Aurora Mendelsohn

Missed opportunities for the secondary prevention of cardiovascular disease in Canada

BACKGROUND Strong evidence supports the use of antithrombotic agents (antiplatelets or oral anticoagulants), statins and angiotensin-converting enzyme inhibitors in patients with atherosclerotic cardiovascular disease; beta-blockers are additionally indicated in patients with coronary artery disease. OBJECTIVES The investigators sought to determine the extent to which guideline-recommended treatments and target goals are adopted in ambulatory patients with cardiovascular disease in Canada. METHODS Two large, prospective, community-based registries (the Vascular Protection Registry and the Guideline Oriented Approach to Lipid Lowering Registry) enrolled 9809 outpatients with coronary artery disease, cerebrovascular disease, peripheral vascular disease or multiple cardiovascular risk factors from primary care settings in nine provinces across Canada between 2001 and 2004. This analysis focused primarily on patients with cardiovascular disease (n=6296). RESULTS At baseline, antithrombotics, statins and angiotensin-converting enzyme inhibitors were used in 92%, 80% and 57% of patients, respectively; beta-blockers were used in 59% of patients with coronary artery disease. The dosing of most drug therapies was suboptimal compared with guideline-recommended dosing derived from clinical trials. Treatment goals for cardiovascular risk factors were suboptimally attained: low-density lipoprotein cholesterol in 50% of patients, total to high-density lipoprotein cholesterol ratio in 51% of patients, systolic and diastolic blood pressure in 58% and 78% of patients, respectively, and waist circumference and body mass index in 45% and 19%, respectively. CONCLUSIONS These data suggest specific opportunities for improving the care of patients with cardiovascular disease in Canada. The focus must now shift from awareness of treatment gaps to implementation of effective solutions.

Discordance Between Physicians' Estimation of Patient Cardiovascular Risk and Use of Evidence-Based Medical Therapy

Despite clinical trial evidence supporting the use of antiplatelets, angiotensin-converting enzyme inhibitors, and statins for cardiovascular risk reduction in high-risk patients, use of such therapies in real-world outpatients in the prospective Vascular Protection Registry and the Guidelines Oriented Approach to Lipid Lowering Registry was suboptimal (78%, 55%, and 75%, respectively). The most frequent reason physicians cited for nonprescription of statins (33%) was that patients were not high risk enough and/or current guidelines did not support statin use. In conclusion, outpatients at high cardiovascular risk continue to be undertreated as a result of a combination of physician underestimation of cardiovascular risk (knowledge gap) and barriers to implementation of evidence-based therapy (practice gap).

Usefulness of Statin-Ezetimibe Combination to Reduce the Care Gap in Dyslipidemia Management in Patients With a High Risk of Atherosclerotic Disease

Lowering of low-density lipoprotein (LDL) cholesterol is a fundamental step in the comprehensive management of patients at high risk for cardiovascular events. The combination of a statin with ezetimibe usually provides additional LDL cholesterol lowering compared to statin monotherapy. This open-label observational study evaluated the impact of a 26-week treatment program with uptitration of statin dosages and incorporation of ezetimibe 10 mg therapy in 2,577 men and women (median age 64 years) with hypercholesterolemia and an LDL cholesterol level >2.5 mmol/L (97 mg/dl). Attainment of an LDL cholesterol target of 2.5 mmol/L (97 mg/dl) increased with consecutive visits (63%, 67%, and 71% at the second, third, and final visits, respectively). Current guideline-recommended LDL cholesterol value <2.0 mmol/L (77 mg/dl) was achieved by 36%, 40%, and 41% of the group at the same consecutive follow-up sessions. Median LDL cholesterol decreased from 3.0 mmol/L (116 mg/dl) at baseline to 2.1 mmol/L (81 mg/dl) at the end of the 26-week monitoring period. Favorable changes were concomitantly observed for median total cholesterol (5.1 to 4.1 mmol/L [197 to 159 mg/dl]), total cholesterol/high-density lipoprotein cholesterol ratio (4.2 to 3.3), and triglyceride (1.6 to 1.4 mmol/L [142 to 124 mg/dl]). Of those who attended visit 4, 48% exhibited LDL cholesterol lowering of > or =1 mmol/L (39 mg/dl) compared to baseline levels. In conclusion, an algorithm-based statin uptitration/ezetimibe combination regimen is useful to increase LDL cholesterol lowering where statin monotherapy has not achieved target lipid values.

