Lipid-modifying efficacy and tolerability of extended-release niacin/laropiprant in patients with primary hypercholesterolaemia or mixed dyslipidaemia.

BACKGROUND: Improving lipids beyond low-density lipoprotein cholesterol (LDL-C) lowering with statin monotherapy may further reduce cardiovascular risk. Niacin has complementary lipid-modifying efficacy to statins and cardiovascular benefit, but is underutilised because of flushing, mediated primarily by prostaglandin D(2) (PGD(2)). Laropiprant (LRPT), a PGD(2) receptor (DP1) antagonist that reduces niacin-induced flushing has been combined with extended-release niacin (ERN) into a fixed-dose tablet. METHODS AND RESULTS: Dyslipidaemic patients were randomised to ERN/LRPT 1 g (n = 800), ERN 1 g (n = 543) or placebo (n = 270) for 4 weeks. Doses were doubled (2 tablets/day; i.e. 2 g for active treatments) for 20 weeks. ERN/LRPT 2 g produced significant changes vs. placebo in LDL-C (-18.4%), high-density lipoprotein cholesterol (HDL-C; 20.0%), LDL-C:HDL-C (-31.2%), non-HDL-C (-19.8%), triglycerides (TG; -25.8%), apolipoprotein (Apo) B (-18.8%), Apo A-I (6.9%), total cholesterol (TC; -8.5%), TC:HDL-C (-23.1%) and lipoprotein(a) (-20.8%) across weeks 12-24. ERN/LRPT produced significantly less flushing than ERN during initiation (week 1) and maintenance (weeks 2-24) for all prespecified flushing end-points (incidence, intensity and discontinuation because of flushing). Except for flushing, ERN/LRPT had a safety/tolerability profile comparable with ERN. CONCLUSION: Extended-release niacin/LRPT 2 g produced significant, durable improvements in multiple lipid/lipoprotein parameters. The improved tolerability of ERN/LRPT supports a simplified 1 g-->2 g dosing regimen of niacin, a therapy proven to reduce cardiovascular risk.

Certain cardiac risk factors predict risk factor interventions and influence communication between physicians and patients.

We assessed predictors of cardiac risk factor testing and services and the degree of concordance among patients, physicians, and the medical records for these services, and found considerable variability among different risk factors. The data suggest that baseline risk factors influence communication and performance of interventions and that physicians appear to be underestimating the importance of treating multiple risk factors simultaneously.

Smoking by patients in a smoke-free hospital: prevalence, predictors, and implications.

BACKGROUND: No-smoking policies are now mandated in all U.S. hospitals. They require hospitalized smokers to abstain temporarily from tobacco. Little is known about patients' compliance with these policies or about their effects on patients' comfort and subsequent smoking behavior. Hospitalization in a smoke-free hospital might precipitate nicotine withdrawal in smokers, but it might also offer smokers an opportunity to stop smoking. METHODS: To assess the prevalence, predictors, and implications of smoking during hospitalization, we analyzed data from a cohort of 650 adult smokers who were admitted to an urban teaching hospital and participating in a smoking intervention trial. We measured nicotine withdrawal symptoms at study entry (24-48 h after admission) and patients' self-reports of smoking while hospitalized, compliance with the hospital no-smoking policy (smoking prohibited indoors but permitted outdoors), and smoking status 1 and 6 months after discharge. RESULTS: One-quarter of smokers admitted to a smoke-free hospital reported smoking during their hospital stay, although only 4% of smokers admitted violating policy by smoking indoors. Within 48 h of admission, 55% of smokers reported cigarette cravings and 29% of smokers reported difficulty refraining from smoking. Smokers with cigarette cravings were more likely to smoke while hospitalized (OR 3.6; 95% CI: 1.9-6.7). Those with nicotine withdrawal symptoms were more likely to violate the hospital no-smoking policy (OR 6.8; 95% CI: 5.3-8.3). Abstaining from tobacco use while hospitalized was a strong independent predictor of continued abstinence after discharge (OR 3.8; 95% CI: 1.4-10.3). CONCLUSIONS: Smoking by patients in a smoke-free hospital was common. Craving for cigarettes and symptoms consistent with nicotine withdrawal occurred frequently in hospitalized smokers and were associated with smoking during hospitalization, which was itself strongly linked with continuing to smoke after discharge. Pharmacologic treatment of cigarette cravings in hospitalized smokers could potentially improve patient comfort, increase compliance with hospital no-smoking policies, and promote smoking cessation after hospital discharge. This approach deserves further study.

