Saturday, September 23, 2023

Medically, you might be interested in…

A regular series on the latest clinical studies from around the world – and what they mean ‘in practice’ – compiled and written by Clare GP Dr Ray O’Connor

1. Cardiovascular health
The average life expectancy has increased substantially in the past few decades in most industrialized countries; however, it is noted that not all of the increased life expectancy is being spent in optimal health. Increasing numbers of middle-aged and elderly individuals live more years affected by various chronic diseases, such as diabetes, cardiovascular disease (CVD), cancer, and dementia.

Dr Ray O’Connor

The objective of this cohort study1 was to quantify the associations between levels of cardiovascular health (CVH), estimated by the American Heart Association’s Life’s Essential 8 (LE8) metrics, with life expectancy free of major chronic disease, including cardiovascular disease (CVD), diabetes, cancer, and dementia, in UK adults. It included 135,199 adults in the UK Biobank study who were initially free of major chronic disease and had complete data on LE8 metrics.

The exposure studied was cardiovascular health levels, as estimated by LE8 score. The LE8 score, which consists of eight components: (1) diet, (2) physical activity, (3) tobacco/nicotine exposure, (4) sleep, (5) body mass index, (6) non–high-density lipoprotein cholesterol, (7) blood glucose, and (8) blood pressure. The CVH level was evaluated at baseline and categorized into low (LE8 score <50), moderate (LE8 score>50 but <80), and high (LE8 score>80) levels. The primary outcome was the life expectancy free of four major chronic diseases (CVD, diabetes, cancer, and dementia).

The findings were that high CVH level was associated with substantially longer life expectancy free of the four major chronic diseases in both men and women. Furthermore, the disease-free life expectancy was similar between low and other socioeconomic groups among participants with high CVH. These findings support improvement in population health by promoting a high CVH level, which may also narrow health disparities associated with socioeconomic status.

Insomnia has been closely associated with CVD including myocardial infarction (MI). This systematic review2 aimed to assess the eligibility of insomnia as a potential risk factor for MI.

The authors concluded that Insomnia and ≤5 h of sleep are highly associated with increased incidence of MI. This is an association comparable to that of other MI risk factors. The authors recommend that it should be considered as a risk factor for MI and to be incorporated into MI prevention guidelines.

For those who have had an MI, there is uncertainty as to whether Beta Blockers (BB) beyond the first year of MI have a role in patients without heart failure or left ventricular systolic dysfunction (LVSD).

This nationwide cohort study was conducted including 43,618 patients with MI between 2005 and 2016 in the Swedish register for coronary heart disease.3 Follow-up started one-year after hospitalisation (index date). Patients with heart failure or LVSD up until the index date were excluded. Overall, 34,253 (78.5 per cent) patients received BB and 9,365 (21.5 per cent) did not at the index date one year following MI.

The median age was 64 years and 25.5 per cent were female. Primary outcome was a composite of all-cause mortality, MI, unscheduled revascularisation and hospitalisation for heart failure. The risk of the primary outcome was not different according to BB treatment. Similar findings were observed when censoring for BB discontinuation or treatment switch during follow-up.

The authors concluded that BB treatment beyond one year of MI for patients without heart failure or LVSD was not associated with improved cardiovascular outcomes.

Hypertension is globally the strongest modifiable risk factor for cardiovascular disease-related disability and death. Despite extensive knowledge about how to prevent and treat hypertension, its global incidence, prevalence and cardiovascular complications are not reducing. Hypertension is among the most common problems managed by general practitioners, yet even among people with treated hypertension, many are not adequately controlled.

Fixed-dose combination (FDC) therapy may provide a solution to treatment gaps by overcoming reasons for therapeutic inertia. The aim of this systematic review was to synthesise and report on available evidence on standard or low-dose combination medicines that combine at least three antihypertensive medicines.4

A literature search was conducted for randomised clinical trials that included adults (>18 years) and examined the impact of at least three antihypertensive medications on blood pressure (BP). A total of 18 trials (n=14 307) were identified.

The authors concluded that triple and quadruple combination antihypertensive medications are effective. Studies of low-dose triple and quadruple combinations involving treatment naïve populations suggest initiating such combinations are safe and effective as first-line therapy for stage 2 hypertension (BP >140/90 mm Hg).

Finally, the European Hypertension guidelines for the management of hypertension have been updated.5 It is a long (over 200 pages) and very comprehensive document. However, it gives clear simple evidence-based advice on when and how to measure BP, the definition of hypertension and its management. It is a useful reference document to have on your desktop.


