John R Kapoor

Systematic Review: The Comparative Effectiveness of Percutaneous Coronary Interventions and Coronary Artery Bypass Graft Surgery

Context The relative benefits and harms of coronary artery bypass graft surgery (CABG) versus percutaneous coronary intervention (PCI) are sometimes unclear. Contribution This systematic review of 23 randomized trials found that survival at 10 years was similar for CABG and PCI, even among diabetic patients. Procedural strokes and angina relief were more common after CABG (risk difference, 0.6% and about 5% to 8%, respectively), whereas repeated revascularization procedures were more common after PCI (risk difference, 24% at 1 year). Caution Only 1 small trial used drug-eluting stents. Few patients with extensive coronary disease or poor ventricular function were enrolled. The Editors Coronary artery bypass graft (CABG) surgery and catheter-based percutaneous coronary intervention (PCI), with or without coronary stents, are alternative approaches to mechanical coronary revascularization. These 2 coronary revascularization techniques are among the most common major medical procedures performed in North America and Europe: In 2005, 261000 CABG procedures and 645000 PCI procedures were performed in the United States alone (1). However, the comparative effectiveness of CABG and PCI remains poorly understood for patients in whom both procedures are technically feasible and coronary revascularization is clinically indicated. In patients with left main or triple-vessel coronary artery disease with reduced left ventricular function, CABG is generally preferred because randomized, controlled trials (RCTs) have shown that it improves survival compared with medical therapy (2, 3). In patients with most forms of single-vessel disease, PCI is generally the preferred form of coronary revascularization (4), in light of its lower clinical risk and the evidence that PCI reduces angina and myocardial ischemia in this subset of patients (5). Most RCTs comparing CABG and PCI have been conducted in populations with coronary artery disease between these extremes, namely patients with single-vessel, proximal left anterior descending disease; most forms of double-vessel disease; or less extensive forms of triple-vessel disease. We sought to evaluate the evidence from RCTs on the comparative effectiveness of PCI and CABG. We included trials using balloon angioplasty or coronary stents because quantitative reviews have shown no differences in mortality or myocardial infarction between these PCI techniques (6, 7). We also included trials using standard or minimally invasive CABG or both procedures (8, 9). We sought to document differences between PCI and CABG in survival, cardiovascular complications (such as stroke and myocardial infarction), and freedom from angina. Finally, we reviewed selected observational studies to assess the generalizability of the RCTs. Methods Data Sources We searched the MEDLINE, EMBASE, and Cochrane databases for studies published between January 1966 and August 2006 by using such terms as angioplasty, coronary, and coronary artery bypass surgery, as reported in detail elsewhere (10). We also sought additional studies by reviewing the reference lists of included articles, conference abstracts, and the bibliographies of expert advisors. We did not limit the searches to the English language. Study Selection We sought RCTs that compared health outcomes of PCI and CABG. We excluded trials that compared PCI alone or CABG alone with medical therapy, those that compared 2 forms of PCI, and those that compared 2 forms of CABG. The outcomes of interest were survival, myocardial infarction, stroke, angina, and use of additional revascularization procedures. Two investigators independently reviewed titles, abstracts, and the full text as needed to determine whether studies met inclusion criteria. Conflicts between reviewers were resolved through re-review and discussion. We did not include results published solely in abstract form. Data Extraction and Quality Assessment Two authors independently abstracted data on study design; setting; population characteristics (sex, age, race/ethnicity, comorbid conditions, and coronary anatomy); eligibility and exclusion criteria; procedures performed; numbers of patients screened, eligible, enrolled, and lost to follow-up; method of outcome assessment; and results for each outcome. We assessed the quality of included trials by using predefined criteria and graded their quality as A, B, or C by using methods described in detail elsewhere (10). In brief, a grade of A indicates a high-quality trial that clearly described the population, setting, interventions, and comparison groups; randomly allocated patients to alternative treatments; had low dropout rates; and reported intention-to-treat analysis of outcomes. A grade of B indicates a randomized trial with incomplete information about methods that might mask important limitations. A grade of C indicates that the trial had evident flaws, such as improper