Usefulness of carotid parameters measured by ultrasonography as a marker of atherothrombotic infarction and lacunar infarction in high-risk elderly people

Aim:   Many studies have reported that carotid parameters measured by ultrasonography are predictors for cerebral infarction. The aim of this study was to investigate by a cross-sectional study whether those carotid parameters are markers for atherothrombotic infarction (AI) and lacunar infarction (LI) in elderly people having cardiovascular risk factors.
Methods:   We studied 314 patients aged 65 years or older who had controlled cardiovascular diseases and assessed carotid arteries by ultrasonography. The subjects were categorized into control, AI and LI groups. Clinical characteristics (biochemical analysis, body mass index, systolic/diastolic blood pressure, smoking habits, hypertension, diabetes mellitus and statin therapy) and carotid parameters (maximum intima-media thickness [Max-IMT], plaque score [PLQ-S] and maximum pulsatility index [Max-PI]) were compared among the three groups.
Results:   PLQ-S, Max-PI, frequency of PLQ-S ≥ 10 mm and frequency of Max-PI ≥ 2.0 were significantly higher in the AI group than in the control group. There were no significant differences between the control and LI groups concerning carotid parameters. Multivariate logistic regression analysis showed that there were significant correlations between AI and PLQ-S ≥ 10 mm (odds ratio 2.980; P  = 0.011), AI and Max-PI ≥ 2.0 (odds ratio 2.458; P  = 0.038), but there were no significant correlations between those carotid parameters and LI.
Conclusions:   This study suggests that in high-risk elderly people, PLQ-S and PI are better markers for AI than IMT, but those carotid parameters do not correlate with LI.     

Hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma: Is the addition of subcutaneous interferon‐α‐2b beneficial?

Aim:  We previously reported the benefits of hepatic arterial infusion chemotherapy (HAIC) using cisplatin (CDDP), 5-fluorouracil (5-FU) [low-dose FP], and leucovorin/isovorin for advanced hepatocellular carcinoma (HCC). In this study, we investigated the efficacy of combination therapy with HAIC and subcutaneous interferon (IFN)- α-2b in patients with advanced HCC.
Methods:  Of the 48 patients, 31 received low-dose FP with leucovorin/isovorin (HAIC group) and 17 received combination therapy comprising low-dose FP with isovorin and subcutaneous IFN-α-2b (combination group). Prognostic factors were evaluated by univariate and multivariate analyses of the patient and the disease characteristics.
Results:  There were no significant differences in the response rate (patients with complete or partial response/all patients; P  = 0.736) and survival ( P  = 0.399) between both groups. Univariate analysis revealed that IFN therapy was not a significant prognostic factor. Multivariate analysis showed 3 variables, namely, Child–Pugh score ( P  = 0.010), α-fetoprotein level ( P  = 0.0047), and additional therapy ( P  = 0.002), to be significant prognostic factors.
Conclusions:  We considered that combination therapy with HAIC and subcutaneous interferon (IFN)-α-2b was not beneficial for advanced HCC.     

l-Ornithine-l-aspartate in the management of hepatic encephalopathy: A meta-analysis

Background and Aim:  Hepatic encephalopathy continues to be a major clinical problem and the current decade has not witnessed major therapeutic breakthroughs in this area. l -ornithine- l -aspartate (LOLA) is not frequently used as there are still some reservations about its benefits. The present study aimed to assess the effectiveness and safety of LOLA in the management of hepatic encephalopathy.
Methods:  We used the method recommended by the Cochrane Collaboration to perform a meta-analysis of randomized controlled trials of LOLA therapy for hepatic encephalopathy including three randomized controlled trials.
Results:  Three randomized trials randomizing 212 patients were included. LOLA versus placebo had a significant effect on improvement of hepatic encephalopathy (relative risk 1.89; 95% CI 1.32 to 2.71; P  = 0.0005). This comparison showed no statistical heterogeneity ( P  = 0.85 and χ² = 0.09). Subgroup analysis showed that LOLA could be effective versus placebo in trials with grade I or II overt hepatic encephalopathy patients (relative risk 1.87; 95% CI 1.30 to 2.68; P  = 0.0007) and had no significant effect in trials with subclinical hepatic encephalopathy patients (relative risk 1.69; 95% CI 0.72 to 3.94; P  = 0.23). Adverse effects were observed in only three patients treated with LOLA in one report.
Conclusions:  LOLA benefited patients with overt hepatic encephalopathy (I or II), whereas these data do not support the use of LOLA for patients with subclinical hepatic encephalopathy.     

