Does management of lipid lowering differ between specialists and primary care: Insights from GOAL Canada.

BACKGROUND: We studied whether significant differences in care gaps exist between specialists and primary care physicians (PCPs). METHODS: GOAL Canada enrolled patients with CVD or familial hypercholesterolemia (FH) and LDL-C > 2.0 mmol/L despite maximally tolerated statin therapy. During follow-up, physicians received online reminders of treatment recommendations based on Canadian Guidelines. RESULTS: A total of 177 physicians (58% PCPs) enrolled 2009 patients; approximately half of the patients were enrolled by each physician group. Patients enrolled by specialists were slightly older (mean age 63 years vs 62), female (45% vs 40%), Caucasian (77% vs 65%), and had a slightly higher systolic pressure and lower heart rate. Patients enrolled by specialists had less frequent history of FH, diabetes, hypertension, chronic kidney disease and liver disease but more frequent history of coronary artery disease, atrial fibrillation and premature family history of CVD. There was no significant baseline difference in LDL-C, HDL-C or non-HDL-C, although total cholesterol and triglycerides were slightly higher in patients managed by PCPs. At baseline, PCPs were more likely to use statins (80% vs 73%, P = .0002) and other therapies such as niacin or fibrate (10% vs 6%, P = .0006) but similar use of ezetimibe (24% vs 27%, P = .15). At the end of follow-up, specialists used less statins (70% vs 77%, P = .0005) and other therapies (6% vs 10%, P = .007) but more ezetimibe (45% vs 38%, P = .01) and the same frequency of PCSK9i (28% vs 27%, P = .65). The proportion of patients achieving the recommended LDL-C level of 2.0 mmol/L or below (primary endpoint) was similar at last available visit between specialists and PCPs (44% vs 42%, P = .32). CONCLUSION: Despite minor differences in the clinical profile of their patients, both PCPs and specialists actively participate in the management of lipid-lowering therapy in high-risk CVD patients and experience similar challenges and care gaps.

Clinical outcomes and cost implications of routine early PCI after fibrinolysis: one-year follow-up of the Trial of Routine Angioplasty and Stenting after Fibrinolysis to Enhance Reperfusion in Acute Myocardial Infarction (TRANSFER-AMI) study.

BACKGROUND: In patients with ST-elevation myocardial infarction treated with fibrinolysis, routine early percutaneous coronary intervention (r-PCI) improves clinical outcomes at 30 days compared with a more standard approach of performing early PCI only for failed fibrinolysis (s-PCI). METHODS: We report prespecified secondary clinical outcomes and cost implications of r-PCI compared with s-PCI from the Canadian TRANSFER-AMI trial. Average cost per patient in each arm was calculated based on a microcosting approach. Bootstrap method (5,000 samples) was used to calculate standard errors and 95% CI. RESULTS: At 1 year, rates of death or reinfarction (10.3% vs 11.6%, P = .50), hospital readmission (15.4% vs 16.5%, P = .64) and subsequent revascularization after index hospitalization (6.9% vs 8.7%, P = .30) were similar between the r-PCI and s-PCI arms. The difference in cost per patient between r-PCI and s-PCI was CAD $1,003 (95% CI, -$247 to $2,211). Since a greater proportion of patients were transported by air (vs land) in the r-PCI arm (9.4% vs 3%), and the ratio of abciximab to eptifibatide use was higher in the r-PCI arm compared with s-PCI (2:1 vs 4:5), we undertook additional post hoc cost scenario analyses. In a scenario where patients are transported by land only and eptifibatide is used as the sole GPIIb/IIIa inhibitor, the difference in cost per patient between r-PCI and s-PCI was estimated to be CAD $108 (95% CI, -$1,114 to $1,344). CONCLUSIONS: At 1 year, there is no difference in the clinical composite outcome of death or reinfarction between r-PCI and s-PCI strategies. Greater cost with r-PCI, although statistically insignificant, is economically important.

Comparative prognostic value of T-wave inversion and ST-segment depression on the admission electrocardiogram in non-ST-segment elevation acute coronary syndromes.

BACKGROUND: ST-segment depression (STD) is predictive of adverse outcomes in non-ST-segment elevation acute coronary syndromes (NSTE-ACS), but there are conflicting data on the incremental prognostic value of T-wave inversions (TWIs) on the admission electrocardiogram. METHODS: Admission electrocardiograms of 7,343 patients with NSTE-ACS from the Global Registry of Acute Coronary Events (GRACE) and ACS I registry were independently analyzed at a core laboratory and stratified by TWI and STD status. We performed multivariable analyses to determine the independent prognostic significance of TWI and tested for interaction between TWI and STD for adverse outcomes. RESULTS: Patients with TWI and/or STD had a higher prevalence of cardiovascular risk factors, higher Killip class, and higher GRACE risk scores. Among the 2,708 patients with available angiographic data, rates of 3-vessel or left main disease were similar between patients with TWI and those without TWI/STD. After adjusting for other established prognosticators, TWI did not independently predict in-hospital (adjusted odds ratio 1.03, 95% CI 0.75-1.42, P = .85) or 6-month mortality (adjusted odds ratio 1.02, 95% CI 0.80-1.30, P = .88); STD remained a strong independent predictor. There was no interaction between TWI and STD for these outcomes. No contiguous lead groups or cumulative number of leads with TWI provided independent prognostic information. CONCLUSIONS: TWI is associated with other high-risk clinical features but is not an independent predictor of adverse short- and long-term mortality in NSTE-ACS. T-wave inversion does not provide additional prognostication beyond the GRACE risk model, and its concomitant presence does not alter the prognostic value of STD.

