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Aggressive Treatment of High LDL Levels and Hypertension in Patients with Diabetes

Three-year results from SANDS supply much-needed information but no definitive answer to the question of how low to set targets in primary prevention of CVD.

Controversy continues about how low to set target LDL and blood pressure levels for primary prevention of cardiovascular disease. The Stop Atherosclerosis in Native Diabetics Study (SANDS) addresses this issue in high-risk patients with type 2 diabetes and no history of CVD events. Investigators compared 3-year progression of subclinical atherosclerosis in 499 American Indian patients aged 40 years who were randomized either to aggressive treatment goals (70 mg/dL for LDL and 115 mm Hg for systolic blood pressure) or to standard-care goals (100 mg/dL for LDL and 130 mm Hg for SBP). The protocol algorithm for LDL reduction relied primarily on statins; the algorithm for blood-pressure reduction relied on ACE inhibitors or angiotensin-receptor blockers, with diuretics added if necessary. The primary endpoint was change in common carotid artery intima–media thickness (IMT). Secondary endpoints included changes in echocardiographic measures and clinical events.

Mean target LDL and SBP measures were achieved in both groups (LDL, 72 mg/dL and 104 mg/dL; SBP, 117 mm Hg and 129 mm Hg in the aggressive-treatment and standard-care groups, respectively); however, fewer than half the patients in the aggressive-treatment group achieved their goals at >75% of follow-up visits. Carotid artery IMT decreased from baseline in the aggressive-treatment group and increased in the standard-care group (P<0.001). Greater reductions in LV mass were achieved in the aggressive-treatment group than in the standard-care group, but at the expense of polypharmacy and increased adverse effects. Although the number of clinical events did not differ significantly between the two groups, the study was not adequately powered to detect such differences.

Comment: In this well-conducted study of American Indians with type 2 diabetes, aggressive LDL and systolic blood pressure reductions improved the surrogate endpoints of carotid artery intima–media thickness and LV hypertrophy, but the effects of such reductions on hard clinical endpoints remain to be determined. By contrast, no such reduction in IMT occurred with aggressive primary-prevention targets for LDL in the ENHANCE trial (Journal Watch Cardiology Mar 30 2008), although ezetimibe was the primary intervention drug in ENHANCE, and the patient populations in the two studies differed considerably at baseline in terms of assessed risk, IMT, and history of statin use. These findings do not answer the question of just how low to set primary prevention targets, but they do underscore the difficulty of achieving aggressive goals even in the idealized setting of a well-funded clinical trial. For now, clinicians should continue to adhere to current guidelines for primary prevention in diabetic patients, choosing statins as first-line therapy for LDL reduction.

— JoAnne M. Foody, MD

Published in Journal Watch Cardiology April 8, 2008

Citation(s):

Howard BV et al. Effect of lower targets for blood pressure and LDL cholesterol on atherosclerosis in diabetes: The SANDS randomized trial. JAMA 2008 Apr 9; 299:1678.

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