Abstract
Population study predicts increased prevalence of atrial fibrillation
A new estimate of atrial fibrillation in Europe has predicted that the number of cases will increase ‘tremendously’ over the next three decades such that prevalence in this latest study (from Italy) will reach 10%. 1 The results, based on opportunistic screening and ECG confirmation in a sample of 6016 subjects aged 65+, found an overall prevalence of 7.3%, which, with male sex deemed an independent risk factor, included a prevalence of 6.2% in women. The other major risk factor, of course, is advancing age and this mainly explained the forecast of greater prevalence (‘a high burden’) over the coming decades. Indeed, an editorial accompanying the study – alongside European projections based on Eurostat data – warned that ‘the increasing incidence, prevalence, and shift in distribution across age groups, will impose a huge burden on health care provision and expenditure’. 2
That burden, the editorial explains, will be evident in a greater risk of cognitive impairment and physical frailty (risk of falls, hospitalisations). There is moreover a much (>70%) greater risk of comorbidities (many cardiovascular) and mortality, thus making necessary a multidisciplinary approach to atrial fibrillation (AF) with personalised cardiac care.
The editorial describes these population trends in AF as ‘worrisome’, especially because ‘effective primary AF prevention strategies are lacking’. Efforts are presently concentrated on control and treatment of cardiovascular risk factors and comorbidities, with some evidence that targeted risk factor modifications may prevent AF recurrence and improve symptoms – but so far an effect on survival in patients with AF has not been robustly proven. Indeed, a large randomised trial last year suggested that targeted therapy of underlying conditions does improve sinus rhythm maintenance in patients with persistent AF. Targeted interventions for prevention were also highlighted in a BMJ Heart review in 2017, although the bottom line – as in all appraisals of cardiovascular risk prevention – was adoption of a heart-healthy lifestyle. 3 Medical treatments aim to reduce heart rate and reduce the risk of stroke.
References
EMA sets limit on high-strength estradiol cream
The use of high-strength creams containing 100 µg/g (0.01%) estradiol has been limited by the European Medicines Agency (EMA) to no more than a single treatment period of up to four weeks. 1 In making its recommendation in October, the EMA’s Pharmacovigilance Risk Assessment Committee said the move was ‘to minimise the risk of side effects such as blood clots, strokes and certain types of cancer’ following intravaginal use for local symptom relief. Reviewing the data, the committee noted ‘higher than normal’ serum levels of estradiol in postmenopausal women using the higher strength creams, with levels up to five times over the upper reference limit (of 10–20 pg/ml). The committee added that absorption of estradiol ‘could result in similar side effects to those seen with hormone replacement therapy’. The side effects were thus listed as endometrial hyperplasia/carcinoma, breast and ovarian cancer and thromboembolic events.
The restriction, which will also limit the size of the tube to 25 g, follows a request to the EMA from the European Commission after the EU Court of Justice annulled the conclusions a 2014 review of estradiol creams on procedural grounds. According to the EMA, although the Court of Justice did not question the scientific conclusions, the partial annulment meant that some of the measures taken to minimise the risk were invalidated.
Heather Currie, former British Menopause Society (BMS) chairman and editor of this journal, reminds readers that the new restriction applies only to the higher strength (100 mcg/g) cream and not to standard formulation creams (1 mg/g) or estradiol tablets for vaginal use.
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Still a bias against women in MI treatment and diagnosis
A report from the British Heart Foundation (BHF) has claimed that too many women are dying needlessly after a heart attack because they fail to recognise the symptoms and receive less effective care than men. 1 According to the study behind the BHF report, symptoms in women are no different from those in men, thus debunking the long-held myth that women have atypical symptoms (still reiterated in guidelines) or even that myocardial infarction (MI) is a male preserve. 2 Thus, the bottom line of the study is that women with MI are at risk of underdiagnosis and undertreatment if correct symptom presentations are not recognised. In the main study, chest pain was similarly reported by men and women (93%), while pain radiating to the left arm was felt by 48% of men and 49% of women.
