Thursday, November 24, 2011
statins
November 23, 2011 — Results from the long-term follow-up of the Heart Protection Study (HPS) may offer reassurance that statins are safe and effective in patients at high risk for vascular disease, according to new research published online November 23 in The Lancet.
The average decline in low-density lipoprotein cholesterol with statins in the initial 5-year period that patients received them was 1.0 mmol/L, with a 23% proportional drop in major vascular events (95% confidence interval [CI], 19 - 28; P < .0001). The benefit persisted largely unchanged during the 11-year follow-up period, with no further improvements in either major vascular events (risk ratio [RR], 0.95; 95% CI, 0.89 - 1.02) or vascular mortality (RR, 0.98; 95% CI, 0.90 - 1.07). There was also no evidence of added harm during the combined in-trial and follow-up period for cancer at all sites (RR, 0.98; 95% CI, 0.92 - 1.05), or any particular site, or in mortality attributed to cancer (RR, 1.01; 95% CI, 0.92 - 1.11), or for nonvascular causes (RR, 0.96; 95% CI, 0.89 - 1.03).
The authors, from the HPS Collaborative Group, Clinical Trial Service Unit, Oxford, United Kingdom, write: "These findings provide further support for the prompt initiation and long-term continuation of statin treatment in people at increased risk of vascular events."
The study is based on extended follow-up data from the randomized HPS, conducted in the United Kingdom. Between July 1994 and May 1997, investigators randomly assigned 20,536 high-risk men and women between the ages of 40 and 80 years to receive 40 mg simvastatin daily or placebo for approximately 5 years. At final follow-up in 2001, investigators instructed the patients to continue taking the statins unless there were any contraindications. The absolute benefits of treatment continued during the 5-year in-trial period and rose year after year, but they plateaued in the years after the trial.
Patients were followed for an average of 5.3 years (standard deviation, 1.2), with posttrial follow-up lasting an average of 11 years (standard deviation, 0.6). Other important findings include that a first diagnosis of any cancer (other than nonmelanoma skin cancers) was the same throughout the in-trial and extended follow-up periods, at 1749 (17.0%) in the simvastatin group vs 1744 (17.0%) in the placebo group (RR, 0.98; 95% CI, 0.92 - 1.05; P = .60). For patients aged 70 years or more at baseline, there was also no increase in genitourinary, gastrointestinal, respiratory, hematological, or any other malignant disease.
The study was blinded for the most part, unless physicians felt it important to know whether their patients were receiving the drug or not. As a result, 18% of the simvastatin-treated patients and 13% of the patients receiving the placebo were unblinded. Some observational studies found that statins were linked to excess cancers, particularly in the elderly, making posttrial follow-up a priority.
In an accompanying commentary, Payal Kohli, MD, and Christopher P. Cannon, MD, from the TIMI Study Group, and Cardiovascular Division of Brigham and Women's Hospital, Boston, Massachusetts, point to several randomized studies that have demonstrated the safety of statins on extended follow-up. They write: "The original concerns about statin safety...were probably heavily confounded. We now have strong evidence from HPS 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."
The study was funded by the UK Medical Research Council, the British Heart Foundation, Merck & Co, and Roche Vitamins. The authors of the HPS Collaborative Group and Dr. Kohli have disclosed no relevant financial relationships. Dr. Cannon states that he has received research funding from Accumetrix, AstraZeneca, Glaxo SmithKline, Merck, and Takeda. He also has received honoraria from Pfizer and AstraZeneca, has participated in advisory boards for Bristol-Myers Squibb/sanofi-aventis, Novartis, and Alnylam, and has equity in Automedics Medical Systems.
Lancet. Published online November 23, 2011. Abstract
