Gender differences in hospital mortality and use of percutaneous coronary intervention in acute myocardial infarction : microsimulation analysis of the 1999 nationwide french hospitals database.

Background— Women with acute myocardial infarction have a higher hospital mortality rate than men. This difference has been ascribed to their older age, more frequent comorbidities, and less frequent use of revascularization. The aim of this study is to assess these factors in relation to excess mortality in women. Methods and Results— All hospital admissions in France with a discharge diagnosis of acute myocardial infarction were extracted from the national payment database. Logistic regression on mortality was performed for age, comorbidities, and coronary interventions. Nonparametric microsimulation models estimated the percutaneous coronary intervention and mortality rates that women would experience if they were "treated like men." Data were analyzed from 74 389 patients hospitalized with acute myocardial infarction, 30.0% of whom were women. Women were older (75 versus 63 years of age; Pacute myocardial infarction gender; revascularization; mortality;

Quality of life with ivabradine in patients with angina pectoris

Background—To explore the effect of ivabradine on angina-related quality of life (QoL) in patients participating in the Study Assessing the Morbidity–Mortality Benefits of the If Inhibitor Ivabradine in Patients with Coronary Artery Disease (SIGNIFY) QoL substudy. Methods and Results—QoL was evaluated in a prespecified subgroup of SIGNIFY patients with angina (Canadian Cardiovascular Society class score, ≥2 at baseline) using the Seattle Angina Questionnaire and a generic visual analogue scale on health status. Data were available for 4187 patients (2084 ivabradine and 2103 placebo). There were improvements in QoL in both treatment groups. The primary outcome of change in physical limitation score at 12 months was 4.56 points for ivabradine versus 3.40 points for placebo (E, 0.96; 95% confidence interval, –0.14 to 2.05; P=0.085). The ivabradine−placebo difference in physical limitation score was significant at 6 months (P=0.048). At 12 months, the visual analogue scale and the other Seattle Angina Questionnaire dimensions were higher among ivabradine-treated patients, notably angina frequency (P<0.001) and disease perception (P=0.006). Patients with the worst QoL at baseline (ie, those in the lowest tertile of score) had the best improvement in QoL for 12 months, with improvements in physical limitation and a significant reduction in angina frequency (P=0.034). The effect on QoL was maintained over the study duration, and ivabradine patients had better scores on angina frequency at every visit to 36 months. Conclusions—Treatment with ivabradine did not affect the primary outcome of change in physical limitation score at 12 months. It did produce consistent improvements in other self-reported QoL parameters related to angina pectoris, notably in terms of angina frequency and disease perception

Bradycardia and atrial fibrillation in patients with stable coronary artery disease treated with ivabradine: an analysis from the SIGNIFY study

Aim: The aim of this study was to determine the impact of emergent bradycardia and atrial fibrillation (AF) on cardiovascular outcomes in 19 083 patients with stable coronary artery disease (CAD) receiving ivabradine or placebo (SIGNIFY, Study assessInG the morbidity–mortality beNefits of the If inhibitor ivabradine in patients with coronarY artery disease). Methods and results: Emergent bradycardia (resting heart rate <50 b.p.m. on 12-lead electrocardiogram) with ivabradine was reported in 3572 patients (37.4%) overall, and in 2242 (37.2%) patients with Canadian Cardiovascular Society (CCS) class ≥2 angina. There was no difference in outcomes over the course of the study in ivabradine-treated patients with and without emergent bradycardia in the whole population (2.5 vs. 2.9% per year, respectively, for primary composite endpoint of cardiovascular death or non-fatal myocardial infarction) or in the angina subgroup (2.5 vs. 3.2% per year). Neither was there an increase in the rate of primary endpoint after emergent bradycardia was recorded compared with those without emergent bradycardia. There were 754 cases of emergent AF on treatment (2.2% per year ivabradine vs. 1.5% per year placebo) and 469 in the patients with angina (2.2 vs. 1.5% per year). While outcomes occurred more frequently in patients in whom emergent AF had been recorded, there was no treatment–placebo difference in outcomes, including stroke, and no difference in treatment effect in patients with limiting angina. Conclusion: Both in the overall population as well as in the angina subset, bradycardia was common in ivabradine-treated patients, but did not appear to impact outcomes. Emergent AF was relatively rare and did not appear to have an impact on outcomes relative to placebo

Relationships between components of blood pressure and cardiovascular events in patients with stable coronary artery disease and hypertension

