STATINS FOR THE PRIMARY PREVENTION OF CARDIOVASCULAR DISEASE (original) (raw)
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Statins in the prevention of cardiovascular disease
2002
This article deals with the harmful effects of stopping treatment with statins on the cardiovascular progress of patients who need it. These statins are very effective cholesterol-lowering agents that are tolerated very well. Pravastatin and simvastatin competitively inhibit the enzyme that controls the cellular synthesis of cholesterol which brings about a drop in the intra-cellular cholesterol an increase in the cellular surface LDL receptors and a decrease in cholesterolemia. However these effects are reversible if the treatment is interrupted. Several clinical studies on cardiovascular prevention have revealed certain clarifications relating to good tolerance of statins and their therapeutic benefits namely primary prevention such as WOSCOPS which is the first study including 6595 men aged 45 to 64 with an average concentration of initial LDL cholesterol of 1.92 g/l and were randomly divided into two groups receiving 40 m per day of pravastatin or placebo. The result shows that ...
The Lancet, 2005
Background Results of previous randomised trials have shown that interventions that lower LDL cholesterol concentrations can significantly reduce the incidence of coronary heart disease (CHD) and other major vascular events in a wide range of individuals. But each separate trial has limited power to assess particular outcomes or particular categories of participant. Methods A prospective meta-analysis of data from 90 056 individuals in 14 randomised trials of statins was done. Weighted estimates were obtained of effects on different clinical outcomes per 1•0 mmol/L reduction in LDL cholesterol. Findings During a mean of 5 years, there were 8186 deaths, 14 348 individuals had major vascular events, and 5103 developed cancer. Mean LDL cholesterol differences at 1 year ranged from 0•35 mmol/L to 1•77 mmol/L (mean 1•09) in these trials. There was a 12% proportional reduction in all-cause mortality per mmol/L reduction in LDL cholesterol (rate ratio [RR] 0•88, 95% CI 0•84-0•91; pϽ0•0001). This reflected a 19% reduction in coronary mortality (0•81, 0•76-0•85; pϽ0•0001), and non-significant reductions in non-coronary vascular mortality (0•93, 0•83-1•03; p=0•2) and non-vascular mortality (0•95, 0•90-1•01; p=0•1). There were corresponding reductions in myocardial infarction or coronary death (0•77, 0•74-0•80; pϽ0•0001), in the need for coronary revascularisation (0•76, 0•73-0•80; pϽ0•0001), in fatal or non-fatal stroke (0•83, 0•78-0•88; pϽ0•0001), and, combining these, of 21% in any such major vascular event (0•79, 0•77-0•81; pϽ0•0001). The proportional reduction in major vascular events differed significantly (pϽ0•0001) according to the absolute reduction in LDL cholesterol achieved, but not otherwise. These benefits were significant within the first year, but were greater in subsequent years. Taking all years together, the overall reduction of about one fifth per mmol/L LDL cholesterol reduction translated into 48 (95% CI 39-57) fewer participants having major vascular events per 1000 among those with pre-existing CHD at baseline, compared with 25 (19-31) per 1000 among participants with no such history. There was no evidence that statins increased the incidence of cancer overall (1•00, 0•95-1•06; p=0•9) or at any particular site. Interpretation Statin therapy can safely reduce the 5-year incidence of major coronary events, coronary revascularisation, and stroke by about one fifth per mmol/L reduction in LDL cholesterol, largely irrespective of the initial lipid profile or other presenting characteristics. The absolute benefit relates chiefly to an individual's absolute risk of such events and to the absolute reduction in LDL cholesterol achieved. These findings reinforce the need to consider prolonged statin treatment with substantial LDL cholesterol reductions in all patients at high risk of any type of major vascular event. Control (45 002
Reducing morbidity and mortality in high risk patients with statins
Vascular Health and Risk Management, 2009
Residual coronary heart disease remains a significant problem even after adequate statin therapy for cardiovascular risk reduction as currently recommended by the Adult Treatment Panel III (ATP-III) of the National Cholesterol Education Program (NCEP). This is particularly true for the high risk patients as defined by ATP-III that includes those patients who have a greater than 20% 10-year risk of adverse cardiac events. For such patients the current goal of a low-density lipoprotein cholesterol (LDL-cholesterol) maintenance level of 100 mg/dL plasma appears to be suboptimal. Accumulating data from several recent randomized studies of more aggressive LDL-cholesterol reduction to levels below 70 mg/dL in the high risk patients favor acceptance of such a new lower target for LDL-cholesterol using more intensive statin therapy which would affect the treatment strategy for patients with coronary heart disease prepercutaneous intervention, metabolic syndrome, diabetes mellitus, congestive heart failure, cerebro-vascular disease and chronic kidney disease.
