Harindra C. Wijeysundera

Association of temporal trends in risk factors and treatment uptake with coronary heart disease mortality, 1994-2005.

CONTEXT Coronary heart disease (CHD) mortality has declined substantially in Canada since 1994. OBJECTIVE To determine what proportion of this decline was associated with temporal trends in CHD risk factors and advancements in medical treatments. DESIGN, SETTING, AND PATIENTS Prospective analytic study of the Ontario, Canada, population aged 25 to 84 years between 1994 and 2005, using an updated version of the validated IMPACT model, which integrates data on population size, CHD mortality, risk factors, and treatment uptake changes. Relative risks and regression coefficients from the published literature quantified the relationship between CHD mortality and (1) evidence-based therapies in 8 distinct CHD subpopulations (acute myocardial infarction [AMI], acute coronary syndromes, secondary prevention post-AMI, chronic coronary artery disease, heart failure in the hospital vs in the community, and primary prevention for hyperlipidemia or hypertension) and (2) population trends in 6 risk factors (smoking, diabetes mellitus, systolic blood pressure, plasma cholesterol level, exercise, and obesity). MAIN OUTCOME MEASURES The number of deaths prevented or delayed in 2005; secondary outcome measures were improvements in medical treatments and trends in risk factors. RESULTS Between 1994 and 2005, the age-adjusted CHD mortality rate in Ontario decreased by 35% from 191 to 125 deaths per 100,000 inhabitants, translating to an estimated 7585 fewer CHD deaths in 2005. Improvements in medical and surgical treatments were associated with 43% (range, 11% to 124%) of the total mortality decrease, most notably in AMI (8%; range, -5% to 40%), chronic stable coronary artery disease (17%; range, 7% to 35%), and heart failure occurring while in the community (10%; range, 6% to 31%). Trends in risk factors accounted for 3660 fewer CHD deaths prevented or delayed (48% of total; range, 28% to 64%), specifically, reductions in total cholesterol (23%; range, 10% to 33%) and systolic blood pressure (20%; range, 13% to 26%). Increasing diabetes prevalence and body mass index had an inverse relationship associated with higher CHD mortality of 6% (range, 4% to 8%) and 2% (range, 1% to 4%), respectively. CONCLUSION Between 1994 and 2005, there was a decrease in CHD mortality rates in Ontario that was associated primarily with trends in risk factors and improvements in medical treatments, each explaining about half of the decrease.

Coronary Artery Bypass Graft Surgery vs Percutaneous Interventions in Coronary Revascularization: A Systematic Review

IMPORTANCE Ischemic heart disease is the leading cause of death globally. Coronary artery bypass graft (CABG) surgery and percutaneous coronary intervention (PCI) are the revascularization options for ischemic heart disease. However, the choice of the most appropriate revascularization modality is controversial in some patient subgroups. OBJECTIVE To summarize the current evidence comparing the effectiveness of CABG surgery and PCI in patients with unprotected left main disease (ULMD, in which there is >50% left main coronary stenosis without protective bypass grafts), multivessel coronary artery disease (CAD), diabetes, or left ventricular dysfunction (LVD). EVIDENCE REVIEW A search of OvidSP MEDLINE, EMBASE, and Cochrane databases between January 2007 and June 2013, limited to randomized clinical trials (RCTs) and meta-analysis of trials and/or observational studies comparing CABG surgery with PCI was performed. Bibliographies of relevant studies were also searched. Mortality and major adverse cardiac and cerebrovascular events (MACCE, defined as all-cause mortality, myocardial infarction, stroke, and repeat revascularization) were reported wherever possible. FINDINGS Thirteen RCTs and 5 meta-analyses were included. CABG surgery should be recommended in patients with ULMD, multivessel CAD, or LVD, if the severity of coronary disease is deemed to be complex (SYNTAX >22) due to lower cardiac events associated with CABG surgery. In cases in which coronary disease is less complex (SYNTAX ≤22) and/or the patient is a higher surgical risk, PCI should be considered. For patients with diabetes and multivessel CAD, CABG surgery should be recommended as standard therapy irrespective of the severity of coronary anatomy, given improved long-term survival and lower cardiac events (5-year MACCE, 18.7% for CABG surgery vs 26.6% for PCI; P = .005). Overall, the incidence of repeat revascularization is higher after PCI, whereas stroke is higher after CABG surgery. Current literature emphasizes the importance of a heart-team approach that should consider coronary anatomy, patient characteristics, and local expertise in revascularization options. Literature pertaining to revascularization options in LVD is scarce predominantly due to LVD being an exclusion factor in most studies. CONCLUSIONS AND RELEVANCE Both CABG surgery and PCI are reasonable options for patients with advanced CAD. Patients with diabetes generally have better outcomes with CABG surgery than PCI. In cases of ULMD, multivessel CAD, or LVD, CABG surgery should be favored in patients with complex coronary lesions and anatomy and PCI in less complicated coronary disease or deemed a high surgical risk. A heart-team approach should evaluate coronary disease complexity, patient comorbidities, patient preferences, and local expertise.

