Meta-analysis of rate ratios with differential follow-up by treatment arm: inferring comparative effectiveness of medical devices

Journal Statistics in Medicine
Authors Kunz, Laura; Normand, Sharon-Lise; Sedrakyan, Art
Year Published 2015
Link to article


Modeling events requires accounting for differential follow-up duration, especially when combining randomized and observational studies. Although events occur at any point over a follow-up period and censoring occurs throughout, most applied researchers use odds ratios as association measures, assuming follow-up duration is similar across treatment groups. We derive the bias of the rate ratio when incorrectly assuming equal followup duration in the single study binary treatment setting. Simulations illustrate bias, efficiency, and coverage and demonstrate that bias and coverage worsen rapidly as the ratio of follow-up duration between arms moves away from one. Combining study rate ratios with hierarchical Poisson regression models, we examine bias and coverage for the overall rate ratio via simulation in three cases: when average arm-specific follow-up duration is available for all studies, some studies, and no study. In the null case, bias and coverage are poor when the study average follow-up is used and improve even if some arm-specific follow-up information is available. As the rate ratio gets further from the null, bias and coverage remain poor. We investigate the effectiveness of cardiac resynchronization therapy devices compared with those with cardioverter-defibrillator capacity where three of eight studies report arm-specific follow-up duration. Copyright © 2015 John Wiley & Sons, Ltd.

National trends in utilization and in-hospital outcomes of mechanical versus bioprosthetic aortic valve replacements

Journal The Journal of Thoracic and Cardiovascular Surgery
Authors Isaacs, Abby; Shuhaiber, Jeffrey; Salemi, Arash; Isom, O. Wayne; Sedrakyan, Art
Year Published 2015
Link to publication


OBJECTIVE: Substantial controversy surrounds the choice between a mechanical versus bioprosthetic prosthesis for aortic valve replacement (AVR), based on age. This study aims to investigate national trends and in-hospital outcomes of the 2 prosthesis choices.

METHODS: All patients aged >18 years in the National Inpatient Sample who received an AVR between 1998 and 2011 were considered. Valve-type use was examined by patient, procedural, and hospital characteristics, after which we matched patients based on their propensity score for receiving a bioprosthetic valve and compared their in-hospital outcomes.<

RESULTS: Bioprosthetic valves comprised 53.3% of 767,375 implanted valves, an increase in use from 37.7% in the period 1998 to 2001 to 63.6% in the period 2007 to 2011. The median age was 74 years for patients receiving bioprosthetic valves, and 67 years for those receiving mechanical valves. Use of bioprosthetic valves increased across all age groups, most markedly in patients age 55 to 64 years. Compared with patients receiving mechanical valves, these patients had a higher incidence of renal disease (8.0% vs 4.2%), coronary artery disease (58.5% vs 50.5%), concomitant coronary artery bypass grafting (46.7% vs 41.9%), and having surgery in a high-volume (>250 cases per year) center (31.3% vs 18.5%). Patients receiving bioprosthetic valves had a higher occurrence of in-hospital complications (55.9% vs 48.6%), but lower in-hospital mortality (4.4% vs 4.9%) than patients receiving mechanical valves. This difference was confirmed in propensity-matched analyses (complications: 52.7% vs 51.5%; mortality: 4.3% vs 5.2%).

CONCLUSIONS: Use of bioprosthetic valves in AVR increased dramatically from 1998 to 2011, particularly in patients age 55 to 64 years. Prosthesis selection varied significantly by facility, with low-volume facilities favoring mechanical valves. Aortic valve replacement with a bioprosthetic valve, compared with a mechanical valve, was associated with lower in-hospital mortality.

Safety and effectiveness of endovascular therapy for claudication in octogenarians

Journal Annals of Vascular Surgery
Authors Jones, Douglas W., Jeffrey J. Siracuse, Ashley Graham, Peter H. Connolly, Art Sedrakyan, Darren B. Schneider, and Andrew J. Meltzer
Year Published 2014
Link to Publication


Advanced age (≥80 years) has been associated with adverse outcomes after lower extremity bypass for critical limb ischemia (CLI), but endovascular therapy (ET) is reported to have comparable safety across age groups. Here, we assess the safety and effectiveness of advanced age on outcomes after ET for lifestyle-limiting intermittent claudication (IC).