Observational studies have shown a J-shaped relationship between diastolic blood pressure (BP) and cardiovascular events in hypertensive patients with coronary artery disease. We investigated whether the increased risk associated with low diastolic BP reflects elevated pulse pressure (PP). In 22 672 hypertensive patients with coronary artery disease from the CLARIFY registry (Prospective Observational Longitudinal Registry of Patients With Stable Coronary Artery Disease), followed for a median of 5.0 years, BP was measured annually and averaged. The relationships between PP and diastolic BP, alone or combined, and the primary composite outcome (cardiovascular death or myocardial infarction) were analyzed using multivariable Cox proportional hazards models. Adjusted hazard ratios for the primary outcome were 1.62 (95% confidence interval [CI], 1.40–1.87), 1.00 (ref), 1.07 (95% CI, 0.94–1.21), 1.54 (95% CI, 1.32–1.79), and 2.34 (95% CI, 1.95–2.81) for PP<45, 45 to 54 (reference), 55 to 64, 65 to 74, and ≥75 mm Hg, respectively, and 1.50 (95% CI, 1.31–1.72), 1.00 (reference), and 1.58 (95% CI, 1.42–1.77) for diastolic BPs of <70, 70 to 79 (ref), and ≥80 mm Hg, respectively. In a cross-classification analysis between diastolic BP and PP, the relationship between diastolic BP and the primary outcome remained J-shaped when the analysis was restricted to patients with the lowest-risk PP (45–64 mm Hg), with adjusted hazard ratios of 1.53 (95% CI, 1.27–1.83), 1.00 (ref), and 1.54 (95% CI, 1.34–1.75) in the <70, 70 to 79 (reference), and ≥80 mm Hg subgroups, respectively. The J-shaped relationship between diastolic BP and cardiovascular events in hypertensive patients with coronary artery disease persists in patients within the lowest-risk PP range and is therefore unlikely to be solely the consequence of an increased PP reflecting advanced vascular disease

Prevalence of anginal symptoms and myocardial ischemia and their effect on clinical outcomes in outpatients with stable coronary artery disease: data from the international observational CLARIFY registry

Importance: In the era of widespread revascularization and effective antianginals, the prevalence and prognostic effect of anginal symptoms and myocardial ischemia among patients with stable coronary artery disease (CAD) are unknown.<p></p> Objective: To describe the current clinical patterns among patients with stable CAD and the association of anginal symptoms or myocardial ischemia with clinical outcomes.<p></p> Design, Setting, and Participants: The Prospective Observational Longitudinal Registry of Patients With Stable Coronary Artery Disease (CLARIFY) registry enrolled outpatients in 45 countries with stable CAD in 2009 to 2010 with 2-year follow-up (median, 24.1 months; range, 1 day to 3 years). Enrollees included 32 105 outpatients with prior myocardial infarction, chest pain, and evidence of myocardial ischemia, evidence of CAD on angiography, or prior revascularization. Of these, 20 291 (63.2%) had undergone a noninvasive test for myocardial ischemia within 12 months of enrollment and were categorized into one of the following 4 groups: no angina or ischemia (n = 13 207 [65.1%]); evidence of myocardial ischemia without angina (silent ischemia) (n = 3028 [14.9%]); anginal symptoms alone (n = 1842 [9.1%]); and angina and ischemia (n = 2214 [10.9%]).<p></p> Exposures: Stable CAD.<p></p> Main Outcome and Measure: The composite of cardiovascular (CV)–related death or nonfatal myocardial infarction.<p></p> Results: Overall, 4056 patients (20.0%) had anginal symptoms and 5242 (25.8%) had evidence of myocardial ischemia on results of noninvasive testing. Of 469 CV-related deaths or myocardial infarctions, 58.2% occurred in patients without angina or ischemia, 12.4% in patients with ischemia alone, 12.2% in patients with angina alone, and 17.3% in patients with both. The hazard ratios for the primary outcome relative to patients without angina or ischemia and adjusted for age, sex, geographic region, smoking status, hypertension, diabetes mellitus, and dyslipidemia were 0.90 (95% CI, 0.68-1.20; P = .47) for ischemia alone, 1.45 (95% CI, 1.08-1.95; P = .01) for angina alone, and 1.75 (95% CI, 1.34-2.29; P <.001) for both. Similar findings were observed for CV-related death and for fatal or nonfatal myocardial infarction.<p></p> Conclusions and Relevance: In outpatients with stable CAD, anginal symptoms (with or without ischemia on noninvasive testing) but not silent ischemia appear to be associated with an increased risk for adverse CV outcomes. Most CV events occurred in patients without angina or ischemia