Clinical implications of a next-day follow-up electrocardiogram in patients with non-ST elevation acute coronary syndromes

BACKGROUND 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. METHOD 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. RESULTS 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. CONCLUSIONS 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.

Use of a Treatment Optimization Algorithm Involving Statin-Ezetimibe Combination Aids in Achievement of Guideline-Based Low-Density Lipoprotein Targets in Patients With Dyslipidemia at High Vascular Risk Guideline-Based Undertaking to Improve Dyslipidemia Management in Canada (GUIDANC)

BACKGROUND Despite the well-established benefits of strategies to reduce low-density lipoprotein cholesterol (LDL-C), many patients fail to achieve the guideline recommended targets. The objective of this study was to evaluate the impact of an enhanced 26-week algorithm-based treatment optimization strategy, involving titration of statin monotherapy and/or combination therapy with statin and ezetimibe, on achievement of guideline-based LDL-C targets in patients at high risk for atherosclerotic disease. METHODS AND RESULTS In this national (172-physician) quality enhancement research initiative involving 2334 Canadian men and women (median age, 65 years) at high vascular risk who were not at the guideline-recommended LDL-C target despite statin therapy, 36.6% and 45.5% of patients achieved an LDL-C <2.0 mmol/L at visit 2 and visit 3, respectively, using the treatment optimization algorithm. The percentage of patients achieving the 2009 Canadian Cardiovascular Society (CCS)-recommended target of either LDL-C <2.0 mmol/L or a 50% or greater reduction from baseline increased from 6.8% at visit 1 to 43.3% at visit 2 and to 52.1% at visit 3. Attainment of LDL-C targets increased significantly with consecutive visits (P < .001). Use of ezetimibe in combination with statin therapy was associated with greater target achievement. CONCLUSIONS Use of a structured treatment optimization algorithm, based on titration of statin dosages and incorporation of ezetimibe therapy when required, enabled the majority of high-risk patients to achieve guideline-recommended targets, thereby narrowing the care gap that exists in dyslipidemia management.

Non-alcoholic fatty liver disease and outcomes in persons with acute coronary syndromes: insights from the GRACE-ALT analysis

Objective Non-alcoholic fatty liver disease (NAFLD) is associated with a higher risk of cardiovascular disease, but no data exist about the relation between NAFLD and adverse outcomes in persons with acute coronary syndromes (ACS). We evaluated elevated serum alanine aminotransferase (ALT) as a marker of NAFLD, in association adverse outcomes following ACS. Methods We conducted a retrospective cohort study of participants enrolled in the Global Registry of Acute Coronary Events (GRACE) admitted for ACS to St Michaels Hospital, Toronto, between 1999 and 2007. Multivariable linear regression was used to determine the change in maximum measured cardiac troponin I (cTnI) per each 1 IU/l increase in serum ALT concentration. The association between an elevated ALT >90th centile, and adverse outcomes in-hospital and at 6 months were calculated using multiple logistic regression analyses, adjusting for age, sex, body mass index, serum creatinine, glucose, triglycerides and LDL-C, as well as chronic statin or other lipid-lowering agent use. Results 528 participants were included. Each 1 IU/l increase in ALT was associated with an increase in maximum measured cTnI of 0.16 µg/l (95% CI 0.10 to 0.22). An elevated ALT concentration >90th percentile was associated with a maximum measured cTnI in the highest quartile (adjusted OR 7.07, 95% CI 1.83 to 27.37). An elevated ALT >90th percentile was also significantly associated with all-cause mortality in-hospital, and up to 6 months after discharge (adjusted OR 8.96, 95% CI 3.28 to 24.49). Conclusions NAFLD, determined by an elevated serum ALT, is associated with a higher risk of adverse outcomes in persons with ACS. Whether ALT is a valid and independent prognostic marker in ACS remains to be determined.