randomization, that could introduce significant bias. Data Synthesis and Analysis We used random-effects models to compute weighted mean rates and SEs for each outcome. We computed summary risk differences and odds ratios between PCI and CABG and the 95% CI for each outcome of interest at annual intervals. Because the results did not differ materially when risk differences and odds ratios (10) were used and the low rate of several outcomes (for example, procedural mortality) made the risk difference a more stable outcome metric (11, 12), we report here only the risk differences. We assessed heterogeneity of effects by using chi-square and I 2 statistics (13). When effects were heterogeneous (I 2 > 50%), we explored the effects of individual studies on summary effects by removing each study individually. We assessed the possibility of publication bias by visual inspection of funnel plots and calculated the number of missing studies required to change a statistically significant summary effect to not statistically significant (11). We performed analyses by using Comprehensive Meta-Analysis software, version 2.0 (Biostat, Englewood, New Jersey). Inclusion of Observational Studies We also searched for observational data to evaluate the generalizability of the RCT results, as reported in detail elsewhere (10). In brief, we included observational studies from clinical or administrative databases that included at least 1000 recipients of each revascularization procedure and provided sufficient information about the patient populations (such as demographic characteristics, preprocedure coronary anatomy, and comorbid conditions) and procedures performed (such as balloon angioplasty vs. bare-metal stents vs. drug-eluting stents). Role of the Funding Source This project was supported by the Agency for Healthcare Research and Quality. Representatives of the funding agency reviewed and commented on the study protocol and drafts of the manuscript, but the authors had final responsibility for the design, conduct, analysis, and reporting of the study. Results We identified 1695 potentially relevant articles, of which 204 merited full-text review (Appendix Figure). A total of 113 articles reporting on 23 unique RCTs met inclusion criteria (Table 1 [14126]). These trials enrolled a total of 9963 patients, of whom 5019 were randomly assigned to PCI and 4944 to CABG. Most trials were conducted in Europe, the United Kingdom, or both locations; only 3 trials were performed in the United States. The early studies (patient entry from 1987 to 1993) used balloon angioplasty as the PCI technique, and the later studies (patient entry from 1994 to 2002) used stents as the PCI technique. Only 1 small trial of PCI versus CABG used drug-eluting stents (116). Nine trials limited entry to patients with single-vessel disease of the proximal left anterior descending artery, whereas the remaining 14 trials enrolled patients with multivessel disease, either predominantly (3 trials) or exclusively (11 trials). Appendix Figure. Study flow diagram. CABG= coronary artery bypass grafting; CAD= coronary artery disease; PCI= percutaneous coronary intervention; RCT= randomized, controlled trial. Table 1. Overview of Randomized, Controlled Trials The quality of 21 trials was graded as A, and 1 trial (117) was graded as B. One trial (116) was graded as C because randomization may not have been properly executed (details are available elsewhere [10]). We performed sensitivity analyses by removing these studies from the analysis, and our summary results did not change statistically significantly. The average age of the trial participants was 61 years, 27% were women, and most were of European ancestry. Roughly 20% had diabetes, half had hypertension, and half had hyperlipidemia. Whereas approximately 40% of patients had a previous myocardial infarction, few had heart failure or poor left ventricular function. Among studies that enrolled patients with multivessel coronary disease, most had double-vessel rather than triple-vessel disease. Revascularization procedures were performed by using standard methods for the time the trial was conducted (Table 1). Among patients with multivessel disease, more grafts were placed during CABG than vessels were dilated during PCI. Among patients assigned to PCI, stents were commonly used in the recent studies, but in the earlier trials, balloon angioplasty was standard. Among patients assigned to CABG, arterial grafting with the left internal mammary artery was frequently done, especially in more recent trials. Some studies used minimally invasive, direct coronary artery bypass and off-pump operations to perform CABG in patients with single-vessel left anterior descending disease (Table 1). Short-Term and Procedural Outcomes Survival (within 30 days of the procedure) was high for both procedures: 98.9% for PCI and 98.2% for CABG. When data from all trials were combined, the survival difference between PCI and CABG was small and not statistically significant (0.2% [95% CI, 0.3% to 0.6%]) (Figure 1