  1. Wang X et al. Association of Cardiovascular Health With Life Expectancy Free of Cardiovascular Disease, Diabetes, Cancer, and Dementia in UK Adults. JAMA Intern Med. DOI:10.1001/jamainternmed.2023.0015. Published online February 27, 2023.
  2. Dean Y et al. Association between insomnia and the incidence of myocardial infarction: A systematic review and meta‐analysis. Clin Cardiol. 2023;1–10. DOI:10.1002/clc.23984.
  3. Ishak D et al. Association of beta-blockers beyond 1 year after myocardial infarction and cardiovascular outcomes. Heart 2023 May 2;heartjnl-2022-322115. DOI:10.1136/heartjnl-2022-322115.
  4. O’Hagan E et al. Hypertension therapy using fixed-dose polypills that contain at least three medications. Heart Epub ahead of print. DOI:10.1136/heartjnl-2022-321496.
  5. 2023 ESH Guidelines for the management of arterial hypertension. The Task Force for the management of arterial hypertension of the European Society of Hypertension. Endorsed by the European Renal Association (ERA) and the International Society of Hypertension (ISH). 2023 ESH Guidelines for the management of arterial hypertension. The Task Force for the management of arterial hypertension of the European Society of Hypertension. Endorsed by the European Renal Association (ERA) and the International Society of Hypertension (ISH). J Hypertens 41:000–000 Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved. DOI:10.1097/HJH.0000000000003480.

2. Long Covid
Covid-19 may subsequently be associated with long Covid, whose symptoms can include persistent respiratory symptoms up to one year later. Rehabilitation is currently recommended by most guidelines for people with this condition. The aim of this study1 was to evaluate the effects of exercise training rehabilitation (ETR) on dyspnoea and health-related quality of life measures in people with continuing respiratory discomfort following Covid-19-related acute respiratory distress syndrome (CARDS).

Participants received either ETR or standard physiotherapy (SP) for 90 days. The primary outcome was dyspnoea.

Some 487 participants with CARDS were screened for inclusion, of whom 60 were randomly assigned to receive either ETR (n = 27) or SP (n = 33). It was found that those treated with ETR therapy for 90 days had significantly improved dyspnoea scores.

So can long Covid be prevented? The aim of this study was to evaluate whether outpatient Covid-19 treatment with metformin, ivermectin, or fluvoxamine soon after SARS-CoV-2 infection could reduce the risk of long Covid.2

The authors conducted a decentralised, randomised, quadruple-blind, parallel-group, phase 3 trial at six sites in the USA. They included adults aged 30–85 years with overweight or obesity who had Covid-19 symptoms for fewer than seven days and a documented SARS-CoV-2 positive PCR or antigen test within three days before enrolment.

Between December 30, 2020, and January 28, 2022, 6,602 people were assessed for eligibility and 1,431 were enrolled and randomly assigned. Of 1,323 participants who received a dose of study treatment and were included in the modified intention-to-treat population, 1,126 consented for long-term follow-up.

The findings were that outpatient treatment with metformin reduced long Covid incidence by about 41 per cent, with an absolute reduction of 4.1 per cent, compared with placebo. Thus, metformin has clinical benefits when used as outpatient treatment for Covid-19 and is globally available, low-cost, and safe.


  1. Romanet C et al. Effectiveness of exercise training on the dyspnoea of individuals with long COVID: A randomised controlled multicentre trial. Ann Phys Rehabil Med. 2023 Jun; 66(5): 101765. Published online 2023 Jun 2. DOI: 10.1016/
  2. Bramante C et al. Outpatient treatment of Covid-19 and incidence of post-Covid-19 condition over 10 months (COVID-OUT): a multicentre, randomised, quadruple-blind, parallel-group, phase 3 trial. Lancet Infect Dis 2023. Published online June 8, 2023.

3. Effects of social factors on health
Pictures are worth a thousand words, they say. This graph from the USA very clearly shows the effects of age and poverty on health.1 The ‘total’ figure on the left shows the effect of age only. As expected, older people are more likely to report their health as fair or poor, and this increases with increasing age.

The other three figures clearly show the effects of poverty on health. Those with incomes below the poverty line have around twice the average rate of poor health, and around three times the rate of those in the highest income cohort. Also note how poor health starts at a much lower age for the poorer groups. Surely this is the strongest argument that eliminating poverty is one of the best ways to improve the health of our populations.

One clue as to how this might come about is in a study of childhood asthma.2 In the USA, black children have two to three times the prevalence of asthma as white children and, among those with asthma, have more than twice the risk for emergency department visits and hospitalizations, compared with white children. Multiple causes of this disproportionate burden of asthma morbidity—many tied to living in disadvantaged urban neighbourhoods—have been identified, including indoor allergen exposures, indoor and outdoor air pollution, and neighbourhood-related stress.