One-Year Risk of Stroke after Transient Ischemic Attack or Minor Stroke

BACKGROUND Previous studies conducted between 1997 and 2003 estimated that the risk of stroke or an acute coronary syndrome was 12 to 20% during the first 3 months after a transient ischemic attack (TIA) or minor stroke. The TIAregistry.org project was designed to describe the contemporary profile, etiologic factors, and outcomes in patients with a TIA or minor ischemic stroke who receive care in health systems that now offer urgent evaluation by stroke specialists. METHODS We recruited patients who had had a TIA or minor stroke within the previous 7 days. Sites were selected if they had systems dedicated to urgent evaluation of patients with TIA. We estimated the 1-year risk of stroke and of the composite outcome of stroke, an acute coronary syndrome, or death from cardiovascular causes. We also examined the association of the ABCD2 score for the risk of stroke (range, 0 [lowest risk] to 7 [highest risk]), findings on brain imaging, and cause of TIA or minor stroke with the risk of recurrent stroke over a period of 1 year. RESULTS From 2009 through 2011, we enrolled 4789 patients at 61 sites in 21 countries. A total of 78.4% of the patients were evaluated by stroke specialists within 24 hours after symptom onset. A total of 33.4% of the patients had an acute brain infarction, 23.2% had at least one extracranial or intracranial stenosis of 50% or more, and 10.4% had atrial fibrillation. The Kaplan–Meier estimate of the 1-year event rate of the composite cardiovascular outcome was 6.2% (95% confidence interval, 5.5 to 7.0). Kaplan–Meier estimates of the stroke rate at days 2, 7, 30, 90, and 365 were 1.5%, 2.1%, 2.8%, 3.7%, and 5.1%, respectively. In multivariable analyses, multiple infarctions on brain imaging, large-artery atherosclerosis, and an ABCD2 score of 6 or 7 were each associated with more than a doubling of the risk of stroke. CONCLUSIONS We observed a lower risk of cardiovascular events after TIA than previously reported. The ABCD2 score, findings on brain imaging, and status with respect to large-artery atherosclerosis helped stratify the risk of recurrent stroke within 1 year after a TIA or minor stroke. (Funded by Sanofi and Bristol-Myers Squibb.)Supported by an unrestricted grant from Sanofi and Bristol-Myers Squibb

REDUCE-IT USA: Results From the 3146 Patients Randomized in the United States.

BackgroundSome trials have found that patients from the United States derive less benefit than patients enrolled outside the United States. This prespecified REDUCE-IT (Reduction of Cardiovascular Events with Icosapent Ethyl - Intervention Trial) subgroup analysis was conducted to determine the degree of benefit of icosapent ethyl in the United States.MethodsREDUCE-IT randomized 8179 statin-treated patients with qualifying triglycerides ≥135 and <500 mg/dL and low-density lipoprotein cholesterol >40 and ≤100 mg/dL and a history of atherosclerosis or diabetes mellitus to icosapent ethyl 4 g/d or placebo. The primary composite end point was cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or hospitalization for unstable angina. The key secondary composite end point was cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. A hierarchy was prespecified for examination of individual and composite end points.ResultsA total of 3146 US patients (38.5% of the trial) were randomized and followed for a median of 4.9 years; 32.3% were women and 9.7% were Hispanic. The primary composite end point occurred in 24.7% of placebo-treated patients versus 18.2% of icosapent ethyl-treated patients (hazard ratio [HR], 0.69 [95% CI, 0.59-0.80]; P=0.000001); the key secondary composite end point occurred in 16.6% versus 12.1% (HR, 0.69 [95% CI, 0.57-0.83]; P=0.00008). All prespecified hierarchical end points were meaningfully and significantly reduced, including cardiovascular death (6.7% to 4.7%; HR, 0.66 [95% CI, 0.49-0.90]; P=0.007), myocardial infarction (8.8% to 6.7%; HR, 0.72 [95% CI, 0.56-0.93]; P=0.01), stroke (4.1% to 2.6%; HR, 0.63 [95% CI, 0.43-0.93]; P=0.02), and all-cause mortality (9.8% to 7.2%; HR, 0.70 [95% CI, 0.55-0.90]; P=0.004); for all-cause mortality in the US versus non-US patients, Pinteraction=0.02. Safety and tolerability findings were consistent with the full study cohort.ConclusionsWhereas the non-US subgroup showed significant reductions in the primary and key secondary end points, the US subgroup demonstrated particularly robust risk reductions across a variety of individual and composite end points, including all-cause mortality.Clinical trial registrationURL: https://www.clinicaltrials.gov. Unique identifier: NCT01492361