Divergent Trends in Survival and Readmission Following a Hospitalization for Heart Failure in the Veterans Affairs Health Care System 2002 to 2006

OBJECTIVES This study sought to determine recent trends over time in heart failure hospitalization, patient characteristics, treatment, rehospitalization, and mortality within the Veterans Affairs health care system. BACKGROUND Use of recommended therapies for heart failure has increased in the U.S. However, it is unclear to what extent hospitalization rates and the associated mortality have improved. METHODS We compared rates of hospitalization for heart failure, 30-day rehospitalization for heart failure, and 30-day mortality following discharge from 2002 to 2006 in the Veterans Affairs Health Care System. Odds ratios for outcome were adjusted for patient diagnoses within the past year, laboratory data, and for clustering of patients within hospitals. RESULTS We identified 50,125 patients with a first hospitalization for heart failure from 2002 to 2006. Mean age did not change (70 years), but increases were noted for most comorbidities (mean Charlson score increased from 1.72 to 1.89, p < 0.0001). Heart failure admission rates remained constant at about 5 per 1,000 veterans. Mortality at 30 days decreased (7.1% to 5.0%, p < 0.0001), whereas rehospitalization for heart failure at 30 days increased (5.6% to 6.1%, p = 0.11). After adjustment for patient characteristics, the odds ratio for rehospitalization in 2006 (vs. 2002) was 0.54 (95% confidence interval [CI]: 0.47 to 0.61) for mortality, but 1.21 (95% CI: 1.04 to 1.41) for heart failure rehospitalization at 30 days. CONCLUSIONS Recent mortality and rehospitalization rates in the Veterans Affairs Health Care System have trended in opposite directions. These results have implications for using rehospitalization as a measure of quality of care.

Radiation induced heart disease

Mediastinal irradiation can improve outcome for a wide range of neoplasms, including that of the lungs, breasts and oesophagus as well as lymphomas such as Hodgkin’s disease. However, when the irradiation field includes the heart, untoward late cardiac effects can develop that were underappreciated in the past. Indeed, until the mid 1960s, the heart was thought to be a relatively radioresistant organ.1 Even as recent as the 1980s, the issue of whether radiation exposure led to coronary artery disease was controversial and a relationship was not established until the mid to late 1990s. It was then becoming clear that the cardiovascular risks of mediastinal irradiation may limit the survival benefit in some cancer patients. Radiation induced heart disease (RIHD) encompasses a range of deleterious effects on the heart, from subclinical histopathological findings to overt clinical disease. The damaging cardiac effects may be manifested in the pericardium, myocardium, valves, conduction system or coronary arteries. Although the cumulative incidence of RIHD is difficult to estimate due to long latency periods from exposure to clinical manifestations, the incidence of coronary heart disease following radiation appears to be greatest when radiation is given for Hodgkin’s disease. This may be due to many years of follow-up leading to a greater chance for detecting disease, since these patients generally received mediastinal irradiation at a young age.2 Survivors of left sided breast cancer who have received mediastinal irradiation have also experienced increased mortality from cardiovascular causes, particularly when the irradiation field included the internal mammary glands resulting in higher dose volumes of irradiation. Mediastinal irradiation for thymomas and oesophageal and lung cancers has also been associated with cardiotoxicity. As oncologic treatment continues to improve with longer survival rates, and the indications for mediastinal irradiation as primary and adjuvant therapy rise, RIHD is likely to be …

Isolated Disease of the Proximal Left Anterior Descending Artery: Comparing the Effectiveness of Percutaneous Coronary Interventions and Coronary Artery Bypass Surgery

OBJECTIVES This study sought to systematically compare the effectiveness of percutaneous coronary intervention and coronary artery bypass surgery in patients with single-vessel disease of the proximal left anterior descending (LAD) coronary artery. BACKGROUND It is uncertain whether percutaneous coronary interventions (PCI) or coronary artery bypass grafting (CABG) surgery provides better clinical outcomes among patients with single-vessel disease of the proximal LAD. METHODS We searched relevant databases (MEDLINE, EMBASE, and Cochrane from 1966 to 2006) to identify randomized controlled trials that compared outcomes for patients with single-vessel proximal LAD assigned to either PCI or CABG. RESULTS We identified 9 randomized controlled trials that enrolled a total of 1,210 patients (633 received PCI and 577 received CABG). There were no differences in survival at 30 days, 1 year, or 5 years, nor were there differences in the rates of procedural strokes or myocardial infarctions, whereas the rate of repeat revascularization was significantly less after CABG than after PCI (at 1 year: 7.3% vs. 19.5%; at 5 years: 7.3% vs. 33.5%). Angina relief was significantly greater after CABG than after PCI (at 1 year: 95.5% vs. 84.6%; at 5 years: 84.2% vs. 75.6%). Patients undergoing CABG spent 3.2 more days in the hospital than those receiving PCI (95% confidence interval: 2.3 to 4.1 days, p < 0.0001), required more transfusions, and were more likely to have arrhythmias immediately post-procedure. CONCLUSIONS In patients with single-vessel, proximal LAD disease, survival was similar in CABG-assigned and PCI-assigned patients; CABG was significantly more effective in relieving angina and led to fewer repeat revascularizations.