The objective of this cohort study was to examine whether participation in a housing mobility program that provided housing vouchers and assistance moving to low-poverty neighbourhoods was associated with reduced asthma morbidity among children, and to explore potential mediating factors.

The study looked at 123 children aged five to 17 years with persistent asthma whose families participated in the Baltimore Regional Housing Partnership housing mobility program from 2016 to 2020.

In essence, the study children moved to a low-poverty neighbourhood.

The median age was 8.4 years, 58 (47.2 per cent) were female, and 120 (97.6 per cent) were black. Prior to moving, 89 of 110 children (81 per cent) lived in a high-poverty census tract (>20 per cent of families below the poverty line); after moving, only one of 106 children with after-move data (0.9 per cent) lived in a high-poverty tract.

The study found that these children who moved neighbourhoods experienced significant improvements in asthma symptom days and exacerbations. It adds to the limited evidence suggesting that programs to counter housing discrimination can reduce childhood asthma morbidity.


  1. National Center for health Statistics. Percentage of Adults Aged ≥18 Years in Fair or Poor Health, by Family Income and Age Group — National Health Interview Survey, United States, 2021. MMWR / March 31, 2023 / Vol. 72 / No. 13.
  2. Pollack C et al. Association of a Housing Mobility Program With Childhood Asthma Symptoms and Exacerbations. JAMA. 2023;329(19):1671-1681. DOI:10.1001/jama.2023.6488.

4. Diabetes: Neuropathy and glucose drug treatment updates
Diabetic peripheral neuropathic pain (DPNP) is common and often distressing. Most guidelines recommend amitriptyline, duloxetine, pregabalin, or gabapentin as initial analgesic treatment for DPNP, but there is little comparative evidence on which one is best or whether they should be combined. This was a multicentre, randomised, double-blind, crossover trial in patients with DPNP from 13 UK centres.1

Participants were randomly assigned to receive one of six ordered sequences of the three treatment pathways: amitriptyline supplemented with pregabalin (A-P), pregabalin supplemented with amitriptyline (P-A), and duloxetine supplemented with pregabalin (D-P), each pathway lasting 16 weeks.

The authors found that all three treatment pathways and monotherapies had similar analgesic efficacy. Combination treatment was well tolerated and led to improved pain relief in patients with suboptimal pain control with a monotherapy.

Drug treatment update for type 2 diabetes. This systematic review2 and network meta-analysis looked to compare the benefits and harms of drug treatments for adults with type 2 diabetes, adding non-steroidal mineralocorticoid receptor antagonists (including finerenone) and tirzepatide (a dual glucose dependent insulinotropic polypeptide (GIP)/glucagon-like peptide-1 (GLP-1) receptor agonist) to previously existing treatment options. The analysis identified 816 trials with 471,038 patients, together evaluating 13 different drug classes; all estimates of benefit refer to the comparison with standard treatments. Sodium glucose cotransporter-2 (SGLT-2) inhibitors and GLP-1 receptor agonists reduce all cause death.

Non-steroidal mineralocorticoid receptor antagonists, so far tested only with finerenone in patients with chronic kidney disease, probably reduce mortality but other drugs may not. The study confirmed the benefits of SGLT-2 inhibitors and GLP-1 receptor agonists in reducing cardiovascular death, non-fatal myocardial infarction, admission to hospital for heart failure, and end stage kidney disease.

Finerenone probably reduces admissions to hospital for heart failure and end stage kidney disease, and possibly cardiovascular death. Only GLP-1 receptor agonists reduce non-fatal stroke; SGLT-2 inhibitors are superior to other drugs in reducing end stage kidney disease. GLP-1 receptor agonists and probably SGLT-2 inhibitors and tirzepatide improve quality of life. Reported harms were largely specific to drug class (eg, genital infections with SGLT-2 inhibitors, severe gastrointestinal adverse events with tirzepatide and GLP-1 receptor agonists, hyperkalaemia leading to admission to hospital with finerenone).


  1. Tesfaye S et al. Comparison of amitriptyline supplemented with pregabalin, pregabalin supplemented with amitriptyline, and duloxetine supplemented with pregabalin for the treatment of diabetic peripheral neuropathic pain (OPTION-DM): a multicentre, double-blind, randomised crossover trial. Lancet 2022; 400: 680–90 Published Online August 22, 2022.
  2. Shi Q et al. Benefits and harms of drug treatment for type 2 diabetes: systematic review and network meta-analysis of randomised controlled trials. BMJ 2023; 381 DOI: Published April 6, 2023.

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