Lifetime Analysis of Hospitalizations and Survival of Patients Newly Admitted With Heart Failure

Background—Hospital readmissions for heart failure (HF) contribute to increased morbidity and resource burden. Predictors of hospitalization and patterns of cardiovascular events over the lifetime of patients with HF have not been elucidated. Methods and Results—We examined recurrent hospitalizations, cardiovascular events, and survival among newly discharged (April 1999–March 2001) patients with HF in the Enhanced Feedback For Effective Cardiac Treatment phase 1 study. During 10-year follow-up, we examined all new cardiovascular hospitalizations and selected predictors of readmission. Among 8543 patients (mean age, 77.4±10.5 years; 51.6% women) followed for 22 567 person-years, 60.7% had ischemic etiology, and 67.3% had HF with reduced ejection fraction (left ventricular ejection fraction ⩽45% versus >45% [HF with preserved ejection fraction]). Overall, 10-year mortality was 98.8%, with 35 966 hospital readmissions occurring over the lifetime of the cohort. Adjusted hazards ratios (HRs) for first cardiovascular hospitalization were 1.36 for ischemic HF (95% CI, 1.28–1.44; P<0.001), 1.10 for HF with reduced ejection fraction (95% CI; 1.00–1.20; P=0.045), and 1.00 for men (95% CI, 0.94–1.06; P=0.979). On repeated-events time-to-event analysis, ischemic HF was a predictor of cardiovascular (HR, 1.24; 95% CI, 1.18–1.29), HF (HR, 1.20; 95% CI, 1.13–1.27), and coronary heart disease (HR, 2.01; 95% CI, 1.81–2.24) hospitalizations (all P<0.001). Of all recurrent HF hospitalizations, 26.8% occurred in the first and 39.8% in the last deciles of cohort survival duration. Similarly, 29.7% and 52.3% of all cardiovascular readmissions occurred in the first and last deciles of the cohort survival duration, respectively. Conclusions—Among newly discharged patients with HF, cardiovascular events were clustered at early postdischarge and prefatal time periods, and were increased among those with ischemic etiology.

Meta-analysis: effects of percutaneous coronary intervention versus medical therapy on angina relief.

BACKGROUND Several meta-analyses have evaluated the efficacy of percutaneous coronary intervention (PCI) compared with medical therapy, but none has focused on angina relief. PURPOSE To summarize the evidence on the degree of angina relief from PCI compared with medical therapy in patients with stable coronary artery disease. DATA SOURCES The Cochrane Library (1993 to June 2009), EMBASE (1980 to June 2009), and MEDLINE (1950 to June 2009), with no language restrictions. STUDY SELECTION Two independent reviewers screened citations to identify randomized, controlled trials of PCI versus medical therapy in patients with stable coronary artery disease. DATA EXTRACTION Two independent reviewers abstracted data on patient characteristics, study conduct, and outcomes. A random-effects model was used to combine data on freedom from angina and to perform stratified analyses based on duration of follow-up, inclusion of patients with recent myocardial infarction, coronary stent utilization, recruitment period, and utilization of evidence-based medications. DATA SYNTHESIS A total of 14 trials, enrolling 7818 patients, met the inclusion criteria. Although PCI was associated with an overall benefit on angina relief (odds ratio, 1.69 [95% CI, 1.24 to 2.30]), important heterogeneity across trials was observed. The incremental benefit of PCI observed in older trials (odds ratio, 3.38 [CI, 1.89 to 6.04]) was substantially less and possibly absent in recent trials (odds ratio, 1.13 [CI, 0.76 to 1.68]). An inverse relationship between use of evidence-based therapies and the incremental benefit of PCI was observed. LIMITATIONS Information about the long-term use of medication was incomplete in most trials. Few trials used drug-eluting stents. Meta-regression analyses used aggregated study-level data from few trials. CONCLUSION Percutaneous coronary intervention was associated with greater freedom from angina compared with medical therapy, but this benefit was largely attenuated in contemporary studies. This observation may be related to greater use of evidence-based medications in contemporary trials. PRIMARY FUNDING SOURCE Canadian Institutes of Health Research.

