelet and vasodilating agent, has shown promise for the secondary prevention of stroke. A systematic review and meta-analysis of randomized controlled trials using Ovid MEDLINE, PubMed, and Excerpta Medica (EMBASE) was searched up to October 2012. Four trials, in 3,917 patients, comparing cilostazol with aspirin were identified. Compared with aspirin, cilostazol was associated with a 73% reduction in hemorrhagic stroke (relative risk [RR] 0.27, 95% confidence interval [CI] 0.13 to 0.54, p = 0.0002), 28% reduction in the composite end point of stroke, myocardial infarction, or vascular death (RR 0.72, 95% CI 0.57 to 0.89, p = 0.003), and 48% reduction in total hemorrhagic events (RR 0.52, 95% CI 0.34 to 0.79, p = 0.002), with trend for lesser gastrointestinal bleeds (RR 0.60, 95% CI 0.34 to 1.06, p = 0.08). In conclusion, compared with aspirin, cilostazol is associated with significantly less hemorrhagic stroke, the combined end point of stroke, myocardial infarction, and vascular death, and total hemorrhagic events, with numerically fewer gastrointestinal bleeds when used for the secondary prevention of stroke.