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Take a look at a selection of our recent media coverage:

No link found between testosterone gel therapy and higher risk of cardiovascular events

23rd June 2023

Topical testosterone therapy for middle-aged and older men with hypogonadism and either pre-existing or at a high-risk of cardiovascular disease, does increase the risk of adverse cardiac events according to a recent, randomised trial.

The cardiovascular risks of using testosterone therapy in men with hypogonadism are still unclear. Some data suggests that replacement therapy in men who underwent coronary angiography was associated with increased risk of adverse outcomes. Conversely, other data from an observational study revealed a lower mortality in those in receipt of replacement therapy compared with no treatment.

With such conflicting results, the current study, published in the New England Journal of Medicine, was designed to determine if testosterone-replacement therapy increased the incidence of major adverse cardiac events among middle-aged and older men with either pre-existing or a high-risk of cardiovascular disease. Individuals at a high-risk included those with hypertension, dyslipidaemia, type 2 diabetes if aged over 65 years of age.

Researchers undertook a phase 4, randomised, double-blind, placebo-controlled, non-inferiority, event-driven trial. Participants were men aged 45-80 years who reported one or more symptoms of hypogonadism, including decreased sexual desire or libido, decreased spontaneous erections, fatigue or decreased energy. These were then randomised in a 1:1 ratio to either daily transdermal 1.62% testosterone gel or matching placebo.

The primary safety endpoint was the first occurrence of any component of major adverse cardiac events, a composite of death from cardiovascular causes, nonfatal myocardial infarction or nonfatal stroke.

Testosterone therapy and adverse cardiac outcomes

Of the 5,204 men, with a mean age of 63.3 years, included in the trial, some 2,601 were assigned to receive testosterone and followed for a mean duration of 33 months.

The primary cardiovascular endpoint event occurred to a similar extent in both groups (hazard ratio, HR = 0.96, 95% CI 0.78 – 1.17, p < 0.001 for non-inferiority). Similarly, an analysis of secondary outcomes, which were the individual components of the primary composite, also revealed no significant differences between either testosterone therapy and the matching placebo.

Adverse events were similar in the two groups with 45.7% and 44.7% of those in the testosterone and placebo group respectively, experiencing any adverse event. However, there was a significantly higher incidence of nonfatal arrhythmias warranting intervention in the testosterone group (p = 0.001).

Nevertheless, the researchers conducted that testosterone therapy was non-inferior to placebo with respect to the incidence of major adverse cardiac events.

Medical cannabis and the cardiovascular system: a dangerous combination?

19th June 2023

With increasing evidence that cannabis use is associated with adverse cardiovascular effects, questions are undoubtedly being asked about the safety of the drug for medical uses. Rod Tucker investigates.

Cannabis was one of the first plants cultivated by man, and its first use can be traced to ancient China where evidence suggests it was used for medical purposes from around 2,700 BC and for textiles and other uses as early as 4,000 BC.

Although the plant contains hundreds of compounds, the two most well studied are tetrahydrocannabinol (THC) and cannabidiol (CBD). In the late 1980s and early 1990s, the site of action for cannabis was identified with the discovery of two major cannabinoid receptors, CB1 and CB2, and their endogenous ligands, which form part of the endocannabinoid system. 

While THC is the main psychoactive compound in cannabis that produces the euphoric ‘high’ sensation, over the last decade it has become increasingly clear that it is CBD that has a number of therapeutic benefits. Recognition of this fact has given rise to the terms ‘medical cannabis’ or ‘medical marijuana’.

Cannabis benefits and adverse effects

In a 2021 meta-analysis published in the BMJ, researchers concluded that there was moderate- to high-certainty evidence that medical cannabis or cannabinoids results in a small to very small improvement in pain relief, physical functioning and sleep quality in patients with both chronic, non-cancer pain and cancer-related pain.

Although medical cannabis use is associated with some adverse effects such as cognitive impairment, vomiting, drowsiness and impaired attention, there has been little attention paid to any potential adverse cardiovascular (CV) sequelae. One likely explanation is that there remains some uncertainty over the magnitude of these effects and therefore whether such risks should be highlighted.