Clinical goals and performance measures for cholesterol management in secondary prevention of coronary heart disease.

Guidelines from the National Cholesterol Education Program (NCEP) recommend reduction of low-density lipoprotein cholesterol (LDL-C) to 100 mg/dL (2.59 mmol/L) or less in patients with established coronary heart disease (CHD). However, the National Committee for Quality Assurance (NCQA) is implementing a new performance measure as part of the Health Plan Employer and Data Information Set (HEDIS) that appears to endorse a different target. The new HEDIS measure will require managed care organizations seeking NCQA accreditation to measure and report the percentage of patients who have had major CHD events who achieve LDL-C levels less than 130 mg/dL (3.36 mmol/L) between 60 and 365 days after discharge. These different LDL-C thresholds emphasize the difference between a clinical goal for the management of individual patients (< or =100 mg/dL) and a performance measure used to evaluate the care of a population of patients (<130 mg/dL). This article discusses the rationale for each threshold and explains the use of 2 different thresholds for these 2 purposes. Both the NCQA and NCEP expect that the new HEDIS measure will encourage managed care organizations to develop systems that improve secondary prevention of CHD.

The use of nicotine-replacement therapy by hospitalized smokers.

BACKGROUND: No-smoking policies are mandatory in U.S. hospitals. Consequently, smokers who are hospitalized must temporarily stop smoking. Nicotine-replacement therapy (NRT) could help hospitalized smokers relieve nicotine withdrawal symptoms, comply with no-smoking policies, and sustain tobacco abstinence after discharge. The extent of NRT use in the hospital setting is unknown. We describe the prevalence and patterns of NRT use in hospitalized smokers. DESIGN: Prospective observational study within a randomized smoking-intervention trial. SETTING/PARTICIPANTS: Six hundred fifty adult smokers admitted to the medical and surgical services of a large urban teaching hospital that prohibits smoking in all indoor areas. Follow-up was at 6 months. MAIN OUTCOME MEASURE: Inpatient pharmacy records of nicotine patch or gum use. RESULTS: Only 34 of 650 smokers (5.2%) received NRT during their hospital stay, including only 9.6% of smokers who reported difficulty refraining from smoking while hospitalized and 9.0% of hospitalized smokers with nicotine withdrawal. NRT was more likely to be prescribed to patients with nicotine withdrawal (OR 2.23; 95% CI: 1.01, 4.90), a higher daily cigarette consumption (OR 1.04; 95% CI: 1.01, 1.06), and a longer hospitalization (OR 1.05; 95% CI: 1.00, 1.10). NRT use was independent of a patient's intention to quit smoking after discharge and was not associated with smoking cessation 1 and 6 months after discharge. CONCLUSIONS: NRT was rarely used in this hospital, even among those who could have benefited from it to treat nicotine-withdrawal symptoms. When NRT was used, relief of nicotine withdrawal, rather than assistance with smoking cessation, appeared to be the primary goal. Greater use of NRT could benefit the estimated 6.5 million smokers who are hospitalized annually by reducing nicotine withdrawal, encouraging smoking cessation, and ensuring compliance with hospital no-smoking policies.

Effects of short-term treatment of hyperlipidemia on coronary vasodilator function and myocardial perfusion in regions having substantial impairment of baseline dilator reverse.