Routine early angioplasty after fibrinolysis for acute myocardial infarction.

BACKGROUND: Patients with a myocardial infarction with ST-segment elevation who present to hospitals that do not have the capability of performing percutaneous coronary intervention (PCI) often cannot undergo timely primary PCI and therefore receive fibrinolysis. The role and optimal timing of routine PCI after fibrinolysis have not been established. METHODS: We randomly assigned 1059 high-risk patients who had a myocardial infarction with ST-segment elevation and who were receiving fibrinolytic therapy at centers that did not have the capability of performing PCI to either standard treatment (including rescue PCI, if required, or delayed angiography) or a strategy of immediate transfer to another hospital and PCI within 6 hours after fibrinolysis. All patients received aspirin, tenecteplase, and heparin or enoxaparin; concomitant clopidogrel was recommended. The primary end point was the composite of death, reinfarction, recurrent ischemia, new or worsening congestive heart failure, or cardiogenic shock within 30 days. RESULTS: Cardiac catheterization was performed in 88.7% of the patients assigned to standard treatment a median of 32.5 hours after randomization and in 98.5% of the patients assigned to routine early PCI a median of 2.8 hours after randomization. At 30 days, the primary end point occurred in 11.0% of the patients who were assigned to routine early PCI and in 17.2% of the patients assigned to standard treatment (relative risk with early PCI, 0.64; 95% confidence interval, 0.47 to 0.87; P=0.004). There were no significant differences between the groups in the incidence of major bleeding. CONCLUSIONS: Among high-risk patients who had a myocardial infarction with ST-segment elevation and who were treated with fibrinolysis, transfer for PCI within 6 hours after fibrinolysis was associated with significantly fewer ischemic complications than was standard treatment. (ClinicalTrials.gov number, NCT00164190.)

The pulmonary arterial hypertension quality enhancement research initiative: comparison of patients with idiopathic PAH to patients with systemic sclerosis-associated PAH.

OBJECTIVE: The objective of this report is to compare baseline, management and survival characteristics in idiopathic pulmonary arterial hypertension (IPAH) with systemic sclerosis-associated pulmonary arterial hypertension (SSc-APAH) using data from the prospectively enrolled PAH Quality Enhancement Research Initiative. METHODS: Between August 2005 and July 2007, patients with IPAH and SSc-APAH were enrolled across 60 US sites and followed up for 3 years. Data on diagnostic tests, clinical variables, pulmonary arterial hypertension (PAH) medication and outcomes were recorded. RESULTS: With some exceptions, baseline clinical and laboratory characteristics were similar between the 279 patients with IPAH and the 228 with SSc-APAH. Patients with SSc-APAH were older at the time of PAH diagnosis, were more likely to be female and were antinuclear antibody positive. Patients with SSc-APAH had poorer spirometric results. During the 3-year follow-up, both groups were managed with prostacyclin and prostacyclin analogue treatment, endothelin receptor antagonists and phosphodiesterase type 5 inhibitors (PDE5i) singly or in combination. At 3 years, patients with SSc-APAH were more likely to be treated with PDE5i alone or with an endothelin receptor antagonist. Patients with SSc-APAH had a significantly lower survival rate compared to patients with IPAH (60% vs 77%, p<0.0001). CONCLUSIONS: The cohort with SSc-APAH was older, was more severely ill, was more likely to be female, was managed with PDE5i and had reduced 3-year survival compared with the cohort with IPAH.

Factors influencing underutilization of evidence-based therapies in women.

Aims Previous studies have reported differences in the use of cardiovascular medications for acute coronary syndromes (ACSs) according to the sex of the patient. We analysed which clinical factors are associated with underutilization of evidence-based therapies in women. Methods and results From the Canadian Registry of ACS I and II, 6558 patients (4471 men and 2087 women) with a final diagnosis of ACS were selected for the current analysis. Covariates were chosen using the approach described by Blackstone. The final selected model included 23 patient clinical variables. Women were less likely than men to receive beta-blockers (75.76 vs. 79.24%; P < 0.01), lipid-modifying agents (56.37 vs. 65.44%; P < 0.0001), and angiotensin-converting enzyme (ACE)-inhibitors (55.52 vs. 59.99%; P < 0.01). Female sex and clinical decision not to investigate with cardiac catheterization were the strongest independent predictors for not receiving lipid-modifying agents and ACE-inhibitors. Age, Killip class 2, and Killip class 3/4 were significant independent predictors of underutilization of beta-blocker use. Women were older (69 ± 12 vs. 64 ± 12; P < 0.01) with a higher prevalence of Killip class ≥ 2 (19.95 vs. 15.54%; P < 0.068), and they were less likely to be referred for cardiac catheterization (41.9 vs. 49.6 %; P < 0.001). Conclusions The current findings demonstrate that underutilization of evidence-based therapies in women with ACS compared with men is associated with multiple factors related to the patient (age), the consequences of the disease (congestive heart failure), and the physician's assessment of patient risk (decision to catheterize). Female gender remains associated with underutilization of lipid-modifying agents and ACE-inhibitors despite adjustment for these confounders.

