Studies spell double trouble for women

There’s been a double whammy of bad health news for women, with one study finding that women with diabetes are more likely to develop cancer, and a second finding that women are twice as likely as men to be under-treated for heart attack.

In the first study, researchers from The George Institute for Global Health reviewed the health outcomes of almost 20 million people involved in 47 studies.

They discovered that having diabetes – type 1 or type 2 – significantly raises the risk of developing cancer, with a significantly higher risk for women.

Women with diabetes were 27 per cent more likely to develop cancer than women without diabetes. For men, the risk was 19 per cent higher.

Overall, women with diabetes were six per cent more likely to develop any form of cancer than men with diabetes.

“The link between diabetes and the risk of developing cancer is now strongly established,” lead author, Dr Toshiaki Ohkuma, said.

“We have also demonstrated, for the first time, that women with diabetes are more likely to develop any form of cancer, and have a significantly higher chance of developing kidney, oral, and stomach cancers, and leukaemia.

“The number of people with diabetes has doubled globally in the past 30 years, but we still have much to learn about the condition.

“It’s vital that we undertake more research into discovering what is driving this, and for both people with diabetes and the medical community to be aware of the heightened cancer risk for women and men with diabetes.”

The George Institute research was published in Diabetologia, the journal of the European Association for the Study of Diabetes.

In the second study, published in the Medical Journal of Australia, University of Sydney researchers found that women admitted to 41 Australian hospitals with ST-Elevation Myocardial Infarction (STEMI) in the past decade were half as likely as men to receive appropriate diagnostic tests and treatment.

They were also less likely to be referred for cardiac rehabilitation, and prescribed preventive medications, at discharge.

Death rates and serious adverse cardiovascular events among these women were more than double the rates seen in men six months after discharge.

“The reasons for the under-treatment and management of women compared to men in Australian hospitals aren’t clear,” lead author and cardiologist, Professor Clara Chow, said.

“It might be due to poor awareness that women with STEMI are generally at higher risk, or by a preference for subjectively assessing risk rather than applying more reliable, objective risk prediction tools.

“Whatever the cause, these differences aren’t justified. We need to do more research to discover why women suffering serious heart attacks are being under-investigated by health services, and urgently identify ways to redress the disparity in treatment and health outcomes.”

[Obituary] Arthur Jay Moss

Cardiologist and authority on cardiac arrhythmias. Born in White Plains, NY, USA, on June 21, 1931, he died of cancer in Brighton, NY, USA, on Feb 14, 2018, aged 86 years.

[Seminar] Acute rheumatic fever

Acute rheumatic fever is caused by an autoimmune response to throat infection with Streptococcus pyogenes. Cardiac involvement during acute rheumatic fever can result in rheumatic heart disease, which can cause heart failure and premature mortality. Poverty and household overcrowding are associated with an increased prevalence of acute rheumatic fever and rheumatic heart disease, both of which remain a public health problem in many low-income countries. Control efforts are hampered by the scarcity of accurate data on disease burden, and effective approaches to diagnosis, prevention, and treatment.

[Department of Error] Department of Error

Devereaux PJ, Duceppe E, Guyatt G, et al. Dabigatran in patients with myocardial injury after non-cardiac surgery (MANAGE): an international, randomised, placebo-controlled trial. Lancet 2018; 391: 2325–34—In the final sentence of the Interpretation in the Summary, the dose of dabigatran was recorded incorrectly. The sentence should read “Patients with MINS have a poor prognosis; dabigatran 110 mg twice daily has the potential to help many of the 8 million adults globally who have MINS to reduce their risk of a major vascular complication.” This correction has been made to the online version as of July 5, 2018.

Which anticoagulant is the safest?

Apixaban was the clear winner in a large observational study looking at the risk of major bleeding and death with the use of the most commonly prescribed anticoagulants.

