CORRESPONDENCE: LETTER TO THE EDITOR
Reply
Edward J. Mills, PhD, MSc* and
Philip J. Devereaux, MD, PhD
* McMaster University, 1200 Main Street West, Hamilton, Ontario L8N 3Z5, Canada (Email: millsej{at}mcmaster.ca).
In our systematic review (1) we decided a priori to include trials in which <50% of the population had a history of coronary heart disease. The complete PROSPER (Pravastatin in Elderly Individuals at Risk of Vascular Disease) trial fulfills our eligibility criteria (2). Although the PROSPER trial reported the results of their primary composite outcome for the primary prevention group, they did not report the results for the individual components of their composite. Thus, this information does not meet our specified end point criteria, because we excluded composite outcomes, for good reason (3).
We believe that there is a continuum of risk among diabetic patients, and we do not believe that younger, lower-risk patients should be considered at the same risk as those patients enrolled in secondary prevention trials (4). We excluded trials in high-risk diabetic patients, because we accept that their expected event rates are similar to patients with established vascular disease.
When we exclude the trials with predominantly diabetic patients and the PROSPER trial, the results of our meta-analyses are unchanged for both all-cause mortality (relative risk [RR]: 0.93, 95% confidence interval [CI]: 0.87 to 0.99, p = 0.039, I2 = 5.6%, p = 0.38) and cardiovascular disease (CVD) mortality (RR: 0.84, 95% CI: 0.72 to 0.98, p = 0.025, I2 = 12.3, p = 0.31). Therefore, we stand by our conclusions.
This letter gives us the opportunity to update our analysis in light of the largest primary prevention trial yet, the JUPITER (Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin) trial of rosuvastatin for primary cardiovascular prevention (n = 17,802) (5). When we add this trial to our primary analysis, all-cause mortality is RR: 0.92 (95% CI: 0.86 to 0.98, p = 0.006, I2 = 14%, p = 0.26) and CVD mortality is RR: 0.85 (95% CI: 0.76 to 0.95, p = 0.004, I2 = 30%, p = 0.10).
There is clear evidence for primary and secondary prevention of clinical events across the broad populations involved, including women (6). History has displayed how naïve subgroup concerns can lead to withholding effective treatments from vulnerable populations (7).
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References
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1. Mills EJ, Rachlis B, Wu P, Devereaux PJ, Arora P, Perri D. Primary prevention of cardiovascular mortality and events with statin treatments: a network meta-analysis involving more than 65,000 patients J Am Coll Cardiol 2008;52:1769-1781.[Abstract/Free Full Text]2. Shepherd J, Blauw GJ, Murphy MB, et al. Pravastatin in Elderly Individuals at Risk of Vascular Disease (PROSPER): a randomised controlled trial Lancet 2002;360:1623-1630.[CrossRef][Web of Science][Medline] 3. Ferreira-González I, Busse JW, Heels-Ansdell D, et al. Problems with use of composite end points in cardiovascular trials: systematic review of randomised controlled trials BMJ 2007;334:786.[Abstract/Free Full Text] 4. Kearney PM, Blackwell L, Collins R, et al. Efficacy of cholesterol-lowering therapy in 18,686 people with diabetes in 14 randomised trials of statins: a meta-analysis Lancet 2008;371:117-125.[CrossRef][Medline] 5. Ridker PM, Danielson E, Fonseca FA, et al. JUPITER Study Group Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein N Engl J Med 2008;359:2195-2207.[Abstract/Free Full Text] 6. Baigent C, Keech A, Kearney PM, et al. Cholesterol Treatment Trialists' (CTT) Collaborators Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins Lancet 2005;366:1267-1278.[CrossRef][Web of Science][Medline] 7. The Canadian Cooperative Study Group A randomized trial of aspirin and sulfinpyrazone in threatened stroke N Engl J Med 1978;299:53-59.[Abstract]
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