June 25th, 2012

Selections from Richard Lehman’s Literature Review: June 25th

CardioExchange is pleased to reprint selections from Dr. Richard Lehman’s weekly journal review blog at BMJ.com. Selected summaries are relevant to our audience, but we encourage members to engage with the entire blog.

JAMA 20 June 2012  Vol 307

Industry Regulation (pg. 2491): Most clinicians assume that the agencies which license new drugs – the Food and Drug Administration in the USA, or the European Medicines Agency over here – apply rigorous standards of effectiveness and safety before they let loose the latest products on the wider public. In fact they can only go by data from the few trials that have been conducted, invariably by the drug manufacturers, and then instruct the manufacturers to carry out phase 4 trials once the drug is in general use. This is a strangely lax system, and finally the US Institute of Medicine and the FDA are intending to do something about it and move towards a “lifecycle approach” in the evaluation of drugs, as Bruce Psaty explains in this article. But we need something much more rigorous and comprehensive, and soon.

The Chronically Comorbid (pg. 2493): Do try and get a copy of this piece by Mary Tinetti and two colleagues: to me it seems the best summary of the real agenda of medicine for generalists in the coming decades. I make no apology for giving you great chunks of it. “Adults with multiple chronic conditions are the major users of health care services at all adult ages, and account for more than two-thirds of health care spending.” Does that sound familiar? “Quality measurement largely ignores the unintended consequences of applying the multiple interventions necessary to adhere to every applicable measure. Uncertain benefit and potential harm of numerous simultaneous treatments, worsening of a single disease by treatment of a coexisting one, and treatment burden arising from following several disease guidelines are the well-documented challenges of clinical decision making for patients with multiple chronic conditions.” Does that sound even more familiar? “Patient goal–oriented health care involves ascertaining a patient’s health outcome priorities and goals, identifying the diseases and other modifiable factors impeding these goals, calculating and communicating the likely effect of alternative treatments on these goals, and guiding shared decision making informed by this information.” So isn’t it time we abolished the Quality and Outcomes Framework and started learning the skills of patient goal-oriented health care? It won’t be easy. It will require a co-ordinator (is that you?) and a team (is that your practice team?). It will be a smarter, better kind of general practice, organized to meet the goals of patients as individuals. It will require new and better science about what works for individuals. “As this evidence becomes available, point-of-care risk calculators will be required to synthesize it to determine the best options for each patient.” Bring it on, say I: this is what I had hoped for ever since I came into general practice.

Population Risk for Cardiovascular Disease (pg. 2499): The Emerging Risk Factors Collaboration must be getting despondent. Every time they publish a paper the conclusion is that whatever has emerged most recently makes little difference to risk scores derived from conventional factors. And happily the population risk for cardiovascular disease keeps going down. Here the Collaboration looked at the additive value of the combination of apolipoprotein B and A-I, lipoprotein(a), or lipoprotein-associated phospholipase A2 mass to risk scores containing total cholesterol and HDL-C. It’s a few per cent here and there.

Lancet  23 June 2012  Vol 379

(pg. 2352) Recombinant tissue plasminogen activator (rt-PA) for ischaemic stroke: a great therapeutic advance or a costly dead-end for health services? “Thrombolysis is of net benefit in patients with acute ischaemic stroke, who are younger than 80 years of age and are treated within 4•5 h of onset. The third International Stroke Trial (IST-3) sought to determine whether a wider range of patients might benefit up to 6 h from stroke onset.” Those who got rt-PA in this trial died faster, though there was no difference in mortality at six months; and at that time there was also no significant difference in the combined end-point of survival plus independence. So among the 3035 patients randomized, a clearly negative result. But wait: we must heed the wisdom of our superiors on this matter. “Didier Leys has been an investigator in European Cooperative Acute Stroke Study (ECASS) 3 (Boehringer-Ingelheim) and participated in two symposia organised by Boehringer-Ingelheim; and is current president of the European Stroke Organisation, which received subventions from several companies including Boehringer-Ingelheim. Charlotte Cordonnier has been an investigator in ECASS 3.” These editorialists declare: “The key message of IST-3 and the updated meta-analysis is that many eligible patients from subgroups excluded by the European licence should now be given rt-PA.” And who is the leading manufacturer of rt-PA? Why, it is Boehringer-Ingelheim.

(pg. 2364) The updated meta-analysis referred to here of rt-PA for ischaemic stroke is one conducted quite without industry influence, by pioneers of stroke research and leading proponents of open data access. And by combining the IST-3 data with those from 11 other trials, the authors do find some evidence of benefit in survival to independent living in all age groups treated within 3 hours: this is best seen in figure 3. The most striking feature is the small effect size. The industry-sponsored editorialists have only got two things wrong: the IST-3 trial shouldn’t appear in support of their declaration, and the words “be offered rt-PA within 3 hours if they are able to give informed consent” should take the place of “be given rt-PA”.

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