Reduced creatine kinase release with statin use at the time of myocardial infarction

BACKGROUND: Statin pre-treatment has been shown to reduce myocardial infarct size in animal models. We evaluated peak creatine kinase levels in humans based on concomitant or very early statin initiation following myocardial infarction. METHODS: We identified 66 consecutive patients who received a statin within 24 h of admission to our coronary care unit for myocardial infarction. Each statin patient was matched with three patients who had not received statin therapy (n=198). Statin patients were subgrouped into those receiving statin therapy at the time of infarction (n=44) and those initiated on statin therapy within 24 h of infarction (n=22). Peak total creatine kinase concentrations were compared between groups. A linear regression model was developed to test for differences in peak creatine kinase after adjusting for differences between groups. RESULTS: Patients receiving statin therapy within 24 h of admission had significantly smaller median peak creatine kinase concentrations compared to those not receiving a statin (416 IU/l [258, 992] vs. 699 IU/l [339, 1728]; p=0.020). Subgroup analysis revealed that the lower peak creatine kinase concentrations within the statin group were a result of lower creatine kinase concentrations in those patients on a statin at the time of myocardial infarction (399 IU/l [255, 869] vs. 678 IU/l [276, 1870]; p<0.05). This difference retained statistical significance after adjustment for differences between groups. CONCLUSION: Statin therapy at the time of myocardial infarction is associated with lower peak creatine kinase concentrations. This suggests that statins may exhibit protective effects in the setting of myocardial ischemia and/or infarction in humans.     

Discontinuation of Statins: What Are the Risks?

The key benefits of statin therapy have been well established in both primary and secondary prevention cardiovascular patients. Many studies have shown a significant statin discontinuation rate within the first year of initiation whether for primary or secondary prevention. National guidelines for the management of dyslipidemia highlight the lack of benefit seen with statin therapy in patients with chronic kidney disease receiving dialysis, heart failure with reduced ejection fraction, and patients greater than 75 years of age without atherosclerotic cardiovascular disease. Available data outside of these patient populations do not support discontinuation of statin therapy. Recent studies support an association with statin discontinuation and increased risk of myocardial infarction and cardiovascular death. Based on the available data, discontinuation of statin therapy should be carefully considered.     

Effects of treatment recommendations and specialist intervention on care provided by primary care physicians to patients with myocardial infarction or heart failure

PURPOSE: To assess the effects of an intervention involving dissemination of treatment recommendations to primary care physicians treating outpatients with acute myocardial infarction or heart failure. METHODS: The study comprised 509 patients with myocardial infarction and 323 patients with heart failure who were discharged from hospital. The primary care physicians caring for these patients were assigned randomly to either the intervention or control group; the intervention group was mailed practice guidelines immediately after patient discharge, and patients were cited by name. During a 6-month assessment period, the records of primary care physicians (and cardiologists, if any) were reviewed to assess mean conformance with the guidelines, using seven measures of care for myocardial infarction and eight measures of care for heart failure. RESULTS: After adjusting for demographic and clinical characteristics of patients, and the number of eligible measures per patient, we observed no effect of the intervention on care of patients with myocardial infarction (odds ratio [OR] = 0.98; 95% confidence interval [CI]: 0.81 to 1.17) or heart failure (OR = 1.25; 95% CI: 0.96 to 1.59). However, there was a higher likelihood of conformance with measures for patients with infarction (OR = 1.56; 95% CI: 1.29 to 1.87) or heart failure (OR = 1.71; 95% CI: 1.29 to 2.23) who had also been seen by a cardiologist during the 6-month assessment period. CONCLUSION: Mailing treatment recommendations did not improve the quality of care of recently discharged patients with myocardial infarction or heart failure. However, efforts to include cardiologists in the care of these patients might be worthwhile.     