In fact, in a statement on the use of cannabis and its CV effects, the American Heart Association (AHA) states that ‘overall, evidence is still inconclusive for cannabis use and adverse cardiovascular outcomes’ and it called for carefully designed prospective studies to examine this issue in more detail.

Since the publication of the AHA statement, more evidence has come to light, which suggests that the use of cannabis has several adverse effect on the CV system.

Cardiovascular risks

For several states in the US and many other countries such as Canada, use of recreational cannabis has been legalised although this has had some unintended consequences, such as an increase cannabis and alcohol poly use, in addition to adverse cardiovascular effects.

In a recent abstract in the Journal of the Society for Cardiovascular Angiography and Interventions, researchers found that cannabis users were at a more than three times greater risk of developing peripheral artery disease than non-users (Odds ratio, OR = 3.68, p<0.001). Fortunately, however, there was no increased risk for any subsequent intervention or mortality from their peripheral ischaemia.

Despite this, a further abstract revealed that cannabis users were at a statistically significant higher risk of having a myocardial infarction (OR = 3.33, p < 0.001) and an increased likelihood of requiring a percutaneous coronary intervention during hospitalisation (OR = 1.76, p <0.001). Furthermore, users were also at a markedly increased risk of all-cause mortality during hospitalisation (OR = 14.77, p < 0.001).

Cannabis use also increases the risk of arrhythmias and in particular, atrial fibrillation (AF) as well as myocardial injury in those without pre-existing cardiovascular disease. While these studies are concerning, a 2020 systematic review on the cardiac effects of cannabis use concluded that while there is an increased risk of cardiac dysrhythmia, which can be life-threatening, this is rare.

A more recent meta-analysis of observational studies published in 2023 in the journal Toxicology Reports, indicated that cannabis use does increase the risk of an acute myocardial infarction, stroke and any adverse cardiovascular event. Nevertheless, while the pooled odds ratio estimates for each event were non-significant there was also a high degree of heterogeneity among studies.

THC vs CBD

With a clear body of evidence implicating the development of adverse CV outcomes among cannabis users, a limitation of the data is that it is derived from self-reported, recreational use. Furthermore, the focus of research has been on the adverse cardiovascular effects of THC, whereas medical cannabis is predominately based on CBD.

So, is there evidence that CBD-based medical cannabis is harmful to the heart? While there is currently a paucity of data on the CV effects of medicinal cannabis, the available information is somewhat reassuring.

One review highlighted the anti-inflammatory and anti-oxidant effects of CBD and suggested that it appears to have positive effect on the CV system. Further evidence to support the beneficial impact of CBD on the CV system comes from studies in patients with hypertension.

For instance, a study of medicinal cannabis use in older hypertensives published in the European Journal of Internal Medicine, found that after only three-months use of mainly cannabis oil, there was a signification drop in blood pressure. Interestingly, the researchers were unable to detect any adverse changes to participant’s ECGs and no new sustained arrhythmias developed, even though the median daily intake of THC and CBD was roughly the same (21 mg). Similar blood pressure reducing effects were seen in a recent randomised, placebo-controlled, cross-over trial in hypertensive patients using an oral CBD product.

Additionally, repeated CBD dosing has been shown to reduce arterial stiffness and improve endothelial function, revealing a potentially valuable role for those with vascular diseases. Whilst studies to date are largely positive and do not suggest harmful effects on the heart, a recent analysis by Danish researchers sounded a note of caution. Using a national registry, the team examined the potential adverse cardiac effects of CBD when used for the management of chronic pain. Their findings revealed a 64% increased risk of arrhythmias among CBD users compared to non-users.

While it has become recognised that the recreational use of cannabis is associated with deleterious effects on the cardiovascular system, this seems to be less likely with medical cannabis. Nonetheless, research to more clearly delineate the cardiovascular risks associated with medicinal cannabis use is urgently required. In the meantime, clinicians need to remain wary, because the jury is still out on whether or not medical cannabis and the cardiovascular system represents a dangerous combination.

Continued smoking after cancer diagnosis increases risk of adverse CVD event

8th June 2023

Ongoing smoking following a cancer diagnosis, elevates the risk of adverse cardiovascular disease (CVD) events, according to the findings of a study by Korean researchers.

Emerging data indicates how continued smoking following a cancer diagnosis increases the risk of cardiovascular disease mortality.