Prognostic significance of electrocardiographic-determined left ventricular hypertrophy and associated ST-segment depression in patients with non-ST-elevation acute coronary syndromes.

BACKGROUND: Left ventricular hypertrophy (LVH) is frequently associated with ST depression (STD) on the electrocardiogram (ECG), a so-called strain pattern. Although STD is a well-established adverse prognosticator in non-ST-elevation acute coronary syndrome (NSTE-ACS), the relative prognostic importance of LVH and associated STD has not been elucidated. METHODS: A total of 7,761 patients with NSTE-ACS in the Global Registry of Acute Coronary Events (GRACE) and ACS-I registries had admission ECGs analyzed at a core laboratory. Left ventricular hypertrophy (determined by Sokolow-Lyon and/or Casale criteria) was observed in 296 (3.8%) patients. We examined the independent association between LVH (determined by the admission ECG) and outcomes in relation to STD. RESULTS: Patients with LVH were older, had more comorbidities and STD, and presented with a higher Killip class. They were less likely to undergo cardiac catheterization (43.1% vs 51.2%, P = .006) and percutaneous coronary intervention (18.3% vs 24.6%, P = .014). Patients with LVH had higher unadjusted mortality at 6 months (10.5% vs 7.1%, P = .038), but similar rates of in-hospital mortality (4.1% vs 3.4%, P = .54) and reinfarction (7.1% vs 7.6%, P = .75). Patients with LVH were more likely to have heart failure in-hospital (21.8% vs 11.8%, P < .001). Among LVH patients, degree of quantitative STD did not predict higher short- or long-term mortality, but was associated with in-hospital heart failure. Multivariable analysis adjusting for other clinical prognosticators of the GRACE risk models revealed that LVH was not a significant independent predictor of in-hospital mortality (adjusted odds ratio = 0.75, 95% CI 0.40-1.41, P = .37) or 6-month mortality (adjusted odds ratio = 0.83, 95% CI 0.52-1.35, P = .44). In contrast, STD remained a strong independent predictor of adverse outcomes. There was no significant interaction between STD and LVH. CONCLUSIONS: Across the broad spectrum of NSTE-ACS, LVH is associated with adverse prognostic factors including STD. Electrocardiographic-determined LVH provides no significant additional prognostic utility beyond comprehensive risk assessment using the GRACE risk score. The adverse prognosis associated with LVH in NSTE-ACS may be attributable to other prognosticators such as STD.

Detection of atrial fibrillation in asymptomatic at-risk individuals.

BACKGROUND: Undiagnosed atrial fibrillation (AF) exposes unsuspecting patients to elevated stroke risks. The optimal algorithm for identifying patients who should be screened for AF remains undetermined. The objective of this study is to determine the AF burden in an asymptomatic, at-risk population. We also sought to investigate potential predictors of undiagnosed AF. METHODS: This registry is a prospective observational study assessing continuous ECG monitoring in screening for AF using a wearable single lead 7-day continuous monitoring device. Patients included were asymptomatic individuals, at risk for AF as determined by either 1) ≥65 years of age with ≥1 high risk factor or; 2) ≥75 years of age and ≥2 moderate risk factors. A multivariable logistic regression was used to explore the predictive value of certain patient characteristics in identifying patients susceptible to have undiagnosed AF. RESULTS: Among the 942 patients included, 25 patients (2.7%) had evidence of AF detected. Only 8 patients had AF duration ≥24 h. History of perioperative AF (OR: 3.25, 95%CI: 1.08-9.79, p = 0.036), age over 85 (OR: 4.71, 95%CI: 1.31-16.92, p = 0.017) and absence of cardiovascular disease (CVD) (OR: 0.27, 95%CI: 0.10-0.76, p = 0.013) were found to be predictive of undiagnosed AF. CONCLUSION: This study demonstrates the feasibility of office-based AF screening in at-risk population. The low rate of AF detection suggests that the optimal algorithm for identifying asymptomatic patients who would benefit from continuous screening remains unclear. Advanced age, history of perioperative AF and absence of CVD are variables that could be explored further.

Treatment Inertia in Patients With Familial Hypercholesterolemia.