The study, which breaks new ground in terms of its scope and design, looked at around 200,000 new users of warfarin, dabigatran, rivaroxaban and apixaban in the UK primary care setting, tracking them over a five-year period. Overall, apixaban was found to be the safest direct oral anticoagulant (DOAC) compared with warfarin for patients with and without atrial fibrillation. Patients on a standard dose of apixaban had a 34% reduced risk of major bleeding and a 60% lower risk of intracranial bleeding over the study period, compared with warfarin. Apixaban users also had reduced rates of gastrointestinal bleeding.

The safety benefits of other DOACs compared with warfarin was less clear cut. There was a reduced risk of intracranial bleeds with rivaroxaban, but only in patients without atrial fibrillation. And in patients with atrial fibrillation, dabigatran lowered the risk of intracranial bleed, compared with warfarin.

Rivaroxaban was associated with higher all-cause mortality across the board, in patients both with and without atrial fibrillation, as was apixaban in low doses, compared with warfarin. But the authors say the higher mortality with these DOAC regimens could be due to closer monitoring of patients on warfarin, or due to prescribing choices related to underlying comorbidities.

The stronger safety profile of apixaban in this study is in line with a recent meta-analysis, which also showed apixaban to be the safest of the DOACs and a better performer than warfarin. But the authors of the present study say that meta-analysis mostly involved indirect rather than head-to-head comparisons. Direct comparison studies are few and far between, because regulatory authorities generally only require studies showing non-inferiority to placebo or standard treatment.

They add that their study is the first to look at a large subset of patients taking anticoagulants for reasons other than atrial fibrillation, such as after deep vein thrombosis, knee or hip replacement or stroke. This accounts for about half of users of anticoagulants.

Overall, they say their study paints a reassuring picture for patients taking DOACs as an alternative to warfarin, particularly for those who have been prescribed apixaban.

You can access the full study here.

[Comment] Sodium bicarbonate for severe metabolic acidaemia

Severe metabolic acidaemia (blood pH ≤7·20) is associated with impaired haemodynamics and increased mortality in critically ill patients.1 Administration of sodium bicarbonate can increase blood pH, but its ability to improve haemodynamics and reduce mortality remains unproven.2–6 Sodium bicarbonate has been shown to increase blood pH levels but did not increase cardiac output compared with saline when examined at 30 min or 60 min after infusion,3,6 and did not reduce mortality in studies involving cohorts of 34–150 individuals with severe acidaemia.

[Articles] Assessment of functional capacity before major non-cardiac surgery: an international, prospective cohort study

Subjectively assessed functional capacity should not be used for preoperative risk evaluation. Clinicians could instead consider a measure such as DASI for cardiac risk assessment.

[Correspondence] Endpoints in diabetes cardiovascular outcome trials

Standardised Medical Dictionary for Regulatory Activities (MedDRA) queries (SMQs)1 and Customised MedDRA queries (CMQs) are routinely used to identify safety signals in clinical trials, including cardiovascular outcome trials. The three-component major adverse cardiac events (MACE) endpoint, often used to assess cardiovascular safety, includes a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke.2,3 Hospital admission for heart failure is another cardiovascular endpoint of interest.

[Comment] Long-term albumin in cirrhosis: is it the ANSWER?

Ascites is the most frequent complication of cirrhosis and carries the worst prognosis.1 Although its development might be delayed by non-selective β-blockers,2 once ascites develops the patient progresses to refractory ascites, hyponatraemia, and renal dysfunction.3 This progression is due to worsening of portal pressure and worsening of the vasodilatory–hyperdynamic circulatory state, leading to progressive decrease in effective blood volume, cardiac dysfunction, and renal perfusion.4 Inflammation from overt or covert (bacterial translocation) infections is a major driver of progression.

[Comment] Direct oral anticoagulants for postoperative myocardial injury

Myocardial injury after non-cardiac surgery (MINS), detected by elevated troponin measurement, is a common postoperative complication and increases the risk of 30-day mortality by three times.1 In The Lancet, P J Devereaux and colleagues2 report the results of the MANAGE trial, a randomised, placebo-controlled study investigating use of the direct oral anticoagulant dabigatran in 1754 patients with MINS. Eligible patients were aged at least 45 years, had undergone non-cardiac surgery, and were within 35 days of MINS.