Steven M. Bradley

Association of Testosterone Therapy With Mortality, Myocardial Infarction, and Stroke in Men With Low Testosterone Levels

IMPORTANCE Rates of testosterone therapy are increasing and the effects of testosterone therapy on cardiovascular outcomes and mortality are unknown. A recent randomized clinical trial of testosterone therapy in men with a high prevalence of cardiovascular diseases was stopped prematurely due to adverse cardiovascular events raising concerns about testosterone therapy safety. OBJECTIVES To assess the association between testosterone therapy and all-cause mortality, myocardial infarction (MI), or stroke among male veterans and to determine whether this association is modified by underlying coronary artery disease. DESIGN, SETTING, AND PATIENTS A retrospective national cohort study of men with low testosterone levels (<300 ng/dL) who underwent coronary angiography in the Veterans Affairs (VA) system between 2005 and 2011. MAIN OUTCOMES AND MEASURES Primary outcome was a composite of all-cause mortality, MI, and ischemic stroke. RESULTS Of the 8709 men with a total testosterone level lower than 300 ng/dL, 1223 patients started testosterone therapy after a median of 531 days following coronary angiography. Of the 1710 outcome events, 748 men died, 443 had MIs, and 519 had strokes. Of 7486 patients not receiving testosterone therapy, 681 died, 420 had MIs, and 486 had strokes. Among 1223 patients receiving testosterone therapy, 67 died, 23 had MIs, and 33 had strokes. At 3 years after coronary angiography, the Kaplan-Meier estimated cumulative percentages with events were 19.9%in the no testosterone therapy group vs 25.7%in the testosterone therapy group,with an absolute risk difference of 5.8%(95%CI, -1.4%to 13.1%) [corrected].The Kaplan-Meier estimated cumulative percentages with events among the no testosterone therapy group vs testosterone therapy group at 1 year after coronary angiography were 10.1% vs 11.3%; at 2 years, 15.4% vs 18.5%; and at 3 years, 19.9% vs 25.7 [corrected].There was no significant difference in the effect size of testosterone therapy among those with and without coronary artery disease (test for interaction, P = .41). CONCLUSIONS AND RELEVANCE Among a cohort of men in the VA health care system who underwent coronary angiography and had a low serum testosterone level, the use of testosterone therapy was associated with increased risk of adverse outcomes. These findings may inform the discussion about the potential risks of testosterone therapy.

Incidence of treated cardiac arrest in hospitalized patients in the United States.

Objective:The incidence and incidence over time of cardiac arrest in hospitalized patients is unknown. We sought to estimate the event rate and temporal trends of adult inhospital cardiac arrest treated with a resuscitation response. Design:Three approaches were used to estimate the inhospital cardiac arrest event rate. First approach: calculate the inhospital cardiac arrest event rate at hospitals (n = 433) in the Get With The Guidelines-Resuscitation registry, years 2003–2007, and multiply this by U.S. annual bed days. Second approach: use the Get With The Guidelines-Resuscitation inhospital cardiac arrest event rate to develop a regression model (including hospital demographic, geographic, and organizational factors), and use the model coefficients to calculate predicted event rates for acute care hospitals (n = 5445) responding to the American Hospital Association survey. Third approach: classify acute care hospitals into groups based on academic, urban, and bed size characteristics, and determine the average event rate for Get With The Guidelines-Resuscitation hospitals in each group, and use weighted averages to calculate the national inhospital cardiac arrest rate. Annual event rates were calculated to estimate temporal trends. Setting:Get With The Guidelines-Resuscitation registry. Patients:Adult inhospital cardiac arrest with a resuscitation response. Measurements and Main Results:The mean adult treated inhospital cardiac arrest event rate at Get With The Guidelines-Resuscitation hospitals was 0.92/1000 bed days (interquartile range 0.58 to 1.2/1000). In hospitals (n = 150) contributing data for all years of the study period, the event rate increased from 2003 to 2007. With 2.09 million annual U.S. bed days, we estimated 192,000 inhospital cardiac arrests throughout the United States annually. Based on the regression model, extrapolating Get With The Guidelines-Resuscitation hospitals to hospitals participating in the American Hospital Association survey projected 211,000 annual inhospital cardiac arrests. Using weighted averages projected 209,000 annual U.S. inhospital cardiac arrests. Conclusions:There are approximately 200,000 treated cardiac arrests among U.S. hospitalized patients annually, and this rate may be increasing. This is important for understanding the burden of inhospital cardiac arrest and developing strategies to improve care for hospitalized patients.

