Cangrelor for patients undergoing percutaneous coronary intervention: evidence from a meta-analysis of randomized trials

Cangrelor is a new parenteral adenosine diphosphate P2Y12 receptor inhibitor with rapid, profound and reversible inhibition of platelet activity. The aim of this meta-analysis was to evaluate efficacy and safety of this new agent in patients undergoing percutaneous coronary intervention (PCI). We searched PubMed, Cochrane Library, EMBASE, Web of Science and CINAHL databases from the inception through April 2013. Randomized controlled trials (RCTs) comparing cangrelor with control (clopidogrel/placebo) were selected. We used the random-effects models to calculate the risk ratio. The primary efficacy outcome was risk of myocardial infarction, and the primary safety outcome was TIMI major bleeding at 48 h. Three RCTs included a total of 25,107 participants. Effects of Cangrelor were not different against comparators for myocardial infarction (MI) (Risk ratio [RR] 0.94, 95 % confidence interval [CI] 0.78–1.13) and all-cause mortality (RR 0.72, 95 % CI 0.36–1.43). However, cangrelor significantly reduced the risk of ischemia-driven revascularization (RR 0.72, 95 % CI 0.52–0.98), stent thrombosis (RR 0.60, 95 % CI 0.44–0.82) and Q wave MI (RR 0.53, 95 % CI 0.30–0.92) without causing extra major bleeding (Thrombolysis in Myocardial infarction criteria) and severe or life-threatening bleeding (Global utilization of streptokinase and tissue plasminogen activator for occluded coronary arteries criteria). Separate analysis against only clopidogrel also showed similar findings except Q wave MI outcome. Use of cangrelor during PCI might reduce the risk of ischemia-driven revascularization and stent thrombosis, without causing extra major bleeding.     

Coronary CT angiography versus standard of care strategies to evaluate patients with potential coronary artery disease; effect on long term clinical outcomes

Background: Previous studies have shown that computed tomography coronary angiography (CTA) in patients with suspected coronary artery disease (CAD) predicts short term adverse events. However, there is no current data on whether identifying atherosclerosis on CTA impacts outcomes. We performed a case–control study to assess whether information from CTA can improve outcomes. Methods: 4244 symptomatic patients (mean age 58 ± 9, 62.5% male) without known CAD who underwent CTA (n = 2538) to rule out CAD were matched to 1706 patients who underwent standard of care in an academic cardiology clinic. Patients were propensity-matched by gender, age, ethnicity, CAD risk factors and follow-up duration. The primary outcome measure was all-cause mortality. Multivariable Cox proportional hazards models incorporated age, gender and traditional risk factors for coronary disease as well as pre-test probability of CAD. Results: There were no significant differences in age, gender, conventional risk factors between groups (p > 0.05). During a mean follow up of 80 ± 11 months, the overall death rate was 6.3% (270 deaths). Death rate was significantly lower in CTA group (n = 106, 4.2%) as compared to the control group (n = 184, 10.8%, p = 0.001). Event free survival was 95.8% and 89.2% in CTA and standard of care groups, respectively. Risk-adjusted hazard ratio of death were 2.5 (95%CI: 1.6–6.7, p = 0.003) in standard of care cohort as compared to CTA group. Multivariate analysis demonstrated that undergoing coronary CTA resulted in a risk reduction of 32%, p = 0·0001. Conclusions: Improved knowledge of atherosclerosis or increased anti-atherosclerotic therapies among those undergoing CTA may have contributed to improved survival. Our results provide evidence of potential benefit from scanning for atherosclerosis with CTA in symptomatic patients. Large randomized trials are warranted.     

