“The Heart Protection Study showed unequivocally that statins could produce substantial benefit in a much wider range of subjects than had ever been contemplated.”
“The study revolutionised the way cholesterol-lowering drugs are used,” says Collins, who tomorrow will deliver the Geoffrey Rose Lecture on Population Sciences. “Until then, the benefits of cholesterol-lowering drugs were thought only applicable to those at high risk with elevated cholesterol levels. But what the Heart Protection Study showed was a reduction in the risk of coronary heart disease even in those with cholesterol levels in the normal range. That really changed the landscape.”
It was also results from the same study which showed the benefits of lowering LDL-cholesterol levels in those with diabetes. Again, the risk reductions were seen in those with relatively low levels of LDL-cholesterol, as well in many other types of high-risk patients.
Cholesterol and risk is the subject of Collins’s Named Lecture this morning, considered from a past, present and future perspective. The past, he notes, was defined by a misguided view (as has now been shown by the statin trials) that lowering LDL-cholesterol levels was not beneficial for many types of patients and, indeed, might even be hazardous. For example, both the elderly and women were excluded from the benefit roster. But the Heart Protection Study showed unequivocally that statins could produce substantial benefit in a much wider range of subjects than had ever been contemplated. From there on, the mantra became “treat the risk, not the cholesterol”.
As for the present, those findings have been confirmed and extended by meta-analysis of the many different trials of statins, most recently in a huge review performed by Collins’s own group at the Clinical Trial Service Unit (CTSU) of Oxford University, collectively known as the Cholesterol Treatment Trialists collaboration. That study, which included 27 randomised trials, showed that, even in healthy people, reducing blood levels of LDL-cholesterol cut the risk of coronary events (including revascularisation) and ischaemic stroke by around one-third. Healthy people given a statin also had lower overall mortality rates than those given placebo. Since their original 2002 study, the message from Collins and his CTSU colleagues has thus been that CVD prevention guidelines should consider the health benefits of statins in a very much wider range of people.
Today, mortality trends in most developed countries show steep and consistent declines in premature death from heart disease and stroke, and in the UK vascular mortality rates in middle age have, remarkably, fallen by more than half in the past three decades. The CTSU, of which Collins and Sir Richard Peto have been co-directors for more than 20 years, has made substantial contribution to these trends in its major studies of smoking, blood lipids, blood pressure, aspirin and streptokinase.
Collins and his colleagues have emphasised the need for large-scale observational and randomised evidence about the prevention and treatment of major diseases. Indeed, it was the CTSU in the 1970s and 80s which pioneered the use of meta-analysis of trials in vascular disease, and with it the demonstration that even modest effects in a widely prevalent condition could have a dramatic public health impact.
As for the future, Collins’s lecture this morning will hold out the promise of even more rapid demonstration of the benefits of adding newer cholesterol-lowering agents to the statins.