ASCOT: Unexplained Long-Term Mortality Benefit Found with Atorvastatin

PARIS, France—Prior exposure to the cholesterol-lowering drug atorvastatin imparts a sustained mortality benefit in hypertensive patients with no history of coronary artery disease, according to data released Sunday, August 28, at the European Society of Cardiology Congress 2011.

The results, from the lipid-lowering arm of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT-LLA), were presented by Peter S. Sever, MD, PhD, of Imperial College (London, United Kingdom), and simultaneously published online ahead of print in the European Heart Journal.

Dr. Sever's presentation documented what happened to trial participants in the 8 years following ASCOT-LLA's early termination in 2003.

Long, Winding Road for Trial Subjects

ASCOT-LLA was a double-blind, randomized trial of 10-mg atorvastatin (Lipitor; Pfizer, New York, NY) vs. placebo in 10,305 hypertensive patients with total mean cholesterol concentrations of less than 6.5 mmol/L. All were also enrolled in the blood-pressure lowering arm (BPLA) of the overall ASCOT study.

At a median of 3.3 years of follow-up, ASCOT-LLA was halted early after a substantial reduction in the composite of nonfatal MI and fatal CHD was seen with atorvastatin, but the subjects continued to participate in ASCOT-BPLA for another 2.2 years. By the end of ASCOT-BPLA, 63% of those originally assigned atorvastatin were still taking the drug. Yet a full 56% of patients originally assigned placebo had also begun taking atorvastatin.

According to Dr. Sever, being assigned to atorvastatin continued to have lingering effects at a median of 11 years after initial randomization. Among the 45% of ASCOT-LLA subjects with available follow-up data, patients in the statin arm still had a 14% lower likelihood of all-cause mortality. The difference was mainly driven by a 15% reduction in non-CV mortality, with CV deaths occurring at similar rates in both groups (table 1).

Table 1. Outcomes at 11 Years After Randomization

Atorvastatin vs. Placebo

HR (95% CI)

P Value

All-Cause Mortality

0.86 (0.76-0.98)

0.02

Non-CV Death

0.85 (0.73-0.99)

0.03

CV Death

0.89 (0.72-1.11)

0.32

 
Most of the difference in non-CV mortality was attributed to a reduction in deaths related to infection and respiratory illness (HR 0.64; 95% CI 0.42-0.97; P = 0.04). The risk of death from cancer, meanwhile, was equivalent between groups.

Dr. Sever pointed out that at 11 years, the cholesterol profiles were exactly the same between patients who had previously been on atorvastatin and those on placebo.

The reduction in all-cause mortality “is a completely new and unexpected finding, and we don’t have a simple explanation for it,” Dr. Sever told TCTMD in a telephone interview. He noted, however, that studies show that patients with HIV or pneumonia are less likely to die from a serious infection if they take a statin.

Following Young Patients Into Old Age

Discussant Guy G. De Backer, MD, PhD, of University Hospital Ghent (Ghent, Belgium), who also wrote an editorial accompanying the published paper, stressed, “These findings can’t appear by chance only.”

“Yet what shall we do with these unexpected findings at 7 years? This drug may have side effects in the elderly,” Dr. De Backer noted, adding that the mean age range for patients in the study was between 55 and 66 years. Some of the patients were as young as 40, he added.

“We can expect these patients will be on the drug for 15 to 25 years if they are prescribed lifelong therapy,” he commented. “There may be competition between cardiovascular and cancer deaths during long-term follow-up in an aging population.”

In response, Dr. Sever said, “I would never advocate atorvastatin to a young, healthy patient.”

 


Sources:
1. Sever PS, Chang CL, Gupta AK, et al. The Anglo-Scandinavian Cardiac Outcomes Trial: 11-year mortality follow-up of the lipid lowering arm in the UK. Eur Heart J. 2011;Epub ahead of print.

2. De Backer GG. Long-term results from statin trials: Answers but more unresolved questions. Eur Heart J. 2011;Epub ahead of print.

 

 

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ASCOT: Unexplained Long-Term Mortality Benefit Found with Atorvastatin

PARIS, France—Prior exposure to the cholesterol lowering drug atorvastatin imparts a sustained mortality benefit in hypertensive patients with no history of coronary artery disease, according to data released Sunday, August 28, at the European Society of Cardiology Congress 2011. The
Disclosures
  • The analyses were supported by an unrestrictive grant from Pfizer.
  • Dr. Sever reports having served as a consultant or received travel expenses or payment for speaking at meetings, or research funding from pharmaceutical companies that market blood-pressure lowering or lipid-lowering drugs, including Pfizer for ASCOT.
  • Dr. De Backer reports no relevant disclosures.

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