Clinical prognosis, pre-existing conditions and the use of reperfusion therapy for patients with ST segment elevation acute myocardial infarction

BACKGROUND: Some evidence-based therapies are underused in patients with a poor prognosis despite the fact that the survival gains would be highest among such patient subgroups. The extent to which this applies for acute, life-saving therapies is unknown. The impact of prognostic characteristics and pre-existing conditions on the use of reperfusion therapy among eligible patients with acute ST segment elevation myocardial infarction is examined. METHODS: Of 2829 acute myocardial infarction patients prospectively identified in 53 acute care hospitals across Ontario, 987 presented with ST segment elevation within 12 h of symptom onset and without any absolute contraindications to reperfusion therapy. The baseline prognosis for each patient was derived from a validated risk-adjustment model of 30-day mortality. Multiple logistical regression was used to examine the relationships among reperfusion therapy, prognosis and the number of pre-existing chronic conditions after adjusting for factors such as age, sex, time since symptom onset and socioeconomic status. RESULTS: Of the 987 appropriate candidates, 725 (73.5%) received reperfusion therapy (70.8% fibrinolysis, 2.6% primary angioplasty). The adjusted odds ratio of reperfusion therapy fell 4% with each 1% increase in baseline risk of death (adjusted OR 0.96, 95% CI 0.92 to 1.00, P=0.04) and fell 18% with each additional pre-existing condition (adjusted OR 0.82, 95% CI 0.76 to 0.90, P<0.001). The number rather than the type of pre-existing conditions inversely correlated with the use of reperfusion therapy. While the impact of baseline risk and pre-existing conditions was additive, pre-existing conditions exerted a greater impact on the nonuse of reperfusion therapy than did baseline risk. CONCLUSIONS: A treatment-risk paradox is demonstrable even within a cohort of lower risk patients with ST segment elevation myocardial infarction. These findings are consistent with the view that these clinical decisions are more likely to be attributable to concerns about patient frailty or side effects than to a misunderstanding of treatment benefits.     

Tissue angiotensin-converting enzyme inhibitors for the prevention of cardiovascular disease in patients with diabetes mellitus without left ventricular systolic dysfunction or clinical evidence of heart failure: a pooled meta-analysis of randomized placebo-controlled clinical trials

Aim:  The aim of this study was to determine the role of tissue angiotensin-converting enzyme (ACE) inhibitors in the prevention of cardiovascular disease in patients with diabetes mellitus without left ventricular systolic dysfunction or clinical evidence of heart failure in randomized placebo-controlled clinical trials using pooled meta-analysis techniques.
Methods:  Randomized placebo-controlled clinical trials of at least 12 months duration in patients with diabetes mellitus without left ventricular systolic dysfunction or heart failure who had experienced a prior cardiovascular event or were at high cardiovascular risk were selected. A total of 10 328 patients (43 517 patient-years) from four selected trials were used for meta-analysis. Relative risk estimations were made using data pooled from the selected trials and statistical significance was determined using the Chi-squared test (two-sided alpha error <0.05). The number of patients needed to treat was also calculated.
Results:  Tissue ACE inhibitors significantly reduced the risk of cardiovascular mortality by 14.9% (p = 0.022), myocardial infarction by 20.8% (p = 0.002) and the need for invasive coronary revascularization by 14% (p = 0.015) when compared to placebo. The risk of all-cause mortality also tended to be lower among patients randomized to tissue ACE inhibitors, whereas the risks of stroke and hospitalization for heart failure were not significantly affected. Treating about 65 patients with tissue ACE inhibitors for about 4.2 years would prevent one myocardial infarction, whereas treating about 85 patients would prevent one cardiovascular death.
Conclusion:  Pooled meta-analysis of randomized placebo-controlled trials suggests that tissue ACE inhibitors modestly reduce the risk of myocardial infarction and cardiovascular death and tend to reduce overall mortality in diabetic patients without left ventricular systolic dysfunction or heart failure.     

