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Statins Associated With Lower All-Cause Mortality, Even in Primary Prevention

Mar 3, 2009

Primary- and secondary-prevention patients who consistently take their statin medication have a significantly lower risk of death than those who do not adhere to therapy, a new study has shown [1]. Individuals who took their medication at least 90% of the time had a 45% reduction in the risk of all-cause mortality, compared with less adherent patients, report investigators.

Dr. Varda Shalev (Tel Aviv University, Israel) writes,  “The observed benefits from statins were greater than expected from randomized clinical trials, emphasizing the importance of promoting statin therapy and increasing its continuation over time for both primary and secondary prevention.”


The study, a retrospective analysis of 229,918 individuals enrolled in a health-maintenance organization, evaluated the effect of statin therapy in patients with and without preexisting coronary heart disease (CHD). As the authors point out, the benefits of statin therapy are well documented, but the effect of lipid-lowering therapy on all-cause mortality in a primary-prevention cohort is more controversial. A 2007 opinion article by Drs John Abramson (Harvard Medical School, Boston, MA) and Jim Wright (University of British Columbia, Vancouver), published in The Lancet [2], at that time, argued that the bulk of the evidence did not support statin therapy for primary prevention in women or in people over age 65.

In this most recent analysis, investigators evaluated the mortality benefit of primary prevention in 136,052 patients without a history of heart disease followed for an average of four years. The secondary-prevention cohort consisted of 93,866 patients followed for an average of five years. Adherence to statin therapy was measured by the number of dispensed statin prescriptions during the interval between the first prescription and the end of follow-up.

In the primary- and secondary-prevention cohorts, continuously taking statins, defined as taking the drugs 90% of the time during the follow-up period, was associated with 45% and 51% reductions, respectively, in the risk of death, compared with individuals who took the medication less than 10% of the time. The reduction in risk was more pronounced among individuals with high baseline low-density lipoprotein-cholesterol (LDL-C) levels and those receiving intensive lipid-lowering therapy.

Proportion of Days Covered With Statins and All-Cause Mortality

Proportion of days covered with statin therapy during study period, %

Hazard ratio (95% CI), primary-prevention cohort

Hazard ratio (95% CI), secondary-prevention cohort


1 (reference)

1 (reference)


1.35 (1.22 – 1.50)

1.28 (1.18 – 1.39)


0.77 (0.67 – 0.88)

0.69 (0.63 – 0.76)


0.55 (0.49 – 0.61)

0.49 (0.46 – 0.53)

Shalev and colleagues write, “Our findings confirm that the benefits of statins extend to unselected patients in community settings…. Higher continuity of treatment and increased drug efficacy are associated with better survival among both primary-prevention and secondary-prevention cohorts.”

The group notes that the benefits observed in this study are much larger than mortality benefits observed in clinical trials, in which only a modest reduction in all-cause mortality or no reduction at all is noted. Studies in unselected patient populations, such as this observational study, might “better capture the overall benefits of statins that may result from their anti-inflammatory, antithrombotic, or antiapoptotic effects, as well as from their action on nitric-oxide synthase,” they suggest.

Practice Pearls

  • Better continuity of statin treatment was associated with an ongoing reduction in cardiovascular mortality in patients without any evidence of coronary heart disease. In this primary prevention cohort, risk reduction was stronger for patients aged 55 to 64 years.
  • Better continuity of statin treatment was also associated with an ongoing reduction in cardiovascular mortality in patients with a known history of coronary heart disease. In this secondary prevention group, there was greater reduction in mortality associated with younger age at baseline.


  • Shalev V, Chodick G, Silber H, et al. Continuation of statin treatment and all-cause mortality. Feb. 9, 2009, Arch Intern Med 2009; 169:260-268.

Abramson J, Wright J. Are lipid-lowering guidelines evidence-based? The Lancet 2007; 369:168-169.