A large study suggests that lowered levels of "bad" LDL cholesterol reduce risk of heart attacks and strokes in high-risk patients, but the trial dashed long-standing hopes that folic acid and vitamin B12 might provide such protection, researchers said on Sunday.
The so-called SEARCH trial, conducted by researchers at Oxford University and financed by Merck & Co, involved 12,000 men and women who had survived a heart attack.
One group of patients took a standard 20mg dose of Merck's Zocor, a member of the statin family of cholesterol drugs now widely sold by generic drugmakers under its chemical name simvastatin. Another group took the maximum available 80mg dose of simvastatin.
During an average 6.7 years of treatment, LDL-cholesterol levels of patients receiving the higher dose fell about 14% more than those receiving the lower dose.
Even so, the magnitude of additional LDL reduction was disappointing.
"We would have expected a 20% incremental reduction," Yale Mitchel, vice president of cardiovascular research at Merck, said at the annual meeting of the American Heart Association in New Orleans, where the results were reported.
The additional reduction in LDL was associated with 6% fewer heart attacks, strokes or need for procedures to clear clogged coronary arteries.
Although the benefit was not deemed statistically significant, researchers said the numerical trend was favourable.
"This new work reinforces the fundamental importance of lowering the bad LDL cholesterol as much as we can in our fight against heart attacks and strokes," said Rory Collins, a professor of medicine at Oxford.
If indeed the lower the level of LDL the better, the modest additional reduction from high dose simvastatin could provide fodder for more powerful statins, such as Pfizer's Lipitor and AstraZeneca's Crestor, in discussions with insurers who give preference to generics in their reimbursement formularies.
"Doctors are reluctant to use 80mg of simvastatin because of drug interactions. There's much more potential for myopathy or rhabdomyolysis with 80mg of simvastatin, so they're more likely to prescribe Lipitor or Crestor," said Dr Carl "Chip" Lavie, director of cardiac rehabilitation and prevention at the Oschner Heart and Vascular Institute in New Orleans.
Although high-dose simvastatin was deemed very safe, 53 patients taking it developed myopathy – a rare type of muscle pain or muscle weakness – compared with only three patients receiving low-dose simvastatin. Moreover, seven of the high-dose patients developed rhabdomyolysis, a more severe form of muscle damage, compared with none of the low-dose patients.
Mitchel said the muscle problems retreated after patients stopped taking high-dose simvastatin and noted that Zocor's drug label already includes most myopathy findings from the SEARCH trial.
The SEARCH trial also examined whether folic acid and Vitamin B12, which are able to reduce blood levels of the potentially harmful amino acid homocysteine, can protect against artery damage.
Half the SEARCH patients took folic acid – a type of B vitamin – and vitamin B12 daily, while remaining patients took dummy tablets. But the vitamins were found to be unable to reduce heart attacks and strokes.
"The homocysteine part of this study is very discouraging," said Dr Peter Wilson, professor of cardiology at Emory University School of Medicine in Atlanta. "Vitamins are just not preventing recurring events," he said, noting that earlier studies had also been unable to prove the hypothesis that they might be heart protective.
By Ransdell Pierson and Bill Berkrot, Reuters.
