Faculty Bibliography

Background: Acute myocardial infarction (AMI) is a significant cardiovascular complication following non-cardiac surgery. We evaluated national trends in perioperative AMI, management, and outcomes using a large administrative database of United States hospital admissions. Methods: Patients who underwent non-cardiac surgery from 2005 to 2013 were identified using the National Inpatient Sample. Perioperative AMI was evaluated over time. Propensity score matching was used to compile cohorts of patients with perioperative AMI matched on their baseline characteristics who were managed invasively (defined as cardiac catheterization, percutaneous coronary intervention [PCI], or coronary artery bypass graft surgery [CABG]) versus conservatively. The primary outcome was in-hospital all-cause mortality. Results: Among 9,566,277 hospitalizations for major non-cardiac surgery, perioperative AMI occurred in 84,093 (0.88%). Over time, the rate of perioperative AMI per 100,000 surgeries declined by 170 (95% CI 158 - 181), from 898 in 2005 to 729 in 2013 (p for trend <0.0001). Perioperative AMI occurred most frequently in patients undergoing vascular (2.0%), transplant (1.6%), and thoracic (1.5%) surgery. In-hospital mortality was higher in patients with perioperative AMI than those without AMI (18.0% vs. 1.5%, p<0.0001; adjusted OR 5.76, 95% CI 5.65 - 5.88). Mortality associated with perioperative AMI declined over time (adjusted OR 0.86, 95% CI 0.84 - 0.88). In a propensity-matched cohort of 34,650 patients with perioperative AMI, invasive management was associated with lower mortality than conservative management (8.9% vs. 18.1%, p<0.001; OR 0.44, 95% CI 0.41-0.47). Conclusion: Perioperative AMI occurs in 0.9% of patients undergoing major non-cardiac surgery and is strongly associated with in-hospital mortality. Invasive management of such patients may mitigate some of this excess risk

Background: The recent AHA/ACC guidelines on duration of dual anti-platelet therapy (DAPT) recommends DAPT for 1 year in patients presenting with acute coronary syndrome (ACS) and undergoing percutaneous coronary intervention (PCI), with a Class IIb recommendation for continuation. Methods: We searched electronic databases to identify randomized trials comparing short-term (<=6 months) vs 12 months vs extended (>12 months) DAPT in patients with ACS undergoing PCI. We evaluated allcause and cardiovascular mortality, myocardial infarction (MI), stent thrombosis and major bleeding. Random effects modeling was used to calculate pooled relative risk (RR) and 95% confidence intervals (CI). Results: We included 8 trials comprising of 12,917 ACS patients; 5 trials compared short-term vs 12 months or extended DAPT, whereas 3 trials compared 12 months vs extended DAPT. There were no significant differences in either ischemic or bleeding outcomes between short-term vs 12 months or extended DAPT. However compared to extended DAPT, 12 months DAPT showed significantly higher risk of MI (RR 2.00, 95% CI: 1.47 to 2.73, p<0.001) but reduced risk of major bleeding (RR 0.58, 95% CI: 0.34 to 0.98, p=0.04). All-cause mortality was similar between 12 months vs extended DAPT. The heterogeneity was low to moderate (I2 ranged from 17% to 39%). Conclusion: In ACS, DAPT beyond 1 year should be based on an individualized patient approach taking into account the competing risks of bleeding and ischemic complications. (Table Presented)

Background Body-weight fluctuation is a risk factor for death and coronary events in patients without cardiovascular disease. It is not known whether variability in body weight affects outcomes in patients with coronary artery disease. Methods We determined intraindividual fluctuations in body weight from baseline weight and follow-up visits and performed a post hoc analysis of the Treating to New Targets trial, which involved assessment of the efficacy and safety of lowering low-density lipoprotein cholesterol levels with atorvastatin. The primary outcome was any coronary event (a composite of death from coronary heart disease, nonfatal myocardial infarction, resuscitated cardiac arrest, revascularization, or angina). Secondary outcomes were any cardiovascular event (a composite of any coronary event, a cerebrovascular event, peripheral vascular disease, or heart failure), death, myocardial infarction, or stroke. Results Among 9509 participants, after adjustment for risk factors, baseline lipid levels, mean body weight, and weight change, each increase of 1 SD in body-weight variability (measured according to average successive variability and used as a time-dependent covariate) was associated with an increase in the risk of any coronary event (2091 events; hazard ratio, 1.04; 95% confidence interval [CI], 1.01 to 1.07; P=0.01), any cardiovascular event (2727 events; hazard ratio, 1.04; 95% CI, 1.02 to 1.07; P<0.001), and death (487 events; hazard ratio,1.09; 95% CI, 1.07 to 1.12; P<0.001). Among patients in the quintile with the highest variation in body weight, the risk of a coronary event was 64% higher, the risk of a cardiovascular event 85% higher, death 124% higher, myocardial infarction 117% higher, and stroke 136% higher than it was among those in the quintile with the lowest variation in body weight in adjusted models. Conclusions Among participants with coronary artery disease, fluctuation in body weight was associated with higher mortality and a higher rate of cardiovascular events independent of traditional cardiovascular risk factors. (Funded by Pfizer; ClinicalTrials.gov number, NCT00327691 .).