Neurotransmitter/neuropeptide interactions in the regulation of neurohypophyseal hormone release

Regulation of neurohypophyseal hormone release reflects the convergence of a large number of afferent pathways on the vasopressin (VP)- and oxytocin-producing neurons. These pathways utilize a broad range of neurotransmitters and neuropeptides. In this review, the mechanisms by which this information is coordinated into appropriate physiological responses is discussed with a focus on the responses to agents that are coreleased from A1 catecholamine nerve terminals in the supraoptic nucleus. The A1 pathway transmits hemodynamic information to the vasopressin neurons by releasing several neuroactive agents including ATP, norepinephrine, neuropeptide Y, and substance P. These substances stimulate VP release from explants of the hypothalamo-neurohypophyseal system and certain combinations of these agents elicit potent but selective synergism. Evaluation of the signal cascades elicited by these agents provides insights into mechanisms underlying these synergistic interactions and suggests mechanisms responsible for coordinated responses of the VP neurons to activation of a range of ion-gated ion channel and G-protein-coupled receptors.

Payment source, quality of care, and outcomes in patients hospitalized with heart failure.

OBJECTIVES The aim of this study was to analyze the relationship between payment source and quality of care and outcomes in heart failure (HF). BACKGROUND HF is a major cause of morbidity and mortality. There is a lack of studies assessing the association of payment source with HF quality of care and outcomes. METHODS A total of 99,508 HF admissions from 244 sites between January 2005 and September 2009 were analyzed. Patients were grouped on the basis of payer status (private/health maintenance organization, no insurance, Medicare, or Medicaid) with private/health maintenance organization as the reference group. RESULTS The no-insurance group was less likely to receive evidence-based beta-blockers (adjusted odds ratio [OR]: 0.73; 95% confidence interval [CI]: 0.62 to 0.86), implantable cardioverter-defibrillator (OR: 0.59; 95% CI: 0.50 to 0.70), or anticoagulation for atrial fibrillation (OR: 0.73; 95% CI: 0.61 to 0.87). Similarly, the Medicaid group was less likely to receive evidence-based beta-blockers (OR: 0.86; 95% CI: 0.78 to 0.95) or implantable cardioverter-defibrillators (OR: 0.86; 95% CI: 0.78 to 0.96). Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers and beta-blockers were prescribed less frequently in the Medicare group (OR: 0.89; 95% CI: 0.81 to 0.98). The Medicare, Medicaid, and no-insurance groups had longer hospital stays. Higher adjusted rates of in-hospital mortality were seen in patients with Medicaid (OR: 1.22; 95% CI: 1.06 to 1.41) and in patients with reduced systolic function with no insurance. CONCLUSIONS Decreased quality of care and outcomes for patients with HF were observed in the no-insurance, Medicaid, and Medicare groups compared with the private/health maintenance organization group.

Heart rate predicts mortality in patients with heart failure and preserved systolic function.

BACKGROUND Elevated resting heart rates have been associated with increased mortality and morbidity in patients with heart failure and decreased left ventricular ejection fraction (EF). It is unclear, though, if this association applies to those with heart failure and preserved EF. METHODS AND RESULTS We determined outcome for 685 consecutive patients with a prior diagnosis of heart failure and a preserved EF (>50%) documented on echocardiography at 1 of 3 laboratories. Patients with non-sinus rhythm were excluded from the analysis. We determined adjusted mortality rates at 1 year after the echocardiogram. The mean age of the cohort was 70 ± 11 years. Of the 685 included patients, 87% had a history of hypertension, 50% had diabetes, and the mean EF was 60% ± 6%. All-cause mortality at 1 year was significantly lower in the group with heart rate below 60 beats/min (10%) when compared with the group with heart rates between 60 and 70 beats/min (18%), 71-90 beats/min (20%), and >90 beats/min (35%) (P < .0001). After adjustment for patient history, demographics, laboratory values, and echocardiographic findings, the hazard ratios for total mortality (relative to a heart rate of <60) were 1.26 (95% CI, 0.88-1.80) for HR 60-69, 1.47 (95% CI, 1.02-2.07) for HR 70-90, and 2.00 (95% CI, 1.31-3.04) for HR>90 (P = .01 across all groups). CONCLUSIONS These data suggest that an elevated resting heart rate is a marker for increased mortality in patients with heart failure and preserved systolic function. Heart rate may be useful in these patients for improved cardiovascular risk assessment.

