Original Research

How to reach LDL targets quickly in patients with diabetes or metabolic syndrome

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With a simple algorithm developed from the ACTFAST trials, most patients can reach goal safely in 6 to 12 weeks



Practice recommendations
  • You can reduce elevated LDL-C levels in more patients with diabetes and metabolic syndrome using this study's algorithm.
  • Choose a starting dose of a statin according to the gap between baseline and target LDL-C values.
  • Using a tailored starting dose of atorvastatin, most patients with type 2 diabetes or metabolic syndrome can achieve LDL-C target levels safely within 6 to 12 weeks, without raising the initial dose or with a single titration step.

Purpose To investigate whether using an algorithm to select the starting dose of a statin according to baseline and target LDL-cholesterol (LDL-C) values would facilitate achieving lipid targets in patients with diabetes or the metabolic syndrome.

Methods Two 12-week, prospective, open-label trials enrolled 2717 high-risk subjects, of whom 1024 had diabetes and 1251 had metabolic syndrome. Subjects with LDL-C between 100 and 220 mg/dL (2.6-5.7 mmol/L) were assigned a starting dose of atorvastatin (10, 20, 40, or 80 mg/d) based on LDL-C level and status of statin use at baseline (statin-free [SF] or statin-treated [ST]), with a single uptitration at 6 weeks, if required.

Results Among patients with diabetes, 81% of SF subjects (82%, 84%, 82%, and 76% with 10, 20, 40, and 80 mg, respectively) and 60% of ST subjects (61%, 68%, and 47% with 20, 40, and 80 mg, respectively) achieved LDL-C target. Among patients with metabolic syndrome, 78% of SF subjects (81%, 84%, 82%, and 66% with 10, 20, 40, and 80 mg, respectively) and 57% of ST subjects (58%, 70%, and 47% with 20, 40, and 80 mg, respectively) achieved LDL-C target. Among ST subjects, we observed reductions in LDL-C with atorvastatin beyond those achieved with other statins used at baseline in patients with diabetes and patients with metabolic syndrome. Atorvastatin was well tolerated.

Conclusions The ACTFAST studies confirm that a targeted starting dose of atorvastatin allows most patients with type 2 diabetes or the metabolic syndrome to achieve their LDL-C target safely with the initial dose or just a single titration. This therapeutic strategy may help overcome the treatment gap still observed in the treatment of lipids in diabetes.

How many of your patients with type 2 diabetes or metabolic syndrome have a low-density lipoprotein cholesterol (LDL-C) level below the target of 100 mg/dL? Your answer, undoubtedly, is not enough of them. The good news we report in this article is that you can safely achieve the target more often, within 6 to 12 weeks, using a simple algorithm that helps you determine the optimal starting dose of a statin.

Good reason for concern. Individuals with coronary heart disease (CHD) or CHD risk equivalents such as diabetes have the highest cardiovascular risk and, according to the National Cholesterol Education Program (NCEP) III and other guidelines, must aim for the lowest target levels of LDL-C.1 As the number of cardiovascular risk factors increases in a population, the percentage of patients reaching targets decreases2,3 —to as low as 37% among those at highest risk.2 The international Analysis and Understanding of Diabetes and Dyslipidaemia: Improving Treatment (AUDIT) survey found that out of all patients with type 2 diabetes being treated, only 54% achieved target.4

Type 2 diabetes purportedly imparts a cardiovascular risk comparable to that of a prior cardiovascular event.1,5-7 Moreover, the outcome of such events in patients with diabetes is worse than in patients without diabetes, with approximately 7 out of 10 patients dying from the event or its complications.7-9

The metabolic syndrome (MetSyn) also increases risk of cardiovascular events and mortality, even in individuals without diabetes or CHD.10-13 In 1 study, the risks of all-cause and cardiovascular mortality in patients with MetSyn were 1.38 to 1.44 and 2.26 to 2.78, respectively, compared with those who did not have MetSyn.12

The algorithm we describe in this article was developed from results of the Achieve Cholesterol Targets Fast with Atorvastatin Stratified Titration (ACTFAST) trials. These trials were designed to assess whether, according to the degree of reduction required in LDL-C, an optimal starting dose of atorvastatin could be identified so that patients would achieve LDL-C targets quickly, with no change in the dose or with just one titration step, and regardless of statin use at baseline.

The main results of ACTFAST 1 and 2 have been published elsewhere.14,15 We report specifically on a prespecified analysis of pooled results in the subset of patients with diabetes or MetSyn.


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