, Volume 67, Supplement 1, pp 43–54 | Cite as

Atorvastatin Efficacy in the Prevention of Cardiovascular Events in Patients with Diabetes Mellitus and/or Metabolic Syndrome

  • Marcello Area
Review Article


Several large-scale clinical trials have assessed the efficacy of atorvastatin in the primary and secondary prevention of cardiovascular events in patients with diabetes mellitus and/or metabolic syndrome. In primary prevention, CARDS (Collaborative Atorvastatin Diabetes Study) showed that atorvastatin 10 mg/day (vs placebo) reduced relative risk of the composite primary endpoint (acute coronary heart disease [CHD] events, coronary revascularisation, or stroke) by 37% (p = 0.001). This decrease was similar to decreases in major cardiovascular events in the ASCOT-LLA (Anglo-Scandinavian Cardiac Outcomes Trial-Lipid Lowering Arm) trial and HPS (Heart Protection Study). However, in CARDS, atorvastatin efficacy was evident as early as 6 months after starting treatment, whereas in HPS, simvastatin efficacy was noticeable only from about 15–18 months after starting treatment. In the ASCOT-LLA trial, in 2226 hypertensive diabetic patients without previous cardiovascular disease, atorvastatin (vs placebo) reduced the relative risk of all cardiovascular events and procedures by 25% (p = 0.038).

In secondary prevention, substudies of the GREACE (GREek Atorvastatin and Coronary-heart-disease Evaluation), TNT (Treating to New Targets) and PROVE-IT (PRavastatin Or atorVastatin Evaluation and Infection Therapy) trials reported results for the approximately 15–25% of study participants who had diabetes. In the GREACE substudy, atorvastatin (vs physicians’ standard care) significantly reduced the relative risk of total mortality by 52% (p = 0.049), coronary mortality by 62% (p = 0.042), coronary morbidity by 59% (p < 0.002) and stroke by 68% (p = 0.046). In the TNT substudy, incidence of the primary endpoint was significantly lower in diabetic patients treated with atorvastatin 80 mg/day rather than 10 mg/day (13.8% vs 17.9%; relative risk 0.75; p = 0.026). In the PROVE-IT substudy, a significantly lower incidence of acute cardiac events was reported for atorvastatin versus pravastatin recipients (21.1% vs 26.6%; p = 0.03) and, therefore, an absolute risk reduction of 5.5% was associated with atorvastatin therapy.

ASPEN (Atorvastatin Study for Prevention of coronary heart disease Endpoints in Non-insulin-dependent diabetes mellitus) — a mixed primary and secondary prevention trial in diabetic patients — found that a 29% lower low-density lipoprotein-cholesterol level was seen with atorvastatin than placebo at endpoint (p < 0.0001); however, the reduction in composite primary endpoint of major cardiovascular events (cardiovascular mortality, nonfatal major cardiovascular event or stroke, and unstable angina requiring hospitalisation) with atorvastatin (13.7% vs 15.0% with placebo), and reduction in acute myocardial infarction relative risk of 27% with atorvastatin were not statistically significant.

In CHD patients with metabolic syndrome (n = 5584) in a sub-analysis of the TNT trial, intensive versus lower-dosage atorvastatin therapy reduced the relative risk of major cardiovascular and cerebrovascular events by 29% (p < 0.0001). The analysis also revealed that CHD patients with, rather than those without, metabolic syndrome had a 44% greater level of absolute cardiovascular risk, thus clearly underscoring the clinical feasibility of administering intensive lipid-lowering therapy to CHD patients with metabolic syndrome.

In summary, several patient populations, from definitive, large-scale studies, are now available to corroborate the integral place of atorvastatin — in line with various regional and internationally accepted disease management guidelines — in the primary and secondary prevention of cardiovascular events in patients with diabetes and/or metabolic syndrome.


Atorvastatin Coronary Heart Disease Patient Major Cardiovascular Event Composite Primary Endpoint Secondary Prevention Study 
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The preparation of this manuscript has been sponsored by Pfizer Italia, who proposed the initial idea of the review. Prof. Marcello Arca has the responsibility of reported data as well as of their interpretation. The sponsor had no role in the approval of the manuscript. Prof. Marcello Arca served as a consultant and/or received speaker honoraria from Merck Sharp & Dhome, Astra Zeneca, Simesa, Sanofi Aventis, Pfizer, Guidotti and Neopharmed. The author wishes to thank Dr Michelangelo Barone from the Medical Department of Pfizer Italia for his technical support in collecting part of the material used for this paper. Editorial support for the preparation of the manuscript was provided by Wolters Kluwer Health Medical Communications.


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© Adis Data Information BV 2007

Authors and Affiliations

  1. 1.Department of Clinical and Therapeutic MedicineLa Sapienza University of Rome, Policlinico Umberto IRomeItaly

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