Statin Treatment For Secondary Prevention Research Articles

Abstract 18396: Low Rate of LDL-Goal-Attainment in 57,855 High-Risk-Patients in Europe, Canada, South-Africa, Middle East and China - Results of DYSIS

Background: Statin treatment is routinely used for secondary prevention world-wide. Little is known about the prevalence of persistent lipid abnormalities under chronic statin treatment for secondary prevention and possible differences in LDL-Cholesterol (LDL-C) goal attainment in clinical practice between countries in different parts of the world. Methods: Between 2008 and 2012, consecutive statin-treated outpatients were enrolled in 26 countries worldwide, (DYSIS = Dyslipidemia International Study; list of countries in table) to assess LDL-C goal attainment for secondary prevention. European Society of Cardiology recommendations were used to classify patient risk, and to define LDL-cholesterol treatment goals. Data were collected under real life conditions in physicians’ offices and hospital outpatient wards. Results: Serum lipid values of 57,885 consecutive statin-treated outpatients were studied in the context of their cardiovascular risk factors, and the potency and composition of their lipid-lowering treatment. In the very-high risk patients only 21.7% did reach the currently recommended LDL-Chol target <70mg/dl with large differences between the countries varying from 9.2% to 44.3%. In the high-risk population the LDL-Chol target <100mg/dl was achieved in 38.0% oft he patients, varying between 16.6% and 66.7% between countries Conclusion: Despite chronic statin treatment, only 21.7% of the very-high-risk patients reached the current recommended LDL-Chol target <70mg/dl in this large multinational cross-sectional trial, highlighting the persistent large gap between guideline recommendations and clinical practice. Further treatment escalations are necessary to reduce the risk of subsequent cardiovascular events.

Evaluation and treatment of older patients with hypercholesterolemia: a clinical review.

Hypercholesterolemia is common among people older than 80 years. Substantial functional heterogeneity exists among older patients, and decision making for statin use differs in older patients relative to younger ones. To discuss the presentation, modifying factors, and treatment of hypercholesterolemia (usually with statins) among persons older than 80 years. MEDLINE and other sources were searched from January 1990 to June 2014. Personal libraries and a hand search of reference lists from guidelines and reviews from January 2000 to June 2014 were also used. No randomized clinical trials (RCTs) of statin or any other hypocholesterolemic medication included persons older than 80 years at baseline. Findings from 75- to 80-year-old patients enrolled in RCTs and information from observational studies support statin treatment for secondary prevention of atherosclerotic cardiovascular disease (ASCVD) and probably in patients with diabetes without ASCVD. Harms from statin drugs are not increased in older patients, so the use of these agents for primary prevention is possible. Because people older than 80 years are biologically heterogeneous with varying life expectancy, may have frailty or comorbid conditions, and may take multiple medications, the decision to treat with statins must be individualized. Ideally, treatment of hypercholesterolemia for patients at risk of ASCVD should start before they turn 80 years old. No RCT evidence exists to guide statin initiation after age 80 years. Decisions to use statins in older individuals are made individually and are not supported by high-quality evidence.

Early intensive vs. a delayed conservative simvastatin strategy in patients with acute coronary syndromes

Study Question: Phase Z of the A to Z trial was designed to evaluate a strategy of early initiation of intensive treatment with simvastatin (80 mg) in ACS patients compared with a delayed, less intensive strategy. Methods: The study was a randomized, double-blind trial of patients with ACS receiving 40 mg/d of simvastatin for 1 month followed by 80 mg/d thereafter (n=2265) compared with placebo for 4 months followed by 20 mg/d of simvastatin (n=2232). The primary end point was a composite of cardiovascular death, nonfatal MI, readmission for ACS, and stroke. Follow-up was at least 6 months and up to 24 months. Results: Among the patients in the placebo plus simvastatin group, the median low-density lipoprotein (LDL) cholesterol level achieved while taking placebo was 122 mg/dL (3.16 mmol/L) at 1 month and was 77 mg/dL (1.99 mmol/L) at 8 months while taking 20 mg/d of simvastatin. Among the patients in the simvastatin-only group, the median LDL cholesterol level achieved at 1 month while taking 40 mg/d of simvastatin was 68 mg/dL (1.76 mmol/L) and was 63 mg/dL (1.63 mmol/L) at 8 months while taking 80 mg/d of simvastatin. A total of 343 patients (16.7%) in the placebo plus simvastatin group experienced the primary end point compared with 309 (14.4%) in the simvastatin-only group (40 mg/80 mg) (hazard ratio [HR], 0.89; 95% confidence interval [CI] 0.76–1.04; p=0.14). Cardiovascular death occurred in 109 (5.4%) and 83 (4.1%) patients in the two groups (HR, 0.75; 95% CI, 0.57–1.00; p=0.05) but no differences were observed in other individual components of the primary end point. No difference was evident during the first 4 months between the groups for the primary end point (HR, 1.01; 95% CI, 0.83–1.25; p=0.89), but from 4 months through the end of the study the primary end point was significantly reduced in the simvastatin-only group (HR, 0.75; 95% CI, 0.60–0.95; p=0.02). Myopathy (creatine kinase >10 times the upper limit of normal associated with muscle symptoms) occurred in 9 patients (0.4%) receiving simvastatin 80 mg/d, in no patients receiving lower doses of simvastatin, and in 1 patient receiving placebo ( p=0.02). Conclusions: The investigators concluded that the trial did not achieve the prespecified end point of benefit with early high-dose simvastatin therapy. Perspective: Early initiation of an intensive simvastatin regimen when compared with the delayed initiation of a less intensive simvastatin regimen did not show significant clinical benefit. The findings from the MIRACL and PROVE-IT studies, however, demonstrated that aggressive LDL cholesterol lowering following ACS prevents death and major cardiovascular events. The unfavorable risk-benefit relationship observed in the A to Z trial should not diminish the value of intensive statin treatment in secondary prevention, including ACS patients. For now, though, the 80-mg/d dose of simvastatin should be used with caution, particularly because other effective agents are available. DM

