John Abramson

Should people at low risk of cardiovascular disease take a statin

A review of statins for primary prevention of cardiovascular disease could alter guidance for those with a 10 year risk of less than 10%. John Abramson and colleagues argue that statins have no overall health benefit in this population and that prescribing guidelines should not be broadened

Clinical Trial Data as a Public Good

This article argues that the public lacks sufficient information about the results of clinical drug trials to make sound decisions about the use of drugs. The lack of public information undermines our knowledge of drug safety and compromises physician prescribing. To address this problem it recommends that clinical study reports (CSRs) be made accessible to the public, a move pharmaceutical companies have opposed. CSRs provide in-depth statistics and analysis of clinical trial data and are required by the FDA when it reviews new drugs. Europe recently agreed to make those reports public.

When health policy is the problem: a report from the field.

We often think of health policy and health services research as offering solutions to cost, quality, and access problems. Many of us see health policy as simply ineffective. But any activity that has the power to cure can also do harm. Is it possible that the health policy enterprise has contributed to the very problems it has been attempting to eliminate? We argue that it has. Reasonable assumptions have led to a series of solutions that have provided political cover for those vested in the status quo. This process is nonpartisan, with those of us on the left and the right unintentionally and inadvertently contributing to the problems we are so committed to solving.

Competition, Capitation, and Case Management: Barriers to Strategic Reform

Political support for competition, capitation, and case management in health services has come from successive Congresses and presidents. Benefits attributed to these organizational/financing strategies are consistent with societys preference for a private market approach. Yet, the promise has not been pursued in effective public policy or program. The systemic barriers to implementation of alternative delivery systems are examined in the context of Medicaid; they are neither trivial nor intractable.

Remediating “Lessons from the controversy over statins”

1 Armitage J, Baigent C, Collins R. Lessons from the controversy over statins—Authors’ reply. Lancet 2016; 388: 2237–38. 2 Horton R. Lessons from the controversy over statins—Editor’s reply. Lancet 2016; 388: 2237. 3 Krumholz HM. Statins evidence: when answers also raise questions. BMJ 2016; 354: i4963. 4 Redberg RF, Katz MH. Statins for primary prevention: the debate is intense but the data are weak. JAMA Intern Med 2017; 177: 21–23. 5 Collins R, Reith C, Emberson J, et al. Interpretation of the evidence for the efficacy and safety of statin therapy. Lancet 2016; 388: 2532–61. 6 Godlee F. Statins: we need an independent review. BMJ 2016; 354: i4992. 7 Jefferson T, Jones M, Doshi P, Spencer EA, Onakpoya I, Heneghan CJ. Oseltamivir for influenza in adults and children: systematic review of clinical study reports and summary of regulatory comments. BMJ 2014; 348: g2545. 8 Deer B. How the case against the MMR vaccine was fixed. BMJ 2011; 342: c5347. 9 Abramson J, Rosenberg HG, Jewell N, Wright JM. Should people at low risk of cardiovascular disease take a statin? BMJ 2013; 347: f6123. 10 Deer B. Secrets of the MMR scare. The Lancet’s two days to bury bad news. BMJ 2011; 342: c7001. herself from handling a complaint against The BMJ was in part due to a change in personnel at The BMJ, which created a conflict of interest partway through the process. COPE investigated the complaint to the full extent of its remit, more quickly than reported in The Lancet, and with due care to ensure independence. COPE’s conclusion was emphatic: that The BMJ had taken “extraordinary steps” and “acted appropriately by completing an internal investigation and audit to a high standard, and promoted transparency by making information on the process publicly available”. Comparisons between the statin saga and the measles, mumps, and rubella vaccine scare also do not serve Horton or Collins well. The BMJ’s article in question was not a poorly done and fraudulent piece of research but an expert reanalysis and commentary; after it was published it was not the journal or the authors but Collins who launched the media scare when he went to the press despite repeated invitations to air his concerns in The BMJ. The BMJ did not attempt to cover up concerns, leading to years of delay, but corrected the article within months and referred the decision about retraction to a panel of experts. Retraction Watch called the panel’s report “the most detailed justification for a journal’s decision not to retract a paper that we’ve seen in a long time, perhaps ever”. I fully support efforts to ensure that everyone involved in creating and publishing medical knowledge can be held accountable. I also support proposals for a radical rethink about how the evidence base is built and used. In this effort, the lessons learnt by all parties involved in the statins saga could play an important part.

