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WOSCOPS: Statins reduce mortality in men with very high LDL long term
Among men with very high LDL followed for 20 years, use of a low-intensity statin conferred reduced risk for CHD, CV and all-cause mortality, according to new data from the WOSCOPS study.
In the initial WOSCOPS trial, men aged 45 to 64 years with LDL of at least 155 mg/dL but no vascular disease were randomly assigned pravastatin 40 mg per day or placebo for 5 years. Participants were then followed in an observational study for another 15 years.
In the present analysis of 5,529 individuals, Kausik K. Ray, MD, MPhil, from the Imperial Center for Cardiovascular Disease Prevention, department of primary care and public health at Imperial College London, and colleagues compared pravastatin vs. placebo for CHD and major adverse CV events during the 5 years of the randomized trial and for various mortality-related outcomes during the full 20-year follow-up.
Participants were stratified by baseline LDL level: 155 mg/dL to 189 mg/dL or at least 190 mg/dL.
At 5 years, compared with placebo, pravastatin reduced the risk for CHD by 27% (P = .002) and major adverse CV events (P = .004), and results were consistent regardless of baseline LDL level, Ray and colleagues wrote.
The researchers found that among patients with LDL of at least 190 mg/dL, pravastatin reduced risk for CHD by 27% (P = .033) and major adverse CV events by 25% (P = .037) at 5 years, and reduced risk for CHD death by 28% (P = .02), CV death by 25% (P = .009) and all-cause death by 18% (P = .004) at 20 years.
The long-term results were not statistically significant in patients with LDL 155 mg/dL to 189 mg/dL at baseline.
“For the first time, we show that statins reduce the risk of death in this specific group of people who appear largely healthy except for very high LDL levels,” Ray said in a press release. “This legitimizes current guidelines, which recommend treating this population with statins. ... Our study lends support to LDL’s status as a major driver of heart disease risk, and suggests that even modest LDL reductions might offer significant mortality benefits in the long term.” – by Erik Swain
Disclosures: The original WOSCOPS trial was funded by Bristol-Myers Squibb and Sankyo. The present analysis was funded in part by a grant from Sanofi. Ray reports he receives grants and/or personal fees from Abbvie, Aegerion, Algorithm, Amgen, AstraZeneca, Cerenis, Cipla, Eli Lilly, Esperion, Kowa, Merck Sharpe & Dohme, Pfizer, Regeneron, Sanofi and The Medicines Company. Please see the study for all other authors’ relevant financial disclosures.
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These findings represent a 20-year follow-up of WOSCOPS, which included individuals with what we would now consider to be very high LDL, greater than 190 mg/dL. They were administered what we now consider to be a modest statin dose, 40 mg of pravastatin. At the time, we didn’t have the more powerful statins such as atorvastatin and rosuvastatin. But the results confirm what we have thought for a long time: People who have the biggest reduction in LDL have the fewest events. The benefit at 20 years was the same as at 5 years: an approximately 25% reduction in events and mortality.
These results further support the cholesterol hypothesis, which with the PCSK9 inhibitor data has been confirmed. The higher your cholesterol, the more damage to your arteries, and the more likely you are going to have an event such as MI, stroke, cardiac arrest or death.
Interestingly, these people still had very elevated LDLs. The data showed some had LDL reduced to 145 mg/dL. We now know that we should be seeking reductions to 70 mg/dL or, in high-risk people, even lower, as shown in the PCSK9 inhibitor data.
These data confirm that we should be looking for people with elevated cholesterol, even in the absence of events. The message is one for primary care doctors. Many of these patients would not be going to see a cardiologist unless they had a family history of CHD. Many of them were in their 40s, a time of peak economic production and family responsibilities. This tells primary care doctors that they need to start checking the cholesterol on these patients as routinely as they would give inoculations. I would prefer to make lipids part of the standard metabolic panel. Today’s tests are all automated, so it is not a big expense to add in a quick screen for total cholesterol, LDL and HDL into the routine blood tests people get at their annual checkup.
Given all the data we have, to me, someone with LDL > 130 mg/dL ought to be on a statin. We know there will be benefit, even in individuals who have never had a vascular event. Statins are inexpensive and the muscle-related adverse events associated with them are exaggerated. Some people have occasional muscle cramps, but those also occur in the absence of statins. Sometimes I have a hard time talking a patient into taking a statin, but they are very well-tolerated in the overwhelming majority of patients. For people who have severe, recurrent muscle aches, often giving a statin three times per week at a smaller dose will work. That still gives a substantial if not ideal reduction in LDL.
Cholesterol testing should be routine in primary care for patients starting in their 30s. If a patient has a family history of vascular disease, I recommend starting screening in their 20s. If a child has a parent who had an event at a young age, my feeling is screening should begin in childhood, with lifestyle issues emphasized, and low-dose statin therapy given if appropriate.