Clinical ResearchInterventional CardiologyRescue Angioplasty or Repeat Fibrinolysis After Failed Fibrinolytic Therapy for ST-Segment Myocardial Infarction: A Meta-Analysis of Randomized Trials

OBJECTIVES We sought to best estimate the benefits and risks associated with rescue percutaneous coronary intervention (PCI) and repeat fibrinolytic therapy as compared with conservative management in patients with failed fibrinolytic therapy for ST-segment myocardial infarction (STEMI). BACKGROUND Fibrinolytic therapy is the most common treatment for STEMI; however, the best therapy in patients who fail to achieve reperfusion after fibrinolytic therapy remains uncertain. METHODS We performed a meta-analysis of randomized trials using a fixed-effects model. We included 8 trials enrolling 1,177 patients with follow-up duration ranging from hospital discharge to 6 months. RESULTS Rescue PCI was associated with no significant reduction in all-cause mortality (relative risk [RR] 0.69; 95% confidence interval [CI] 0.46 to 1.05), but was associated with significant risk reductions in heart failure (RR 0.73; 95% CI 0.54 to 1.00) and reinfarction (RR 0.58; 95% CI 0.35 to 0.97) when compared with conservative treatment. Rescue PCI was associated with an increased risk of stroke (RR 4.98; 95% CI 1.10 to 22.5) and minor bleeding (RR 4.58; 95% CI 2.46 to 8.55). Repeat fibrinolytic therapy was not associated with significant improvements in all-cause mortality (RR 0.68; 95% CI 0.41 to 1.14) or reinfarction (RR 1.79; 95% CI 0.92 to 3.48), but was associated with an increased risk for minor bleeding (RR 1.84; 95% CI 1.06 to 3.18). CONCLUSIONS Rescue PCI is associated with improved clinical outcomes for STEMI patients after failed fibrinolytic therapy, but these benefits must be interpreted in the context of potential risks. On the other hand, repeat fibrinolytic therapy is not associated with significant clinical improvement and may be associated with increased harm.

Risk of Elective Major Noncardiac Surgery After Coronary Stent Insertion A Population-Based Study

Background— Guidelines recommend that noncardiac surgery be delayed until 30 to 45 days after bare-metal stent implantation and 1 year after drug-eluting stent implantation. Methods and Results— We used linked registry data and population-based administrative health care databases to conduct a cohort study of 8116 patients (≥40 years of age) who underwent major elective noncardiac surgery in Ontario, Canada between 2003 and 2009, and received coronary stents within 10 years before surgery. Approximately 34% (n=2725) underwent stent insertion within 2 years before surgery, of whom 905 (33%) received drug-eluting stents. For comparison, we assembled a separate cohort of 341 350 surgical patients who had not undergone coronary revascularization. The primary outcome was 30-day major adverse cardiac events (mortality, readmission for acute coronary syndrome, or repeat coronary revascularization). The overall rate of 30-day events in patients with coronary stents was 2.1% (n=170). When the interval between stent insertion and surgery was <45 days, event rates were high for bare-metal (6.7%) and drug-eluting (20.0%) stents. When the interval was 45 to 180 days, the event rate for bare-metal stents was 2.6%, approaching that of intermediate-risk nonrevascularized individuals. Adjusted analyses suggested that event rates were increased if this interval exceeded 180 days. For drug-eluting stents, the event rate was 1.2% once the interval exceeded 180 days, approaching that of intermediate-risk nonrevascularized individuals. Conclusions— The earliest optimal time for elective surgery is 46 to 180 days after bare-metal stent implantation or >180 days after drug-eluting stent implantation.