Impact of Texting Laws on Motor Vehicular Fatalities in the United States

Using a panel study design, we examined the effects of different types of texting bans on motor vehicular fatalities.We used the Fatality Analysis Reporting System and a difference-in-differences approach to examine the incidence of fatal crashes in 2000 through 2010 in 48 US states with and without texting bans. Age cohorts were constructed to examine the impact of these bans on age-specific traffic fatalities.Primarily enforced laws banning all drivers from texting were significantly associated with a 3% reduction in traffic fatalities in all age groups, and those banning only young drivers from texting had the greatest impact on reducing deaths among those aged 15 to 21 years. Secondarily enforced restrictions were not associated with traffic fatality reductions in any of our analyses.Motor vehicle safety has been described as one of the 10 great public health achievements in the United States in the past decade,1 with car manufacturers and highway engineers making significant improvements to car and roadway safety features.2 Despite these improvements, traffic fatalities remain one of the leading causes of death in the United States,3 with an estimated 32 788 such deaths in 2010.4 Thus, road traffic fatalities continue to be a significant public health concern,5,6 garnering much attention from state lawmakers.In an effort to reduce motor vehicle fatalities, states have enacted restrictions on drunk driving, implemented graduated driver’s license programs, and mandated seatbelt use and special licensing procedures for older adults. Most recently, states have focused on restricting texting while driving.7–9 Generally, states define texting as reading, manual composition, or sending of electronic communications—text messages, instant messages, or e-mails—via a portable electronic device. Portable electronic devices include mobile (i.e., cellular) phones, personal digital assistants, and laptop computers. Texting while driving is a serious threat to road safety,10–13 given that research has shown that mobile phone use is associated with impaired following distance,14 improper lane position,11,15 longer reaction times,11,14,16 and crashes,11,17 which can all lead to significant adverse public health outcomes, including death.18 Unlike talking on a mobile phone while driving, texting poses a unique threat in that it requires drivers to take their eyes off the road for several seconds at a time.14Our current understanding of the impact of texting laws on driving outcomes is limited. To our knowledge, 2 studies have empirically examined the impact of texting laws on adverse motor vehicle outcomes. The first was published by the Highway Loss Data Institute.19 It examined the relationship of collision claim frequency and texting bans in just 4 states (CA, LA, MN, and WA). The authors found that texting bans were associated with increased collision claims. They speculated that this increase might be due to drivers hiding their phones from view to avoid fines and, in so doing, taking their eyes off the road more than they did before the bans. More recently, Abouk and Adams20 published the first national-level study of texting bans’ impacts on traffic fatalities. They examined the impact of texting-while-driving bans on the occurrence of only single-vehicle, single-occupant accidents between 2007 and 2010. Their findings indicated that stronger bans that are applied to all drivers were associated with decreases in single-vehicle, single-occupant accidents.The purpose of this study is to add to the knowledge base concerning the effectiveness of texting laws, particularly by considering the varying stringency levels of these laws. Texting bans can be secondarily enforced (i.e., an officer must have another reason to stop a vehicle before citing a driver for texting while driving) or primarily enforced (i.e., an officer does not have to have another reason for stopping a vehicle). Furthermore, some states ban texting among learner’s permit holders, and some ban texting among all those aged 18 years, 21 years, or younger, and still other states ban all drivers from texting. Some states have no texting laws at all. We consider the impact of each of these policy nuances on traffic fatalities in 48 states over an 11-year period. Moreover, given that younger individuals are more likely to text while driving,21 we examine the impact of texting laws on age-specific traffic fatalities. Overall, this study will be of interest to policymakers, law enforcement personnel, and other stakeholders interested in improving roadway safety and, by extension, public health.     

The efficacy and safety of cyclosporine reduction in de novo renal allograft patients receiving sirolimus and corticosteroids: results from an open‐label comparative study

This study evaluated the safety and efficacy of a sirolimus, corticosteroid, and cyclosporine reduction regimen in an open‐label, 12‐month trial of 420 de novo renal allograft recipients at 49 European transplant centers. One month post‐transplantation, 357 patients were randomized to receive standard‐dose cyclosporine (sCsA, n = 179) or reduced‐dose cyclosporine (rCsA, n = 178). All patients also received sirolimus and corticosteroids. The primary end points were the rate of biopsy‐confirmed acute rejection (BCAR) and renal function, as measured by serum creatinine. Baseline demographic and donor characteristics were similar between groups. BCAR rates at 12 months were not significantly different: 11.2% for rCsA patients and 16.2% for sCsA patients. Mean serum creatinine (±SEM) was significantly lower (1.75 ± 0.10 vs. 1.97 ± 0.07 mg/dl, P < 0.001), and creatinine clearance (±SEM; Nankivell method) was significantly higher (57.8 ± 1.78 vs. 49.5 ± 2.46 ml/min, P < 0.001) in patients receiving rCsA versus sCsA at 1 year, respectively. Patient and graft survival exceeded 98% in both groups. No significant differences in infection or malignancy were noted between groups. The rCsA with sirolimus and corticosteroid regimen resulted in excellent 12‐month patient and graft survival, a low incidence of BCAR, and improved renal function in renal allograft recipients. Sirolimus administered with rCsA and corticosteroids provided adequate immunosuppression while reducing the potential for the nephrotoxic effects of cyclosporine. These findings may help to improve long‐term renal allograft outcomes.