Anthony Vo

Coronary calcium and atherosclerosis by ultrafast computed tomography in asymptomatic men and women : relation to age and risk factors

We evaluated 675 men and 190 women who had no symptoms or history of clinical CHD, to determine the prevalence and risk factor correlates of CAC deposits as a marker of atherosclerosis. Measurements were taken noninvasively by ultrafast CT. The presence and extent of CAC deposits as measured by ultrafast CT was determined in all subjects, who also received personal and family medical history and risk factor questionnaire. The prevalence of CAC deposits increased significantly with age, ranging from 15% and 30% in men and women, respectively, < 40 years of age to 93% and 75% in those aged > or = 70 years. Prevalence and total score also increased by the number of risk factors present, although in those aged > 60 years a high prevalence (> 80% in men) of calcium was present regardless of the presence of risk factors. In multiple logistic regression, age, male gender, hypertension, diabetes, hypercholesterolemia, and obesity were independently associated with CAC deposits. These results suggest a high prevalence of atherosclerosis with increasing age and the presence of risk factors in men and women who have no symptoms. Studies to determine the prognostic value of CAC in individuals with no symptoms are needed to determine which populations may benefit most from CAC deposit screening.

Detection of coronary artery calcium by ultrafast computed tomography and its relation to clinical evidence of coronary artery disease

Ultrafast computed tomography (CT) was used to evaluate the relation of coronary artery calcium, a marker of atherosclerosis, with a reported history of coronary artery disease (CAD) in 928 men and 290 women (mean age 53 +/- 10 years; 11% with previous CAD). Total calcium score was calculated as the sum of each lesion-specific score, calculated as the product of pixel area and density > 130 Hounsfeld units. Total score was 3 to 6 times greater (p < 0.01) and the probability of coronary artery calcium 30 to 40% greater (p < 0.01) in patients with a reported history of myocardial infarction, positive angiography, bypass surgery or angioplasty. From score cutoffs ranging from 1 to 500 for defining calcium, a negative test was accurate 93 to 98% of the time in ruling out CAD, whereas specificity increased from 43 to 93%; however, sensitivity decreased from 92 to 42%. A score cutoff of 50 showed modest sensitivity (78%) and specificity (71%); however, the predictive value for CAD from a positive test remained low (< or = 40%), regardless of score cutoff. From multiple logistic regression, total score was also an independent indicator of CAD after considering any effects due to age, sex and other CAD risk factors. Further study is needed to document the long-term prognostic use of coronary calcium screening, including criteria that best project future risk of CAD.

Efficacy and safety of combination therapy with niacin extended-release and simvastatin versus atorvastatin in patients with dyslipidemia: The SUPREME Study

BACKGROUND Aggressive treatment of low-density lipoprotein cholesterol (LDL-C) fails to prevent most cardiovascular (CV) events. Concurrent treatment of LDL-C, high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) should be considered in patients with dyslipidemia. OBJECTIVE The efficacy and safety of a proprietary niacin extended-release and simvastatin (NER/S) combination were compared to atorvastatin monotherapy in a multicenter, Prospective, Randomized (3:2), Open-label, Blinded Endpoint (PROBE) study. METHODS Following ≥4 weeks without lipid-modifying therapies, 193 patients with dyslipidemia were treated with NER/S (n = 114; 1000/40 mg/day, weeks 1 to 4; 2000/40 mg/day weeks 5 to 12) or atorvastatin (n = 79; 40 mg/day, weeks 1 to 12). RESULTS Compared to atorvastatin, NER/S had a larger beneficial effect on HDL-C (primary end point: 30.1 ± 2.3% and 9.4 ± 2.6%, respectively; P <.001), TG (P = .02), and lipoprotein(a) (Lp[a]; P <.001), and similar effects on LDL-C and non-HDL-C. Two-thirds of patients treated with NER/S concurrently attained LDL-C (CV risk-adjusted goals), HDL-C (≥40 mg/dL), and TG (<150 mg/dL) targets, compared to one-third of patients treated with atorvastatin (P <.001). Flushing was the most common treatment-emergent adverse event (TEAE) (67.5% NER/S and 10.1% atorvastatin; P <.001). Seventy-five percent of flushing episodes were mild to moderate. More patients treated with NER/S discontinued due to TEAEs (21.1% and 3.8%; P <.001); the most common TEAE was flushing. CONCLUSION Compared to atorvastatin, NER/S provided superior improvements in HDL-C, TG, and Lp(a) and comparable improvements in non-HDL-C and LDL-C. Treatment with NER/S should be considered for patients with dyslipidemia requiring comprehensive lipid control.

Niacin Extended-Release Therapy in Phase III Clinical Trials is Associated with Relatively Low Rates of Drug Discontinuation due to Flushing and Treatment-Related Adverse Events

