WOSCOPS: 20-year follow-up demonstrates clinical benefit of statins in men

Issue: January 2015

CHICAGO — At 20 years, men assigned statin therapy during the 5-year West of Scotland Coronary Prevention Study had lower rates for mortality and CV events compared with men assigned placebo, regardless of whether they continued taking statins, according to findings presented at the American Heart Association Scientific Sessions.

From 1989 to 1995, researchers randomly assigned 6,595 men aged 45 to 64 years to pravastatin 40 mg/day or placebo. For the original West of Scotland Coronary Prevention Study (WOSCOPS), they remained randomly assigned for 5 years. After the initial 5-year period, in which the pravastatin group had LDL lowered by approximately 20% more than the placebo group, participants continued to be followed, but their general practitioners decided whether to initiate or continue statin therapy. An interim analysis had found that after the original trial, statin usage was equal in both treatment arms, with 31% of men in both groups using statins.

Chris J. Packard, CBE, PhD, FRCPath, DSc, FRCP(Gla), FRSE, reported 20-year follow-up of events, based on data from death registries, cancer registries and the National Health Service’s Information Services Division hospitalization data sets.

Mortality risk reduction

At 20 years, men assigned pravastatin had a 27% risk reduction for CHD mortality (P<.001) and a 13% risk reduction for all-cause mortality (P<.001) compared with men assigned placebo, said Packard, honorary professor at the Institute of Cardiovascular and Medical Sciences at the University of Glasgow, United Kingdom.

“We would argue that this is a good picture of the lifetime benefit,” he said. “This is real events happening to real people, not a prediction.”

There was no difference between the groups in cancer (adjusted HR=0.96; 95% CI, 0.87-1.06) or non-CVD death (adjusted HR=0.92; 95% CI, 0.83-1.02) at 20 years, he said.

“There were no safety aspects that we could detect in terms of serious disease in this population over such a long period of time,” Packard said.

The 20-year hospitalization data indicated that assignment to statin therapy in the WOSCOPS trial was associated with lower hospitalization rates compared with controls for CABG or PCI (HR=0.81; P=.0032) and for HF (HR=0.69; P=.0068) but not for stroke (HR=0.9; P=.19), according to Packard.

“Stroke [curves] parted initially, but possibly due to the changing nature of stroke later in life, the curves came together again, which is a rather interesting phenomenon,” he said. “HF was our biggest surprise; we got no result for HF at all within 5 years [because] these were middle-aged men with just high cholesterol, so we didn’t see much in the way of incident HF. But extrapolating 20 years, there is a 31% risk reduction in the incidence of HF hospitalization in the statin-treated group compared to the placebo-treated group. This is a remarkable finding.”

Although there was no difference between the groups in those who had HF without a prior MI, fewer people from the statin group had HF after more than one MI compared with controls (18 vs. 32; P=.022). “It might be that that is the root by which HF was reduced by about 31% in our population,” Packard said.

Persistence of benefit

Compared with controls, the group assigned pravastatin also had significantly lower total length of hospital stay for any CV event (24,038 days vs. 30,342 days; P<.0001) and for MI (3,462 days vs. 4,964 days; P<.0001), and for CHD events other than stroke, MI or HF (6,458 days vs. 7,774 days; P=.019), the researchers found. “This is a real saving to the health service and the health care providers to offset the cost of drugs,” Packard said.

When the researchers examined whether outcomes differed by age at baseline, “there was no suggestion that starting younger got you a bigger risk reduction,” he said.

The WOSCOPS cohort showed a 22% relative risk reduction per 1 mmol/L (39 mg/dL) fall in LDL at 5 years and a 21% relative risk reduction per 1 mmol/L fall in LDL at 20 years, which means that “over 20 years, you’ll need to treat six people to prevent one CVD admission,” Packard said. “And you save about two hospital days per person treated.”

At 20 years, men in the pravastatin group gained 5 event-free years compared with men in the placebo group in the trial’s original primary endpoint of nonfatal MI or CHD death, he said.

“There is a rather remarkable persistence of benefit in terms of risk reduction over a long period,” he said. “You’ve changed the natural history of the disease in some way by lowering LDL.” – by Erik Swain

For more information:

Packard CJ. CS.01: Update on Randomized Trials. Presented at: American Heart Association Scientific Sessions; Nov. 15-19, 2014; Chicago.

Disclosure: Packard reports financial ties with AstraZeneca, Merck Sharpe & Dohme and Roche.