Clinical trials of lipid-lowering medication in diabetes

Evidence that patients with type 2 diabetes can benefit from statin therapy is strong. Issues remain to be resolved about whether all patients with type 2 diabetes should receive statin treatment. For the present the National Institute for Clinical Excellence has recommended statin treatment in secondary prevention and in primary prevention when coronary heart disease (CHD) risk exceeds 15% over the next 10 years or lipid levels are high. Fibrates are a better first-line drug therapy when triglycerides exceed 10 mmol/L. Consideration should also be given to combining a fibrate with a statin in patients with CHD whose triglycerides exceed 2.3 mmol/L despite statin treatment, but this requires careful monitoring for myositis. Clinical guidelines are needed for the use of lipid-lowering medication in type 1 diabetes.

Debate: at what level of coronary heart disease risk should a statin be prescribed?

3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are effective treatments for the primary and secondary prevention of coronary heart disease, but an outstanding issue is determining who should have such treatment. The benefit from treatment with statins appears to be proportional to the underlying risk of coronary heart disease and independent of the factors increasing risk. Most benefit will therefore be achieved by treating people at increased risk of coronary heart disease. Statins reduce coronary morbidity even when the risk of coronary heart disease is relatively low (6% over 10 years), but reduction in all-cause mortality, the true measure of safety has been shown only when the risk of a major coronary heart disease event is 15% over 10 years or greater. At this level of risk patients appear willing to take treatment to gain the benefit expected from statin treatment, and the cost effectiveness of statin treatment is within the range accepted for other treatments. The major impediments to the systematic introduction of statin treatment at this level of risk are the very high overall cost and the large workload in countries like Britain, where the population risk of coronary heart disease is high. For this reason, recent British guidelines correctly advise statin treatment for secondary prevention and primary prevention when the 10 year coronary heart disease risk is 30% or greater as the first priority, moving to a lower coronary heart disease threshold for primary prevention only when resources permit.

Implication of recent trials with b-hydroxy-b-methylglutaryl coenzyme A reductase inhibitors for hypertension management.

There is broad agreement that statin treatment should be targeted at absolute coronary heart disease (CHD) risk but no consensus on the level of risk to target. We have examined the implications of adopting three different treatment policies for the management of hypertensive patients in the UK using data from treated hypertensives aged 35-69 years included in the Health Survey for England (1993). We calculated the proportion of hypertensive patients with existing atherosclerotic cardiovascular disease requiring statin treatment for secondary prevention of CHD. For those without atherosclerotic cardiovascular disease (primary prevention), we estimated CHD risk from the Framingham equation and examined the proportion with CHD risk exceeding thresholds of 4.5, 3 and 1.5% per year. Twenty-one percent of treated hypertensives would require statin treatment for secondary prevention of CHD. When the CHD event threshold for statin treatment was set at > or =4.5% per year [equivalent to a number needed to treat (NNT) in 5 years of 13] a further 0.6% of hypertensive patients were identified for treatment; at a threshold of 3.0% per year (NNT = 20) 5.5% of patients were identified for primary prevention; and at a threshold of 1.5% per year (NNT = 40) 28.5% of patients were identified for primary prevention. Those needing secondary prevention are first priority for statins and 21% of hypertensive patients will require treatment Formulation of guidelines for primary prevention should take into account the NNT; the proportion of patients targeted for treatment; the cost-effectiveness and the total cost of treatment. Current British guidance will entail treating an additional 5.5% of hypertensive patients for primary prevention and therefore 27% of hypertensive patients.

Cost effectiveness of HMG-CoA reductase inhibitor (statin) treatment related to the risk of coronary heart disease and cost of drug treatment

OBJECTIVESTo estimate the cost effectiveness of statin treatment in preventing coronary heart disease (CHD) and to examine the effect of the CHD risk level targeted and the cost of statins...