A retrospective review of a prospectively maintained institutional database (2007–2012) identified all patients undergoing ET for IC. Demographics, procedural details, and outcomes were assessed via univariate analysis and multivariate Cox regression. Effectiveness was assessed across a panel of outcome metrics including the following: overall survival, freedom from major adverse limb event (MALE), and freedom from reintervention, amputation, or restenosis (RAS). Freedom from MALE + perioperative death (MALE + POD) was the primary safety end point.


Two hundred thirty-six patients underwent primary ET for 284 affected limbs. Of these, 46 interventions (16%) were performed in patients ≥80 years old. The average age of octogenarians treated was 84.4 years compared with 67.4 years among those aged <80 (P < 0.001). Compared with younger claudicants, octogenarians were less likely to have hypercholesterolemia (43.5% vs. 63.9%, P = 0.01) and more likely to deny a history of smoking (41.3% vs. 14.7%, P < 0.001). Octogenarians were also more likely to undergo interventions involving the popliteal artery (50% vs. 31.9%, P = 0.03). There were no other significant differences in demographics, comorbidities, TransAtlantic Inter-Society Consensus II classification, or treated arterial segment. Thirty-day freedom from MALE + POD was 100% in octogenarians and 99.6% in patients <80 years, with no difference between age groups. There were no differences in freedom from MALE, freedom from RAS, or overall survival at 1- and 3-year follow-up.


Although age >80 years has been identified as an independent risk factor for poor outcomes in the surgical treatment of CLI, our results suggest that ET for selected octogenarians with lifestyle-limiting claudication is as safe and effective as ET in younger patients. Advanced age alone should not prohibit consideration of ET for patients with IC.

Comparative effectiveness of drug-eluting stents on long-term outcomes in elderly patients treated for in-stent restenosis: a report from the National Cardiovascular Data Registry.

Journal Catheterization and Cardiovascular interventions
Authors Kutcher, Michael A.; Brennan, J. Matthew; Rao, Sunil V.; Dai, David; Anstrom, Kevin J.; Mustafa, Nowwar; Sedrakayan, Art
Year Published 2014
Link to Publication



We assessed the long-term outcomes of elderly patients who had in-stent restenosis (ISR) treated with drug-eluting stents (DES) compared with other treatment strategies.


Elderly patients with ISR represent a vulnerable group of which little is known regarding the safety and efficacy of repeat percutaneous coronary intervention (PCI).


We analyzed patients ≥ 65 years of age who underwent PCI for ISR in the National Cardiovascular Data Registry(®) from 2004 to 2008. Death, myocardial infarction (MI), revascularization, stroke, and bleeding were assessed for up to 30 months by a linkage with Medicare rehospitalization claims.


Of 43,679 linked patients, 30,012 were treated with DES, 8,277 with balloon angioplasty (BA), and 4,917 with bare metal stents (BMS). Compared with BMS, DES use was associated with a lower propensity score-matched (PM) risk of death (hazard ratio [HR] 0.72; 95% confidence interval [CI] 0.66-0.80, P < 0.001), MI (HR 0.81; 95% CI 0.70-0.93, P = 0.003), and revascularization (HR 0.90; 95% CI 0.82-1.00, P = 0.055). Compared with BA, DES use was associated with a lower PM risk of death (HR 0.82; 95% CI 0.76-0.89, P < 0.001) and revascularization (HR 0.86; 95% CI 0.80-0.93, P < 0.001), but no statistically significant difference across other endpoints. There were no significant differences in long-term outcomes for BA compared with BMS.


There was lower mortality and reduced risk for MI, revascularization, and stroke, but a similar rate of bleeding with DES compared with other modalities. Our results indicate that DES use is a comparatively effective strategy to treat elderly patients with ISR.

Comparative effectiveness research: does one size fit all?

Journal Statistics in Medicine
Authors Kunz, Lauren M.; Yeh, Robert W.; Normand, Sharon-Lise T.
Year Published 2012
Link to Publication


In this commentary, we argue that although randomization has many benefits, not all questions we seek to answer fit into a randomized setting. Our argument utilizes the clinical setting of carotid atherosclerosis management where specific clinical questions are answered by using a variety of comparative effectiveness designs. Observational studies should not be ruled out when designing studies to address questions of comparative effectiveness.