Contemporary Management of Dyslipidemia in High-Risk Patients: Targets Still Not Met

Yan, Andrew T.; Yan, Raymond T.; Tan, Mary; Hackam, Daniel G.; Leblanc, Kori; Kertland, Heather; Tsang, Jennifer; Jaffer, Shahin; Kates, Martin; Leiter, Lawrence A.; Fitchett, David; Langer, Anatoly

doi:10.1016/j.amjmed.2005.11.015

Cited by 147 publications

(97 citation statements)

References 26 publications

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“…While the value of ezetimibe in reducing adverse cardiovascular outcomes remains unproven, these findings highlight the potential opportunities to improve guideline-recommended target achievement in the Canadian context. The observations that older age and male sex were independent predictors of treatment success are consistent with those observed in Canadian (4,5), American (10,11) and international (12) settings. Even after adjusting for age and other factors -in fact, older patients were more likely to achieve target LDL-C and both target LDL-C and TC/HDL-C ratio -women were less likely to be at the Canadian guideline-recommended LDL-C goal, suggesting that previously documented sex disparities in the management of dyslipidemia appear to persist (4,5,7,12).…”

Section: Discussionsupporting

confidence: 83%

“…These contemporary findings are supported by other recently published Canadian reports (4,5) including a study (9) that used a flexible starting dose of a statin to quickly achieve an LDL-C target.…”

Section: Discussionsupporting

confidence: 78%

“…These may include suboptimal drug or dose selection, failure to titrate therapy, patient adherence or limited efficacy (4). While 88% of all patients received one of the more 'potent' statins, the median daily doses of atorvastatin (20 mg) and rosuvastatin (10 mg) were lower than those used in clinical outcome Hemoglobin A1c, % 6.8 (6.3-7.6) 6.9 (6.3-7.7) 6.7 (6.3-7.5) Lipid profile studies demonstrating benefit of those agents using a higher versus a lower dose or versus other less potent statins.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, based on the results of the main DYSIS study (data not shown) and the Canadian cohort, the vast majority of patients not at target were on low-to-medium doses of statins and, thus, there was an opportunity for upward titration as the initial step rather than addition of a second drug. It has previously been noted that only a minority of undertreated patients not achieving treatment targets experienced documented drug intolerance or side effects (4). Furthermore, a strategy employing an algorithm-based statin uptitration followed by the addition of ezetimibe was useful to further LDL-C lowering where statin monotherapy had not achieved target lipid values; attainment of an LDL-C target increased with consecutive visits (63%, 67% and 71% at the second, third and final visits, respectively) (5).…”

Section: Discussionmentioning

confidence: 99%

“…Multivariable logistic regression analysis was performed to determine the factors in high-risk patients associated with LDL-C values and TC/HDL-C ratios not at goal (less than 2.0 mmol/L and less than 4, respectively) (2). Based on the results of previous studies (4,7), the predictor variables considered in the models were age, sex, current smoker, sedentary lifestyle (physical activity less than the equivalent of walking 20 min to 30 min, three to four days a week), body mass index 30 kg/m 2 or greater, waist circumference greater than 102 cm in men and greater than 88 cm in women, hypertension, diabetes mellitus, history of ischemic heart disease, cerebrovascular disease and peripheral artery disease. Adjusted ORs with 95% CIs were calculated.…”

Section: Methodsmentioning

confidence: 99%

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Prevalence of dyslipidemia in statin-treated patients in Canada: Results of the DYSlipidemia International Study (DYSIS)

Goodman

Langer

Bastien

et al. 2010

Canadian Journal of Cardiology

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Section: Discussionsupporting

confidence: 83%

Section: Discussionsupporting

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Prevalence of dyslipidemia in statin-treated patients in Canada: Results of the DYSlipidemia International Study (DYSIS)

Goodman

Langer

Bastien

et al. 2010

Canadian Journal of Cardiology

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Combination Rosuvastatin Plus Fenofibric Acid in a Cohort of Patients 65 Years or Older With Mixed Dyslipidemia: Subanalysis of Two Randomized, Controlled Studies

