Pitavastatin - from clinical trials to clinical practice

Managing dyslipidaemia is central to the management of cardiovascular disease. Most statins can reduce the 5-year incidence of major vascular events by 20%. In Europe, however, up to 53% of statin-treated patients fail to attain their low-density lipoprotein-cholesterol (LDL-C) target and residual risk remains high, even when targets are reached. Reasons for this include under-treatment due to insufficient starting doses/failure to uptitrate; poor persistence with therapy due to adverse events (AEs) or drug-drug interactions (DDIs); and failure to treat non-LDL-C risk factors, such as high triglycerides (TGs) and low high-density lipoprotein-C (HDL-C). Phase III and IV studies demonstrate that pitavastatin 1-4 mg has a similar or greater lipid-lowering efficacy to atorvastatin 10-20 mg, simvastatin 20-40 mg and pravastatin 10-40 mg, and is well-tolerated with a low incidence of adverse events (AEs). The SmPC recommends a usual starting dose of 1 mg, with dose-escalation if required. However, since the lower doses (1-2 mg) bring the majority of people with hypercholesterolaemia or combined dyslipidaemia to LDL-C target, the need for pitavastatin uptitration and the risk of under-treatment is low. In addition to reducing LDL-C, pitavastatin has a sustained beneficial effect on other atherogenic lipids, including TGs and HDL-C. Recent studies reveal that pitavastatin reduces coronary atheroma plaque volume as efficiently as atorvastatin and can improve the composition of coronary plaques, effects that are likely to reduce the risk of CV endpoints in patients with acute coronary syndrome. Moreover, pitavastatin has a number of pleiotropic effects that can reduce inflammation and lipid oxidation, improve endothelial function, reduce the metabolic changes associated with adiposity, and improve glucose metabolism and renal function. Compared to other statins, pitavastatin has a unique metabolic profile that could reduce the risk of DDIs, thereby providing a clear benefit in patients receiving polypharmacy. Overall, pitavastatin is a well tolerated and effective treatment for patients with hypercholesterolaemia and combined dyslipidaemia, especially in those with low HDL-C, and it should help improve LDL-C-target attainment rates by reducing the risk of under-treatment, minimising AE rates, and reducing the risk of DDIs in people requiring polypharmacy. Future and ongoing studies will directly compare the effects of pitavastatin vs. other statins on hard clinical endpoints.     

Issues in extrapolating from clinical trials to clinical practice and outcomes

Extrapolation of clinical trial results to clinical practice requires consideration of whether the trial patients were representative of clinical practice, whether the trial therapy studied was optimal, whether the sample size was adequate, and the impact of adjunctive treatments.
In thrombolytic trials in particular, regional variations in attitudes to coronary angiography may have affected outcomes. Clinical trial results need to be interpreted in the light of the cost effectiveness of the application.
The assessment of clinical outcomes depends on interplay between the structure and process of care, patient factors and chance. Large standardised databases are necessary to assess clinical practice and outcomes.     

Goal-oriented hypertension management: translating clinical trials to practice

Several clinical trials using a blood pressure (BP) treatment algorithm focused on a predetermined goal have achieved better control rates than those of national survey data. These trials reached the Sixth Joint National Committee on the Prevention, Detection, Evaluation and Treatment of High Blood Pressure (JNC VI) diastolic blood pressure (DBP) goal of <90 mm Hg in >90% of volunteers and systolic blood pressure (SBP) goal of <140 mm Hg in >60% of volunteers. We evaluated BP control of 437 consecutive patients after at least one year of follow up in a specialist clinic which employed "goal-oriented management," ie, treating to a specific BP goal without a formal drug treatment algorithm, to determine whether JNC VI goals could be achieved. Overall, 276 (63%) patients achieved SBP goal, with 376 (86%) at DBP goal and 358 (59%) at both goals. Only 23% of patients were on monotherapy, with 34% requiring 2 drugs and 37% requiring 3 or more medications. There was no substantial difference in BP control rates among age, gender, and ethnicity subgroups. However, in the 20% of patients who were diabetic, only 52% had a BP of <140 mm Hg and <90 mm Hg, whereas fewer (22% and 15%, respectively) achieved the more stringent goals of JNC VI and the American Diabetic Association (ADA)/National Kidney Foundation (NKF). Goal-oriented management achieved dramatically better control rates than what is reported. Although DBP control was easy to achieve, achieving SBP goal still remained difficult. Employing goal-oriented management can translate BP control results achieved in clinical trials into outpatient practice.     

肺癌免疫检查点抑制剂治疗:从临床研究到临床实践

肺癌是全球范围内发生率和死亡率最高的恶性肿瘤.近年来,免疫检查点抑制剂在非小细胞肺癌和小细胞肺癌的治疗中均有突破,改变了肺癌治疗策略的格局,也改善了患者的生存结局.本文对免疫检查点抑制剂在肺癌治疗中的使用时机、疗效、安全性和适用人群进行探讨.     