Background We studied care gap in patients with familial hypercholesterolemia (FH) with respect to lipid-lowering therapy. Methods and Results We enrolled patients with cardiovascular disease (CVD) or FH and low-density lipoprotein-cholesterol >2.0 mmol/L despite maximally tolerated statin therapy. During follow-up physicians received online reminders of treatment recommendations of 2009 patients (median age, 63 years, 42% women), 52.4% had CVD only, 31.7% FH only, and 15.9% both CVD and FH. Patients with FH were younger and more likely to be women and non-White with significantly higher baseline low-density lipoprotein-cholesterol level (mmol/L) as compared with patients with CVD (FH 3.92±1.48 versus CVD 2.96±0.94, P<0.0001). Patients with FH received less statin (70.6% versus 79.2%, P=0.0001) at baseline but not ezetimibe (28.1% versus 20.4%, P=0.0003). Among patients with FH only, 45.3% were at low-density lipoprotein target (≥ 50% reduction from pre-treatment level or low-density lipoprotein <2.5 mmol/L) at baseline and increasing to 65.8% and 73.6% by visit 2 and 3, respectively. Among patients with CVD only, none were at recommended level (≤2.0 mmol/L) at baseline and 44.3% and 53.3% were at recommended level on second and third visit, respectively. When primary end point was analyzed as a difference between baseline and last available follow-up observation, only 22.0% of patients with FH only achieved it as compared with 45.8% with CVD only (P<0.0001) and 55.2% with both FH+CVD (P<0.0001). Conclusions There is significant treatment inertia in patients with FH including those with CVD. Education focused on patients with FH should continue to be undertaken.

Cardiovascular risk factor management in patients with diabetes: Does management differ with disease duration?

AIMS: Our objective was to examine risk factor modification targets and treatment in relation to duration of diabetes. METHODS: The Diabetes Mellitus Status in Canada (DM-SCAN) study collected data on 5109 patients with type 2 diabetes mellitus (T2DM) in 2012 in primary care. We compared the prevalence of vascular complications, treatment targets, and interventions between patients with diagnosed diabetes duration ≤10 and > 10 years. RESULTS: Physicians more frequently assigned HbA1c (glycated hemoglobin) targets of 7.1-8.5% (54-69 mmol/mol) to patients with longer duration of diabetes (n = 1647) (19.8% vs 9.5%, p < 0.001). Patients with longer duration of diabetes were less likely to achieve HbA1c targets of ≤7.0% (53 mmol/mol) (39% vs. 55%, p < 0.001), had similar likelihood of achieving blood pressure targets of ≤130/80 mmHg (38% vs. 36%, p = 0.26) and were more likely to achieve LDL-C targets of ≤2.0 mmol/L (≤77.3 mg/dL) (63% vs. 53%, p < 0.001) compared to patients with shorter duration of diabetes (n = 3462). Achievement of all three targets between both groups were similar (13% vs. 13%, p = 0.82). Overall, patients with longer duration of diabetes were more likely to be prescribed anti-hyperglycemic, anti-hypertensive, lipid-lowering medications and referred for diabetes education. CONCLUSIONS: Only 13% of patients achieved glycemic, blood pressure, and LDL-C targets irrespective of duration of diabetes. Despite being managed with more medications, patients with longer duration of diabetes were less likely to achieve glycemic targets. More focus is needed on developing methods to bridge best care and real-world practice.

Glycemic Control and Cardiovascular Risk Factor Management in Adults With Type 2 Diabetes With and Without Chronic Kidney Disease Before Sodium-Glucose Cotransporter Protein 2 Inhibitors: Insights From the Diabetes Mellitus Status in Canada Survey.

OBJECTIVES: Optimal control of cardiovascular risk factors in adults with type 2 diabetes (T2D) and chronic kidney disease (CKD) is challenging. Limited data are available from the primary care setting on achievement of guideline-recommended targets in this population before the use of sodium-glucose cotransporter protein 2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists. METHODS: The Diabetes Mellitus Status in Canada survey included 5,172 patients with T2D seen by primary care physicians (PCPs) in November 2012. We compared treatment targets and therapeutic interventions in patients with and without CKD. RESULTS: Compared with those without CKD (n=3,804), patients with CKD (n=1,368) were older, more likely to be female, had a longer duration of diabetes and had more vascular complications. Patients with CKD more frequently had a less stringent glycated hemoglobin (A1C) target of ≤8.0% set by PCPs (10.3% vs 20%, p<0.001), and fewer patients with CKD met the A1C target of ≤7.0% (50.9% vs 47.1%, p=0.016) than those without CKD. Both groups had a similar likelihood of achieving the blood pressure (BP) target of ≤130/80 mmHg (36.8% vs 34.8%, p=0.20), whereas patients with CKD more frequently achieved a low-density lipoprotein cholesterol target of ≤2.0 mmol/L (54.8% vs 61.3%, p<0.001). Overall, only 12.5% in both groups achieved all 3 targets (12.3% vs 13.3%, p=0.33). CONCLUSIONS: Only 1 of 8 patients with T2D achieved optimal glycemic, BP and cholesterol targets, regardless of the presence or absence of CKD. Although more medical interventions were used in patients with CKD, a lower proportion achieved guideline-recommended targets for A1C. These findings provide a benchmark for future comparison.

Update to Evidence-Based Secondary Prevention Strategies After Acute Coronary Syndrome.

A recent acute coronary syndrome provides an opportunity to optimise secondary prevention strategies to reduce the risk of future cardiovascular events. This review provides an updated synopsis of current evidence-based approaches. New clinical trial data on the use of antiplatelet and anticoagulants allow choices of the selection and duration of treatment. Lipid lowering after an acute coronary syndrome is now enhanced, with proprotein convertase subtilisin-kexin type 9 inhibitors providing added benefit on top of statin and ezetimibe treatment in high-risk patients. In addition, a recent trial of icosapent ethyl, a highly purified ethyl ester of eicosapentaenoic acid, addresses residual risk in patients with elevated triglycerides already treated with statins. The use of both sodium-glucose co-transporter 2 inhibitors and glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes reduces cardiovascular events independently of glucose lowering.