BACKGROUND: Although hypertension guidelines define treatment resistant hypertension as blood pressure uncontrolled by >/=3 antihypertensive medications, including a diuretic, it is unknown whether patient prognosis differs when a diuretic is included. METHODS: Participants in the Antihypertensive and Lipid-Lowering to Prevent Heart Attack Trial were randomly assigned to first-step therapy with chlorthalidone, amlodipine, or lisinopril. At a Year 2 follow-up visit, those with average BP>/=140 mmHg systolic or >/=90 mmHg diastolic on >/=3 antihypertensive medications, or BP<140/90 mmHg on >/=4 antihypertensive medications, were identified as having apparent treatment resistant hypertension. The prevalence of treatment resistant hypertension and its association with ALLHAT primary (combined fatal coronary heart disease or nonfatal myocardial infarction) and secondary (all-cause mortality, stroke, heart failure, combined coronary heart disease, and combined cardiovascular disease) outcomes were identified for each treatment group. RESULTS: Of participants assigned to chlorthalidone, amlodipine and lisinopril, 9.6%, 11.4% and 19.7%, respectively, had treatment resistant hypertension. During mean follow-up of 2.9 years, primary outcome incidence was similar for those assigned to chlorthalidone compared to amlodipine or lisinopril (amlodipine vs. chlorthalidone adjusted HR=0.86; 95% CI 0.53-1.39; P=0.53; lisinopril vs. chlorthalidone adjusted HR=1.06; 95% CI 0.70-1.60; P=0.78). Secondary outcome risks were similar for most comparisons except coronary revascularization, which was higher with amlodipine than with chlorthalidone (HR=1.86; 95% CI 1.11-3.11; P=0.02). An as-treated analysis based on diuretic use produced similar results. CONCLUSIONS: In this study, which titrated medications to a goal, participants assigned to chlorthalidone were less likely to develop treatment resistant hypertension. However, prognoses in those with treatment resistant hypertension were similar across treatment groups. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov, NCT00000542.

Patients with chronic kidney disease (CKD) have a high prevalence of atherosclerotic cardiovascular disease, likely reflecting the presence of traditional risk factors. A greater distinguishing feature of atherosclerotic cardiovascular disease in CKD is the severity of the disease, which is reflective of an increase in inflammatory mediators and vascular calcification secondary to hyperparathyroidism of renal origin that are unique to patients with CKD. Additional components of atherosclerotic cardiovascular disease that are prominent in patients with CKD include microvascular disease and myocardial fibrosis. Therapeutic interventions that minimize cardiovascular events related to atherosclerotic cardiovascular disease in patients with CKD, as determined by well-designed clinical trials, are limited to statins. Data are lacking regarding other available therapeutic measures primarily due to exclusion of patients with CKD from major trials studying cardiovascular disease. Data from well-designed randomized controlled trials are needed to guide clinicians who care for this high-risk population in the management of atherosclerotic cardiovascular disease to improve clinical outcomes.

OBJECTIVES: The authors sought to perform a meta-analysis of randomized clinical trials (RCTs) comparing the safety and efficacy of biodegradable polymer drug-eluting stents (BP-DES) to second-generation durable polymer drug-eluting stents (DP-DES). BACKGROUND: Prior meta-analyses have established the superiority of BP-DES over bare-metal stents and first-generation DP-DES; however, their advantage compared with second-generation DP-DES remains controversial. METHODS: The authors searched PubMed and Scopus databases for RCTs comparing BP-DES to the second-generation DP-DES. Outcomes included target vessel revascularization (TVR) as efficacy outcome and cardiac death, myocardial infarction (MI), and definite or probable stent thrombosis (ST) as safety outcomes. In addition, we performed landmark analysis for endpoints beyond 1 year of follow-up and a subgroup analysis based on the stent characteristics. RESULTS: The authors included 16 RCTs comprising 19,886 patients in the meta-analysis. At the longest available follow-up (mean duration 26 months), we observed no significant differences in TVR (p = 0.62), cardiac death (p = 0.46), MI (p = 0.98), or ST (risk ratio: 0.83, 95% confidence interval: 0.64 to 1.09; p = 0.19). Our landmark analysis showed that BP-DES were not associated with a reduction in the risk of very late ST (risk ratio: 0.87, 95% confidence interval: 0.49 to 1.53; p = 0.62). Similar outcomes were seen regardless of the eluting drug (biolimus vs. sirolimus), the stent platform (stainless steel vs. alloy), the kinetics of polymer degradation or drug release (<6 months vs. >6 months), the strut thickness of the BP-DES (thin <100 mum vs. thick >100 mum), or the DAPT duration (>/=6 months vs. >/=12 months). CONCLUSIONS: BP-DES have similar safety and efficacy profiles to second-generation DP-DES.