Rediscovering bile acid sequestrants

Aim: In the recently published The Justification for the Use of statins in Primary prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) mega-trial, rosuvastatin significantly reduced cardiovascular events at the expense of a small but significant increase in the risk of developing type 2 diabetes. The increased risk of new-onset diabetes was in keeping with a recent meta-analysis which suggested that statins, with the possible exception of pravastatin, marginally increase the risk of developing type 2 diabetes.
Methods: Although the net effect of rosuvastatin was obviously very positive, we hypothesized that the addition of a bile aid sequestrant to a statin would not only further decrease lipid levels and potentially further decrease cardiovascular events but also protect against the development of diabetes. This is particularly relevant because the bile acid sequestrant, colesevelam, has recently been approved for therapy of diabetes.
Results: Colesevelam like other bile acid sequestrants lowers low-density lipoprotein levels by 16% and C-reactive protein by 22% beyond the reductions that occur with statin therapy alone. Bile acid sequestrants confer lipid-lowering, glucose-lowering, and anti-inflammatory benefits, and have been shown to reduce risk of cardiovascular events.
Conclusions: Therefore, colesevelam should be the most effective and logical agent to add to a statin in the diabetic and insulin-resistant patient, because in addition to lowering cardiac risk it may prevent the development of diabetes, as well as improving glycaemic control in the established diabetic patient.     

Effect of interferon α-2b plus ribavirin therapy on incidence of hepatocellular carcinoma in patients with chronic hepatitis

Aim:  The objective of this study was to elucidate the long-term effects of interferon (IFN)α-2b plus ribavirin combination therapy and to clarify whether this therapy can reduce the incidence of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C.
Methods:  A total of 403 patients infected with hepatitis C virus (HCV) were enrolled in a multicenter trial. All patients were treated with a combination of IFN-α-2b plus ribavirin therapy. We examined the incidence of HCC after combination therapy and analyzed the risk factors for liver carcinogenesis.
Results:  A sustained virological response (SVR) was achieved by 139 (34%) of the patients. The cumulative rate of incidence of HCC was significantly lower in SVR patients than in non-SVR patients ( P  = 0.03), while there was no difference in the cumulative incidence of HCC between the transient response (TR) group and the no response (NR) group. Cox's regression analysis indicated the following risk factors as independently significant in relation to the development of HCC: age being > 60 years ( P  = 0.006), advanced histological staging ( P  = 0.033), non-SVR to IFN therapy ( P  = 0.044). The cumulative incidence rate of HCC was significantly lower in patients who had average serum alanine aminotransferase (ALT) levels of < 40 IU/L than in those who showed average serum ALT levels of ≧ 40 IU/L after the combination therapy ( P  = 0.021).
Conclusions:  These results suggest that the attainment of SVR or continuous normalization of ALT levels after IFN therapy can affect patients apart from HCC development.     

Insulin-induced weight gain and cardiovascular events in patients with type 2 diabetes. A report from the DIGAMI 2 study

Aim:  We investigated whether insulin treatment-induced weight gain was accompanied by increased cardiovascular (CV) mortality and morbidity in the second Diabetes Insulin Glucose in Acute Myocardial Infarction (DIGAMI 2) study.
Methods:  We studied the 865 patients who survived during 12 months without any change in their glucose-lowering (GL) therapy. They were divided into four subgroups according to GL treatment: group I, no pharmacological GL treatment (n = 99); group II, oral hypoglycaemic agents (n = 250); group III, new insulin treatment (n = 245) and group IV, insulin before inclusion continued during the first year of follow up (n = 271).
Results:  Patients who started on insulin (group III) experienced an average body weight increase of 2.3 (1.5–3.2) kg during the first year of treatment, whereas weight remained unchanged in groups I, II and IV. The incidence of non-fatal reinfarction was higher in group III compared with the other groups (hazard ratio (HR) = 2.5, p   = 0.011) and CV mortality was higher in group IV (HR = 2.4, p   = 0.003). When the subjects were grouped in quartiles according to maximal body weight increase, those in the lowest quartile experienced the highest CV mortality. Each kilogram increase in weight reduced the risk for CV death with 6%. The incidence of reinfarction did not differ between quartiles.
Conclusions:  Initiation of insulin treatment after myocardial infarction was associated with a significant increase in weight and incidence of reinfarction. The increase in weight did, however, not explain the increased rate of reinfarction.     