La survenue récente d'un syndrome coronarien aigu offre l'occasion d'optimiser les stratégies de prévention secondaire en vue de réduire le risque d'événements cardiovasculaires futurs. Le présent article de synthèse offre une vue d'ensemble actualisée des approches contemporaines fondées sur des données probantes. Les nouvelles données d'essais cliniques sur l'utilisation d'antiplaquettaires et d'anticoagulants permettent de choisir un traitement et sa durée. La réduction des lipides après la survenue d'un syndrome coronarien aigu se trouve maintenant améliorée, les bienfaits des inhibiteurs de la proprotéine convertase subtilisine/kexine de type 9 s'ajoutant à ceux du traitement par des statines et l'ézétimibe chez les patients à haut risque. En outre, un essai récent portant sur l'icosapent éthyl, un ester éthylique hautement purifié de l'acide eicosapentaénoïque, aborde le risque résiduel chez les patients présentant une hypertriglycéridémie déjà traités par des statines. L'utilisation d'inhibiteurs du cotransporteur sodium-glucose de type 2 et d'agonistes des récepteurs du peptide-1 apparenté au glucagon chez les patients atteints de diabète de type 2 limite les événements cardiovasculaires indépendamment de la diminution de la glycémie.

GOAL Canada: Physician Education and Support Can Improve Patient Management.

BACKGROUND: Despite the widespread use of statins, approximately 40% to 50% of Canadian patients with known cardiovascular disease do not achieve the low-density lipoprotein cholesterol (LDL-C) goal. Guidelines Oriented Approach to Lipid lowering (GOAL) is an investigator-initiated study aiming to ascertain the use of second- and third-line therapy and its impact on LDL-C goal achievement in a real-world setting. METHODS: GOAL enrolled patients with clinical vascular disease or familial hypercholesterolemia and LDL-C > 2.0 mmol/L despite maximally tolerated statin therapy. During follow-up, physicians managed patients as clinically indicated but with online reminders of guideline recommendations. RESULTS: Of 2009 patients enrolled (median age 63 years, 42% were female), baseline total cholesterol was 5.5 ± 1.4 mmol/L, LDL-C was 3.3 ± 1.3 mmol/L, non-high-density lipoprotein cholesterol was 4.1 ± 1.4 mmol/L, high-density lipoprotein cholesterol was 1.3 ± 0.4 mmol/L, and triglycerides were 2.0 ± 1.5 mmol/L. Lipid-lowering therapy used at baseline was statin therapy in 76% (with 24% statin intolerant) and ezetimibe in 25%. During follow-up, the proportion of patients achieving an LDL-C level of < 2.0 mmol/L increased significantly to 50.8% as a result of additional lipid-lowering therapy. Patients achieving the recommended LDL-C level were more likely to not be statin intolerant (83.8% vs 70.7%, P < 0.0001) and to be taking a high-efficacy type and dose of statin (52.4% vs 35.9%, P < 0.0001). The 3 top reasons for not using the recommended therapy with ezetimibe were patient refusal in 33%, not needed in 22%, and intolerance in 20%, whereas for PCSK9i the reasons were cost in 26%, not needed in 27%, or patient refusal in 25%. CONCLUSION: The results indicate the feasibility of optimizing management, resulting in achievement of the guideline-recommended LDL-C level. This has the potential to translate into reductions in cardiovascular morbidity and mortality of Canadian patients.

CONTEXTE: Malgré l'utilisation répandue des statines, environ 40 à 50 % des patients canadiens atteints d'une maladie cardiovasculaire connue n'atteignent pas les taux cibles de cholestérol à lipoprotéines de basse densité (C-LDL). L'étude GOAL ( G uidelines O riented A pproach to L ipid lowering) est une étude entreprise par un chercheur afin d'évaluer, en contexte réel, l'utilisation de traitements de deuxième et de troisième intention et les effets de ceux-ci sur l'atteinte des taux cibles de C-LDL. MÉTHODOLOGIE: Des patients atteints d'une maladie vasculaire clinique ou d'une hypercholestérolémie familiale, présentant un taux de C-LDL > 2,0 mmol/l malgré un traitement par une statine à la dose maximale tolérée, ont été inscrits à l'étude GOAL. Pendant la période de suivi, les médecins prenaient en charge le traitement de leurs patients selon les besoins cliniques, mais en recevant par voie électronique des rappels des recommandations formulées dans les lignes directrices. RÉSULTATS: Chez les 2009 patients inscrits à l'étude (âge médian : 63 ans; femmes : 42 %), les taux initiaux moyens étaient les suivants : cholestérol total initial : 5,5 ± 1,4 mmol/l, C-LDL : 3,3 ± 1,3 mmol/l, C non HDL (autre que le cholestérol à lipoprotéines de haute densité) : 4,1 ± 1,4 mmol/l, C-HDL (des lipoprotéines de haute densité) : 1,3 ± 0,4 mmol/l et triglycérides : 2,0 ± 1,5 mmol/l. Le traitement hypolipidémiant utilisé au début de l'étude était composé d'une statine chez 76 % des participants (24 % des patients ne toléraient pas les statines) et d'ézétimibe chez 25 %. Pendant la période de suivi, la proportion de patients atteignant un taux de C-LDL < 2,0 mmol/l a augmenté de façon significative, jusqu'à atteindre 50,8 %, en raison de l'utilisation d'hypolipidémiants additionnels. Les patients atteignant les taux cibles de C-LDL étaient plus susceptibles de ne pas être intolérants aux statines (83,8 % vs 70,7 %, p < 0,0001) et de prendre un type et une dose de statine hautement efficaces (52,4 % vs 35,9 %, p < 0,0001). Les trois principales raisons évoquées pour expliquer le fait de n'avoir pas eu recours au traitement recommandé par l'ézétimibe étaient le refus du patient (33 %), l'absence de besoin (22 %) et l'intolérance (20 %), alors que dans le cas des inhibiteurs de la PCSK9, les raisons données étaient plutôt le coût élevé (26 %), l'absence de besoin (27 %) et le refus du patient (25 %). CONCLUSION: Les résultats de cette étude montrent la faisabilité de l'optimisation de la prise en charge, qui entraîne l'atteinte des taux de C-LDL recommandés dans les lignes directrices. Ces résultats pourraient se traduire par des réductions de la morbidité et de la mortalité d'origine cardiovasculaire chez les patients canadiens.

