Showing papers on "Heart Protection Study published in 2007"

Atorvastatin Efficacy in the Prevention of Cardiovascular Events in Patients with Diabetes Mellitus and/or Metabolic Syndrome

Abstract: Several large-scale clinical trials have assessed the efficacy of atorvastatin in the primary and secondary prevention of cardiovascular events in patients with diabetes mellitus and/or metabolic syndrome. In primary prevention, CARDS (Collaborative Atorvastatin Diabetes Study) showed that atorvastatin 10 mg/day (vs placebo) reduced relative risk of the composite primary endpoint (acute coronary heart disease [CHD] events, coronary revascularisation, or stroke) by 37% (p = 0.001). This decrease was similar to decreases in major cardiovascular events in the ASCOT-LLA (Anglo-Scandinavian Cardiac Outcomes Trial-Lipid Lowering Arm) trial and HPS (Heart Protection Study). However, in CARDS, atorvastatin efficacy was evident as early as 6 months after starting treatment, whereas in HPS, simvastatin efficacy was noticeable only from about 15–18 months after starting treatment. In the ASCOT-LLA trial, in 2226 hypertensive diabetic patients without previous cardiovascular disease, atorvastatin (vs placebo) reduced the relative risk of all cardiovascular events and procedures by 25% (p = 0.038). In secondary prevention, substudies of the GREACE (GREek Atorvastatin and Coronary-heart-disease Evaluation), TNT (Treating to New Targets) and PROVE-IT (PRavastatin Or atorVastatin Evaluation and Infection Therapy) trials reported results for the approximately 15–25% of study participants who had diabetes. In the GREACE substudy, atorvastatin (vs physicians’ standard care) significantly reduced the relative risk of total mortality by 52% (p = 0.049), coronary mortality by 62% (p = 0.042), coronary morbidity by 59% (p < 0.002) and stroke by 68% (p = 0.046). In the TNT substudy, incidence of the primary endpoint was significantly lower in diabetic patients treated with atorvastatin 80 mg/day rather than 10 mg/day (13.8% vs 17.9%; relative risk 0.75; p = 0.026). In the PROVE-IT substudy, a significantly lower incidence of acute cardiac events was reported for atorvastatin versus pravastatin recipients (21.1% vs 26.6%; p = 0.03) and, therefore, an absolute risk reduction of 5.5% was associated with atorvastatin therapy. ASPEN (Atorvastatin Study for Prevention of coronary heart disease Endpoints in Non-insulin-dependent diabetes mellitus) — a mixed primary and secondary prevention trial in diabetic patients — found that a 29% lower low-density lipoprotein-cholesterol level was seen with atorvastatin than placebo at endpoint (p < 0.0001); however, the reduction in composite primary endpoint of major cardiovascular events (cardiovascular mortality, nonfatal major cardiovascular event or stroke, and unstable angina requiring hospitalisation) with atorvastatin (13.7% vs 15.0% with placebo), and reduction in acute myocardial infarction relative risk of 27% with atorvastatin were not statistically significant. In CHD patients with metabolic syndrome (n = 5584) in a sub-analysis of the TNT trial, intensive versus lower-dosage atorvastatin therapy reduced the relative risk of major cardiovascular and cerebrovascular events by 29% (p < 0.0001). The analysis also revealed that CHD patients with, rather than those without, metabolic syndrome had a 44% greater level of absolute cardiovascular risk, thus clearly underscoring the clinical feasibility of administering intensive lipid-lowering therapy to CHD patients with metabolic syndrome. In summary, several patient populations, from definitive, large-scale studies, are now available to corroborate the integral place of atorvastatin — in line with various regional and internationally accepted disease management guidelines — in the primary and secondary prevention of cardiovascular events in patients with diabetes and/or metabolic syndrome.