Incidence, Timing, and Predictors of Valve Hemodynamic Deterioration After Transcatheter Aortic Valve Replacement: Multicenter Registry.

BACKGROUND Scarce data exist on the incidence of and factors associated with valve hemodynamic deterioration (VHD) after transcatheter aortic valve replacement (TAVR). OBJECTIVES This study sought to determine the incidence, timing, and predictors of VHD in a large cohort of patients undergoing TAVR. METHODS This multicenter registry included 1,521 patients (48% male; 80 ± 7 years of age) who underwent TAVR. Mean echocardiographic follow-up was 20 ± 13 months (minimum: 6 months). Echocardiographic examinations were performed at discharge, at 6 to 12 months, and yearly thereafter. Annualized changes in mean gradient (mm Hg/year) were calculated by dividing the difference between the mean gradient at last follow-up and the gradient at discharge by the time between examinations. VHD was defined as a ≥10 mm Hg increase in transprosthetic mean gradient during follow-up compared with discharge assessment. RESULTS The overall mean annualized rate of transprosthetic gradient progression during follow-up was 0.30 ± 4.99 mm Hg/year. A total of 68 patients met criteria of VHD (incidence: 4.5% during follow-up). The absence of anticoagulation therapy at hospital discharge (p = 0.002), a valve-in-valve (TAVR in a surgical valve) procedure (p = 0.032), the use of a 23-mm valve (p = 0.016), and a greater body mass index (p = 0.001) were independent predictors of VHD. CONCLUSIONS There was a mild but significant increase in transvalvular gradients over time after TAVR. The lack of anticoagulation therapy, a valve-in-valve procedure, a greater body mass index, and the use of a 23-mm transcatheter valve were associated with higher rates of VHD post-TAVR. Further prospective studies are required to determine whether a specific antithrombotic therapy post-TAVR may reduce the risk of VHD.

Assessing the Association of Appropriateness of Coronary Revascularization and Clinical Outcomes for Patients With Stable Coronary Artery Disease

OBJECTIVES The study assessed the appropriateness of coronary revascularization in Ontario, Canada, and examined its association with longer-term outcomes. BACKGROUND Although appropriate use criteria for coronary revascularization have been developed to improve the rational use of cardiac invasive procedures, it is unknown whether greater adherence to appropriateness guidelines is associated with improved clinical outcomes in stable coronary artery disease. METHODS A population-based cohort of stable patients undergoing cardiac catheterization was assembled from April 1, 2006, to March 31, 2007. The appropriateness for coronary revascularization at the time of coronary angiography was retrospectively adjudicated using the appropriate use criteria. Clinical outcomes between coronary revascularization and medical treatment without revascularization, stratified by appropriateness categories, were compared. RESULTS In 1,625 patients with stable coronary artery disease, percutaneous coronary intervention or coronary artery bypass grafting was only performed in 69% who had an appropriate indication for coronary revascularization. Coronary revascularization was associated with a lower adjusted hazard of death or acute coronary syndrome (hazard ratio [HR]: 0.61; 95% confidence interval [CI]: 0.42 to 0.88) at 3 years compared with medical therapy in appropriate patients. The rate of coronary revascularization was 54% in the uncertain category and 45% in the inappropriate category. No significant difference in death or acute coronary syndrome between coronary revascularization and no revascularization in the uncertain category (HR: 0.57; 95% CI: 0.28 to 1.16) and the inappropriate category (HR: 0.99; 95% CI: 0.48 to 2.02) was observed. CONCLUSIONS Using the appropriateness use criteria, we identified substantial underutilization and overutilization of coronary revascularization in contemporary clinical practice. Underutilization of coronary revascularization is associated with significantly increased risks of adverse outcomes in patients with appropriate indications.

