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CLINICAL RESEARCH: LIPID REDUCTION THERAPY

Statins, Low-Density Lipoprotein Cholesterol, and Risk of Cancer

Alawi A. Alsheikh-Ali, MD^_*,, Thomas A. Trikalinos, MD^_*, David M. Kent, MD, MS^_* and Richard H. Karas, MD, PhD^,_*

^_* Institute for Clinical Research and Health Policy Studies, Tufts Medical Center and Tufts University School of Medicine, Boston, Massachusetts
Molecular Cardiology Research Institute and Division of Cardiology, Department of Medicine, Tufts Medical Center and Tufts University School of Medicine, Boston, Massachusetts

Manuscript received March 4, 2008; revised manuscript received May 27, 2008, accepted June 6, 2008.

^_* Reprint requests and correspondence: Dr. Richard H. Karas, Molecular Cardiology Research Institute, Box # 80, Tufts Medical Center, 800 Washington Street, Boston, Massachusetts 02111 (Email: rkaras{at}tuftsmedicalcenter.org).

Objectives: We sought to assess whether statin-mediated reductions in low-density lipoprotein cholesterol (LDL-C) are associated with an increased risk of cancer.

Background: We recently reported an inverse association between on-treatment LDL-C levels and incident cancer in statin-treated patients enrolled in large randomized controlled trials, raising concern that LDL-C lowering by statins may increase cancer risk. However, meta-analyses suggest a neutral overall effect of statins on incident cancer.

Methods: A systematic literature search identified 15 eligible randomized controlled trials of statins with 1,000 person-years of follow-up that provided on-treatment LDL-C levels and rates of incident cancers (19 statin and 14 control arms, 437,017 person-years cumulative follow-up, and 5,752 incident cancers).

Results: In the statin arms, meta-regression analysis demonstrated an inverse association between on-treatment LDL-C and incident cancer, with an excess of 2.2 (95% confidence interval: 0.7 to 3.6) cancers per 1,000 person-years for every 10 mg/dl decrement in on-treatment LDL-C (p = 0.006). The corresponding difference among control arms was 1.2 (95% confidence interval: –0.2 to 2.7, p = 0.09). Compared with the control arms, the statin regression line was significantly shifted leftward, such that similar rates of incident cancer were associated with lower on-treatment LDL-C (p < 0.05). Meta-regression demonstrated that statins lack an effect on cancer risk across all levels of on-treatment LDL-C.

Conclusions: There is an inverse association between on-treatment LDL-C and incident cancer. However, statins, despite producing marked reductions in LDL-C, are not associated with an increased risk of cancer.

Key Words: cholesterol • cancer • lipids • risk

Abbreviations and Acronyms   CI = confidence interval   IRR = incidence rate ratio   LDL-C = low-density lipoprotein cholesterol   RCT = randomized controlled trial

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