The statin studies: from targeting hypercholesterolaemia to targeting the high-risk patient
QJM: An International Journal of Medicine, 2005
The landmark HMG-CoA reductase inhibitor (statin) studies have practical lessons for clinicans. The 4S trial established the importance of treating the hypercholesterolaemic patient with cardiovascular heart disease. Next, WOSCOPS showed the benefit of treating healthy, high-risk hypercholesterolaemic men. CARE, a secondary prevention trial, showed the benefit of treating patients with cholesterol levels within normal limits. This was confirmed by the LIPID trial, another secondary prevention study, which enrolled patients with cholesterol levels 155-271 mg/dl (4-7 mmol/l). The importance of treating patients with established ischaemic heart disease, and those at high risk of developing heart disease, regardless of cholesterol level, was being realized. In the MIRACL trial, hypocholesterolaemic therapy was useful in the setting of an acute coronary syndrome, while the AVERT study showed that aggressive statin therapy is as good as angioplasty in reducing ischaemic events in patients with stable angina. By showing the value of fluvastatin after percutaneous intervention, LIPS confirmed that benefit is a class action of the statins. The HPS randomized over 20 000 patients, and showed beyond doubt the value of statins in reducing cardiovascular events in the high-risk patient. Although PROSPER showed benefit in treating the elderly patients above 70 years, statin therapy in this trial was associated with an increase in cancer incidence. The comparative statin trials, PROVE-IT, REVERSAL, Phase Z of the A to Z, ALLIANCE and TNT, all showed that highdose statins will better reduce cardiovascular events in the high-risk patient, although the adverse effects of therapy will also be increased. ALLHAT-LLT, ASCOT-LLA and CARDS showed that for statin therapy to demonstrate a significant benefit, hypertensive or diabetic patients must be at sufficiently high risk of cardiovascular events. The emphasis is now on the risk level for developing cardiovascular events, and treatment should target the high-risk group and not the lipid level of the patient. No therapy is free of adverse effect. Treatment of those most at risk will bring the most benefit; treatment of those not at high risk of cardiovascular disease may expose patients who would not benefit much from therapy to its adverse effects.
Efficacy, effectiveness and real life goal attainment of statins in managing cardiovascular risk
Vascular Health and Risk Management, 2009
Statins became available for the treatment of hypercholesterolemia in 1987. Multiple, well-designed, placebo-controlled, double-blind studies revealed that each 1% reduction in serum cholesterol level was associated with about 1% reduction in risk of cardiovascular events. Low-density lipoprotein (LDL) cholesterol reduction to less than 78 mg/dL may be associated with reduction of atheroma burden. Patients with high levels of high specifi city C-reactive protein and having LDL cholesterol less than 3.4 mmol/L (130 mg/dL) in primary prevention settings benefi ted from aggressive LDL cholesterol reduction with rosuvastatin over a 2-year period. However, in real life practice, about half of patients who are prescribed statins discontinue the medication by the end of the year. Medication adherence is lower in younger patients, women, and absence of known coronary heart disease. Personal features of the prescribing physician and dispensing pharmacies also affect patients' compliance. More studies are needed to evaluate if "compliance packets" would benefi t patients in a real life situation.
Clinical relevance of statins: their role in secondary prevention
Atherosclerosis Supplements, 2001
Five large randomized clinical trials show the benefits of lipid lowering with statins on cardiac morbidity and mortality. Three of these were secondary-prevention trials -the Long-term Intervention with Pravastatin in Ischemic Disease (LIPID) study, Cholesterol and Recurrent Events (CARE), and Scandinavian Simvastatin Survival Study (4S). The CARE and LIPID studies, performed with pravastatin, comprise populations that are representative of the majority of patients with coronary disease in that they included subjects with 'average' cholesterol levels. The 4S study, using simvastatin, comprised a patient population with elevated lipid levels. Pooled data from three trials, CARE, LIPID, and the West of Scotland Coronary Prevention Study (WOSCOPS), were examined in the Pravastatin Pooling Project (PPP). Individual patient data from these three event trials were pooled into a single database, permitting subgroup analyses and providing increased power. In the PPP, pravastatin-treated patients had significantly lower all-cause mortality (7.9, vs. 9.8% in those receiving placebo, a relative risk reduction of 20%). Pravastatin treatment was associated with a significant 24% reduction in CHD mortality and a nonsignificant difference in other vascular deaths (17%) and noncardiovascular deaths (12%). However, the reductions in absolute risk were much larger in those with a history of coronary heart disease than in those without. In the combined analysis of CARE and LIPID, there was also a uniform relative risk reduction in both men and women. In high-risk groups such as diabetics, smokers, hypertensives, and the elderly, there were also significant risk reductions in clinical end points. Finally, in the 598 participants, who had a stroke (90% of which were non-fatal), CARE and LIPID individually demonstrated reductions in non-fatal and total stroke. These data confirm that benefits of treatment in secondary prevention of coronary heart disease encompasses prevention of stroke as well as coronary heart disease events. The benefits are found in those who have had unstable angina as well as myocardial infarction. These findings strengthen even further the case for much more widespread use of statins in secondary prevention.
