“…However, it is less likely that use of an active run-in would prevent the emergence of genuine side-effects during the later years of such trials. For example, it was the SEARCH randomized trial with an active run-in phase that identified a substantial increase in the risk of myopathy with simvastatin 80mg daily (a regimen recommended for routine care 77 ) compared to simvastatin 20 mg daily (see webtable). 78 For all of these reasons, evidence about side-effects from randomized trials is likely to be far more widely generalizable to routine practice than is often asserted.…”
Section: Generalizability Of Evidence On Side-effects From Randomizedmentioning
General rightsThis document is made available in accordance with publisher policies. Please cite only the published version using the reference above. Full terms of use are available: http://www.bristol.ac.uk/pure/about/ebr-terms
SummaryThis review is intended to help clinicians, patients and the public make informed decisions about statin therapy for the prevention of heart attacks and strokes. It explains how the evidence that is available from randomized controlled trials yields reliable information about both the efficacy and safety of statin therapy. In addition, it discusses how claims that statins commonly cause adverse effects reflect a failure to recognise the limitations of other sources of evidence about the effects of treatment.Large-scale randomized trial evidence shows that statin therapy reduces the risk of heart attacks, ischaemic strokes and coronary revascularization procedures ("major vascular events") by about one quarter for each mmol/L reduction in low density lipoprotein (LDL) cholesterol during each year (after the first) that it continues to be taken. The absolute benefits of statin therapy depend on an individual's absolute risk of occlusive vascular events and the absolute reduction in LDL cholesterol that is achieved. For example, lowering LDL cholesterol by 2 mmol/L (77 mg/dL) with an effective low-cost statin regimen (e.g. atorvastatin 40 mg daily, costing about £2 per
“…However, it is less likely that use of an active run-in would prevent the emergence of genuine side-effects during the later years of such trials. For example, it was the SEARCH randomized trial with an active run-in phase that identified a substantial increase in the risk of myopathy with simvastatin 80mg daily (a regimen recommended for routine care 77 ) compared to simvastatin 20 mg daily (see webtable). 78 For all of these reasons, evidence about side-effects from randomized trials is likely to be far more widely generalizable to routine practice than is often asserted.…”
Section: Generalizability Of Evidence On Side-effects From Randomizedmentioning
General rightsThis document is made available in accordance with publisher policies. Please cite only the published version using the reference above. Full terms of use are available: http://www.bristol.ac.uk/pure/about/ebr-terms
SummaryThis review is intended to help clinicians, patients and the public make informed decisions about statin therapy for the prevention of heart attacks and strokes. It explains how the evidence that is available from randomized controlled trials yields reliable information about both the efficacy and safety of statin therapy. In addition, it discusses how claims that statins commonly cause adverse effects reflect a failure to recognise the limitations of other sources of evidence about the effects of treatment.Large-scale randomized trial evidence shows that statin therapy reduces the risk of heart attacks, ischaemic strokes and coronary revascularization procedures ("major vascular events") by about one quarter for each mmol/L reduction in low density lipoprotein (LDL) cholesterol during each year (after the first) that it continues to be taken. The absolute benefits of statin therapy depend on an individual's absolute risk of occlusive vascular events and the absolute reduction in LDL cholesterol that is achieved. For example, lowering LDL cholesterol by 2 mmol/L (77 mg/dL) with an effective low-cost statin regimen (e.g. atorvastatin 40 mg daily, costing about £2 per
“…Depending on their CVD event history, patients enter the model at the no CVD health state (61.7%), a post-event health state (14.9%), or the ECVD health state (23.4%). Revascularisation is included as a procedure, not as a separate health state, and the costs of revascularisation are included for a proportion of patients in the ECVD, MI, and post-MI health states according to published data [30,31]. Figure 1.Evolocumab economic model structure.CHD, coronary heart disease; CVD, cardiovascular disease; ECVD, established CVD; IS, ischaemic stroke; HF, heart failure; MI, myocardial infarction
…”
Background: An elevated level of low-density lipoprotein cholesterol (LDL-C) constitutes one of the most important modifiable risk factors for cardiovascular disease (CVD). Individuals with heterozygous familial hypercholesterolaemia (HeFH) are particularly vulnerable to CVD events. The addition of evolocumab to statins has shown marked reductions in LDL-C levels. The objective of this analysis is to demonstrate the clinical and economic value of LDL-C lowering with evolocumab from the Bulgarian public health care perspective.
