Maria Koh

Comparative Effectiveness of Generic Atorvastatin and Lipitor® in Patients Hospitalized with an Acute Coronary Syndrome

Background Although generic medications are approved based on bioequivalence with brand‐name medications, there remains substantial concern regarding their clinical effectiveness and safety. Lipitor®, available as generic atorvastatin, is one of the most commonly prescribed statins. Therefore, we compared the effectiveness of generic atorvastatin products and Lipitor®. Methods and Results We conducted a population‐based cohort study, using propensity score matching to minimize potential confounding of patients ≥65 years, discharged alive after acute coronary syndrome (ACS) hospitalization between 2008 and 2012 in Ontario, Canada, who were prescribed Lipitor® or generic atorvastatin within 7 days of discharge. The primary outcome was 1‐year death/recurrent ACS hospitalization. Secondary outcomes included hospitalization for heart failure, stroke, new‐onset diabetes, rhabdomyolysis, and renal failure. In the 7863 propensity‐matched pairs (15 726 patients), mean age was 76.9 years, 56.3% were male, 87.6% had myocardial infarction, and all patients had complete follow‐up. At 1 year, 17.7% of those prescribed generic atorvastatin and 17.7% of those prescribed Lipitor® experienced death or recurrent ACS (hazard ratio, 1.00; 95% CI, 0.93–1.08; P=0.94). No significant differences in rates of secondary outcomes between groups were observed. Prespecified subgroup analyses by age, sex, diabetes, atorvastatin dose, or admission diagnosis found no outcome difference between groups. Conclusions Among older adults discharged alive after ACS hospitalization, we found no significant difference in cardiovascular outcomes or serious, infrequent side effects in patients prescribed generic atorvastatin compared with those prescribed Lipitor® at 1 year. Our findings support the use of generic atorvastatin in ACS, which could lead to substantial cost saving for patients and health care plans without diminishing population clinical effectiveness.

Long-term clinical outcomes and predictors for survivors of out-of-hospital cardiac arrest ☆

AIMS Improvement in resuscitation efforts has translated to an increasing number of survivors after out-of-hospital cardiac arrest (OHCA). Our objectives were to assess the long-term outcomes and predictors of mortality for patients who survived OHCA. METHODS We conducted a population-based cohort study linking the Toronto RescuNET cardiac arrest database with administrative databases in Ontario, Canada. We included patients with non-traumatic OHCA from December 1, 2005 to December 31, 2014. The primary outcomes were mortality at 1 year and 3 years. Cox proportional hazard models were constructed to evaluate the predictors of mortality. RESULTS Among the 28,611 OHCA patients who received treatment at the scene of arrest, 1591 patients survived to hospital discharge. During hospitalization, 36% received coronary revascularizations and 27% received an implantable cardioverter defibrillator. At one year after discharge, 12.6% of patients had died and 37.3% were readmitted. At 3 years, mortality rate was 20% and all-cause readmission rate was 54.1%. Older age and a history of cancer were associated with higher risk of 3-year mortality. Shockable rhythm at presentation (hazard ratio [HR] 0.62, 95% CI 0.45-0.85), use of coronary revascularization (HR 0.37, 95% CI 0.28-0.51) or implantable cardioverter defibrillator (HR 0.28, 95% CI 0.20-0.41) was associated with substantially lower 3-year mortality. Prior cardiac conditions and other arrest characteristics were not associated with long-term mortality. CONCLUSIONS Survivors of OHCA face significant morbidity and mortality after hospital discharge. Clinical trials are needed to evaluate the potential benefits of invasive cardiac procedures in OHCA survivors.