Trends in Short- and Long-Term Survival Among Out-of-Hospital Cardiac Arrest Patients Alive at Hospital Arrival

Background— Out-of-hospital cardiac arrest (OHCA) is associated with a poor prognosis and poses a significant burden to the healthcare system, but few studies have evaluated whether OHCA incidence and survival have changed over time. Methods and Results— A population-based cohort study was conducted, including 34 291 OHCA patients >20 years of age who were transported alive to the emergency department of an acute-care hospital from April 1, 2002, to March 31, 2012, in Ontario, Canada. Patients with life-threatening trauma and those who died before hospital arrival were excluded. The overall age- and sex-standardized incidence of OHCA patients who were transported alive was 36 cases per 100 000 persons and did not significantly change over the study period. Cardiac risk factor prevalence increased significantly, whereas the rate of most cardiovascular conditions decreased significantly. The 30-day survival improved from 9.4% in 2002 to 13.6% in 2011; 1-year survival improved from 7.7% to 11.8% (P<0.001). Patients hospitalized in 2011 were significantly more likely to survive 30 days (adjusted odds ratio, 1.47 [95% CI, 1.22–1.77]) and 1 year (adjusted odds ratio, 1.55 [95% CI, 1.27–1.91]) compared with 2002. A significant interaction between temporal trends in survival improvement and age group was observed in which the improvement in survival was largest in the youngest age groups. Conclusions— OHCA patients who were transported alive are increasingly likely to have cardiovascular risk factors but less likely to have previous cardiovascular conditions. The overall incidence of OHCA patients transported to hospital alive did not change over the past decade. Short- and longer-term survival after OHCA has substantially improved, with younger patients experiencing the greatest improvement.

Prevalence and Extent of Obstructive Coronary Artery Disease Among PatientsUndergoing Elective Coronary Catheterization in New York State and Ontario

IMPORTANCE Prior studies have shown that physicians in New York State (New York) perform twice as many cardiac catheterizations per capita as those in Ontario for stable patients. However, the role of patient selection in these findings and their implications for detection of obstructive coronary artery disease (CAD) are largely unknown. OBJECTIVE To evaluate the extent of obstructive CAD and to compare the probability of detecting obstructive CAD for patients undergoing cardiac catheterization. DESIGN, SETTING, AND PATIENTS An observational study was conducted involving patients without a history of cardiac disease who underwent elective cardiac catheterization between October 1, 2008, and September 30, 2011. Obstructive CAD was defined as diameter stenosis of 50% or more in the left main coronary artery or stenosis of 70% or more in a major epicardial vessel. MAIN OUTCOMES AND MEASURES Observed rates and predicted probabilities of obstructive CAD. Predicted probabilities were estimated using logistic regression models. RESULTS A total of 18,114 patients from New York and 54,933 from Ontario were included. The observed rate of obstructive CAD was significantly lower in New York at 30.4% (95% CI, 29.7%-31.0%) than in Ontario at 44.8% (95% CI, 44.4%-45.3%; P < .001). The percentage of patients with left main or 3-vessel CAD was also significantly lower in New York than in Ontario (7.0% [95% CI, 6.6%-7.3%] vs 13.0% [95% CI, 12.8%-13.3%]; P < .001). In New York, a substantially higher percentage of patients with low predicted probability of obstructive CAD underwent cardiac catheterization; for example, only 19.3% (95% CI, 18.7%-19.9%) of patients undergoing cardiac catheterization in New York had a greater than 50% predicted probability of having obstructive CAD than those in Ontario at 41% (95% CI, 40.6%-41.4%; P < .001). At 30 days, crude mortality for patients undergoing cardiac catheterization was slightly higher in New York at 0.65% (90 of 13,824; 95% CI, 0.51%-0.78%) than in Ontario at 0.38% (153 of 40,794; 95% CI, 0.32%-0.43%; P < .001). CONCLUSIONS AND RELEVANCE In Ontario compared with New York State, patients undergoing elective cardiac catheterization were significantly more likely to have obstructive CAD. This appears to be related to a higher percentage of patients in New York with low predicted probability of CAD undergoing cardiac catheterization.