Nonobstructive coronary artery disease and risk of myocardial infarction.

IMPORTANCE Little is known about cardiac adverse events among patients with nonobstructive coronary artery disease (CAD). OBJECTIVE To compare myocardial infarction (MI) and mortality rates between patients with nonobstructive CAD, obstructive CAD, and no apparent CAD in a national cohort. DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort study of all US veterans undergoing elective coronary angiography for CAD between October 2007 and September 2012 in the Veterans Affairs health care system. Patients with prior CAD events were excluded. EXPOSURES Angiographic CAD extent, defined by degree (no apparent CAD: no stenosis >20%; nonobstructive CAD: ≥1 stenosis ≥20% but no stenosis ≥70%; obstructive CAD: any stenosis ≥70% or left main [LM] stenosis ≥50%) and distribution (1, 2, or 3 vessel). MAIN OUTCOMES AND MEASURES The primary outcome was 1-year hospitalization for nonfatal MI after the index angiography. Secondary outcomes included 1-year all-cause mortality and combined 1-year MI and mortality. RESULTS Among 37,674 patients, 8384 patients (22.3%) had nonobstructive CAD and 20,899 patients (55.4%) had obstructive CAD. Within 1 year, 845 patients died and 385 were rehospitalized for MI. Among patients with no apparent CAD, the 1-year MI rate was 0.11% (n = 8, 95% CI, 0.10%-0.20%) and increased progressively by 1-vessel nonobstructive CAD, 0.24% (n = 10, 95% CI, 0.10%-0.40%); 2-vessel nonobstructive CAD, 0.56% (n = 13, 95% CI, 0.30%-1.00%); 3-vessel nonobstructive CAD, 0.59% (n = 6, 95% CI, 0.30%-1.30%); 1-vessel obstructive CAD, 1.18% (n = 101, 95% CI, 1.00%-1.40%); 2-vessel obstructive CAD, 2.18% (n = 110, 95% CI, 1.80%-2.60%); and 3-vessel or LM obstructive CAD, 2.47% (n = 137, 95% CI, 2.10%-2.90%). After adjustment, 1-year MI rates increased with increasing CAD extent. Relative to patients with no apparent CAD, patients with 1-vessel nonobstructive CAD had a hazard ratio (HR) for 1-year MI of 2.0 (95% CI, 0.8-5.1); 2-vessel nonobstructive HR, 4.6 (95% CI, 2.0-10.5); 3-vessel nonobstructive HR, 4.5 (95% CI, 1.6-12.5); 1-vessel obstructive HR, 9.0 (95% CI, 4.2-19.0); 2-vessel obstructive HR, 16.5 (95% CI, 8.1-33.7); and 3-vessel or LM obstructive HR, 19.5 (95% CI, 9.9-38.2). One-year mortality rates were associated with increasing CAD extent, ranging from 1.38% among patients without apparent CAD to 4.30% with 3-vessel or LM obstructive CAD. After risk adjustment, there was no significant association between 1- or 2-vessel nonobstructive CAD and mortality, but there were significant associations with mortality for 3-vessel nonobstructive CAD (HR, 1.6; 95% CI, 1.1-2.5), 1-vessel obstructive CAD (HR, 1.9; 95% CI, 1.4-2.6), 2-vessel obstructive CAD (HR, 2.8; 95% CI, 2.1-3.7), and 3-vessel or LM obstructive CAD (HR, 3.4; 95% CI, 2.6-4.4). Similar associations were noted with the combined outcome. CONCLUSIONS AND RELEVANCE In this cohort of patients undergoing elective coronary angiography, nonobstructive CAD, compared with no apparent CAD, was associated with a significantly greater 1-year risk of MI and all-cause mortality. These findings suggest clinical importance of nonobstructive CAD and warrant further investigation of interventions to improve outcomes among these patients.