Comparison of Outcomes of Balloon-Expandable Versus Self-Expandable Transcatheter Heart Valves for Severe Aortic Stenosis

Transcatheter aortic valve implantation (TAVI) is the treatment of choice for inoperable and high-risk patients with severe aortic stenosis. Our objectives were to elucidate potential differences in clinical outcomes and safety between balloon-expandable versus self-expandable transcatheter heart valves (THV). We performed a retrospective cohort study of all transfemoral TAVI procedures in Ontario, Canada, from 2007 to 2013. Patients were categorized into either balloon-expandable or self-expandable THV groups. The primary outcomes were 30-day and 1-year death, with secondary outcomes of all-cause readmission. Safety outcomes included bleeding, permanent pacemaker implantation, need for a second THV device, postprocedural paravalvular aortic regurgitation, stroke, vascular access complication, and intensive care unit length of stay. Inverse probability of treatment-weighted regression analyses using a propensity score were used to account for differences in baseline confounders. Our cohort consisted of 714 patients, of whom 397 received a self-expandable THV, whereas 317 had a balloon-expandable THV system. There were no differences in death or all-cause readmission. In terms of safety, the self-expandable group was associated with significantly higher rates of inhospital stroke (p value <0.05), need for a second THV device (5.3% vs 2.7%; p value = 0.013), and permanent pacemaker (22.6% vs 8.9%; p value <0.001), whereas the balloon-expandable group had more vascular access site complications (23.1% vs 16.7%; p value = 0.002). Thus, we found similar clinical outcomes of death or readmission for patients who underwent transfemoral TAVI with either balloon-expandable or self-expandable THV systems. However, there were important differences in their safety profiles.

Factors associated with out-of-hospital cardiac arrest with pulseless electric activity: A population-based study.

BACKGROUND Many patients with out-of-hospital cardiac arrest present with pulseless electric activity (PEA) rather than shockable rhythm. Despite improvements in resuscitation care, survival of PEA patients remains dismal. Our main objective was to characterize out-of-hospital cardiac arrest patients by initial presenting rhythm and to evaluate independent determinants of PEA. METHODS A population-based study was conducted using the Toronto Rescu Epistry database with linkage to administrative data in Ontario, Canada. We included patients older than 20 years who had nontraumatic cardiac arrests from 2005 to 2010. Multivariable logistic regression models were constructed to determine factors predicting the occurrence of PEA vs shockable rhythm vs asystole. RESULTS Of the 9,882 included patients who received treatment, 24.5% had PEA, 26.3% had shockable rhythm, and 49.2% had asystole. Patients with PEA had a mean age of 72 years, 41.2% were female and had multiple comorbidities, and 53.4% were hospitalized in the past year. As compared with shockable rhythm, PEA patients were older, were more likely to be women, and had more comorbidities. As compared with asystole, PEA patients had similar baseline and clinical characteristics, but were substantially more likely to have an arrest witnessed by emergency medical services (odds ratio 13) or by bystander (odds ratio 3.24). Mortality at 30 days was 95.5%, 77.9%, and 98.9% for patients with PEA, shockable rhythm, asystole, respectively. CONCLUSIONS Patient characteristics differed substantially in those presenting with PEA and shockable rhythm. In contrast, the main distinguishing factor between PEA and asystole cardiac arrest related mainly to factors at the time of the cardiac arrest.

Factors associated with physician follow-up among patients with chest pain discharged from the emergency department