In fact, nearly 20% of cancer survivors continue to smoke. However, the differential effect on adverse cardiovascular outcomes, of either quitting smoking, cutting down or continuing to smoke is less clear.

The current study, published in the European Heart Journal, assessed the effect of changes to smoking habits on adverse cardiovascular outcomes.

Smoking status was assessed two years before and three years after a cancer diagnosis. Participants were categorised as non-smokers; quitters, initiators and relapsers, and continued smokers.

The primary outcome was a composite of CVD events, comprising hospitalisation for myocardial infarction or stroke, or CVD death.

Smoking status and adverse cardiovascular outcomes

Among 309,095 cancer survivors with a median age of 59 years (51.8% women), 80.9% were non-smokers, 10.1% quit, 7.5% initiated or relapsed to smoking and 7.5% continued to smoke.

During a median follow-up of 5.5 years, 10,255 new CVD events occurred. Using non-smokers as the reference point, the adjusted hazard ratio (aHR) for a CVD event among quitters was 20% higher (aHR = 1.20, 95% CI 1.12 – 1.28). But among those who continued to smoke, the risk was 86% higher (aHR = 1.86, 95% CI 1.74 – 1.98).

There were clear benefits for those who quit smoking. For example, the CVD event risk was significantly lower among those who quit compared to participants continuing to smoke (aHR = 0.64, 95% CI 0.59 – 0.70).

These findings were consistent across both sexes as well as when classifying participants according to their primary cancers. Among those who continued to smoke, cutting down had no effect on their risk of a CVD event (HR = 0.99, 95% CI 0.80 – 1.22).

The authors suggested that continued smoking after a cancer diagnosis and its association with CVD events highlighted the urgent need for initiatives to promote smoking cessation and prevent smoking initiation and/or relapse among patients with cancer.

Pemafibrate fails to reduce cardiovascular events in type 2 diabetes

15th November 2022

An RCT has found that use of Pemafibrate in patients with type 2 diabetes failed to reduce adverse cardiovascular outcomes compared to placebo

The use of pemafibrate in patients with type 2 diabetes, mild-to-moderate hypertriglyceridemia and low levels of HLD cholesterol, failed to lower the incidence of adverse cardiovascular outcomes compared to placebo according to a randomised, doubler-blind, placebo-controlled trial by US researchers.

Elevated levels of triglycerides confer an increased risk of cardiovascular disease but whether reducing levels also reduces adverse cardiovascular events such as myocardial infarction is actually less clear. For example, in a trial with fenofibrate while there was a 25% reduction in mean triglyceride levels, there was no difference in the rate of fatal cardiovascular events, nonfatal myocardial infarction, or nonfatal stroke. Pemafibrate is a peroxisome proliferator-activated receptor modulator which lowers plasma triglycerides and increase HDL cholesterol and both of these effects are associated with cardiovascular benefit. Moreover, the drug is superior to fenofibrate at lowering serum triglycerides and has a good renal and hepatic safety profile.

But whether the drug also reduced adverse cardiovascular outcomes in patients with type 2 diabetes is uncertain and was the subject of the present trial. Included patients had triglyceride levels between 2.3 and 5.6 mmol/l and HDL cholesterol levels < 1 mmol/l. The primary endpoint was the first occurrence of a major adverse cardiovascular event and which was a composite that included myocardial infarction, ischaemic stroke and hospitalisation for unstable angina.

Pemafibrate and cardiovascular outcomes

A total of 10,497 patients with a median age of 64 years (27.5% female) were included and randomised to pemafibrate (5,240) or placebo. and followed by a median of 3.4 years. Two thirds of those enrolled were a secondary prevention cohort and 95% of the whole study population were prescribed a statin.

The median reduction in triglyceride levels was 31.1% in the pemafibrate group and 6.9% in the placebo group. In addition, HDL cholesterol levels rose by 8.3% in those taking pemafibrate but only 3.1% in the placebo arm.

The primary endpoint occurred in a similar number of patients and the difference was not significant (Hazard ratio, HR = 1.03, 95% CI 0.91 – 1.15, p = 0.67). Mortality from any cause was also similar and non-significant (HR = 1.04, 95% CI 0.91 – 1.20).

