Effect of Lower Targets for Blood Pressure and LDL Cholesterol on Atherosclerosis in Diabetes

Howard, Barbara V.; Roman, Mary J.; Devereux, Richard B.; Fleg, Jerome L.; Galloway, James M.; Henderson, Jeffrey A.; Howard, Wm. James; Lee, Elisa T.; Méte, Mihriye; Poolaw, Bryce; Ratner, Robert E.; Russell, Marie; Silverman, Angela; Stylianou, Mario; Umans, Jason G.; Wang, Wenyu; Weir, Matthew R.; Weissman, Neil J.; Wilson, Charlton; Yeh, Fawn; Zhu, Jianhui

doi:10.1001/jama.299.14.1678

Cited by 221 publications

(88 citation statements)

References 75 publications

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“…Among these 59 surrogate endpoint trials that had a subsequent clinical endpoint trial, in 24 cases the clinical endpoint trial results validated the positive surrogate trials, while in 20 the subsequent clinical endpoint trial was negative (Table 3). 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50 A negative surrogate endpoint trial was less likely to be followed by a positive outcome trial and we identified only 3 such examples ( P =0.02, Figure 2). …”

Section: Resultsmentioning

confidence: 99%

Two Decades of Cardiovascular Trials With Primary Surrogate Endpoints: 1990–2011

Bikdeli

Punnanithinont

Akram

et al. 2017

JAHA

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BackgroundSurrogate endpoint trials test strategies more efficiently but are accompanied by uncertainty about the relationship between changes in surrogate markers and clinical outcomes.Methods and ResultsWe identified cardiovascular trials with primary surrogate endpoints published in the New England Journal of Medicine, Lancet, and JAMA: Journal of the American Medical Association from 1990 to 2011 and determined the trends in publication of surrogate endpoint trials and the success of the trials in meeting their primary endpoints. We tracked for publication of clinical outcome trials on the interventions tested in surrogate trials. We screened 3016 articles and identified 220 surrogate endpoint trials. From the total of 220 surrogate trials, 157 (71.4%) were positive for their primary endpoint. Only 59 (26.8%) surrogate trials had a subsequent clinical outcomes trial. Among these 59 trials, 24 outcomes trial results validated the positive surrogates, whereas 20 subsequent outcome trials were negative following positive results on a surrogate. We identified only 3 examples in which the surrogate trial was negative but a subsequent outcomes trial was conducted and showed benefit. Findings were consistent in a sample cohort of 383 screened articles inclusive of 37 surrogate endpoint trials from 6 other high‐impact journals.ConclusionsAlthough cardiovascular surrogate outcomes trials frequently show superiority of the tested intervention, they are infrequently followed by a prominent outcomes trial. When there was a high‐profile clinical outcomes study, nearly half of the positive surrogate trials were not validated. Cardiovascular surrogate outcome trials may be more appropriate for excluding benefit from the patient perspective than for identifying it.

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Section: Resultsmentioning

confidence: 99%

Two Decades of Cardiovascular Trials With Primary Surrogate Endpoints: 1990–2011

Bikdeli

Punnanithinont

Akram

et al. 2017

JAHA

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“…Native American men and women (n=499) with type 2 diabetes and LDL-C>100 mg/dL, systolic blood pressure >130 mm Hg, and no prior cardiovascular events were randomized to aggressive-treatment or standard-treatment groups [21]. The LDL-C goal in the aggressive-treatment group was < 70 mg/dL and the goal in the standard treatment group was <100 mg/dL.…”

Section: Statins Plus Ezetimibe Combinationsmentioning

confidence: 99%

What Combination Therapy with a Statin, If Any, Would You Recommend?

