November 21, 2006
The National Heart, Lung, and Blood Institute (NHLBI) convened an ad hoc expert panel of thought leaders in the lipid field on November 21, 2006 in Bethesda, Maryland to advise the NHLBI on the lipid research question that could be best advanced by an NHLBI-sponsored randomized clinical trial.
There was a strong consensus among the panel that the major gap area for trials in the lipid field was in primary prevention. Primary prevention trials require larger sample sizes because their cardiovascular (CV) event rates are smaller than in patients with known CV disease and because CV events comprise a smaller proportion of their overall morbidity and mortality in primary prevention. Secondary prevention trials are therefore a less expensive and risky venue for drug companies to test new drugs. Once their drugs are proven effective in a secondary prevention setting, the manufacturer may be content to rely on treating physicians and guideline authors to extrapolate to primary prevention.
There was also a strong consensus that a primary prevention trial of any of the newer drugs that modify HDL metabolism would be premature. None of these agents is FDA-approved.
Several options for a primary prevention trial of LDL cholesterol lowering were discussed. These included trials of intensive versus moderate cholesterol lowering in moderately high-risk patients and trials focused on moderate-risk patients, women and minorities and the elderly. The proposal that received the most support was one that focused on the elderly, which would include 50% women. There were differing views about the appropriate age cutoff for such a trial and the appropriate interventions (placebo or low-dose statin in the control group, aggressiveness of LDL lowering in the active group). The required sample size depends on the details of the design, but there was a general preference for a conservative sample size (perhaps 10,000).
- Support a primary prevention trial of LDL-cholesterol lowering in the elderly. This was considered the most timely and important research question that NHLBI could now address in the lipid area.
- Collaborate with the National Institute on Aging and possibly with the National Cancer Institute (if a vitamin D intervention were added as a second question in a factorial design) in support of the primary prevention trial recommended above.
- Embed a study of the clinical utility of emerging imaging technologies in this trial and in any future lipid trials we undertake.
- Seek the collaboration and support of industry for the above recommended trial.
David Gordon, M.D., Ph.D., M.P.H.
Working Group Members:
Chair: Eugene Braunwald, M.D.
- Colin Baigent, M.D.
- Noel Bairey Merz, M.D.
- Robert Bonow, M.D.
- Gregory Burke, M.D., M.Sc.
- Valentin Fuster, M.D., Ph.D.
- Antonio Gotto, M.D., D.Phil.
- Scott Grundy, M.D., Ph.D.
- Steven Haffner, M.D.
- John LaRosa, M.D.
- David Orloff, M.D.
- Frank Sacks, M.D.
- Neil Stone, M.D.;
- Allen Taylor, M.D.
- Nanette Wenger, M.D.
Last updated: September 20, 2007