Adherence to evidence-based therapies after discharge for acute coronary syndromes: an ongoing prospective, observational study

PURPOSE: To determine the rates of patient adherence to key evidence-based therapies at 6 months after hospital discharge for an acute coronary syndrome. METHODS: In this nonrandomized, prospective, multinational, multicenter study, adherence to aspirin, beta-blockers, statins, or angiotensin-converting enzyme (ACE) inhibitors 6 months after discharge for myocardial infarction or unstable angina was assessed in 21,408 patients aged 18 years or older. Patients were enrolled at 104 tertiary and community hospitals representing a broad range of care facilities and practice settings (e.g., teaching vs. nonteaching). RESULTS: Of 13,830 patients, discontinuation of therapy was observed at 6-month follow-up in 8% of those taking aspirin on discharge, 12% of those taking beta-blockers, 20% of those taking ACE inhibitors, and 13% of those taking statins. In a multivariate analysis, adherence to beta-blocker therapy was higher in patients with a myocardial infarction (odds ratio [OR] = 1.25; 95% confidence interval [CI]: 1.06 to 1.47), hypertension (OR = 1.33; 95% CI: 1.15 to 1.54), ST-segment elevation myocardial infarction (OR = 1.33; 95% CI: 1.11 to 1.61), or non-ST-segment elevation myocardial infarction (OR = 1.25; 95% CI: 1.08 to 1.45). Aspirin adherence was higher among patients cared for by cardiologists (OR = 1.45; 95% CI: 1.19 to 1.75; P <0.001) than among those cared for by nonspecialists. Male sex and prior heart failure were associated with improved adherence to ACE inhibitor therapy. Hypertension was associated with poorer adherence to statin therapy (OR = 0.85; 95% CI: 0.74 to 0.99; P = 0.04). CONCLUSION: Among patients prescribed key evidence-based medications at discharge, 8% to 20% were no longer taking their medication after 6 months. The reasons for noncompliance are complex, and may be elucidated by future studies of medical and social determinants.     

An evaluation of the relationship between specialist training in cardiology and implementation of evidence-based care of patients following acute myocardial infarction

AIMS: Large clinical trials have provided evidence of prognostically beneficial treatment strategies for patients with acute myocardial infarction. However, the implementation of this evidence into routine clinical practice is suboptimal. We hypothesised that the speciality of the attending physician (cardiologist or not) would affect the use of evidence-based strategies. METHODS: Over a 3-month period (1st September to 30th November 1995), 3684 consecutive potential cases of acute myocardial infarction (AMI) in 20 adjacent hospitals in the Yorkshire Region were identified from coronary care registers, clinical coding and biochemistry records of cardiac enzyme assay requests. There were 2153 consecutive cases of AMI identified, of which 1643 patients were alive at discharge. We compared the admission use of aspirin and thrombolysis, and the use of aspirin, beta-blockers, angiotensin-converting enzyme (ACE) inhibitors and statins at discharge between cardiologists and other physicians. RESULTS: AMI patients under the care of cardiologists are more likely to receive aspirin and thrombolysis on the day of their event and to be prescribed aspirin, beta-blockers and statins on discharge. After correction for contraindications to their use, the above findings were broadly confirmed. DISCUSSION: Cardiologists are more likely than general physicians to use evidence-based treatment strategies recognised to improve AMI patient outcome. It is likely that this will translate into a reduction of mortality or other hard endpoints in patient outcomes.     