Dujovne

Williams

Ito

2010

Curr Atheroscler Rep

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The latest recommended goals for blood lipid levels may require multiple lipid drugs. Lower doses in combination may render more efficacy and safety than highest doses of single agents. Except for isolated hypoalphalipoproteinemia (a low level of high-density lipoprotein cholesterol), therapies will start with a statin. All marketed statins are acceptable. The choice may be based on dose- efficacy and patient's tolerability. High-potency statins (eg, atorvastatin, simvastatin, or rosuvastatin) are often chosen. Currently, generic statins, such as simvastatin, lovastatin, pravastatin, and fluvastatin, offer cost benefits. The choice of added agent depends on the "residual lipoprotein abnormalities" after statin therapy, efficacy, compliance issues, and cost. Approved "combined" preparations improve cost and compliance. To further lower low-density lipoprotein cholesterol, ezetimibe is a safe, efficacious choice, pending resolution of a controversial trial's results. Colesevelam is moderately effective and the best tolerated bile acids sequestrant. In combined dyslipidemias, extended-release niacin is the best tolerated niacin preparation; other quality-controlled immediate-release preparations have similar safety and efficacy but produce more flushing of the skin. Niacin or fenofibrate is effective in normalizing high-density lipoprotein and triglyceride levels persisting after statin therapy. Agents approved by the US Food and Drug Administration and the latest guidelines of the National Cholesterol Education Program, American Heart Association/American College of Cardiology provide choices and indications of drug combinations.

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“…However, since patients with both diabetes and peripheral vascular disease are a high-risk group for cardiovascular events, and since regression of carotid intimal medial thickness was observed with aggressive targets of LDL (Յ 70 mg/dl) and systolic blood pressure (Յ 115 mmHg) in the SANDS study (28), levels of LDL should be aimed at 70 mg/dl or lower (6). This is also the target for patients with previous history of cardiovascular disease (secondary prevention).…”

Section: Dyslipidemiamentioning

confidence: 99%

Diabetes and Peripheral Vascular Disease

Mathieu

2009

Acta Chirurgica Belgica

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The risk of peripheral vascular disease (PVD) is increased in diabetic patients, occurs earlier and is often more severe and diffuse. Endothelial dysfunction, vascular smooth muscle cell dysfunction, inflammation and hypercoagubility are the key factors in diabetic arteriopathy. The presence of PVD, apart from its increased risk of claudication, ischemic ulcers, gangrene and possible amputation, is also a marker for generalized atherosclerosis and a strong predictor for cardiovascular ischemic events. However, despite the recognition that PVD is associated with increased ischemic event rates and death, particularly in diabetic patients, this specific manifestation of systemic atherosclerosis is largely underdiagnosed and undertreated. In type-1 diabetes, early intensive insulin treatment reduces both microvascular (nephropathy, retinopathy and neuropathy) and macrovascular complications of diabetes (DCCT/EDIC study). In type-2 diabetes, UKPDS showed that tight glucose control reduces micro- and macrovascular complications, when therapy is started early after diagnosis and that early intervention has long lasting protective effects. However recently published trials (ADVANCE, ACCORD and VADT) pointed out that lowering glycemic targets to nearly normal glycaemia does not further reduce cardiovascular events in individuals with longstanding type 2 diabetes and that hypoglycaemia is to be avoided in individuals with ischemic heart disease. Finally, the small but important Steno-2 trial demonstrated that to significantly reduce peripheral vascular disease, ischemic events and mortality in type-2 diabetes, intensified multifactorial treatment of all modifiable risk factors is needed. Therefore, to prevent micro- and macrovascular complications, like PVD, in type-1 and type-2 diabetes, intensive therapy, targeting glycemia and all other modifiable cardiovascular risk factors, should be initiated as soon after diagnosis as possible and maintained in a safe way throughout life.

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Effect of Lower Targets for Blood Pressure and LDL Cholesterol on Atherosclerosis in Diabetes

Cited by 221 publications

References 75 publications

Two Decades of Cardiovascular Trials With Primary Surrogate Endpoints: 1990–2011

Two Decades of Cardiovascular Trials With Primary Surrogate Endpoints: 1990–2011

What Combination Therapy with a Statin, If Any, Would You Recommend?

Diabetes and Peripheral Vascular Disease

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