Diabetes, quality of care, and in-hospital outcomes in patients hospitalized with heart failure.

BACKGROUND Diabetes mellitus is frequently comorbid with heart failure (HF). It is unclear if comorbid diabetes is associated with quality of care and in-hospital mortality. METHODS We analyzed 133,971 HF admissions from 431 hospitals between January 2005 and January 2010 comparing patients with and without diabetes. RESULTS There were 54,352 (41%) patients hospitalized with HF with a history or newly diagnosed diabetes. After adjustment, patients with diabetes were as likely as patients without diabetes to appropriately receive the composite of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker and β-blockers (odds ratio [OR] 0.99, 95% CI 0.94-1.04), angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (OR 0.98, 95% CI 0.92-1.05), evidence-based β-blockers (OR 1.04, 95% CI 0.98-1.1), and hydralazine/nitrates (OR 1.09, 95% CI 0.99-1.2). However, patients with diabetes were less likely to receive smoking cessation counseling (OR 0.89, 95% CI 0.81-0.98) and blood pressure control (OR 0.81, 95% CI 0.78-0.84) and to attain the all-or-none composite measure (OR 0.96, 95% CI 0.93-0.99). Patients with diabetes were more likely to receive an aldosterone antagonist for reduced left ventricular ejection fraction (OR 1.05, 95% CI 1.00-1.11), lipid-lowering agent (OR 1.33, 95% CI 1.26-1.41), and influenza vaccination (OR 1.05, 95% CI 1.01-1.09). Diabetes was independently associated with longer hospital stay but not within-hospital mortality. CONCLUSIONS With few exceptions, the application of evidence-based care and in-hospital outcomes were similar whether or not diabetes was present in this large contemporary cohort of patients hospitalized with HF.

Association between Stroke Severity and Fall Risk among Stroke Patients

Background: Falls are common after stroke. Simple, clinically practical tools are needed to easily identify patients with stroke who are at risk of falls. The objective of this study was to identify the factors associated with increased fall risk in a poststroke population. Methods: We assessed factors associated with fall risk among poststroke patients. Fall risk was determined through a history of falls, physical examination, observations of transfers, gait, balance, strength, range of motion, and use of assistive devices. Stroke severity was evaluated using the NIH Stroke Scale (NIHSS); mild or moderate-severe stroke was defined as a NIHSS score of <4 or ≧4, respectively. Results: Among 52 poststroke patients, 26 (50%) were considered at risk of falls. Patients at risk of falls compared with those without fall risk were more likely to have greater stroke severity, decreased functional status, and to be more dependent in activities of daily living. Increased stroke severity was independently associated with higher fall risk (NIHSS ≧4: OR = 5.73; 95% CI: 1.645–19.94). Conclusion: Poststroke patients at risk of falls can be identified by an NIHSS score of ≧4. Clinicians should screen patients for fall risk so that fall prevention strategies can be instituted.

Role of Heart Rate as a Marker and Mediator of Poor Outcome for Patients with Heart Failure

Tachycardia has been associated with worse outcomes for patients with heart failure and is also thought to have a direct adverse impact on the myocardium. This report highlights the current evidence for heart rate as both a risk factor and mediator for poor outcome for patients with heart failure. We summarize the large number of studies evaluating heart rate in patients with systolic dysfunction and newer studies that examine patients with preserved systolic function. The effect on outcomes in heart failure of medications known to slow the heart rate such as β-blockers and the more recently developed drug ivabradine are discussed. The data clearly show that a high heart rate is a marker of increased mortality. There is also a strong suggestion that a higher heart rate directly worsens outcome and that this can be mitigated by heart rate–reducing medications.