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.

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.

Risk factors and outcome of in-hospital ischemic stroke in patients with non-ST elevation acute coronary syndromes.

OBJECTIVES: To identify predictors of ischemic stroke in patients with suspected non-ST elevation (NSTE) acute coronary syndrome (ACS) and to evaluate in-hospital and 1-year outcomes. METHODS: We analyzed 5842 patients with diagnosed NSTE ACS included in the multi-center Canadian ACS registries. Patients with in-hospital stroke (n=28, 0.5%) were compared to patients without stroke. Risk factors and short- and long-term outcome were evaluated. RESULTS: Baseline characteristics of patients with and without stroke were similar except for a significantly higher proportion of women, higher rates of in-hospital CABG, and greater use of unfractionated heparin. Crude event rates were significantly higher in patients with stroke: in-hospital death 21.4% vs. 1.6% (p<0.0001), MI 10.7% vs. 4.0% (p=0.10), and death or MI 32.1% vs. 5.1% (p<0.0001). One-year event rates were also higher in patients with stroke: death 32.1% vs. 7.4% (p<0.0001), and death or MI 39.3% vs. 13.5% (p<0.001). In multivariable analysis, independent predictors for stroke were female gender (OR 3.12, 95%CI 1.36-7.14, p=0.007), and Killip class >/=2 on admission (OR 2.87, 1.18-6.99, p=0.02). Stroke was an independent predictor of in-hospital death (OR 14.52, 4.57-46.12, p<0.0001), death or MI (6.0, 2.44-14.75, p<0.0001), as well as 1-year death (5.50, 1.94-15.60, p=0.0014), and death or MI (2.89, 1.15-7.27, p=0.025). CONCLUSIONS: In patients with NSTE ACS, stroke is associated with increased short- and long-term rates of death and MI. Stroke is highly predicted by female gender and Killip class on admission.

Prognostic significance of admission heart failure in patients with non-ST-elevation acute coronary syndromes (from the Canadian Acute Coronary Syndrome Registries).

We evaluated the in-hospital and 1-year outcomes and predictors of admission heart failure in patients with non-ST-elevation acute coronary syndromes (NSTE-ACSs) without previous heart failure. We analyzed 4,825 patients with NSTE-ACS without a history of congestive heart failure who were included in the multicenter Canadian ACS Registries. Patients in Killip's class II/III on admission (n = 559, 11.6%) were compared with patients in Killip's class I. Patients with heart failure on admission were older (72 [64, 79] vs 64 [54, 73] years, p < 0.0001), with higher baseline creatinine levels (96 vs 88 mmol/dl, p <0.0001), more diabetes (32.2% vs 22.8%, p < 0.0001), hypertension (58% vs 52.4%, p = 0.014), previous myocardial infarction (MI; 38.9% vs 30.3%, p < 0.0001), previous stroke (13.5% vs 7.4%, p < 0.0001), and had more ST depression on admission (27.7% vs 17.3%, p < 0.0001). In-hospital treatment was similar except for a lower rate of aspirin therapy and fewer coronary interventions. Crude event rates were significantly higher in patients with heart failure (in-hospital death 3.6% vs 1.1%, p < 0.0001; death or MI 7.9% vs 4.7%, p = 0.0011; stroke 1.1% vs 0.4%, p = 0.03). One-year event rates were also higher in patients with heart failure (death 14.6% vs 4.4%, p < 0.0001; MI 9.3% vs 6.6%, p = 0.03; death or MI 21.5% vs 10.3%, p < 0.0001). Variables independently associated with heart failure were age (odds ratio 1.57, 95% confidence interval 1.43 to 1.73), diabetes mellitus (odds ratio 1.53, 95% confidence interval 1.24 to 1.89), admission ST depression (odds ratio 1.52, 95% confidence interval 1.22 to 1.90), previous MI, and baseline creatinine. Heart failure on admission was an independent predictor of in-hospital death, death or MI, and stroke and of 1-year death and death or MI. In conclusion, in patients with NSTE-ACS, heart failure on admission is associated with increased short- and long-term rates of death and MI.