The authors concluded that while pemafibrate reduced triglyceride levels by over 30% in patients with type 2 diabetes, there was no significant reduction in the risk of adverse cardiovascular events.

Citation
Das Pradham A et al. Triglyceride Lowering with Pemafibrate to Reduce Cardiovascular Risk N Eng J Med 2022

Adverse cardiovascular outcomes higher in patients hospitalised with COVID-19

4th November 2022

The risk of adverse cardiovascular outcomes is significantly higher in patients hospitalised with COVID-19 compared to uninfected controls

There is an elevated risk of several adverse cardiovascular outcomes among patients hospitalised with COVID-19 but the risk of both venous thromboembolism and death is still significant in non-hospitalised cases compared to a group of uninfected, matched controls. These were the key findings from a prospective analysis of participants in the UK Biobank by UK researchers.

Studies have suggested that infection with COVID-19 is a risk factor for acute myocardial infarction and ischaemic stroke. Moreover, a retrospective study has revealed how cardiac arrhythmia is also a clinical sequelae following an acute infection with the virus. Nevertheless, whether these adverse cardiovascular events are restricted to patients with more severe disease, i.e., those who are hospitalised, or whether there is an increased risk among patients with less severe disease remains unclear. In the present study, UK researchers examined if exposure to COVID-19 was associated with incident cardiovascular disease and mortality. The used data from the UK Biobank and identified those infected with COVID-19, linking to Public Health England laboratory information to identify PCR test results. These individuals were then propensity matched to 2 control patients based on a number of factors including age, sex, body mass index, various co-morbidities (e.g., hypertension, diabetes), smoking status and ethnicity. The researchers considered several adverse cardiovascular outcomes including myocardial infarction (MI), venous thromboembolism (VTE), cardiovascular disease (CVD) mortality, stroke, heart failure, atrial fibrillation and pericarditis. In a further analysis, the team assessed if the risk of these adverse cardiovascular outcomes reduced over time.

Adverse cardiovascular outcomes and COVID-19

A total of 471,227 individuals with a median age of 69 years (44.7% male) were included in the analysis which included 17,871 COVID-19 patient cases. Individuals were followed-up for an average of 141 days. Among those with COVID-19, the majority (80%) were not hospitalised and in the hospitalised cohort (3567), 75.7% had primary diagnosis of COVID-19 whereas the remainder had COVID-19 recorded as a secondary diagnosis.

Among non-hospitalised COVID-19 patients (14,304), there was a more than two-fold higher risk of VTE compared to uninfected controls (Hazard ratio, HR = 2.74, 95% CI 1.38 – 5.45, p = 0.004). Additionally, there was a significantly increased risk of death (HR = 10.23, 95% 7.63 – 13.7, p < 0.0001). Interestingly, the risk of incident MI among the non-hospitalised COVID-19 group was significantly lower (HR = 0.19, 95% CI 0.06 – 0.65, p = 0.008).

In contrast to the non-hospitalised group, patients hospitalised with COVID-19 had significantly elevated risks of MI (HR = 9.9), heart failure (HR = 21.6), atrial fibrillation (HR = 14.9), VTE (HR = 27.6) and cardiovascular mortality (HR = 8.76). Furthermore, there were also increased adverse cardiovascular risks in patients for whom COVID-19 was the secondary diagnosis, e.g., MI (HR = 22.2), heart failure (HR = 13.1), atrial fibrillation (HR = 29.3) and cardiovascular mortality (HR = 14.6).

Next researchers examined the interaction with time and considered the risk of events 30 days before and after their acute infection. Although the risks for atrial fibrillation, VTE and heart failure were largely attenuated after 30 days, these risks still remained significant, e.g., for VTE (HR = 3.97) and heart failure (HR = 2.78).

The authors concluded that while infection with COVID-19 is associated with a higher risk of adverse cardiovascular outcomes, the risks are largely confined to hospitalised patients and highest within the first 30 days following infection.

Citation
Raisi-Estabragh Z et al. Cardiovascular disease and mortality sequelae of COVID-19 in the UK Biobank Heart 2022

Higher C-reactive protein and lipoprotein(a) levels linked to worse outcomes after PCI

3rd November 2022

High C-reactive protein and lipoprotein A levels in percutaneous coronary intervention (PCI) patients leads to worse cardiovascular outcomes

Elevated levels of both C-reactive protein (CRP) levels and lipoprotein A (LpA) in those with coronary heart disease undergoing a percutaneous coronary intervention (PCI) result in a greater risk of major adverse cardiovascular and cerebrovascular events according to the results of a study by Chinese researchers.

