STATINS FOR PRIMARY PREVENTION

July 3, 2009 (Rotterdam, The Netherlands) — Use of statins is associated with significantly improved survival and large reductions in the risk of major cardiovascular events in patients who have risk factors but who do not have established cardiovascular disease, according to a new meta-analysis of major statin trials published online June 30 in BMJ [1].

It shows that the relative risk reduction from long-term statin use in a primary-care setting is comparable to that observed in secondary prevention and confirms the results of the JUPITER study regarding the beneficial effects of statins across a range of patient groups, say the researchers.

"Our data suggest that people without established CVD should not be denied the relative benefits of long-term statin use," lead author Dr Jasper J Brugts (Thoraxcenter, Rotterdam, the Netherlands) told heartwire .

"However, the exact threshold for cost-effectiveness of such treatment should be investigated further and probably depends on the [individual] level of risk for cardiovascular disease due to specific combinations of risk factors," he added.

Statins Cut Deaths by 12%, Coronary Events by 30%, CV Events by 19%

Brugts said it is well-established that statins are effective in the setting of secondary prevention (ie, in patients with cardiovascular disease), "but whether the benefits apply to primary prevention is unknown, and previous research has provided ambiguous answers on statin use in people at relatively lower risk." In addition, there is debate about the efficacy of statins in certain subgroups, such as people aged over 65, women, and those with diabetes mellitus, he explained.

He and his colleagues combed the Cochrane controlled trials register, Embase, and Medline for studies on the clinical effects of statins compared with a placebo or control group and with follow-up of at least one year that also had at least 80% or more participants without established CVD and outcome data on mortality and major CVD events. They identified 10 trials including a total of 70 388 people, of whom 34% were women and 23% had diabetes mellitus. Mean follow-up was 4.1 years.

The trials included were: WOSCOPS, AFCAPS/TexCAPS, PROSPER, ALLHAT-LLT, ASCOT-LLA, HPS, CARDS, ASPEN, MEGA, and JUPITER.

The results are in line with those previously published on the effects of statins in secondary prevention, but the researchers note they were also able to include several recently published studies targeted at primary prevention that enrolled large numbers of women and diabetics and from which they were able to obtain data on clinically defined subgroups by contacting the principal investigators of each trial.

Overall, treatment with statins significantly reduced the risk of all-cause mortality (odds ratio 0.88), major coronary events (OR 0.70), and major cerebrovascular events (OR 0.81). "We demonstrated in 70 388 subjects without established cardiovascular disease but with risk factors that statin use improves survival and reduces the risk of major cardiovascular and cerebrovascular events," Brugt commented.

And the researchers saw the same effects of statins regardless of age, gender, or diabetic status. "It is reassuring that no significant treatment heterogeneity was found between the sexes, in elderly and young people, and between people with and without diabetes," they observe.

Cancer Numbers Reassuring But Not Unequivocal

Also important, says Brugts, "No increased risk of cancer was observed," something that has been of concern previously, sparked by an increased risk of cancer seen with use of statins in those aged over 70 in PROSPER. Follow-up of patients in WOSCOPS for 10 years, for example, did not show higher rates of malignancies.

But he and his colleagues caution, "Although our results show that statins do not seem to increase the risk of cancer, longer follow-up would be helpful to determine whether new cancer events could occur with time. This is especially critical when statins are used in primary prevention," they note.

And concerns might remain about the higher risk of cancer in elderly patients (70–82 years), as in PROSPER, "and further follow-up studies in such patients are required. Although this meta-analysis cannot fully remove that uncertainty, it confirms that the risk of cancer is not increased in middle-aged patients," they observe.

Cost/Benefits Must Be Weighed, As Ever

In conclusion, the authors say that despite their positive findings, the absolute overall treatment benefit in the current study population "would certainly be less than 1%, and significant numbers of participants would need to be treated to prevent one event."

It is not possible from these data to exactly define one group of people who would benefit most from statin use, and the correct identification of such people "remains a challenge," they add.

However, they also state "it is obvious that older men (>65 years) with risk factors or older women with diabetes and risk factors constitute the highest-risk group . . . [and] it is likely that a considerable number of such people would benefit from long-term statin use at reasonable costs."