Beyond Lipid Lowering: The Anti-Hypertensive Role of Statins

Abstract: Introduction The management of the hypercholesterolemic patient has evolved tremendously with the introduction of the HMG-CoA Reductase inhibitors, a class of drugs better known as the statins. Statins modify cholesterol metabolism by inhibiting the rate-limiting enzyme of cholesterol biosynthesis, producing greater decreases in plasma cholesterol levels than previously realized with hypolipidemic therapy. With the advent of the classic statin-megatrials such as the Scandinavian Simvastatin Survival Study (4S), WOSCOPS, CARE, and the more recent Heart Protection Study (HPS), the role of statins in both the primary and secondary prevention and ultimate risk reduction of patients with coronary disease has been firmly established.

Atorvastatin: its clinical role in cerebrovascular prevention.

Abstract: An association between hypercholesterolaemia and ischaemic stroke has not yet been clearly defined by observational studies. In clinical trials, however, cholesterol-lowering treatments appear to consistently reduce stroke risk. Data are now available from various primary prevention studies - ALLHAT-LLT (Antihypertensive and Lipid-Lowering treatment to prevent Heart Attack, Lipid-Lowering Therapy), ASCOT-LLA (Anglo-Scandinavian Cardiac Outcomes Trial, Lipid-Lowering Arm), CARDS (Collaborative Atorvastatin Diabetes Study, WOSCOPS (West of Scotland COronary Prevention Study) - and secondary prevention studies - 4S (Scandinavian Simvastatin Survival Study), CARE (Cholesterol and Recurrent Events), GREACE (GREek Atorvastatin and Coronary-heart-disease Evaluation), HPS (Heart Protection Study), LIPID (Long-term Intervention with Pravastatin in Ischaemic Disease), MIRACL (Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering), SPARCL (Stroke Prevention by Aggressive Reduction in Cholesterol Levels), TNT (Treating to New Targets) - confirming the ability of statins to reduce stroke risk. Regarding primary prevention, post hoc analyses showed pravastatin reduced the relative risk of stroke by 9-11% (not statistically significant) in the ALLHAT-LLT and WOSCOPS trials, whereas atorvastatin reduced this risk by 27-48% in the ASCOT-LLA (p = 0.024) and CARDS trials. It remains to be established in prospective studies whether cholesterol-lowering is effective in the primary prevention of stroke. Regarding secondary prevention, in five placebo-controlled studies (4S, CARE, HPS, LIPID, MIRACL) involving a total of >40 000 patients with coronary heart disease (CHD), statin therapy reduced the relative risk of fatal or nonfatal stroke by 19-50% (p < or = 0.048); the largest decrease was produced by atorvastatin in the MIRACL study (-50%, p = 0.045). In addition, high-dosage atorvastatin reduced stroke risk by 25% (p = 0.02) relative to lower-dosage therapy in the TNT trial, and by 47% (p = 0.034) relative to 'usual' care in the GREACE study. A post hoc analysis of data for 3280 HPS study participants who had had a previous stroke revealed that simvastatin reduced major vascular events by 20% (p = 0.001).The SPARCL study assessed the secondary preventive efficacy of atorvastatin versus placebo in 4731 patients with a history of stroke or transient ischaemic attack (TIA), but without CHD. Atorvastatin reduced the adjusted relative risk of fatal or nonfatal stroke by 16% (p = 0.03), and that of fatal stroke alone by 43% (p = 0.03). Among secondary study endpoints, atorvastatin reduced the relative risks of stroke and TIA (-23%; p < 0.001), TIA alone (-26%; p = 0.004), and ischaemic stroke (-22%; p = 0.01). Overall, SPARCL study findings suggest that intensive atorvastatin therapy should be started immediately after a stroke or TIA. In summary, atorvastatin has developed a well defined role in the primary and secondary prevention of cerebrovascular disease, and appears to have a particularly prominent place in preventing such disease in CHD patients, and in the post-stroke and post-TIA setting in patients without CHD.

Intensive statin therapy after stroke or transient ischemic attack: a SPARCLing success?