Clinical InvestigationElectrophysiologyAdherence to dabigatran therapy and longitudinal patient outcomes: Insights from the Veterans Health Administration

BACKGROUND Dabigatran is a novel oral anti-coagulant (NOAC) that reduces risk of stroke in patients with non-valvular atrial fibrillation (NVAF). It does not require routine monitoring with laboratory testing which may have an adverse impact on adherence. We aimed to describe adherence to dabigatran in the first year after initiation and assess the association between non-adherence to dabigatran and clinical outcomes in a large integrated healthcare system. METHODS We studied a national cohort of 5,376 patients with NVAF, initiated on dabigatran between October-2010 and September-2012 at all Veterans Affairs hospitals. Adherence to dabigatran was calculated as proportion of days covered (PDC) and association between PDC and outcomes was assessed using standard regression techniques. RESULTS Mean age of the study cohort was 71.3 ± 9.7 years; 98.3% were men and mean CHADS2 score was 2.4 ± 1.2 (mean CHA2DS2VASc score 3.2 ± 1.4). Median PDC was 94% (IQR 76%-100%; mean PDC 84% ± 22%) over a median follow-up of 244 days (IQR 140-351). A total of 1,494 (27.8%) patients had a PDC <80% and were classified as non-adherent. After multivariable adjustment, lower adherence was associated with increased risk for combined all-cause mortality and stroke (HR 1.13, 95% CI 1.07-1.19 per 10% decrease in PDC). Adherence to dabigatran was not associated with non-fatal bleeding or myocardial infarction. CONCLUSIONS In the year after initiation, adherence to dabigatran for a majority of patients is very good. However, 28% of patients in our cohort had poor adherence. Furthermore, lower adherence to dabigatran was associated with increased adverse outcomes. Concerted efforts are needed to optimize adherence to NOACs.

Appropriate Use Criteria for Coronary Revascularization and Trends in Utilization, Patient Selection, and Appropriateness of Percutaneous Coronary Intervention

IMPORTANCE Appropriate Use Criteria for Coronary Revascularization were developed to critically evaluate and improve patient selection for percutaneous coronary intervention (PCI). National trends in the appropriateness of PCI have not been examined. OBJECTIVE To examine trends in PCI utilization, patient selection, and procedural appropriateness following the introduction of Appropriate Use Criteria. DESIGN, SETTING, AND PARTICIPANTS Multicenter, longitudinal, cross-sectional analysis of patients undergoing PCI between July 1, 2009, and December 31, 2014, at hospitals continuously participating in the National Cardiovascular Data Registry CathPCI registry over the study period. MAIN OUTCOMES AND MEASURES Proportion of nonacute PCIs classified as inappropriate at the patient and hospital level using the 2012 Appropriate Use Criteria for Coronary Revascularization. RESULTS A total of 2.7 million PCI procedures from 766 hospitals were included. Annual PCI volume of acute indications was consistent over the study period (377,540 in 2010; 374,543 in 2014), but the volume of nonacute PCIs decreased from 89,704 in 2010 to 59,375 in 2014. Among patients undergoing nonacute PCI, there were significant increases in angina severity (Canadian Cardiovascular Society grade III/IV angina, 15.8% in 2010 and 38.4% in 2014), use of antianginal medications prior to PCI (at least 2 antianginal medications, 22.3% in 2010 and 35.1% in 2014), and high-risk findings on noninvasive testing (22.2% in 2010 and 33.2% in 2014) (P < .001 for all), but only modest increases in multivessel coronary artery disease (43.7% in 2010 and 47.5% in 2014, P < .001). The proportion of nonacute PCIs classified as inappropriate decreased from 26.2% (95% CI, 25.8%-26.6%) to 13.3% (95% CI, 13.1%-13.6%), and the absolute number of inappropriate PCIs decreased from 21,781 to 7921. Hospital-level variation in the proportion of PCIs classified as inappropriate persisted over the study period (median, 12.6% [interquartile range, 5.9%-22.9%] in 2014). CONCLUSIONS AND RELEVANCE Since the publication of the Appropriate Use Criteria for Coronary Revascularization in 2009, there have been significant reductions in the volume of nonacute PCI. The proportion of nonacute PCIs classified as inappropriate has declined, although hospital-level variation in inappropriate PCI persists.