Pepine

Jacobson

Carlson

et al. 2010

Clinical Cardiology

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Background: Coronary heart disease risk increases with advancing age and is further increased in patients with mixed dyslipidemia, characterized by elevated low-density lipoprotein cholesterol (LDL-C), low high-density lipoprotein cholesterol (HDL-C), and high triglycerides (TG). Combination lipid therapy is an option; however, efficacy and safety data among elderly patients are lacking. Hypothesis: The combination of rosuvastatin and fenofibric acid (R + FA) results in more comprehensive lipid improvements than corresponding-dose monotherapies, without additional safety concerns, in elderly patients with mixed dyslipidemia. Methods: This post-hoc analysis evaluated data from patients age ≥ 65 years (n = 401) with mixed dyslipidemia (LDL-C ≥ 130 mg/dL, HDL-C <40 mg/dL [men] or <50 mg/dL [women], and TG ≥ 150 mg/dL) in 2 randomized studies. Patients included in this analysis received either monotherapy (as R 5, 10, or 20 mg or FA 135 mg), or combination therapy with R (5, 10, or 20 mg) + FA 135 mg, for 12 weeks. Data were pooled and analyzed, and mean/median percent changes in multiple lipid parameters and biomarkers were compared. Results: Combination therapy decreased LDL-C by 31.8%-47.2% vs 10.6% with FA monotherapy (P < 0.001). Combination therapy also increased HDL-C by 21.9%-27.0% vs 5.9%-9.9% with R monotherapy (P < 0.001), and decreased TG by 48.3%-53.5% vs 20.7%-32.8% with R monotherapy (P < 0.001). In general, safety profiles were consistent between combination therapy and individual monotherapies. Conclusions: In these elderly patients with mixed dyslipidemia, R 5, 10, or 20 mg in combination with FA 135 mg improved the overall lipid profile, without new or unexpected safety issues. IntroductionThe elderly (age ≥ 65 years) population in the United States is estimated to more than double in the next 40 years to

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Pharmacogenetics in Cardiovascular Disease: The Challenge of Moving From Promise to Realization

Joseph

Paré

Ross

et al. 2013

Clinical Cardiology

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Pharmacogenetics in cardiovascular medicine brings the potential for personalized therapeutic strategies that improve efficacy and reduce harm. Studies evaluating the impact of genetic variation on pharmacologic effects have been undertaken for most major cardiovascular drugs, including antithrombotic agents, β-adrenergic receptor blockers, statins, and angiotensin-converting enzyme inhibitors. Across these drug classes, many polymorphisms associated with pharmacodynamic, pharmacokinetic, or surrogate outcomes have been identified. However, their impact on clinical outcomes and their ability to improve clinical practice remains unclear. This review will examine the current clinical evidence supporting pharmacogenetic testing in cardiovascular medicine, provide clinical guidance based on the current evidence, and identify further steps needed to determine the utility of pharmacogenetics in cardiovascular care. IntroductionPharmacologic effects can vary significantly between individuals, leading to reduced drug efficacy, decreased adherence, or increased adverse events. Identifying individuals who are at risk for poor therapeutic responses may be useful for amending treatment decisions to optimize benefit and minimize harm. 1 Many factors influence the effectiveness of a given pharmacologic agent, including adherence, pharmacologic and environmental interactions, and genetic effects. 2 Genetic markers have been proposed as stratification tools to predict therapeutic effects, such that pharmacologic regimens are tailored to specific genetic profiles to maximize efficacy and minimize harm. Although this approach could herald an innovative departure from current clinical cardiology practice, significant limitations in the current literature exist that make the realization of this practice difficult. This review will evaluate the clinical evidence examining pharmacogenetics in the management of cardiovascularThe authors have no funding, financial relationships, or conflicts of interest to disclose.(CV) disease (CVD) across major drug classes. We will focus on common drugs used for the treatment of CVD and thrombosis: warfarin, aspirin, clopidogrel, β-blockers, statins, and angiotensin-converting enzyme (ACE) inhibitors (ACEis). Moreover, based on the current evidence, we will provide clinical guidance regarding the current use of pharmacogenetic testing in CVD and outline future directions in research. Warfarin ResponseWarfarin is among the most effective agents to prevent thromboembolic events in patients with atrial fibrillation. However, the efficacy of warfarin is highly dependent on achieving and maintaining a narrow therapeutic window (usually an international normalized ratio [INR] between 2 and 3). Through the inhibition of vitamin K epoxide reductase complex 1 (VKORC1), warfarin limits the generation of the vitamin K hydroquinone, a necessary cofactor to sustain vitamin K-dependent coagulation factors II, VII, IX, and X. 3 Metabolism of warfarin to its inactive metabolites occurs through the cytochrome p450 ...

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Contemporary Management of Dyslipidemia in High-Risk Patients: Targets Still Not Met

Cited by 147 publications

References 26 publications

Prevalence of dyslipidemia in statin-treated patients in Canada: Results of the DYSlipidemia International Study (DYSIS)

Prevalence of dyslipidemia in statin-treated patients in Canada: Results of the DYSlipidemia International Study (DYSIS)

Combination Rosuvastatin Plus Fenofibric Acid in a Cohort of Patients 65 Years or Older With Mixed Dyslipidemia: Subanalysis of Two Randomized, Controlled Studies

Pharmacogenetics in Cardiovascular Disease: The Challenge of Moving From Promise to Realization

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