Achieving cholesterol targets by individualizing starting doses of statin according to baseline low-density lipoprotein cholesterol and coronary artery disease risk category: the CANadians Achieve Cholesterol Targets Fast with Atorvastatin Stratified Titration (CanACTFAST) study.
Despite an increasing body of evidence on the benefit of lowering elevated levels of low-density lipoprotein cholesterol (LDL-C), there is still considerable concern that patients are not achieving target LDL-C levels.
The CANadians Achieve Cholesterol Targets Fast with Atorvastatin Stratified Titration (CanACTFAST) trial tested whether an algorithm-based statin dosing approach would enable patients to achieve LDL-C and total cholesterol/high-density lipoprotein cholesterol (TC/HDL-C) ratio targets quickly.
Subjects requiring statin therapy, but with an LDL-C level of 5.7 mmol/L or lower, and triglycerides of 6.8 mmol/L or lower at screening participated in the 12-week study, which had two open-label, six-week phases: a treatment period during which patients received 10 mg, 20 mg, 40 mg or 80 mg of atorvastatin based on an algorithm incorporating baseline LDL-C value and cardiovascular risk; and patients who achieved both LDL-C and TC/HDL-C ratio targets at six weeks continued on the same atorvastatin dose. Patients who did not achieve both targets received dose uptitration using a single-step titration regimen. The primary efficacy outcome was the proportion of patients achieving target LDL-C levels after 12 weeks.
Of 2016 subjects screened at 88 Canadian sites, 1258 were assigned to a study drug (1101 were statin-free and 157 were statin-treated at baseline). The proportion of subjects who achieved LDL-C targets after 12 weeks of treatment was 86% (95% CI 84% to 88%) for statin-free patients and 54% (95% CI 46% to 61%) for statin-treated patients. Overall, 1003 subjects (80%; 95% CI 78% to 82%) achieved both lipid targets.
Algorithm-based statin dosing enables patients to achieve LDL-C and TC/HDL-C ratio targets quickly, with either no titration or a single titration.
Age-related differences in patients with an acute coronary syndrome (ACS) have not been well characterized in prior observational studies that often included only certain age groups or subjects with myocardial infarction (MI).
We stratified 4627 patients admitted with an ACS across 9 provinces between 1999 and 2001 enrolled in the Canadian ACS Registry into 3 age groups ( or = 75 years) to evaluate differences in clinical characteristics, management, and 1-year outcome.
Older patients more frequently had previous angina, MI, or heart failure and were less likely to have positive cardiac markers, ST elevation, and Q-wave MI or to receive thrombolytics, beta-blockers, and cholesterol-lowering and antiplatelet agents in hospital, at discharge, and at 1 year. In multivariable analyses controlling for patient factors, every decade increase in age was independently associated with reduced use of coronary angiography (odds ratio [OR] 0.79, 95% CI 0.74-0.84, P
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.
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)
Recent Canadian lipid guidelines recommend that all high-risk patients receive medication to reduce low density lipoprotein cholesterol (LDL-C) below 2.5 mmol/L. The recently published Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) and Pravastatin or Atorvastatin Evaluation and Infection Therapy (PROVE IT) studies compared strategies of cholesterol lowering with atorvastatin 80 mg versus pravastatin 40 mg. Atorvastatin halted the progression of atherosclerosis (whereas atherosclerosis progressed in the patients receiving pravastatin), and resulted in a 16% reduction in the primary composite end point (all-cause death, myocardial infarction, unstable angina, revascularization and stroke) compared with the pravastatin-treated group. In the PROVE IT trial, LDL-C was reduced by atorvastatin to 1.6 mmol/L and by pravastatin to 2.46 mmol/L. Although lower LDL-C levels are one explanation for the improved outcomes with atorvastatin, pleiotropic differences of the two statins, such as their effects on inflammation and coagulation, cannot be excluded. Until trials are completed that compare outcomes from LDL-C lowering to different targets with the same statin, it is premature to recommend changes to the current Canadian guidelines. However, future recommendations may suggest much lower LDL-C targets than those currently recommended.
The prognostic value of admission ST-segment changes in patients with non-ST elevation acute coronary syndromes (NSTE ACS) is well established; however, the value of a next-day follow-up electrocardiogram (ECG) is unclear.
We evaluated ST-depression (ST(downward arrow)) and Q-wave status on the admission and 24 to 36-hour follow-up ECG in 2,743 patients in a prospective Canadian ACS registry.