Background and ObjectiveNiacin is a highly effective agent for increasing low high-density lipoprotein cholesterol (HDL-C) levels. It also has beneficial effects on key pro-atherogenic lipoprotein parameters. However, the side effect of flushing can challenge patient adherence to treatment. In this study, we pooled safety data from available trials of at least 16 weeks’ duration to evaluate the impact of flushing on patient adherence to niacin extended-release (NER) therapy.MethodsData were pooled from eight NER studies (administered as NER with a maximum dosage of 1000, 1500, and 2000 mg/day, either as monotherapy or in combination with simvastatin 20 or 40mg/day [NER/S], or lovastatin 20 or 40 mg/day [NER/L]) to evaluate rates of study discontinuation due to flushing or any treatment-related adverse events.ResultsWhile 66.6% of patients experienced flushing, only 5.2% of patients discontinued treatment due to flushing. Of the total number of patients treated with NER (n = 307), NER/S (n = 912), or NER/L (n = 928), 34 (11%), 105 (11%), and 127 (14%) patients discontinued due to any treatment-related adverse event, respectively, while 14 (5%), 43 (5%), and 55 (6%) discontinued due to flushing. Discontinuation for flushing did not differ with regard to maximum dose, or to the presence or type of statin combined with NER.ConclusionAlthough flushing was common with NER treatment, discontinuation due to flushing occurred in only 5–6% of patients in this pooled analysis. This could be due to several factors, including the fact that all patients in the NER trials were educated about flushing and its management. Translation of methodology employed in these trials into clinical practice may improve long-term adherence to NER therapy, which would enhance the therapeutic benefit of NER for reducing cardiovascular risk.

Toward an ecological perspective of resident teaching clinic.

Teaching clinic managers struggle to convert performance data into meaningful behavioral change in their trainees, and quality improvement measures in medicine have had modest results. This may be due to several factors including clinical performance being based more on team function than individual action, models of best practice that are over-simplified for real patients with multiple chronic diseases, and local features that influence behavior but are not aligned with core values. Many are looking for a new conceptual structure to guide them. In this paper we briefly review several theories of action from the social and complexity sciences, and synthesize these into a coherent ‘ecological perspective’. This perspective focuses on stabilizing features and narrative, which select for behaviors in clinic much like organisms are selected for in an ecosystem. We have found this perspective to be a useful guide for design, measurement, and joint learning in the teaching clinic.

Fixed-dose combination of extended-release niacin plus simvastatin for lipid disorders

Coronary heart disease (CHD) carries significant morbidity and mortality worldwide. Elevated LDL-cholesterol and reduced HDL-cholesterol levels are well-recognized CHD risk factors. Despite guideline recommendations for intensive therapy among patients at high risk for CHD to lower LDL-cholesterol, such lowering has failed to prevent approximately two-thirds of cardiovascular events. As a result of new data, guidelines have begun to focus on non-HDL-cholesterol, HDL-cholesterol and triglycerides as treatment targets, with the end result being a recommendation for combination therapy, such as niacin plus statin for the treatment of dyslipidemia. Compared with statin monotherapy, a combination of niacin and statin therapy provides beneficial effects on a broad range of lipid particles and some evidence suggests a further reduction in CHD risk. Recent studies have shown that the combination of a fixed dose of extended-release niacin plus simvastatin reduces non-HDL-cholesterol, LDL-cholesterol, triglycerides and total cholesterol:HDL-cholesterol ratio by approximately 50% while increasing HDL-cholesterol by 25%. The safety of this combination is consistent with the safety profiles of each individual component and is well tolerated. A long-term study is currently being conducted to evaluate whether this combination therapy confers an additive impact on clinical end points.

204: Aspirin Use Prior to Initiation of Therapy with a Proprietary Niacin Extended-Release Reduces Discontinuation Rates Due to Flushing

Synopsis: Niacin has beneficial effects across all elements of the lipid profile; however, flushing can limit long-term adherence to therapy. Aspirin (ASA) can mitigate niacininduced flushing. Purpose: To evaluate the effect of ASA use prior to initiation of niacin therapy on tolerability of a novel combination of a proprietary, niacin extended-release with simvastatin (NER/S) as determined by discontinuation rates due to flushing. Methods: Data from 403 patients, who reported aspirin use prior to randomization to NER/S 1000/20, 2000/20, 1000/40, or 2000/40 mg/d for 24 weeks from two international studies, SEACOAST I and II, were pooled for this analysis. All patients had mixed dyslipidemia, including elevated cardiac risk-adjusted non-HDL-C, and were niacin-treatment-naive. After the end of the study, patients were retrospectively categorized based on ASA use prior to randomization: (1) those taking any dose of ASA (ASA ) at randomization and (2) those not taking ASA (ASA ). Results: The ASA subgroup included 192 of the 403 patients (47.6%), of whom 40 patients (9.9%) used 325 mg/d ASA, 101 (25.1%) used 81 or 100 mg/d ASA, and 51 (12.7%) used other doses. Most ASA patients reported that the ASA was being taken for cardiovascular disease prevention, therefore, frequency of ASA use at baseline differed based on coronary heart disease (CHD) risk (p 0.001 compared with ASA ). Of 271 patients with CHD or its risk equivalent, 164 (60.5%) used ASA; 24 of 100 patients (24.0%) with 2 risk factors used ASA; and 4 of 32 patients (12.5%) with 0 –1 risk factors used ASA. During NER/S treatment, fewer ASA than ASA patients experienced 1 flushing episode, 54.2% and 62.1%, respectively. Discontinuation rates due to flushing at week 24 were lower in ASA versus ASA patients, 4.2% and 7.6%, respectively. Of the 40 patients using 325 mg/d ASA at baseline, only one (2.5%) discontinued NER/S due to flushing. Treatment-emergent adverse events classified within the gastrointestinal system-organ class occurred with similar frequency in ASA and ASA patients (17.7% and 13.3%, respectively; p 0.27); no individual gastrointestinal adverse events occurred more frequently in ASA versus ASA patients (all p 0.1). Conclusions: Flushing and discontinuation due to flushing tended to be reduced in subjects reporting use of cardioprotective ASA before niacin therapy, suggesting that prior experience with ASA improves niacin tolerability. Relationships between ASA use and niacin persistence should be further explored in prospective studies.