Use of patient-reported outcomes in heart failure: from clinical trials to routine practice

Heart failure (HF) is a complex syndrome that affects mortality/morbidity and acts at different levels in the patient's life, resulting in a drastic impairment in multiple aspects of daily activities (e.g. physical, mental/emotional, and social) and leading to a reduction in quality of life. The definition of disease status and symptom severity has been traditionally based on the physician assessment, while the patient's experience of disease has been long overlooked. The active participation of patients in their own care is necessary to better understand the perception of disease and the multiple aspects of life affected, and to improve adherence to treatments. Patient-reported outcomes (PROs) aim to switch traditional care to a more patient-centred approach. Although PROs demonstrated precision in the evaluation of disease status and have a good association with prognosis in several randomized controlled trials, their implementation into clinical practice is limited. This review discusses the modalities of use of PROs in HF, summarizes the most largely adopted PROs in HF care, and provides an overview on the application of PROs in trials and the potential for their transition to clinical practice. By discussing the advantages and the disadvantages of their use, the reasons limiting their application in daily clinical routine, and the strategies that may promote their implementation, this review aims to foster the systematic integration of the patient's standpoint in HF care.     

Ezetimibe: from pharmacology to clinical trials

LDL-cholesterol (LDL-C) is a key factor in primary and secondary prevention of coronary heart disease. Statins have become a mainstay in the first-line treatment of hypercholestorelomia. Nevertheless, in clinical practice, there is a major gap between treatment guidelines and real life treatment patterns. It is not uncommon that statins lack sufficient efficacy in the most severe cases of dyslipidemia, even when the highest doses are used. Therapy combining statins with other cholesterol-lowering agents is often used, although it may be poorly tolerated. These limitations have directed research towards new mechanisms of action, additive to those of statins which inhibit the hepatic biosynthesis of cholesterol. Ezetimibe is the first once-daily potent and selective inhibitor of cholesterol absorption which has been shown to reduce the overall delivery to the liver, with a subsequent reduction of serum LDL-C. As monotherapy, mean decrease in LDL-C with ezetimibe was 19.1% versus placebo, whereas in addition to ongoing statin therapy, there was a 21.8% incremental reduction of LDL-C (p<0.001) and a 11.1% of triglycerides (p<0.001) with an increase of HDL-C of about 1.7% (p<0.05). Phase III factorial co-administration studies with various statins at increasing dosages have shown a mean supplementary decrease of LDL-C (-12.1 to -13.8%) and triglycerides (-7.4 to -10.5%) and raising HDL-C (+1.4 to 4.5%) (versus pooled statins). Co-administration of ezetimibe (10 mg once a day) with a statin permits a degree of LDL-C lowering similar to that achieved with the highest doses of statins. The efficacy of ezetimibe has also been demonstrated in familial homozygous hypercholesterolemia and sistosterolemia. In both monotherapy and combination studies, clinical and biological safety of ezetimibe was good.     

Monitoring disease activity of rheumatoid arthritis in clinical practice: contributions from clinical trials

Rheumatoid arthritis is a heterogeneous and progressive autoimmune disease, and patients with this condition show varied responses to treatment. Practical, reliable, individually tailored measures of disease activity and treatment responses are needed. Outcome measures used in randomized, controlled trials, including American College of Rheumatology response criteria and Disease Activity Scores, identify when treatment should be initiated or changed, but can be time consuming and impractical in daily practice. Simplified disease activity indices, abbreviated joint counts and patient-report questionnaires are more-convenient ways to assess therapeutic responses in the clinic. Patient-reported measures of physical function, pain and global disease activity best differentiate the results of active treatment from those of placebo treatment in randomized, controlled trials. Improvements in physical function closely reflect changes in health-related quality of life. Recent trials have demonstrated limited correlations between clinical responses and radiographically demonstrated responses; both should be assessed on a regular basis. It is recommended that three domains be assessed in the clinic for therapeutic responses: patient-reported measures of physical function and/or global disease activity; physician assessment of disease activity; and imaging of the hands and/or feet on a biannual basis. Problematic joints and cervical spine involvement should be followed as clinically indicated. Measures of improvement for individually relevant physical activities need to be defined for each patient.     

Treatment of chronic hepatitis C in HIV-infected patients: from clinical trials to field practice

In a prospective cohort of 87 HIV coinfected patients with chronic hepatitis C, 63% had been treated for HCV, with global success rate (47%, 95% CI 34-61) close to or higher than that reported in therapeutic trials. These results argue for earlier, more frequent and improved HCV treatment in HIV-infected patients.     

最新临床研究带给心源性脑栓塞预防的启示

缺血性卒中（ischemic stroke,IS）是病因和发病机制高度异质性的一组疾病。从1996年TOAST分型到2009年的ASCO分型,均将心源性脑栓塞（cardiac embolism,CE）作为一个单独的疾病,而不使用“脑栓塞”这一诊断名称。因为动脉粥样硬化导致的动脉一动脉栓塞,实质上属于动脉粥样硬化性脑梗死。大量循证医学证据汪实,CE的抗栓预防措施有别于非心源性卒中,     

Translation of clinical trials into clinical practice

The results of well-conducted clinical trials should be translated into practice but there is good evidence that this is not happening. There are a number of reasons for this - ignorance of doctors and patients, uncertainty as to the applicability of trials to individual patients, indolence and inefficiency on the part of practitioners, and financial considerations. More attention needs to be paid to correct all these factors.     

Reconciling subject differences in recruitment to clinical trials and clinical practice

The special interest group on Reconciling Subject Differences was centered around the issue that the results from randomized clinical trials do not predict response to therapies in clinical practice, and around the hypothesis that this might be explained by differences in subjects selected for clinical trials compared to those treated in routine practice.