BACKGROUND: We tested the hypothesis that correction of hyperlipidemia improves coronary vasodilator response and maximal perfusion in myocardial regions having substantial impairment of pretreatment vasodilator capacity. METHODS AND RESULTS: Measurements of myocardial blood flow were made with PET [13N]ammonia in 12 patients with ischemic heart disease (11 men; age, 65+/-8 years [mean+/-SD]) at rest and during adenosine at 70 and then 140 microg . kg-1 . min-1 for 5 minutes each before and approximately 4 months after simvastatin treatment (40 mg daily). Simvastatin reduced LDL (171+/-13 before versus 99+/-18 mg/dL after simvastatin, P<0.001) and increased HDL (39+/-8 versus 45+/-9 mg/dL, P<0.05). Myocardial segments were classified on the basis of pretreatment blood flow response to 140 microg . kg-1 . min-1 adenosine as normal (flow >/=2 mL . min-1 . g-1) or abnormal (flow <2 mL . min-1 . g-1). In normal segments, baseline myocardial blood flow (0.95+/-0.32) increased (P<0.001) at both low- (1.62+/-0.81) and high- (2.63+/-0.41) dose adenosine and was unchanged both at rest and with adenosine after simvastatin. In abnormal segments, myocardial blood flow at rest (0. 73+/-0.19) increased at low- (1.06+/-0.59, P<0.02) and high- (1. 29+/-0.33, P<0.01) dose adenosine. After simvastatin, myocardial blood flow increased more compared with pretreatment at both low- (1. 37+/-0.66, P<0.05 versus pretreatment) and high- (1.89+/-0.79, P<0. 01 versus pretreatment) dose adenosine. CONCLUSIONS: Short-term lipid-lowering therapy increases stenotic segment maximal myocardial blood flow by approximately 45%. The mechanism involves enhanced, flow-mediated dilation of stenotic epicardial conduit vessels and may account at least in part for the efficacy of lipid lowering in secondary prevention trials and in reducing ischemic episodes in ambulatory patients.

Variations in cholesterol management practices of U.S. physicians.

OBJECTIVES: This study sought to evaluate national cholesterol management practices of U.S. physicians. BACKGROUND: Past studies show that nonclinical factors affect physician practices. We tested the hypothesis that physician and patient characteristics influence cholesterol management. METHODS: We used a stratified, random sample of 2,332 office-based physicians providing 56,215 visits to adults in the 1991-1992 National Ambulatory Medical Care Surveys. We investigated physicians' reporting of cholesterol-related screening, counseling or medications during office visits and used multiple logistic regression to assess independent predictors. RESULTS: An estimated 1.12 billion adult office visits occurred in 1991 and 1992 (95% confidence interval 1.06 to 1.18 billion). For the 1.03 billion visits by patients without reported hyperlipidemia, cholesterol screening (2.8% of visits) and counseling (1.2%) were not frequent. The likelihood of screening increased with older age, cardiovascular disease risk factors, white race and private insurance. We estimate that only 1 in 12 adults received cholesterol screening annually. In the 85 million visits by patients with hyperlipidemia, cholesterol testing was reported in 22.9%, cholesterol counseling in 34.4% and lipid-lowering medications in 23.1%. Testing was more likely in diabetic and nonobese patients. Counseling was more likely with younger age, cardiovascular disease and private insurance. Medications use was associated with cardiovascular disease, Northeast region of the United States, nonobese patients and visits to internists. Physician practices did not differ by patient gender. CONCLUSIONS: Although clinical conditions strongly influence cholesterol management, the appropriateness of variations noted by payment source, geographic region and physician specialty deserve further evaluation. These variations and the low estimated volume of services suggest that physicians have not fully adopted recommended cholesterol management practices.

Efficacy of a smoking cessation program for hospital patients.