Authors’ reply to Huffman and colleagues

We thank the Cochrane review authors for their thoughtful comments (highlighted in quotes below), which give us the opportunity to clarify unresolved issues about the benefits and harms of statins in low risk people.1 > “This article predated by three weeks the publication of the 2013 American College of Cardiology/American Heart Association (ACC/AHA) cholesterol treatment guidelines (12 November 2013), but statements were made about ‘proposed standards’ without full knowledge of these guidelines.” The “proposed standards” that we referred to in our article were not the yet to be published 2013 American College of Cardiology/American Heart Association (ACC/AHA) guidelines on cholesterol treatment.2 3 Rather, they were the 2013 update of the Cochrane review on statins for the primary prevention of cardiovascular disease,4 which had incorporated the findings and recommendations of the 2012 Cholesterol Treatment Trialists’ (CTT) meta-analysis.5 The 2012 CTT meta-analysis reported that statins significantly reduce major vascular events in people “with 5-year risk of major vascular events lower than 10%.” It concluded that the current major guidelines—ATP-III in the US, the European Society of Cardiology task force, and the National Institute for Health and Care Excellence guidelines in the UK—“might need to be reconsidered.” The 2013 Cochrane review stated: “in light of new evidence derived from the CTT Collaboration on primary prevention, there is a need to update existing cost-effective analysis.” We based our comments about “proposed standards” on these calls to update existing recommendations. Although we had no advanced knowledge of the contents of the forthcoming ACC/AHA cholesterol treatment guidelines, we anticipated that these findings and recommendations would be influential. > “Abramson and colleagues state: ‘Under the proposed 2013 standards, however, no level of risk would preclude statin therapy’” The 2012 CTT meta-analysis concluded: “The present report shows that statins are indeed both effective and safe for …

Safety and efficacy of statins

www.thelancet.com Vol 389 March 18, 2017 1097 reduction in LDL for 5 years would avoid 15 major vascular events per 1 000 people in the 5% to 10% risk category (ie, 1·5% absolute benefit). Furthermore, a third of these events were revascularisation procedures, so the absolute risk reduction in so-called hard events (ie, heart attacks and strokes) is 100 per 10 000 patients, or 1%. In other words, the 2012 CTT metaanalysis shows that 100 patients in this risk category would have to be treated for 5 years to prevent one heart attack or stroke. Thus, the real benefit shown by the CTT data is 80% lower than that claimed by Collins and colleagues. Finally, the Review cites our 2013 BMJ paper, but fails to report our primary research finding—that statin therapy does not significantly reduce all-cause mortality (the CTT primary outcome) for patients with less than 10% 5-year risk of cardiovascular disease. This result was upheld by two independent statistical reviews as part of the expert panel review that adjudicated Collins’ (unanimously rejected) demand for retraction of our paper. Omission of this crucial finding is misleading.

Authors’ reply to Davis and Dietrich

Davis and Dietrich raise important concerns about our analysis of the effect of statins in people at low risk of cardiovascular disease.1 2 On the basis of Cholesterol Treatment Trialists’ (CTT) data published in 2012,3 we showed that statins do not reduce overall mortality in people with less than a 20% 10 year risk of a major vascular event. Davis and Dietrich are correct that all cause mortality was significantly reduced in patients treated with rosuvastatin compared with controls in the JUPITER trial.4 However, the data from this study were included in the CTT meta-analysis of 2012, so singling out the all cause mortality findings from this study alone would undermine the purpose of the meta-analysis. That said, other aspects of the JUPITER trial merit consideration. At the time that the study was prematurely stopped, the number of deaths from cardiovascular causes (myocardial infarction and …