Benefits of statin therapy confirmed in large, long-term trial

Eleven years of follow-up data from more than 20,000 patients indicate that prolonged statin use leads to greater reductions in vascular events, even after discontinuing treatment, without increasing the risk for nonvascular mortality or major morbidity such as site-specific cancers.

Researchers for the Heart Protection Study randomly assigned 20,536 high-risk patients aged 40 to 80 years to 40 mg of daily simvastatin (Zocor, Merck) or placebo. The mean in-trial follow-up period was 5.3 years and mean total follow-up, including post-trial, was 11 years.

During the trial, patients in the simvastatin group experienced a mean 1-mmol/L decrease in LDL. Although benefits were small during the first year, statin treatment was linked to a 23% reduction in MI, stroke and other vascular disease for each subsequent, in-trial year (95% CI, 19-28). Additionally, the researchers also found an 18% decrease in vascular mortality among patients taking statins vs. those receiving placebo (P<.0001).

During the 6-year post-trial period, statin use and lipid concentrations were similar between groups. The researchers noted a further 14% decrease in the simvastatin group during the first year (95% CI, 0-26), but observed no significant differences between study arms thereafter in vascular events (RR=0.95; 95% CI, 0.89-1.02) or vascular mortality (RR=0.98; 95% CI, 0.9-1.07).

According to combined in-trial and post-trial results, there were no significant differences between the simvastatin and placebo groups in terms of cancer incidence at all sites or any particular site (RR=0.98; 95% CI, 0.92-1.05), as well as cancer-related mortality (RR=1.01; 95% CI, 0.92-1.11). Further, there was no significant difference between study arms in nonvascular mortality (RR=0.96; 95% CI, 0.89-1.03).

Evidence of long-term benefit

The researchers said these long-term data “provide further support for the prompt initiation and long-term continuation of statin treatment.”

In a press release, Richard Bulbulia, MD, of the University of Oxford, said: “The persistence of benefit we observed among participants originally allocated simvastatin during the subsequent 6-year post-trial period is remarkable. In addition, the reliable evidence of safety, with no excess risk of cancer or other major illnesses during 11 years of follow-up is very reassuring for doctors who prescribe statins and the increasingly large numbers of patients who take them long-term to reduce their risk of vascular disease.”

Encouraging results

In an accompanying editorial, Payal Kohli, MD, and Christopher P. Cannon, MD, both of Brigham and Women’s Hospital and members of the TIMI Study Group, said previous data did not provide information on the safety and tolerability of statins beyond 5 years and did little to alleviate major concerns about their long-term use. These results, however, are encouraging, they added.

“We now have strong evidence from [the Heart Protection Study] and several other randomized controlled trials that prolonged treatment with statins is indeed efficacious, safe and has long-lasting beneficial effects, even after discontinuation of therapy,” Kholi and Cannon wrote. “For this reason, concerns should be put to rest and doctors should feel reassured about the long-term safety of this life-saving treatment for patients at increased CV risk.”

For more information:

• Heart Protection Study Collaborative Group. Lancet. 2011;doi:10.1016/S0140-6736(11)61125-2.
• Kohli P. Lancet. 2011;doi:10.1016/S0140-6736(11)61544-4.

Disclosure: The Heart Protection Study was funded by the UK Medical Research Council, the British Heart Foundation, Merck and Roche Vitamins. Drs. Bulbulia and Kohli report no relevant financial disclosures. Dr. Cannon has received research funding, honoraria, participation on advisory boards or equity in Accumetrics, Alnylam, AstraZeneca, Automedics Medical Systems, Bristol-Myers Squibb/Sanofi, GlaxoSmithKline, Merck, Novartis, Pfizer and Takeda.

Joseph S. Alpert

Statins have now been proven without a shadow of a doubt to decrease CV mortality and morbidity in a huge variety of atherosclerotic clinical situations. It is indeed interesting that even after discontinuation these agents continue to provide a 'memory' benefit. Now that most of these agents are generic and very reasonable in price, their use should increase. Physicians should be strongly urged to consider statin therapy in any patient with known or highly likely atherosclerotic disease.

– Joseph S. Alpert, MD
Cardiology Today Editorial Board member

Disclosure: Dr. Alpert reports no relevant financial disclosures.

Follow CardiologyToday.com on Twitter.