By: Dr. Geoffrey Modest
There was a recent article looking at statins and fibrates in the primary prevention of vascular events in elderly patients. I will also add to this review a meta-analysis of statin use as primary prevention in the elderly.
- A French cohort study reviewed a random sample of patients comparing those on lipid-lowering drugs(LLDs) vs not to assess the incidence of vascular disease (see doi.org/10.1136/bmj.h2335). This 3-city study was designed as a prospective ongoing population based cohort study designed to look at the association between vascular diseases and the risk of dementia. details:
–7484 community-living men and women (63% women, mean age 73.9 and no known vascular events) followed 9.1 years.
–Of the 27.4% on LLDs, 13.5% were on statins (38% of them were on simvastatin and 23% on pravastatin) and 13.8% were on fibrates (73% on fenofibrate). There were some demographic differences: those on LLDs were younger, more likely to be women, and had higher vascular risk (blood pressure, BMI, diabetes, cholesterol). Comparing those on fibrates vs statins in those taking LLDs: fibrate users were older, had lower diastolic BP, and were less likely to be on antithrombotic agents.
–Results:
–those on LLDs had a decreased risk of stroke [HR 0.66 (0.49-0.90)]. There was no difference between –those on LLDs did NOT have a decreased risk of coronary heart disease [HR 1.12 (0.90-1.40)]
- A meta-analysis of 8 trials looked at statins in the elderly without known cardiovascular disease (see J Am Coll Cardiol 2013;62:2090–9). details:
–8 very high-quality trials with 24,674 patients (42.7% female, mean age 73), had a mean follow-up of 3.5 years
–results:
–statins were associated with 20% decrease in total cholesterol (232 mg/dl to 185 mg/dl), LDL decreased 31% (from 145 to 100 mg/dl), HDL was 50 mg/dl without change, triglycerides decreased 14% from 147 mg/dl to 126 mg/dl
–statins were associated with reduced risk of MI by 39% [RR 0.606 (0.434-0.847), p=0.003], from 3.9% placebo to 2.7% with statins over 3.5 years; NNT 24 for one year to prevent one MI
–statins were associated with reduced risk of stroke by 24% [RR 0.762 (0.626-0.926), p=0.006], from 2.8% to 2.1% over 3.5 years; NNT 42 for one year to prevent one stroke
— these numbers translate to: each 1 mmol/l (39 mg/dl) decrease in LDL is associated with a 57.1% MI risk reduction and a 34.5% stroke reduction
–statins were not associated with reduced all-cause mortality [RR 0.941 (0.856-1.035)], or cardiovascular deaths [RR 0.907 (0.686-1.119)]
–no difference in new cancer onset with statins vs placebo
So, these studies bring up a few issues:
–the first study was observational, so it is hard to assess accurately the role of statins and fibrates. The lack of association with cardiovascular outcomes is quite surprising, as is the equivalent efficacy of statins and fibrate (especially since the data on fenofibrate from the FIELD study and several others suggest overall that fenofibrate has much less efficacy than gemfibrozil, which also pales in comparison to statins). Not sure what to make of their results. It turns out that elderly French people do succumb to cardiovascular disease (in 2010, those >85 yo accounted for 43% of deaths from CAD and 49% of deaths from stroke), despite the “French paradox”.
–the second study was quite impressive and confirms/extends the primary prevention data on statins into the elderly. We know that elderly, even without known vascular disease, are still more likely to die from a vascular cause than any other problem. We also know that although the relative risk reduction is pretty similar in primary and secondary prevention trials (around 30% for all of the studies), the actual event rate (absolute risk) is so much higher in those with known atherosclerotic vascular disease as well in the elderly (>2/3 of those >65yo have cardiovascular events) that the similar relative risk reduction with statins translates to a much higher absolute risk reduction/protection. The Framingham Study found that of those free of coronary artery disease at age 70, 35% of men and 24% of women still had a lifetime risk of CAD. By the way, this brings up another reason why I disagreed with the recent AHA guidelines. They reinforce treading softly in the elderly and only using moderate intensity statins, commenting that in general only moderate intensity statins be used over age 75, with more intense statins only on an individualized basis. My continuing approach to treat to a target LDL of <100 for primary prevention in those at high risk, which often includes the elderly, which frequently leads me to use the higher intensity therapy. And, high intensity statins are really well tolerated even in the elderly (I have been using high intensity statins in the elderly for many, many years and have had no, as in zero, problems with them). Another reason to treat hyperlipidemia in the elderly is that studies have mostly found significant decreases in cardiovascular events within 6-12 months of starting a statin, usually within a reasonable time-frame for elderly patients.
–the lack of clear association between statins and all-cause or cardiovascular deaths is not so surprising. There was a favorable trend to decreased events, though not statistically significant, but this is likely because of the small numbers of cardiovascular deaths (about 1% of the patients) that occurred over a pretty short follow-up period.