Statin therapy and long-term adverse limb outcomes in patients with peripheral artery disease: insights from the REACH registry

Aims Due to a high burden of systemic cardiovascular events, current guidelines recommend the use of statins in all patients with peripheral artery disease (PAD). We sought to study the impact of statin use on limb prognosis in patients with symptomatic PAD enrolled in the international REACH registry. Methods Statin use was assessed at study enrolment, as well as a time-varying covariate. Rates of the primary adverse limb outcome (worsening claudication/new episode of critical limb ischaemia, new percutaneous/surgical revascularization, or amputation) at 4 years and the composite of cardiovascular death/myocardial infarction/stroke were compared among statin users vs. non-users. Results A total of 5861 patients with symptomatic PAD were included. Statin use at baseline was 62.2%. Patients who were on statins had a significantly lower risk of the primary adverse limb outcome at 4 years when compared with those who were not taking statins [22.0 vs. 26.2%; hazard ratio (HR), 0.82; 95% confidence interval (CI), 0.72-0.92; P = 0.0013]. Results were similar when statin use was considered as a time-dependent variable (P = 0.018) and on propensity analysis (P < 0.0001). The composite of cardiovascular death/myocardial infarction/stroke was similarly reduced (HR, 0.83; 95% CI, 0.73-0.96; P = 0.01). Conclusion Among patients with PAD in the REACH registry, statin use was associated with an ∼18% lower rate of adverse limb outcomes, including worsening symptoms, peripheral revascularization, and ischaemic amputations. These findings suggest that statin therapy not only reduces the risk of adverse cardiovascular events, but also favourably affects limb prognosis in patients with PA

Women and men with stable coronary artery disease have similar clinical outcomes: insights from the international prospective CLARIFY registry

&lt;p&gt;Aims Men and women differ in terms of presentation and management in coronary artery disease (CAD). Whether these differences translate into different clinical outcomes in stable CAD is unclear. We analysed data from the international prospective CLARIFY registry to compare cardiovascular clinical outcomes in men and women with stable CAD.&lt;/p&gt; &lt;p&gt;Methods and results We analysed 1-year outcomes in 30 977 outpatients with stable CAD [23 975 (77.4%) men; 7002 (22.6%) women]. Women were older than men, more likely to have hypertension and diabetes, and less likely to exercise or smoke. They had more frequent angina, but were less likely to have undergone diagnostic non-invasive testing or coronary angiography. Women received less optimized treatment for stable CAD. One-year outcomes were similar for men and women for the composite of cardiovascular death, non-fatal myocardial infarction, or stroke [adjusted rates 1.7 vs. 1.8%, respectively, odds ratio (OR) 0.93, 95% confidence interval (CI) 0.75–1.15]; all-cause death (adjusted 1.5 vs. 1.6%, OR: 0.91, 95% CI: 0.72–1.13); fatal or non-fatal myocardial infarction (adjusted 1.0 vs. 0.9%, OR: 0.81, 95 CI: 0.60–1.08); and cardiovascular death or non-fatal myocardial infarction (adjusted 1.4 vs. 1.4%, OR: 0.89, 95% CI: 0.70–1.12). Fewer women underwent revascularization (2.6 vs. 2.2%, OR: 0.77, 95% CI: 0.64–0.93), although appropriateness was not analysed.1522-9645&lt;/p&gt; &lt;p&gt;Conclusion The risk profiles of women and men with stable CAD differ substantially. However, 1-year outcomes were similar. Fewer women underwent revascularization. Further research is needed to better understand gender determinants of outcome and devise strategies to minimize bias in the management and treatment of women.&lt;/p&gt

Gender Differences in Hospital Mortality and Use of Percutaneous Coronary Intervention in Acute Myocardial Infarction. Microsimulation Analysis of the 1999 Nationwide French Hospitals Database

The difference in mortality rate between men and women with acute myocardial infarction is due largely to the different age structure of these populations. However, age-adjusted hospital mortality was higher for women and was associated with a lower rate of percutaneous coronary intervention. Simulations suggest that women would derive benefit from more frequent use of percutaneous coronary intervention, although these procedures appear less protective in women than in men