December 3rd, 2012

Selections from Richard Lehman’s Literature Review: December 3rd

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

JAMA  28 Nov 2012  Vol 308

Aldosterone Antagonist Therapy, Mortality, and Readmission Among Patients with HF and Reduced EF (pg. 2097): Heart failure is a common process of dying which mostly affects people over the age of 75. Living with heart failure can be burdensome and unpredictable, and dying from heart failure can be awful, unless you are lucky enough to die suddenly. I thought I’d get those sentences out of the way first, because when we look at the evidence base for treating heart failure it’s easy to regard it as a “disease” rather than a process, and to regard death and hospitalization as the most important aspects of it, and as things that are potentially avoidable. Most people in their late seventies expect to have something wrong with them and to die before too many more years have gone by: their fear is not so much death itself as what they will have to go through before they die. So when I look at a paper about heart failure, I first check out the age of the population and then see if there are any clues about what the patients experienced as a result of the intervention, other than death and hospitalization.

The patients in this study of associations between aldosterone antagonist therapy and risks of mortality and readmission among patients with heart failure and reduced ejection fraction had a mean age of 77: they were the same age as the real patients you and I deal with all the time. And in this observational study, it didn’t make a jot of difference to either end point whether they were taking aldosterone antagonists or not. They died and went to hospital at exactly the same rate, unlike the patients in the original landmark randomized trials of spironolactone and eplerenone, who showed a 30% decrease in both endpoints during these trials, which were both stopped early because of the magnitude of the effect. So why is there such a difference between the benefit in those studies and the lack of benefit we seem to observe here? There could be several reasons. The patients in the RALES trial were younger (mean age 65) and 45% of them had a non-ischaemic cause for their heart failure, whereas in this study it was less than 30%. The same applies to a lesser extent to the eplerenone trials. But I think the main clue in this observational study is that the patients who were taking these drugs were already taking higher doses of ACE inhibitors and ß-blockers than the comparison group. In other words, they were at a later stage of the heart failure process, and that’s why they had been given what most clinicians regard as third-stage treatment. And whether they felt any better on it is a question this study can’t answer: very few studies have ever bothered to ask.

Renin-Angiotensin System Antagonists and Mortality in Patients with HF and Preserved EF (pg. 2108): Half of all the elderly patients who have heart failure do not have a reduced systolic ejection fraction, and they live in a diagnostic and therapeutic no-mans land, despite being just as likely to die. Attempts to treat this kind of heart failure with renin-angiotensin system inhibitors have met with no success in randomized trials. But in this Swedish database study of patients with heart failure and preserved ejection fraction (defined as over 40%), the use of RAS antagonists was associated with lower all-cause mortality. A good editorial by James Fang speculates as to why this might be so, and sensibly suggests that rather than trying out RSA antagonists on everyone with this form of HF, we should use them preferentially to treat the large number who have elevated blood pressure.

Warfarin Therapy Duration After Bioprosthetic AVR and Risk of Mortality, Thromboembolic Complications, and Bleeding (pg. 2118): Travelling south across the straits from Sweden to Denmark, we turn to another registry-based study for cardiovascular enlightenment. “Through a search in the Danish National Patient Registry, 4075 patients were identified who had bioprosthetic aortic valve replacement surgery performed between January 1, 1997, and December 31, 2009. Concomitant comorbidity and medication were retrieved. Poisson regression models were used to determine risk.” The question here is whether warfarin therapy can safely be stopped at three months, as is common practice. But the analysis convincingly demonstrates that discontinuation of warfarin treatment within 6 months after bioprosthetic AVR surgery was associated with increased cardiovascular death. Usual practice may need to change.

NEJM  29 Nov 2012  Vol 367

Dalcetrapib in Patients with a Recent ACS (pg. 2089): The new blockbuster drugs to follow the statins were going to be high density lipoprotein cholesterol increasing drugs, such as the rapibs—inhibitors of cholesteryl ester transfer protein (CETP). But we are rapibly becoming disillusioned. First torcetrapib bit the dust, and now it is the turn of dalcetrapib. In this trial it increased HDL cholesterol levels but did not reduce the risk of recurrent cardiovascular events in patients who had recently had an acute coronary syndrome. The manufacturers of the last CETP inhibitor standing, anacetrapib, continue to pour money into a massive trial being organised by Oxford’s Clinical Trials Support Unit, which will not REVEAL its results until 2017. I am not holding my breath.

Bedside Monitoring to Adjust Antiplatelet Therapy for Coronary Stenting (pg. 2100): Another great money-spinner was going to be platelet function monitoring at the bedside to individualize treatment with the latest antiplatelet therapies: but this too is proving a dead end. “This study showed no significant improvements in clinical outcomes with platelet-function monitoring and treatment adjustment for coronary stenting, as compared with standard antiplatelet therapy without monitoring” say the investigators of this large French trial. So it’s clopidogrel all round folks, and remember that it is now a very cheap drug.

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