Anglo-Scandinavian Cardiac Outcomes Trial ( ASCOT ) - Lipid Arm

Last reviewed 02/2021

There is evidence that lipid lowering with atorvastatin significantly reduced the risk of major cardiovascular events in hypertensive patients with normal cholesterol levels in the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT).

• results showed a significant 36% reduction in the primary end point of fatal CHD/nonfatal MI in the atorvastatin group after a median follow-up of 3.3 years
• the ASCOT trial is made up of two studies in hypertensive patients-a comparison of two different antihypertensive regimens, and a lipid-lowering study. The lipid part of the ASCOT trial involved 10 305 hypertensive patients aged 40 to 79 years with at least three other cardiovascular risk factors and with total cholesterol below 6.5 mmol/L (250 mg/dL)
  • they were randomized to 10-mg atorvastatin or placebo
  • follow-up was planned for 5 years, but treatment was stopped after 3.3 years because of significant benefits in the atorvastatin group
  • this benefit emerged in the first year of follow-up. As well as a reduction in the primary end point, fatal and nonfatal stroke, total cardiovascular events, and total coronary events were also significantly lowered
    
    ASCOT - primary end point
    
    

    End point	atorvastatin (%)	placebo (%)	hazard ratio	p
    MI/fatal CHD	1.9	3.0	0.64	0.0005

    
    ASCOT - secondary end points
    
    

    End point	atorvastatin (%)	placebo (%)	hazard ratio	p
    Total CV events/procedures	7.5	9.5	0.79	0.0005
    Total coronary events	3.4	4.8	0.71	0.0005
    All-cause mortality	3.6	4.1	0.87	0.16
    CV mortality	1.4	1.6	0.90	0.50
    Fatal/nonfatal stroke	1.7	2.4	0.73	0.02
    Fatal/nonfatal CHF	0.8	0.7	1.13	0.58

    
    
    
  • atorvastatin lowered total serum cholesterol by about 1.3 mmol/L compared with placebo at 12 months and by 1.1 mmol/L after three years of follow-up

Drs Lars Lindholm and Ola Samuelsson in an accompanying Lancet commetary (2) note that while the ASCOT trial showed fairly large relative reductions in cardiovascular events associated with active lipid-lowering therapy, the absolute benefits are not so impressive. "In absolute terms the difference between active treatment and placebo in the incidence of cardiovascular disease was only 3.4 per 1000 patient-years for the primary event and 2.0 per 1000 patient-years for stroke. Hence, active lipid-lowering treatment can be estimated to result in only a small increase in the probability of remaining free from a myocardial infarction over five years, from 95% to 97%, in patients with good control of blood pressure," they write. "The ASCOT investigators hope that their data will have implications for future lipid-lowering guidelines. However, any guideline changes should be left to the guidelines committees to decide, when they balance the limited absolute benefits against the treatment cost of lipid lowering," Drs Lindholm and Samuelsson conclude.

Reference:

1. Sever PS, Dahlöf B, Poulter NR et al. Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial-Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial. [1149-1158]. 2003.
2. Lindholm LH and Samuelsson O. What are the odds at ASCOT today? Lancet [1144-1145]. 2003.