Of patients with ST(downward arrow) > or =1 mm on admission (n = 533 [19.4%]), 366 (68.7%) normalized their ST segment on follow-up ECG. Among patients without ST(downward arrow) on admission (n = 2,110), 97 (4.4%) developed new ST(downward arrow) at follow-up. Patients with normalized ST(downward arrow) at follow-up had higher 1-year myocardial infarction (MI) (10.1% vs 5.7%, odds ratio [OR] 1.77, 95% CI 1.12-2.81, P = .015) and death/MI rates (19.5% vs 10.2%, OR 1.69, 95% CI 1.18-2.41, P = .004), respectively, as compared to those who never had ST(downward arrow). Patients with persistent ST(downward arrow) had higher 1-year MI (10.8% vs 5.7%, OR 1.95, 95% CI 1.09-3.51, P = .025) and death/MI rates (25.6% vs 10.2%, OR 1.78, 95% CI 1.13-2.79, P = .013), respectively. In multivariable analysis, ST(downward arrow) on baseline ECG was an independent predictor of 1-year mortality; however, ST(downward arrow) on the follow-up ECG did not provide additional prognostic value. There were no differences in outcomes between the 4 different Q-wave status groups.
Although dynamic and persistent ST(downward arrow) are associated with worse unadjusted outcome in patients with NSTE ACS, there was no incremental prognostic value of a follow-up ECG evaluating ST depression and/or Q-wave status beyond that already provided by the initial ECG together with established prognostic factors.
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.
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).
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.
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).
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.
Accurate risk stratification can guide clinical decision-making in the management of acute coronary syndromes (ACS). However, the applicability of risk models to the general ACS population remains unclear. The purpose of this study was to validate and compare a modified international clinical trial and a registry-based risk model in a contemporary, less selected ACS population.
In the prospective, observational Canadian ACS Registry, 4627 patients with ACS were enrolled from 51 centers. Baseline patient data were recorded on standardized case report forms. We evaluated risk models derived from the Platelet glycoprotein IIb/IIIa in Unstable angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) and the Global Registry of Acute Cardiac Events (GRACE) predicting in-hospital death among patients with non-ST-elevation ACS. Model discrimination was measured by the c-statistic, and calibration was assessed graphically and by the Hosmer-Lemeshow goodness-of-fit test.
In-hospital mortality rates were 2.4% overall and 1.5% among the patients with non-ST-elevation ACS (n = 2925; 63.2%) in our validation cohort. Both the in-hospital PURSUIT and GRACE risk models showed similar and good prognostic discrimination (c-statistics = 0.84 and 0.83, respectively; P = .69 for difference). The GRACE model also demonstrated good calibration (Hosmer-Lemeshow P = .40). In contrast, calibration in the PURSUIT model was poor (Hosmer-Lemeshow P
Our objective was to evaluate treatment patterns and the attainment of current National Cholesterol Education Program (NCEP)-recommended lipid targets in unselected high-risk ambulatory patients.
Between December 2001 and December 2004, the prospective Vascular Protection and Guidelines Oriented Approach to Lipid Lowering Registries recruited 8056 outpatients with diabetes, established cardiovascular disease (CVD), or both, who had a complete lipid profile measured within 6 months before enrollment. The primary outcome measure was treatment success, defined as the achievement of LDL-cholesterol
The low molecular weight heparin enoxaparin is commonly used in the management of patients with non-ST segment elevation acute coronary syndromes (ACS). It is perceived that there is variable acceptance of the use of enoxaparin in patients with ACS in conjunction with percutaneous coronary intervention (PCI) by Canadian interventional cardiologists, as well as diverse approaches to the procedural (ie, PCI) management of anticoagulation.
A survey assessing physician and centre demographics, as well as the opinion and approach to the use of enoxaparin in patients undergoing PCI, was developed. All 141 interventional cardiologists performing PCI in Canada were sent the survey, with a 52% response rate. The majority (64%) of respondents were comfortable performing PCI during enoxaparin treatment, but almost one-half (46.5%) stated a preference to have a point-of-care measurement of the anticoagulation level during the procedure. Various 'top-up' protocols are used across the country, including fixed-dose intravenous (IV) enoxaparin, weight-adjusted IV enoxaparin, fixed-dose IV unfractionated heparin, weight-adjusted IV unfractionated heparin and IV unfractionated heparin titrated to a target activated clotting time. Although the median time threshold for administering a 'top-up' dose of anticoagulation matched current recommendations, there was a wide variation ranging from 2 h to 10 h (median 8 h).
Although the majority of Canadian interventional cardiologists were comfortable performing PCI in patients treated with enoxaparin, the survey demonstrated various levels of confidence and a diverse range of 'top-up' anticoagulation procedures. Nationwide guidelines for the management of anticoagulation in patients with ACS undergoing PCI with enoxaparin should be developed from the best available clinical and research evidence to limit potential patient risk of inadequate or excessive anticoagulation. This is especially relevant in view of the association between switching among anticoagulant therapies and an increased bleeding risk in patients undergoing early cardiac catheterization and PCI that was found in the recently reported Superior Yield of the New Strategy of Enoxaparin, Revascularization and Glycoprotein IIb/IIIa Inhibitors (SYNERGY) trial.
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
Comment In: Eur Heart J. 2011 Jun;32(11):1313-521393339