The risk of a recurrent vascular event in patients with established cardiovascular disease remains even in those with optimal treatment. For example, one study has found that when risk factors are modified to achieve guideline recommended targets, the residual 10-year risk while < 10% in 47% of patients is >30% in 9%. One factor associated with this residual risk is inflammation and it has been found that patients who have low CRP levels after statin therapy, had better clinical outcomes than those with higher CRP levels, regardless of the resultant level of LDL cholesterol. Furthermore, clinical and genetic research studies have also shown that lipoprotein A has a crucial role in the pathogenesis of cardiovascular disease. In fact, it has been found that elevated LpA levels during treatment of cardiovascular disease are related to cardiovascular-related death when CRP levels are > 2 mg/L. Nevertheless, much less is known about the relationship between CRP and LpA levels in patients undergoing PCI.

For the present study, the Chinese team set out to examine the joint and independent association between LpA and CRP levels among patients with coronary artery disease who underwent a PCI. The researchers used data from a prospective, observational cohort at a national tertiary care centre and identified patients undergoing PCI and where LpA and CRP levels had been measured. Patients were followed-up for 5 years after discharge and the team set the primary endpoint as major adverse cardiac and cerebrovascular events (MACCE), which was a composite of all-cause mortality, myocardial infarction, unplanned revascularisation and ischaemic stroke.

C-reactive protein and lipoprotein A levels and MACCE

A total of 10,424 patients with a mean age of 58.4 years (77.2% male) were included in the analysis. The median level of LpA was 18.53 mg/dL and CRP 1.62 mg/L. After 5 years of follow-up, the primary endpoint (MACCE) occurred in 20.5% of participants.

Multivariable analysis showed that when LpA levels were > 30 mg/dL there was a higher risk of MACCE (Hazard ratio, HR = 1.14, 95% CI 1.05 – 1.25, p < 0.05) compared to levels below 30 mg/dL. Similarly, CRP levels above 2 mg/L were also significantly associated with a greater risk of MACCE (HR = 1.10, 95% CI 1.01 – 1.20, p < 0.05).

But when both LpA and CRP were higher than 30 mg/dL and 2 mg/L respectively, in fully adjusted models, there was a 22% higher risk of MACCE (HR = 1.22, 95% CI 1.07 – 1.39, p < 0.05).

The authors concluded that elevated LpA levels were associated with a higher risk of adverse cardiovascular events and that this risk was even higher when C-reactive protein levels were above 2 mg/L. They suggested that measuring levels of both could help identify high-risk individuals and who might benefit from further therapeutic interventions.

Citation
Yuan D et al. Lipoprotein(a), high-sensitivity C-reactive protein, and cardiovascular risk in patients undergoing percutaneous coronary intervention Atherosclerosis 2022

Polypill effective for secondary prevention

1st September 2022

A polypill containing aspirin, ramipril and atorvastatin used in secondary prevention reduces the risk of a composite cardiovascular outcome

A polypill which contains aspirin, ramipril and atorvastatin given to patients who have experienced a previous myocardial infarction reduces the risk of a subsequent adverse cardiovascular outcome according to the findings of a randomised trial by the SECURE investigators.

Medication adherence is used to define the extent to which a patient takes medication as prescribed by their healthcare providers. Higher levels of adherence are associated with better treatment outcomes although poor adherence leads to considerable morbidity, mortality, and avoidable health care costs.

In a meta-analysis specifically focusing on cardiovascular medicine, only 60% of included participants had good adherence, i.e., ≥ 80%. However, the authors estimated that ∼9% of all cardiovascular disease (CVD) cases could be attributable to poor adherence.

In contrast, good adherence to cardiac therapies could be associated with a 20% lower risk of CVD and a 35% reduced risk of all-cause mortality, irrespective of most clinically relevant patient and study characteristics.