BACKGROUND: Hospitalization may be an opportune time to change smoking behavior because it requires smokers to abstain from tobacco at the same time that illness can motivate them to quit. A hospital-based intervention may promote smoking cessation after discharge. METHODS: We tested the efficacy of a brief bedside smoking counseling program in a randomized controlled trial at Massachusetts General Hospital, Boston. The 650 adult smokers admitted to the medical and surgical services were randomly assigned to receive usual care or a hospital-based smoking intervention consisting of (1) a 15-minute bedside counseling session, (2) written self-help material, (3) a chart prompt reminding physicians to advise smoking cessation, and (4) up to 3 weekly counseling telephone calls after discharge. Smoking status was assessed 1 and 6 months after hospital discharge by self-report and validated at 6 months by measurement of saliva cotinine levels. RESULTS: One month after discharge, more intervention than control patients were not smoking (28.9% vs 18.9%; P=.003). The effect persisted after multiple logistic regression analyses adjusted for baseline group differences, length of stay, postdischarge smoking treatment, and hospital readmission (adjusted odds ratio, 2.19; 95% confidence interval, 1.34-3.57). At 6 months, the intervention and control groups did not differ in smoking cessation rate by self-report (17.3% vs 14.0%; P=.26) or biochemical validation (8.1% vs 8.7%; P=.72), although the program appeared to be effective among the 167 patients who had not previously tried to quit smoking (15.3% vs 3.7%; P=.01). CONCLUSIONS: A low-intensity, hospital-based smoking cessation program increased smoking cessation rates for 1 month after discharge but did not lead to long-term tobacco abstinence. A longer period of telephone contact after discharge might build on this initial success to produce permanent smoking cessation among hospitalized smokers.

Effect of combination therapy with lipid-reducing drugs in patients with coronary heart disease and "normal" cholesterol levels. A randomized, placebo-controlled trial. Harvard Atherosclerosis Reversibility Project (HARP) Study Group.

BACKGROUND: Combination drug therapy has been shown to decrease cholesterol levels in hyperlipidemic patients. However, its efficacy has not been well studied in patients previously considered to be normolipidemic, many of whom are now candidates for this therapy. OBJECTIVE: To determine the efficacy and tolerability of multidrug therapy designed to improve low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol levels in patients with coronary heart disease and average lipid levels. DESIGN: Randomized, placebo-controlled, 2.5-year trial comparing patients receiving usual care with patients receiving stepped-care drug therapy. INTERVENTION: Stepped-care therapy (pravastatin, nicotinic acid, cholestyramine, and gemfibrozil) to decrease total cholesterol levels to less than 4.1 mmol/L (160 mg/dL) and the ratio of LDL cholesterol to HDL cholesterol to less than 2.0. SETTING: 2 academic, urban, tertiary care hospitals. PATIENTS: 91 patients (80 men and 11 women) with coronary heart disease, a mean age of 60 years, total cholesterol levels less than 6.4 mmol/L (250 mg/dL) at baseline, and ratios of total cholesterol to HDL cholesterol greater than 4.0 at baseline. MEASUREMENTS: Fasting serum lipoprotein profile, fasting apolipoprotein levels, and frequency of adverse effects. Patients were assessed every 6 weeks during drug titration and every 3 months thereafter. RESULTS: Mean lipid levels at baseline were as follows: total cholesterol, 5.5 mmol/L (214 mg/dL); LDL cholesterol, 3.6 mmol/L (140 mg/dL); HDL cholesterol, 1.1 mmol/L (42 mg/dL); and triglycerides, 1.8 mmol/L (159 mg/dL). With pravastatin, changes in levels from baseline were -22% for total cholesterol, -32% for LDL cholesterol +8% for HDL cholesterol, and -15% for triglycerides (P < 0.001 for all comparisons). With the addition of 1.5 g of nicotinic acid, additional changes were -6% for total cholesterol (P < 0.002). -11% for LDL cholesterol, +8% for HDL cholesterol, and -10% for triglycerides (P < 0.001 for all comparisons). With 2.25 to 3 g of nicotinic acid, these changes were -7% for total cholesterol (P = 0.007), -14% for LDL cholesterol (P < 0.001), +6% for HDL cholesterol (P = 0.02), and -13% for triglycerides (P = 0.03). With cholestyramine, total cholesterol and LDL cholesterol levels were unchanged compared with the previous step; the change in HDL cholesterol level was -8% (P = 0.03); and the change in triglyceride level was +46% (P < 0.001). With gemfibrozil, total cholesterol level was unchanged; the additional change in LDL cholesterol level was +12% (P = 0.09); the change in HDL cholesterol level was +12% (P = 0.03); and the change in triglyceride level was -37% (P < 0.001). Apolipoprotein B levels decreased by 25% overall (P < 0.001); lipoprotein(a) levels did not change significantly. Adverse effects were primarily attributable to nicotinic acid or cholestyramine. In 18 of the 35 patients (50%) whose baseline LDL cholesterol levels were greater than 3.35 mmol/L (130 mg/dL), pravastatin decreased LDL cholesterol levels to 2.6 mmol/L (100 mg/dL) or less by 6 weeks; 70% of patients needed combination therapy to reach this National Cholesterol Education Program goal during the 2.5 years of the study. Adding nicotinic acid to pravastatin produced LDL cholesterol levels of 2.6 mmol/L or less in 15 more of these 35 patients, so that 94% (n = 33) of the patients receiving these two drugs reached this goal. CONCLUSIONS: To reach current goals for LDL cholesterol levels, most normolipidemic patients with coronary heart disease in this study needed combination therapy. Pravastatin with nicotinic acid and pravastatin with gemfibrozil are well-tolerated combinations that can maintain target LDL cholesterol levels, decrease triglyceride levels, and increase HDL cholesterol levels. Adding resin to these combinations produced no further benefit.