Background: Many patients with chest pain do not receive follow-up from a physician after discharge from the emergency department despite significant survival benefit associated with follow-up care. Our objective was to evaluate factors associated with physician follow-up to understand this gap in practice. Methods: We conducted an observational study involving patients at high risk who were assessed for chest pain and discharged from an emergency department in Ontario between April 2004 and March 2010. We used multivariable logistic regression to determine the association of clinical and nonclinical characteristics with physician follow-up. Results: We identified 56 767 patients, of whom 25.1% did not receive any follow-up by a physician, 69.0% were seen by their primary care physician, and 17.3% were seen by a cardiologist within 30 days. Patients who had medical comorbidities and cardiac conditions such as myocardial infarction or heart failure were less likely to have follow-up. In contrast, a previous visit to a primary care physician was associated with the highest odds of having physician follow-up (odds ratio [OR] 6.44, 95% confidence interval [CI] 5.91–7.01). Similarly, a previous visit to a cardiologist was strongly associated with follow-up by a cardiologist (OR 3.01, 95% CI 2.85–3.17). Patients evaluated in emergency departments with the highest tertile of chest pain volume were more likely to receive follow-up from any physician (OR 1.52, 95% CI 1.31–1.77) and from a cardiologist (OR 2.04, 95% CI 1.61–2.57). Interpretation: Nonclinical factors are strongly associated with physician follow-up for patients with chest pain after discharge from the emergency department. However, patients with comorbidities and at higher risk for future adverse events are less likely to receive follow-up care.

Clinical outcomes after trans‐catheter aortic valve replacement in men and women in Ontario, Canada

Our objective was to evaluate sex‐differences in outcomes after trans‐catheter aortic valve replacement (TAVR) in a population‐based cohort from Ontario, Canada.

Association of prior β-blocker use and the outcomes of patients with out-of-hospital cardiac arrest.

UNLABELLED β-Blocker therapy is one of the most commonly prescribed treatments for patients with cardiac conditions. In patients with out-of-hospital cardiac arrest (OHCA), however, recent data suggest that prior treatment with β-blockers could be harmful by lowering the incidence of a shockable presenting rhythm. The main objective of our study was to determine the association between prior β-blocker use and mortality in OHCA patients. METHODS An observational study was conducted using the Toronto Rescu Epistry database that captured consecutive OHCA patients from 2005 to 2010. Patients older than 65 years with nontraumatic cardiac arrest and attempted resuscitation were included. Patients prescribed β-blockers within 90 days of the arrest were compared with those without such therapy. The primary outcome was all-cause mortality at 30 days. Potential confounders were accounted for by inverse probability of treatment weighting using the propensity score. RESULTS The median age of 8,266 OHCA patients was 79 years, 41% were women, and 2,911 (35.2%) were prescribed a β-blocker prior to cardiac arrest. Patients prescribed β-blockers were more likely to have existing cardiac risk factors and cardiovascular conditions. In the propensity-weighted cohort, there were no differences in the presenting rhythm, with 18.4% of patients in the β-blocker group having a shockable rhythm vs 17.5% in the no β-blocker group (standardized difference .023). In addition, 30-day mortality was not significantly different between patients prescribed β-blockers and no β-blockers (95.6% vs 95.1%, P = .36). CONCLUSION β-Blocker use was not associated with lower rates of shockable rhythms or mortality among older patients with OHCA.

Population-Based Study on Patterns of Cardiac Stress Testing After Percutaneous Coronary Intervention

Background— The appropriate use criteria considers cardiac stress testing within 2 years after percutaneous coronary intervention (PCI) to be rarely appropriate, unless prompted by symptoms or change in clinical status. Little is known about the patterns of cardiac stress testing after PCI in the single-payer Canadian healthcare system, where mechanisms for reimbursement are different from the United States. Methods and Results— Frequency and timing of cardiac stress testing within 2 years of PCI performed between April 2004 and March 2013 in Ontario, Canada, was determined from linked provincial databases. Subsequent rates of coronary angiography and revascularization after stress testing were ascertained. Of the 112 691 patients with PCI, 67 442 (59.8%) underwent at least 1 stress test, with 38 267 (34.0%) undergoing repeat stress testing (ie, >1 stress test) within 2 years. Patients who underwent stress testing were younger, had less medical comorbidities, were more likely to reside in urban areas, and had higher incomes. Spikes in incidence of repeat stress testing were observed at 3 to 4 months, 6 to 7 months, and 12 to 13 months after the prior stress test. Of those tested, only 5.9% underwent subsequent coronary angiography, and only 3.1% underwent repeat revascularization within 60 days of stress testing. Conclusions— More than half of all patients undergo cardiac stress testing within 2 years of PCI, with one third undergoing repeat stress tests. Only 1 of 30 tested patients underwent repeat revascularization. These findings reinforce the appropriate use criteria recommendations against routine stress testing after PCI. Further work is needed to aid with the selection of patients most likely to benefit from stress testing after PCI.