Abstract: Anyone aware of the conflicting data regarding the importance of circulating cholesterol in stroke will welcome the results of the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial.1 Unlike with coronary heart disease, epidemiological studies often failed to demonstrate an association between elevated cholesterol levels and stroke incidence.2 However, many studies did not take into account the distinct underlying pathophysiological mechanisms of stroke and instead examined conflated end points such as a combination of ischemic and hemorrhagic stroke, or total ischemic stroke without subtyping, and others did not evaluate cholesterol subfractions. In contrast, epidemiological studies that carefully distinguished ischemic and hemorrhagic strokes generally found both a modest association of elevated cholesterol with increased risk of ischemic events and of low cholesterol with an increased risk of intracerebral hemorrhage.3 HMG-CoA reductase inhibitors or “statins,” which inhibit the synthesis of cholesterol that contributes to atheroma development and progression, have been shown to reduce the risk of first stroke in patients with established coronary heart disease, diabetes, or multiple cardiovascular risk factors.4 Indeed, as our cardiology colleagues kept finding the benefit of lower and lower cholesterol targets for reducing the risk of coronary heart disease events,5 the jury remained out as to what role, if any, that statins played in stroke patients without established coronary heart disease. Subset analyses of prior clinical trials had suggested, but not definitely proved, a benefit of statin therapy in patients with prior strokes. A retrospective subset analysis of 3280 subjects with a remote (mean 4.3 years) history of symptomatic ischemic cerebrovascular disease enrolled in the Heart Protection Study (HPS) showed that simvastatin therapy yield a 20% reduction in major vascular events (0.80, 0.71 to 0.92).6 This benefit was driven by a reduction in myocardial infarction and vascular death end …

Lipid goals in metabolic syndrome and diabetes

Abstract: There is considerable disparity between the major clinical guidelines on lipid targets in diabetes and metabolic syndrome. Over the past few years, several trials have reported results that contribute to the evidence base for such lipid targets. The Treat to New Targets study data provide support for the efficacy and safety of using high-dose statin therapy for reducing low-density lipoprotein cholesterol (LDL-C) to at least 2 mmol/L in patients with diabetes and established cardiovascular disease (CVD). The Collaborative Atorvastatin Diabetes Study and the Heart Protection Study provide support for the efficacy and safety of lowering LDL-C to at least 2 mmol/L with lower doses of statins. Once these LDL-C targets have been reached, it is unknown whether targeting high-density lipoprotein cholesterol (HDL-C) and triglycerides is more efficacious than further lowering of LDL-C. The optimal treatment strategy, therefore, is unclear. Trials are underway to resolve this question. Patients with metabolic syndrome derive similar relative reduction in CVD from statin therapy as those without, and the appropriate treatment and targets depend on the estimated CVD risk. Prediction of CVD risk with currently available risk scores is imperfect but there is little evidence that including metabolic syndrome improves risk prediction beyond Framingham Risk Score mainly because the latter already includes blood pressure and HDL-C.

Statin Therapy for Secondary Stroke Prevention: Evidence Catches Up to Practice:

Abstract: Current approaches for the secondary prevention of ischemic stroke include the aggressive use of antithrombotic therapy, particularly antiplatelet agents, and carotid endarterectomy for eligible patients. Blood pressure lowering with angiotensin converting enzyme inhibitors and diuretics in hypertensives, glucose control to a hemoglobin A1C of less than 7% in diabetics, and statin therapy in patients with hyperlipidemia and/or cardiovascular disease are also important measures forsecondary prevention of stroke. Support for the routine use of statin therapy in all patients with ischemic stroke, regardless of lipid profile or a history of cardiovascular disease, has been, until recently, of debate. Clinical evidence found in studies such as the SPARCL trial and the Heart Protection Study now support the routine use of statin therapy in all ischemic stroke patients. This article focuses on the potential and proven benefits of statins in ischemic stroke.