Methods: A disease-specific measure of health benefit was devised: Effectively treated patient-years (ETPYs) combine length of life with the likelihood of attaining best-practice recommendations on LDL-C lowering. “Effective treatment” was defined as a reduction in LDL-C levels of ≥50%. A Markov cohort state-transition model was adapted, considering a life-long treatment duration. Demographics, baseline characteristics and efficacy data were taken from the RUTHERFORD-2 trial. The model uses the relationship between LDL-C lowering and reduced CVD event rates observed in the meta-analyses conducted by the Cholesterol Treatment Trialists’ Collaboration. Outcomes and costs (from year 2015) were discounted at an annual rate of 5%. Sensitivity analyses were conducted to assess uncertainty surrounding the results.
Results: The total incremental costs of evolocumab added to statins versus statins alone are BGN 120,329 while adding 9.30 ETPYs over lifetime. These results imply an incremental cost per ETPY of BGN 12,937 (US$ 7,215; € 6,604). The use of evolocumab is associated with a relative reduction in the CVD event rate by 38% (18% per 1 mmol/L).
Conclusions: Adding evolocumab to statins may be considered cost-effective in light of an additional expense per patient-year gained in which individuals with HeFH receive effective treatment under the terms of international prevention guidelines. ETPYs are an intuitive and clinically meaningful measure of patient benefit that, in relation to costs, can support health care decision-making that considers quality of care.
“…Our finding confirms and extends existing literature demonstrating that some ethnic groups (especially South Asians) are at higher risk of CVD. This is reflected in some [44][45][46] but not all [47,48] guidelines targeting cardiovascular risk; only one currently advises recording of ethnicity but does not recommend different specific treatment or prevention strategies [46]. The QRISK2 risk calculator (www.…”
Aims/hypothesis Potential differences in cardiovascular risk by ethnicity remain uncertain. We evaluated the association of ethnicity with cardiovascular disease (CVD) incidence in a large cohort of people with type 2 diabetes living in Scotland. Methods Data from Scottish Care Information-Diabetes (SCIDiabetes) were linked to Scottish Morbidity Records (SMR01) and National Records of Scotland data for mortality for dates between 2005 and 2011. Of 156,991 people with type 2 diabetes with coded ethnicity, 121,535 (77.4%) had no CVD at baseline (White: 114,461; Multiple Ethnic: 2, 554; Indian: 797; Other Asian: 319; Pakistani: 2,250; Chinese: 387; African-Caribbean: 301 and Other: 466) and were followed up (mean±SD: 4.8±2.3 years) for the development of fatal and non-fatal CVD. Results During follow-up, 16,265 (13.4%) patients developed CVD (ischaemic heart or cerebrovascular diseases). At baseline, Pakistanis were younger and had developed diabetes earlier, had higher HbA 1c and longer duration of diabetes, but had lower BP, BMI, creatinine, proportion of smokers and proportion on antihypertensive therapy than whites. The age and sex adjusted HRs for CVD were HR 1.31 (CI 1.17, 1.47), p<0.001 in Pakistanis and HR 0.66 (CI 0.47, 0.92), p= 0.014 in Chinese compared with whites. Adjusting additionally for an area measure of deprivation, duration of diabetes, conventional CVD and other risk factors, the HR for Pakistanis (HR 1.45 [CI 1.14, 1.85], p=0.002) was significantly higher, and that for Chinese (HR=0.58 [CI 0.24, 1.40], p=0.228) lower, compared with whites. Conclusions/interpretation Compared with whites with type 2 diabetes, those of Pakistani ethnicity in Scotland were at increased risk of CVD, whereas Chinese were at lower risk, with these differences unexplained by known risk factors.Electronic supplementary material The online version of this article (doi:10.1007/s00125-015-3492-0) contains peer-reviewed but unedited supplementary material, which is available to authorised users.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