Prevalence and outcome of fungal infection in patients with severe acute pancreatitis

Background and Aim:  To study the prevalence of risk factors and outcome of fungal infections in patients with severe acute pancreatitis.
Methods:  Fifty consecutive patients with severe acute pancreatitis were investigated for evidence of fungal infection by weekly culture of body fluids and aspirate from pancreatic/peripancreatic tissue and samples collected at necrosectomy. All patients were managed as per a standard protocol. Patients with documented fungal infection were treated with intravenous amphotericin or fluconazole. Data were analyzed using SPSS software (version 13), and risk factors for fungal infection and mortality were determined.
Results:  Fungal infection was documented in 18 (36%) of 50 patients with Candida albicans (the commonest species). The incidence of fungal infection steadily increased with increasing duration of hospital stay. Those with fungal infection more often had evidence of respiratory failure ( P  = 0.031) and hypotension ( P  = 0.031) at admission, prolonged hospital stay > 4 weeks ( P  = 0.034), longer duration of antibiotics ( P  = 0.003), received total parenteral nutrition ( P  = 0.005), and required mechanical ventilation ( P  = 0.001) in contrast to those without fungal infection. The logistic regression analysis found the independent risk factors for fungal infection to be antibiotic therapy for > 4 weeks and hypotension at hospitalization. Of the 18 patients with fungal infection, 13 were administered intravenous antifungals; eight of these patients survived, while the five who did not receive antifungals died.
Conclusion:  Fungal infection was detected in 36% of our patients. The independent risk factors associated with it were hypotension at hospitalization and prolonged antibiotic therapy. Antifungal therapy improved their chances of survival.     

Early withdrawal of statin therapy in patients with non-ST-segment elevation myocardial infarction: national registry of myocardial infarction

BACKGROUND: There is increasing interest in the non-lipid-lowering effects of statins and their effect on outcomes in patients with acute coronary syndrome. It has been suggested that withdrawal of statin therapy during an acute coronary syndrome may attenuate any benefits of pretreatment, thereby providing indirect evidence of the importance of their non-lipid-lowering effects. METHODS: This observational study compared the demographic and clinical characteristics and hospital outcomes in patients with non-ST-segment elevation myocardial infarction enrolled in the National Registry of Myocardial Infarction 4. Comparison groups consisted of patients previously receiving statins who also received statins within 24 hours of hospital admission (n = 9,001), patients previously using statins in whom therapy was discontinued (n = 4,870), and patients who did not receive statins at any time before or during hospitalization (n = 54,635). RESULTS: Of 13,871 patients receiving statins before hospital admission, 35.1% had treatment withdrawn during the first 24 hours of hospitalization. These patients had increased hospital morbidity and mortality rates relative to patients in whom therapy was continued, with higher rates of heart failure, ventricular arrhythmias, shock, and death. In multivariate analyses, these patients were at statistically significant increased risk of hospital death compared with those continuing statin therapy and at similar risk compared with those not receiving statins before or during hospitalization. CONCLUSIONS: Withdrawal of statin therapy in the first 24 hours of hospitalization for non-ST-segment elevation myocardial infarction is associated with worse hospital outcomes. In the absence of data from randomized clinical trials, our findings suggest that statin therapy should be continued during hospitalization for myocardial infarction unless strongly contraindicated.     

The effects of antifungal therapy on severe asthma with fungal sensitization and allergic bronchopulmonary aspergillosis

Background and objective:   Very little is known about the response rates to or appropriateness of treatment for patients with allergic fungal diseases of the lung. This study assessed the effect of antifungal therapy in patients with severe asthma with fungal sensitization (SAFS) and allergic bronchopulmonary aspergillosis (ABPA).
Methods:   A retrospective cohort study of 33 adult patients who fulfilled the criteria for either SAFS ( n  = 22) or ABPA ( n  = 11) was conducted. All patients had received antifungal therapy for at least 6 months. The primary study end point was the effect of antifungal therapy on patients' lung function.
Results:   Overall, total IgE values and radioallergosorbent test (RAST) for A. fumigatus markedly decreased after 6 months of therapy in both SAFS and ABPA patients ( P  = 0.004 and P  = 0.005, respectively). Reduction was seen in the eosinophil count ( P  = 0.037), dose of oral steroids ( P  = 0.043) and courses of systemic steroids required ( P  = 0.041). Lung function also improved ( P  = 0.016). Four of 10 patients discontinued oral steroids after 6 months of therapy. Reduction in IgE levels ( P  = 0.015) and RAST for A. fumigatus was also observed ( P  = 0.006) for those patients treated for at least 1 year with antifungal drugs.
Conclusions:   Both ABPA and SAFS patients benefited from oral antifungal therapy. The antifungal therapy may act by reducing the antigenic load, interacting with corticosteroids or by a direct immunological effect.     