Applying the evidence: do patients with stroke, coronary artery disease, or both achieve similar treatment goals?

BACKGROUND AND PURPOSE: The importance of early and aggressive initiation of secondary prevention strategies for patients with both coronary artery disease (CAD) and cerebrovascular disease (CVD) is emphasized by multiple guidelines. However, limited information is available on cardiovascular protection and stroke prevention in an outpatient setting from community-based populations. We sought to evaluate and compare differences in treatment patterns and the attainment of current guideline-recommended targets in unselected high-risk ambulatory patients with CAD, CVD, or both. METHODS: This multicenter, prospective, cohort study was conducted from December 2001 to December 2004 among ambulatory patients in a primary care setting. The prospective Vascular Protection and Guidelines-Oriented Approach to Lipid-Lowering Registries recruited 4933 outpatients with established CAD, CVD, or both. All patients had a complete fasting lipid profile measured within 6 months before enrollment. The primary outcome measure was the achievement of blood pressure (BP) <140/90 mm Hg (or <130/80 mm Hg for patients with diabetes) and LDL cholesterol <2.5 mmol/L (<97 mg/dL) according to the Canadian guidelines in place at that time (similar to the National Cholesterol Education Program's value of 100 mg/dL). Secondary outcomes include use of antithrombotic, antihypertensive, and lipid-modifying therapies. RESULTS: Of the 4933 patients, 3817 (77%) had CAD only; 647 (13%) had CVD only; and 469 (10%) had both CAD and CVD. Mean+/-SD age was 67+/-10 years, and 3466 (71%) were male. Mean systolic and diastolic BPs were 130+/-16 and 75+/-9 mm Hg, respectively. Minor but significant differences were observed on baseline BP, total cholesterol, and LDL cholesterol measurements among the 3 groups. Overall, 83% of patients were taking a statin and 93% were receiving antithrombotic therapy (antiplatelet and/or anticoagulant agents). Compared with patients with CAD, those with CVD only were less likely to achieve the recommended BP (45.3% vs 57.3%, respectively; P<0.001) and lipid (19.4% vs 30.5%, respectively; P<0.001) targets. Among patients with CVD only, women were less likely to achieve the recommended BP and lipid targets compared with their male counterparts (for LDL cholesterol <2.5 mmol/L, 18.7% vs 23.8%, respectively; P=0.048). In multivariable analysis, patients with CVD alone were less likely to achieve treatment success (BP or lipid targets) after adjusting for age, sex, diabetes, and use of pharmacologic therapy. CONCLUSIONS: Despite the proven benefits of available antihypertensive and lipid-lowering therapies, current management of hypertension and dyslipidemia continues to be suboptimal. A considerable proportion of patients failed to achieve guideline-recommended targets, and this apparent treatment gap was more pronounced among patients with CVD and women. Quality improvement strategies should target these patient subgroups.

Use of cardiac catheterization for non-ST-segment elevation acute coronary syndromes according to initial risk: reasons why physicians choose not to refer their patients.

BACKGROUND: Despite the recommendation for an early invasive strategy in the treatment of patients who present with non-ST-segment elevation (NSTE) acute coronary syndromes (ACS), referral for cardiac catheterization is suboptimal; the reasons why some patients are not referred remain unclear. METHODS: Patients were recruited into the prospective, observational Canadian ACS Registry II between October 1, 2002, and December 31, 2003; 2136 patients with NSTE ACS identified through the registry were divided into tertiles according to the Thrombolysis in Myocardial Infarction risk score and the rates of catheterization compared. In addition, the most responsible physicians were asked to indicate the main reason they did not refer their patients for catheterization. RESULTS: The rate of referral for catheterization was 64.7%. Patients who underwent catheterization had lower in-hospital (0.8% vs 3.7%; P < .001) and 1-year mortality rates (4.0% vs 10.9%; P < .001) compared with those who did not. Higher-risk patients were referred at a similar rate as low-risk patients (62.5% vs 66.9%; P = .25). Among the reasons provided by the most responsible physician as to why patients were not referred for catheterization, 68.4% of patients were thought to be "not at high enough risk"; however, 59.1% of these patients were found to be at intermediate to high risk according to their baseline Thrombolysis in Myocardial Infarction risk score. CONCLUSIONS: Cardiac catheterization is not used optimally in patients who present with NSTE ACS. Despite better in-hospital and 1-year outcomes in those patients who are referred for catheterization, many higher-risk patients are not being referred because of the perception that they are not at high enough risk. A significant opportunity remains to improve on accurate risk stratification and adherence to an early invasive strategy for higher-risk patients.