Previous research funded by the BHF had shown that women having a heart attack are up to 50% more likely than men to receive the wrong initial diagnosis and are also less likely to get a pre-hospital ECG – although NICE guidelines state that men and women with suspected acute coronary syndromes should not be assessed differently.
Professor Jeremy Pearson, Associate Medical Director of the BHF, said in a statement: Heart attacks are often seen as a male health issue, but more women die from coronary heart disease than breast cancer in the UK. Three women die of coronary heart disease every hour, many of them due to a heart attack. We know that women tend to wait longer before calling 999 after first experiencing heart attack symptoms. But that delay can dramatically reduce your chance of survival.
In response to such criticisms and speculations, the FDA has since 1994 run its own Office of Women’s Health dedicated exclusively to sex differences in the diagnosis and treatment of cardiovascular disease. Among their challenges is the fact that men have more heart attacks than women, but women still have a higher heart attack mortality rate. The latter may well be explained by the findings of the BHF study that women are still less well diagnosed and less well treated than men.
References
Low-value or high-value care?
Because statins are commonly used by postmenopausal women, their association with osteoporosis has been carefully studied, and particularly whether any underlying pathophysiological mechanism may exert an osteoprotective effect. Several observational studies have indeed suggested such an effect on bone mineral density and fracture risk, but so far the strength of evidence is not sufficient to support the prophylactic benefit of statins. Moreover, according to background detail in a new study of the statin/osteoporosis association, because ‘statins act by inhibiting the endogenous synthesis of cholesterol, the main substrate for the synthesis of sex hormones … we cannot disregard the possibility of a negative effect of statins on bone health, especially in higher dosages’. 1 This study therefore aimed to investigate the link between different kinds and dosages of statins with osteoporosis, hypothesising that the inhibition of the synthesis of cholesterol could influence sex-hormones and therefore the diagnosis of osteoporosis.
It was a complicated population study based on medical claims of all Austrians made from 2006 to 2007 from which all patients treated with statins were identified (along with the statin type and dose). Overall, the study showed that statin treatment was associated with an ‘overrepresentation’ of diagnosed osteoporosis (OR 3.62), with a ‘highly non-trivial’ dependence on dosage. There was an ‘underrepresentation’ in low dosages. ‘The results were surprising for us’, said senior author Alexandra Kautzky-Willer of the Medical University of Vienna in a statement. ‘We propose that monitoring high-risk patients, that is, postmenopausal female patients under high-dosage statin therapy, might be useful in order to offer an individual therapy to prevent or treat osteoporosis’.
Meanwhile, controversy over the widespread use of statins for the primary prevention of cardiovascular disease continues, following a review suggesting that statin use in low-risk patients ‘may be an example of low value care’ (of little benefit and potential to cause harm). 2 The story began, of course, when clinical guidelines in the US and UK extended the eligibility criteria for statins and introduced a new patient population to primary prevention. While statins in people with established cardiovascular disease (CVD) is generally uncontroversial, this new indication raised many protests of doubt. In Ireland, for example, the BMJ reviewers reported that nearly two-thirds of statin use was now for primary prevention, especially in women (73%). And by further applying evolving guideline recommendations over the past 30 years to their Irish cohort, the reviewers found that according to the 1987 guidelines 8% of their population would have been eligible for statins, but by 2016 the guidelines were recommending such greater use of statins that 61% of the cohort were eligible. ‘That is a huge increase’, first author Byrne commented.
And did the evidence support such an increase? First, they found little evidence which actually separated out the primary and secondary populations. From those that did the researchers calculated that based on earlier guideline recommendations for statin use, the number needed to treat (NNT) to prevent one cardiovascular event in the primary prevention population was 40 (‘quite a reasonable number’), but, when applying the 2016 guidelines to the data, they found an NNT of 400. ‘So we are getting far less bang for our buck with the 2016 guidelines’, said Byrne, adding: ‘When the benefits are of such a small magnitude, the decision to take a medication may rest on any potential harms caused by the drugs’. And this, of course, takes us back to the source of the controversy – the benefit of statins in people at low CVD risk, many of whom according to the Irish data are postmenopausal women.