Appropriateness of Percutaneous Coronary Interventions in Washington State

Background— In anticipation of applying Appropriate Use Criteria for percutaneous coronary intervention (PCI) quality improvement, we determined the prevalence of appropriate, uncertain, and inappropriate PCIs stratified by indication for all PCIs performed in the state of Washington. Methods and Results— Within the Clinical Outcomes Assessment Program, we assigned appropriateness ratings to all PCIs performed in 2010 in accordance with published Appropriate Use Criteria. Of 13 291 PCIs, we successfully mapped the clinical scenario to the Appropriate Use Criteria in 9924 (75%) cases. Of the 3367 PCIs not classified, common failures to map to the criteria included nonacute PCI without prior noninvasive stress results (n = 1906; 57%) and unstable angina without high-risk features (n = 902; 27%). Of mapped PCIs, 8010 (71%) were for acute indications, with 7887 (98%) rated as appropriate, 39 (<1%) as uncertain, and 84 (1%) as inappropriate. Of 1914 mapped nonacute indications, 847 (44%) were rated as appropriate, 748 (39%) as uncertain, and 319 (17%) as inappropriate. Assuming results for noninvasive stress tests when data were missing, in the best-case scenario, 319 (8%) of nonacute PCIs were classified as inappropriate compared with 1459 (38%) in the worst-case scenario. Variation in inappropriate PCIs by facility was greatest for mapped nonacute indications (median = 14%; 25th to 75th percentiles = 9% to 24%) and nonacute indications with missing data precluding appropriateness classification (median = 54%; 25th to 75th percentiles = 35% to 66%). Conclusions— In a complete cohort of PCIs performed in Washington state, 1% of PCIs for acute indications and 17% of PCIs for nonacute indications were classified as inappropriate. Missing data on noninvasive stress tests present a challenge in the application of the criteria for quality improvement.

Improving bystander cardiopulmonary resuscitation

Purpose of reviewSummary estimates indicate that bystander cardiopulmonary resuscitation (CPR) can improve the chances of out-of-hospital cardiac arrest survival two-fold to three-fold. And yet, only a minority of arrest victims receive bystander CPR. This summary will review the challenges and approaches to achieve early and effective bystander CPR. Recent findingsGiven the host of barriers, a successful strategy to improve bystander CPR must enable more timely and comprehensive arrest identification, encourage and empower bystanders to act, and help assure effective CPR. Arrest identification can be simplified so that bystanders should start CPR when a person is unconscious and not breathing normally. Evidence from observational studies and interventional trials supports the effectiveness of chest compression-only CPR for bystanders. As a consequence, the emphasis of bystander CPR training has been modified to feature and assure chest compressions. Bystanders should initiate CPR with compressions and consider the addition of rescue breathing based on their CPR training and skills as well as special circumstances of the victim. Bystander CPR training has evolved to incorporate this emphasis. Although general community-level CPR training remains a cornerstone strategy, training directed to those most likely to witness an arrest also has a useful role. In particular, ‘just-in-time’ dispatcher-assisted CPR instruction can increase bystander CPR and improve the likelihood of survival. SummaryRecent developments in bystander CPR have simplified arrest recognition and improved CPR training, while retaining CPR effectiveness. The goal of these developments is to increase and improve bystander CPR and in turn improve resuscitation.

Cost-Consequences of Ultrafiltration for Acute Heart Failure A Decision Model Analysis

Background—Ultrafiltration for heart failure may reduce costs associated with acute heart failure by decreasing rehospitalization rates compared to intravenous diuretics. Methods and Results—We developed a decision-analytic model to explore the clinical outcomes and associated costs of ultrafiltration compared to intravenous diuretics for index and subsequent acute heart failure hospitalizations to 90 days from index hospitalization. We evaluated the model from societal, Medicare, and hospital payer perspectives. Base-case probabilities and costs were derived from the Ultrafiltration versus Intravenous Diuretics for Patients Hospitalized for Acute Decompensated Congestive Heart Failure clinical trial, Medicare reimbursement schedules, and published data. From a societal perspective, treatment with ultrafiltration had an 86% probability of being more expensive than intravenous diuretics in probabilistic sensitivity analysis, with a base-case estimate of

Variations in coronary artery disease secondary prevention prescriptions among outpatient cardiology practices: insights from the NCDR (National Cardiovascular Data Registry).

13 469 per patient treated with ultrafiltration compared to

Change in Hospital-Level Use of Transradial Percutaneous Coronary Intervention and Periprocedural Outcomes

11 610 per patient treated with intravenous diuretics. Cost estimates were most influenced by length of index hospitalization, daily cost of rehospitalization, number of days rehospitalized, and number and cost of ultrafiltration filters. From a Medicare payer perspective, ultrafiltration had a >99% probability of being cost saving. From a hospital perspective, there was a 97% probability ultrafiltration was more expensive. Our model suggested similar 90-day mortality rates between treatment arms. Conclusion—Despite a reduction in rehospitalization rates, it is unlikely ultrafiltration results in cost savings from a societal perspective. The discordance in cost between societal, Medicare, and hospital perspectives underscores the importance of payer perspective in formulating strategies and reimbursement structures to reduce heart failure hospitalizations.