Glycated Hemoglobin Level Goal Achievement in Adults With Type 2 Diabetes in Canada: Still Room for Improvement.

OBJECTIVES: To describe the clinical histories and management of adults with type 2 diabetes who were not reaching their target glycated hemoglobin (A1C) levels and to identify barriers to achieving therapeutic goals. METHODS: Practice assessment surveys and practice audits were completed by 88 primary care physicians (PCPs) in the Diabetes Mellitus Assessment of Clinical managemenT In ONtario (DM-ACTION) program and by 56 diabetes specialists in the Diabetes Mellitus IMproving PAtient Care in our communiTies (DM-IMPACT) program. The DM-ACTION audit analyzed data from 1,173 adults with A1C levels ≥7.3% who were not prescribed insulin; the DM-IMPACT audit included 135 individuals with similar characteristics. RESULTS: Most PCPs (92%) and specialists (88%) stated that they typically recommend A1C levels of ≤7.0%; more than 90% indicated that they adjusted antihyperglycemic therapy within 3 months if suboptimal A1C targets endured. Among the DM-ACTION patients, the median A1C level was 7.8%; the median time between the last 2 A1C tests was 5 months; 58% were taking ≤2 noninsulin antihyperglycemic agents; and adjustment of glucose-lowering therapy was noted for only 56%. The corresponding values for the DM-IMPACT patients were 8.0%, 4 months, 43% and 68%, respectively. PCPs and specialists attributed patients' factors and patients' adherence as primary causes of poor achievement of guideline-recommended targets. PCPs perceived patients' factors as the predominant barrier to optimizing care, but the specialists believed that therapeutic inertia stems from a wide range and a varied combination of patient-centric factors. CONCLUSIONS: Type 2 diabetes remains a health-care challenge in Canada and globally. Primary care physicians and specialists attributed patients' factors as principal obstacles to optimal diabetes management. However, physician-associated therapeutic inertia may also be an important barrier to unmet therapeutic goals.

Association Between Patient and Physician Sex and Physician-Estimated Stroke and Bleeding Risks in Atrial Fibrillation.

BACKGROUND: Physicians treating nonvalvular atrial fibrillation (AF) assess stroke and bleeding risks when deciding on anticoagulation. The agreement between empirical and physician-estimated risks is unclear. Furthermore, the association between patient and physician sex and anticoagulation decision-making is uncertain. METHODS: We pooled data from 2 national primary care physician chart audit databases of patients with AF (Facilitating Review and Education to Optimize Stroke Prevention in Atrial Fibrillation and Coordinated National Network to Engage Physicians in the Care and Treatment of Patients with Atrial Fibrillation Chart Audit) with a combined 1035 physicians (133 female, 902 male) and 10,927 patients (4567 female and 6360 male). RESULTS: Male physicians underestimated stroke risk in female patients and overestimated risk in male patients. Female physicians estimated stroke risk well in female patients but underestimated the risk in male patients. Risk of bleeding was underestimated in all. Despite differences in risk assessment by physician and patient sex, > 90% of patients received anticoagulation across all subgroups. There was modest agreement between physician estimated and calculated (ie, CHADS2 score) stroke risk: Kappa scores were 0.41 (0.35-0.47) for female physicians and 0.34 (0.32-0.36) for male physicians. CONCLUSIONS: Our study is the first to examine the association between patient and physician sex influences and stroke and bleeding risk estimation in AF. Although there were differences in agreement between physician estimated stroke risk and calculated CHADS2 scores, these differences were small and unlikely to affect clinical practice; further, despite any perceived differences in the accuracy of risk assessment by sex, most patients received anticoagulation.

Time to coronary angiography and outcomes among patients with high-risk non ST-segment elevation acute coronary syndromes: results from the SYNERGY trial.