Cigarette smoking and coronary heart disease: risks and management.

Tobacco smoking is the leading preventable cause of death in the United States and an important cause of CHD. The effect of smoking on the cardiovascular system and coronary risk factors is pervasive. Unfavorable effects include acute increases in blood pressure and coronary vascular resistance, reduction in oxygen delivery, enhancement of platelet aggregation, increased fibrinogen, and depression of HDL cholesterol. Smoking cessation reduces cardiovascular morbidity and mortality rates relatively rapidly, even among individuals who stop smoking only after the age of 65 or after developing the clinical manifestations of CHD including myocardial infarction. Behavioral smoking-cessation programs and nicotine-replacement therapy each have been demonstrated to be effective for the treatment of smoking. The most effective treatment currently available is to combine the two. Nicotine-replacement therapy is safe and effective in patients with stable coronary heart disease. Although the threat or diagnosis of CHD is a powerful stimulus to spontaneous smoking cessation, many smokers continue to smoke after events such as myocardial infarction or CABG surgery. Studies have demonstrated that physician advice to stop smoking, supplemented by brief counseling by a nurse and follow-up, dramatically increases the smoking-cessation rate of patients hospitalized with myocardial infarction and is highly cost effective. In the outpatient setting, physician advice and counseling is also effective in helping smokers with or without CHD to stop smoking. This article outlines a simple protocol that has been demonstrated to be effective for counseling smokers.

The influence of pretreatment low density lipoprotein cholesterol concentrations on the effect of hypocholesterolemic therapy on coronary atherosclerosis in angiographic trials. Harvard Atherosclerosis Reversibility Project Research Group.

Angiographic trials of coronary atherosclerosis treatment have demonstrated that lowering low density lipoprotein (LDL) cholesterol concentrations improves coronary artery stenosis. Most patients in previous trials have had at least mildly elevated LDL. Recently, however, the Harvard Atherosclerosis Reversibility Project (HARP) did not find such benefit in patients with lower baseline LDL levels compared with previous trials. We reviewed and analyzed all cholesterol-lowering trials that used angiographic endpoints. Unifactorial trials of hypocholesterolemic dietary or drug therapy demonstrated that the higher the baseline LDL, the greater the improvement in quantitatively determined stenosis in the treatment group compared with the controls (r = .83). Considering the change in stenosis in the treatment group alone, regression was more common in trials in which baseline mean LDL was > 170 mg/dl (> 4.4 mmol/liter), whereas progression occurred when baseline mean LDL was < 170 mg/dl (< 4.4 mmol/liter). HARP had the lowest baseline LDL (137 mg/dl [3.54 mmol/liter]), and showed no tendency for improvement in lesions. In contrast to the influence of baseline LDL levels, neither a low LDL level achieved on treatment nor a large percentage reduction in LDL was related to improvement in lesions. Sample size differences between HARP and the other trials are unlikely to be a major explanatory factor, since trials of comparable sample size to HARP, but with higher initial LDL, demonstrated favorable results. We conclude that coronary lesions that develop in the context of average LDL levels show less angiographic improvement in response to substantial LDL reduction than lesions in hypercholesterolemic patients.(ABSTRACT TRUNCATED AT 250 WORDS)