Clinical Outcomes of Plavix and Generic Clopidogrel for Patients Hospitalized With an Acute Coronary Syndrome

Background: Clopidogrel is one of the most commonly prescribed medications because of its ability to improve clinical outcomes for a broad range of cardiovascular conditions. After patent protection expired for Plavix in 2012, many healthcare systems adopted generic clopidogrel as a strategy to reduce healthcare costs. Methods and Results: We conducted a population-based observational study to determine whether generic clopidogrel was noninferior to Plavix. Patients who were hospitalized with an acute coronary syndrome (ACS) from 2009 to 2014 in Ontario, Canada, >65 years, survived ≥7 days after discharge, were eligible for inclusion. The primary outcome was a composite of death and recurrent ACS at 1 year. The noninferiority margin was prespecified at a relative hazard difference of 10%. Inverse propensity of treatment weighting of the propensity score was used to account for differences in baseline characteristics between the treatment groups. The effect of clopidogrel on the hazard of clinical outcomes was estimated using a Cox proportional hazards model within the propensity-weighted cohort using Plavix as a reference. Our study included 24 530 patients with ACS, 12 643 were prescribed Plavix and 11  887 were prescribed generic clopidogrel at hospital discharge. The mean age was 77 years, 57% were men, and 21% had an ST-segment–elevation myocardial infarction. At 1 year, 17.6% of patients prescribed Plavix and 17.9% of patients prescribed clopidogrel experienced the primary outcome (hazard ratio, 1.02; 95% confidence interval, 0.96–1.08; P=0.005 for noninferiority). No significant differences between rates of death, all-cause readmission, ACS, stroke or transient ischemic attack, or bleeding were observed. Conclusions: Generic clopidogrel was noninferior to Plavix with respect to the composite end point of death and recurrent hospitalization for ACS at 1 year among adults >65 years after an ACS hospitalization. Our findings support generic clopidogrel in ACS, which could lead to substantial healthcare cost savings.

Trends in the incidence and outcomes of patients with aortic stenosis hospitalization

Background: Although the burden of aortic stenosis (AS) on our health care system is expected to rise, little is known regarding its epidemiology at the population level. Our primary objective was to evaluate trends in AS hospitalization, treatment and outcomes. Methods: We performed a population‐based observational study including 37,970 patients newly hospitalized with AS from 2004 and 2013 in Ontario, Canada. We calculated age‐ and sex‐standardized rate of AS hospitalization through direct standardization. The independent association between year of the hospitalization, and 30‐day and 1‐year mortality rate was evaluated using logistic regression models to account for temporal changes in patient characteristics. Results: The overall age‐ and sex‐standardized AS hospitalization rate increased slightly from 36 per 100,000 in 2004 to 39 per 100,000 in 2013. A substantial increase was seen in patients ≥85 years, where hospitalization rates increased 29% from 400 to 516 per 100,000 from 2004 to 2013 (P < .001). In this study period, 36.2% of patients received aortic valve interventions within 30 days of hospitalization. Among treated patients, an improving mortality trend was observed in which the adjusted odds ratio (OR) was significantly lower in 2013 as compared to 2004 (OR 0.55 for 30‐day mortality, 0.74 for 1‐year morality). In contrast, no significant temporal change in mortality was seen among patients without aortic valve intervention. Conclusion: AS hospitalizations in the elderly increased significantly beyond that was expected from population growth. Many AS patients did not receive aortic valve intervention after hospitalization. Mortality among the treated patients improved significantly over time.