BACKGROUND: Optimal timing for an early invasive strategy in patients with non-ST-segment-elevation acute coronary syndrome remains unclear. We evaluated the relationship between time from hospital admission to coronary angiography and outcomes in high-risk patients with non-ST-segment-elevation acute coronary syndrome who underwent angiography within 48 hours of admission. METHODS AND RESULTS: Data from 10 027 patients enrolled in the Superior Yield of the New Strategy of Enoxaparin, Revascularization, and Glycoprotein IIb/IIIa Inhibitors (SYNERGY) trial were analyzed. Patients were grouped by 6-hour intervals of time from hospital admission to coronary angiography. Primary outcomes were 30-day death or myocardial infarction, in-hospital Thrombolysis In Myocardial Infarction (TIMI) and Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) major bleeding, and blood transfusion. Adjusted estimates of event rates were obtained by use of a multivariable methodology that included possible confounders through baseline and accounted for propensity of time to angiography. The landmark method was used to calculate odds ratios and 95% confidence intervals of outcomes for each time period adjusted for baseline and postbaseline clinical events. Overall, 9216 patients (92%) underwent angiography, 6352 (63%) within 48 hours. Unadjusted and adjusted rates of death/myocardial infarction increased with increasing time to angiography. The adjusted odds ratio for death/myocardial infarction in patients receiving angiography in <6 hours was 0.56 (95% confidence interval 0.41 to 0.74), whereas after 30 hours, there was no significant benefit compared with further delayed angiography. Major bleeding and transfusion did not vary significantly across time-to-angiography intervals. CONCLUSIONS: A decrease in the time to coronary angiography was associated with fewer ischemic outcomes and no increase in bleeding. Randomized clinical trials are needed to provide definitive evidence on optimal timing of coronary angiography but are difficult to design and conduct. Ongoing trials should instead clarify whether delaying angiography to administer aggressive upstream antithrombotic therapies is effective in the current setting of non-ST-segment-elevation acute coronary syndrome management.

Quantitative troponin elevation does not provide incremental prognostic value beyond comprehensive risk stratification in patients with non-ST-segment elevation acute coronary syndromes.

BACKGROUND: The aim of this study was to evaluate whether quantitative cardiac troponin (cTn) assessment can improve risk stratification in a spectrum of patients with non-ST-segment elevation (NSTE) acute coronary syndrome (ACS) using the validated Global Registry of Acute Cardiac Events (GRACE) risk model. METHODS: The Canadian ACS Registry II is a prospective, multicenter study that enrolled patients admitted to hospital with a suspected NSTE ACS within 24 hours of symptom onset. Of the total 2297 patients, those with elevated cTn (n = 1013) were further stratified into tertiles of cTn ranges. Our primary end point was death and our secondary end point was a composite of death or/and recurrent myocardial infarction at 1-year follow-up. RESULTS: Multivariable analysis adjusting for validated predictors of death confirmed the independent prognostic value of any abnormal cTn (vs normal) for death (adjusted odds ratio 2.28, 95% CI 1.49-3.49, P < .001) and for the composite outcome (adjusted odds ratio 2.18, 95% CI 1.61-2.95, P < .001) at 1 year. With quantitative assessment, the gradient of mortality risk with increasing cTn level was not evident after adjusting for other prognosticators. Quantitative (compared to qualitative) assessment of cTn level did not improve either the GRACE risk model discrimination for 1-year death. CONCLUSIONS: Any cTn elevation is associated with higher rate of death at 1 year, but its quantitative assessment did not prove as important as its mere presence as an independent long-term prognosticator in a nonclinical trial, "real-world" NSTE ACS population.

Bleeding and outcome in acute coronary syndrome: insights from continuous electrocardiogram monitoring in the Integrilin and Enoxaparin Randomized Assessment of Acute Coronary Syndrome Treatment (INTERACT) Trial.

BACKGROUND: Bleeding is associated with adverse outcome in acute coronary syndromes. However, the precise pathophysiologic mechanisms have not been elucidated. We sought to determine the relationship between bleeding and myocardial ischemia detected by concurrent continuous electrocardiogram (ECG) monitoring and their independent long-term prognostic significance. METHODS: The INTERACT trial was a randomized controlled trial of enoxaparin versus unfractionated heparin in patients with high-risk non-ST-elevation acute coronary syndromes. Continuous ECG monitoring, performed after enrollment up to 96 hours, was analyzed by an automated algorithm and reviewed by a blinded cardiologist. We centrally adjudicated all bleeding and clinical events in a blinded fashion and calculated the Global Registry of Acute Coronary Events risk score (a validated predictor of mortality) for each patient. RESULTS: Of the 746 patients enrolled, 34 (4.6%) developed major bleeding within 96 hours. After a median follow-up of 2.4 years, patients with bleeding had a higher risk of death (28.4% vs 7.3%, P < .001) and death/myocardial infarction (38.0% vs 12.9%, P < .001) compared with those without bleeding. Overall, 619 patients survived the first 96 hours with complete data on continuous ECG monitoring. Bleeding was associated with the simultaneous presence of ST-segment shifts on continuous ECG monitoring (P = .03). After adjusting for Global Registry of Acute Coronary Events risk score and myocardial ischemia detected by continuous ECG monitoring, major bleeding remained an independent predictor of death (adjusted hazard ratio = 3.48, 95% confidence interval 1.51-8.03, P = .003) and death/myocardial infarction (adjusted hazard ratio = 2.85, 95% confidence interval 1.40-5.78, P = .004). CONCLUSIONS: Bleeding is a powerful independent predictor of poor long-term outcome, even after adjusting for other associated prognostic factors such as advanced age and renal dysfunction. Although bleeding is associated with concurrent myocardial ischemia, its adverse prognostic impact may be mediated by complex pathophysiologic mechanisms rather than myocardial ischemia alone. Our findings suggest that future investigations should focus on other biologically plausible mechanisms.