Use of the statins in patients after acute myocardial infarction: does evidence change practice?

OBJECTIVE: To compare the use of lipid-lowering agents in 42 628 elderly patients (aged > or =65 years) after acute myocardial infarction, before and after the publication of the Scandinavian Simvastatin Survival Study (4S), using the Ontario Myocardial Infarction Database. METHODS: Multivariate regression models were created to estimate changes in the rate of statin use over time in monthly cohorts of elderly patients after acute myocardial infarction in Ontario from April 1, 1992, to March 31, 1997. Changes in the rate of statin use over time were estimated using patient and prescriber characteristics. RESULTS: We found a 3.6-fold significant increase in the monthly rate of statin use after the publication of 4S compared with before the publication of 4S (P<.001); specifically, the rate of increase in simvastatin and pravastatin sodium use was higher after the publication of 4S (P<.001 for each). Before the publication of 4S, the rate of increase in statin use in younger patients (aged 65-74 years) was 2.7 times higher than in older patients (aged > or =75 years) (P =.02), while after the publication of 4S, the rate of increase in statin use was only 1.8-fold higher in the younger group (P<.001). After the publication of 4S, there was a 1.6-fold higher rate of increase in statin use in male compared with female patients (P =.006). Also after the publication of 4S, specialists (cardiologists and internists) had a 2-fold higher rate of increased use of the statins than did generalists (P<.001). CONCLUSION: It is possible to shift practice if the evidence of benefit is strong, the intervention is easy to implement, and the intervention is marketed aggressively.     

Systemic inflammatory markers in acute coronary syndrome: association with cardiovascular risk factors and effect of early lipid lowering

BACKGROUND: Evidence for statin therapy in prevention of coronary artery disease is overwhelming. In spite of theoretical benefits, any additional advantage of its early introduction in the management of acute coronary syndrome is, however, uncertain. We therefore investigated differences between plasma levels of the systemic inflammatory markers intercellular adhesion molecule-1, vascular cell adhesion molecule-1, E-selectin, C-reactive protein and interleukin-6 in patients presenting with unstable angina or acute myocardial infarction, and assessed whether the 30-day levels of these markers are influenced by early instigation of the HMG-CoA reductase inhibitor pravastatin. MATERIALS AND METHODS: 170 (134 male) patients presenting with acute coronary syndrome, but without previous statin therapy, participated. Blood was taken within 24 h of onset of ischaemic pain and again at 30 days. In all, 87 (71 male) participants were treated with pravastatin (20-40 mg daily) and 83 (63 male) with a matched placebo. RESULTS: At presentation, interleukin-6 was higher in males than in females (P=0.008) and lower in those with a pre-existing history of myocardial infarction (P=0.038). C-reactive protein and interleukin-6 were greater in myocardial infarction, but this difference was lost at 30 days. Thirty-day changes in all parameters were inversely related to level at presentation but not to treatment with pravastatin. Hypertension (P=0.011) and smoking (P=0.042) were associated with elevation of C-reactive protein with no difference between unstable angina or acute myocardial infarction. The effect of these individual factors was cumulative. CONCLUSIONS: Interleukin-6 was greater in acute myocardial infarction than in unstable angina; E-selectin was positively associated with a previous myocardial infarction and inversely related to age. We found no effect of early introduction of pravastatin on systemic inflammatory markers 30 days after acute coronary syndrome.