Lowering Low-Density Lipoprotein Cholesterol Levels to Reduce Atherosclerotic Coronary Heart Disease Risk

Abstract: Dyslipidemia is an important risk factor for the development of atherosclerotic coronary artery disease (CHD). Clinical trial evidence supports that improving dyslipidemia reduces the progression of atherosclerosis, reduces CHD events, reduces CHD morbidity, and reduces CHD mortality, and several CHD outcome studies have demonstrated that therapies directed toward improvement in dyslipidemia significantly reduces overall mortality—due to reductions in CHD deaths (1). Various lipid-altering drugs are available for the treatment of dyslipidemia (Table 1). Examples of agents that predominantly lower low-density lipoprotein cholesterol (LDL-C) levels include 3-hydroxy-3-methyl-glutaryl coenzyme A reductase inhibitors (“statins”), cholesterol absorption inhibitors [(such as ezetimibe (EZE)] and bile acid binding agents/sequestrants (such as polymers and resins), as well as combination LDL-C lowering drugs such as the combination pill of EZE and statin.

Lipids and Peripheral Arterial Disease

Abstract: Peripheral arterial disease (PAD) is associated with a high risk of vascular events [1, 2, 14, 18, 19, 31, 32]. This is true whether PAD is symptomatic or asymptomatic.This risk is so high that PAD is considered as a coronary heart disease (CHD) equivalent [5, 13]. It follows that these patients need to have their modifiable vascular risk fac- tors controlled. Dyslipidaemia, a modifiable vascular risk factor, should be treated aggressively with lipid-lowering drugs, according to international guidelines [5, 13, 16, 37]. The earlier low density lipoprotein-cholesterol (LDL-C) targets {European LDL-C target <96 mg/dl (2.5 mmol/l)

Statins Possibly More Cost-Effective Than Initially Thought

Abstract: In the large, partly industry-funded placebo-controlled Heart Protection Study, simvastatin was shown to be both clinically beneficial and

Prevention of Cardiovascular Risk in Diabetic Patients - An Update

Abstract: Patients with type 2 diabetes have a well-documented increased risk of cardiovascular disease (CVD) that is more than two to three times higher than the risk seen in non-diabetic subjects.1 In spite of modern methods to treat diabetes and its complications, the increased risk is still substantial even if data on risk factor controls in national surveys have shown improving trends for blood pressure and lipid control, for example from Sweden.2 The most important CVD risk factors to detect, treat and make follow-up visits for are elevated blood-pressure levels, dyslipidaemia and elevated low-density lipoprotein (LDL) cholesterol, as well as hyperglycaemia and smoking. In addition, chronic inflammation, defects in fibrinolytic function and adverse psychosocial conditions could all contribute to this risk, besides the impact of background factors that it is not possible to change such as age, gender and diabetes duration. For a number of years data have been accumulating on treatment benefits of risk-factor control based on reports from large-scale clinical trials involving patients with type 1 diabetes ‐ i.e. Diabetes Control and Complications Trial (DCCT) ‐ or type 2 diabetes ‐ i.e. UK Prospective Diabetes Study (UKPDS), Heart Protection Study (HPS), Reduction of Endpoints in NIDDM [non-insulin-dependent diabetes mellitus] with the Angiotensin II Antagonist Losartan (RENAAL), Irbesartan Diabetic Nephropathy Trial (IDNT), Collaborative Atorvastatin Diabetes Study (CARDS), Losartan Intervention For Endpoint Reduction in Hypertension (LIFE) and Anglo‐Scandinavian Cardiac Outcomes Trial (ASCOT). Therefore, we have so far had strong support for some, but not all, of the goals for risk factor control stated in contemporary guidelines for treatment of patients with diabetes, from both the joint American Diabetes Association (ADA) and American Heart Association (AHA) guidelines3 and the corresponding joint European Society of Cardiology (ESC) and European Association for the Study of Diabetes (EASD) guidelines.4 For example, the recommended goal of blood-pressure control in patients with diabetes and hypertension (<130/80mmHg)3,4 was not based on solid evidence from intervention studies, but from observational studies, most notably from the observational arm of UKPDS where a linear association between systolic blood pressure and risk of coronary artery disease (CAD) was noticed.5