Preventing chronic …, 2005
IntroductionTherapy with 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, or statins, has proven to be effective in the treatment of lipid disorders. However, statin therapy continues to be underused, even though statins are a relatively safe and well-tolerated class of agents. In this study, we assessed trends in lipid control in patients with heart disease who receive most of their health care in primary care clinics. The objective was to determine whether systems of care implemented within a large medical group are associated with improved treatment and control of dyslipidemia in a high-risk group of coronary heart disease patients.MethodsAll adults with heart disease in a Minnesota medical group (N = 2947) were identified using diagnosis and procedure codes related to coronary heart disease (sensitivity = 0.85; positive predictive value = 0.89) in 1996. Study subjects were observed from 1995 to 1998. Subjects had a baseline and follow-up test for low-density lipoprotein cholesterol and high-density lipoprotein cholesterol. Changes between baseline and follow-up measurements and trends in the use of statins and other lipid-active agents among the study subjects were analyzed.ResultsAmong 1388 subjects with two or more eligible lipid measurements, mean low-density lipoprotein cholesterol improved from 137.6 mg/dL to 111.0 mg/dL (P < .001), and mean high-density lipoprotein cholesterol improved from 42.3 mg/dL to 46.3 mg/dL (P < .001). The percentage of patients with low-density lipoprotein cholesterol ≤100 mg/dL rose from 12.5% to 39.8% (P < .001), and the percentage with high-density lipoprotein cholesterol ≥40 mg/dL rose from 52.5% to 67.6% (P < .001). In multivariate models, statin use was identified as the main factor that contributed to the improvement in low-density lipoprotein cholesterol (P < .001). Men had greater decreases in low-density lipoprotein cholesterol than women after adjusting for other variables (P < .001). Statin use rose from 24.3% at baseline to 69.6% at follow-up. The statin discontinuation rate was 8.3% for baseline statin users and 12.2% for subjects who used statins at any time during the study period.ConclusionInvestment in better heart disease care for patients in primary care clinics led to major improvement in lipid control over 30 months, primarily due to increased statin use. Improvements in low-density lipoprotein cholesterol and high-density lipoprotein cholesterol were sufficient to substantially reduce risk of subsequent major cardiovascular events.
Statins: Can we advocate them for primary prevention of heart disease?
Medical Journal Armed Forces India, 2013
The discovery of cholesterol-lowering agents, namely HMG-CoA reductase inhibitors or statins, ushered in a series of large cholesterol reduction trials. The first of these studies was the Scandinavian Simvastatin Survival Study (4S) in which hypercholesterolemic men with CHD who were treated with simvastatin had a reduction in major coronary events of 44% and a reduction in total mortality of 30%. Many more secondary prevention trials followed to establish unequivocally the benefit of cholesterol reduction. Strategies that aim to improve primary prevention are important for managing the overall burden of disease.
Statins and cardiovascular diseases: the multiple effects of lipid-lowering therapy by statins
Atherosclerosis, 2000
Cholesterol lowering involving different therapies improves the clinical outcome of patients. To define the underlying pathomechanism, we studied whether treatment with statins was associated with changes in blood thrombogenicity, endothelial dysfunction and soluble adhesion molecule levels. Fifty hypercholesterolemic patients were treated with pravastatin (40 mg/day, n= 24) or simvastatin (20 mg/day, n=26). Lipid profile and blood thrombogenicity were assessed in all patients before and after 3 months of cholesterol reducing therapy. Blood thrombogenicity was assessed as thrombus formation, perfusing non-anticoagulated blood directly from the patients' vein through the Badimon perfusion chamber (shear rate 1690/s). Endothelial-dependent vasomotor response was tested by laser-Doppler flowmeter. Soluble adhesion molecule level were measured by ELISA. Total and LDL cholesterol were reduced in the two treatment groups by statin therapy. Statin therapy was associated with a significant reduction in blood thrombogenicity and endothelium-dependent vasoresponse. No differences were observed between simvastatin or pravastatin treatment. Lipid lowering by statins had no effect on plasma levels of fibrinogen, sL-selectin, sP-selectin and sICAM-1 antigen. Cholesterol lowering by both statins reduced the increased blood reactivity and endothelial dysfunction present under hypercholesterolemia. The multiple effects of lipid lowering therapy by statins may explain the benefits observed in recent epidemiological trials.