The use of a polypill is designed to simplify a medication regime and in a meta-analysis of three large trials, it was concluded that the fixed-dose combination (i.e., polypill) substantially reduced cardiovascular disease, myocardial infarction, stroke, revascularisation, and cardiovascular death in primary cardiovascular disease prevention.

But it is less clear whether the polypill is an effective strategy for secondary prevention. As a result, researchers undertook the Secondary Prevention of Cardiovascular Disease in the Elderly (SECURE) trial, which compared the efficacy of a polypill compared to usual care as a means of reducing major cardiovascular outcomes in older patients.

To be included in the trial, patients were required to have a history of a myocardial infarction within the previous six months and at least one risk factor such as diabetes, kidney dysfunction or prior stroke, although those receiving oral anticoagulation were excluded. Individuals were randomised 1:1 to the polypill which contained aspirin 100 mg, ramipril 2.5, 5 or 10 mg and atorvastatin 40 mg although the dose of statin could be reduced to 20 mg (using a similar lower dose polypill) based on blood test results and a patient’s history.

Treatment adherence was assessed using the Morisky Medication Adherence Scale (MMAS), which ranges from 0 to 8 with higher scores reflecting better adherence. The primary outcome was a composite of cardiovascular death, non-fatal type 1 myocardial infarction, non-fatal ischaemic stroke or urgent coronary revascularisation.

A key secondary outcome was a composite of cardiovascular death, non-fatal type 1 myocardial infarction, non-fatal ischaemic stroke.

Polypill and cardiovascular outcomes

A total of 2466 patients were randomised, 1237 with a mean age of 75.8 years (69% male) to the polypill and followed for a a median of 36 months.

The primary outcome occurred in 9.5% of those assigned to the polypill and 12.7% of those assigned to usual care (hazard ratio, HR = 0.76, 95% CI 0.60 – 0.96, p = 0.02). The main secondary outcome also occurred in less patients taking the polypill (HR = 0.70, 95% CI 0.54 – 0.90, P = 0.005).

After 24 months, 74.1% of those receiving the fixed-dose combination had a high level of adherence (MMAS score of 8) compared to 63.2% in the usual care group.

The authors concluded that the use of a cardiovascular polypill could serve as a substitute for separate drugs and decrease the risk of recurrent cardiovascular events.

Citation
Castellano JM et al. Polypill Strategy in Secondary Cardiovascular Prevention N Eng J Med 2022

Neither metformin nor lifestyle interventions reduce risk of major adverse CV outcomes in pre-diabetics

1st June 2022

Use of either metformin or lifestyle interventions was unable to reduce the risk of a major adverse cardiovascular (CV) event in patients with pre-diabetes.

This was the key finding from a 21-year follow-up study by the Diabetes Prevention Program Research Group.

A 2018 global review of cardiovascular disease (CVD) in patients with type 2 diabetes found a prevalence of 32.2% and noted that CVD mortality accounts for approximately half of all deaths in these patients. In 1998, results from the UK Prospective Diabetes Study showed that metformin use reduced all-cause mortality by 36%.

Moreover, a study of the long-term effects of lifestyle interventions in people with impaired glucose tolerance found that such interventions delayed the onset of type 2 diabetes, as well as reducing the incidence of cardiovascular and all-cause mortality.

With a potential cardiovascular and mortality benefit from both metformin or lifestyle interventions aimed at weight reduction and increased physical activity, the Diabetes Prevention Program Research Group examined the value of each intervention in a randomised trial (the Diabetes Prevention Program (DPP) study) which was published in 2002.

The study assigned 3234 non-diabetic participants with elevated fasting and post-load plasma glucose concentrations, to either placebo, metformin (850mg twice daily), or a lifestyle-modification programme. The results showed that both metformin and lifestyle interventions, reduced the incidence of diabetes in persons at high risk by 58% and 31% respectively over an average of 2.8 years.

Based on these findings, the researchers invited pre-diabetic participants from the original DPP to enrol in a follow-on study to determine whether metformin and lifestyle interventions could reduce the incidence of adverse cardiovascular outcomes.

Participants continued with the same dose of metformin (850mg twice daily) and the lifestyle intervention. The primary outcome was the first occurrence of a major cardiovascular event which was pre-specified as non-fatal myocardial infarction, non-fatal stroke or fatal CVD.

Metformin or lifestyle interventions and CVD outcomes

A total of 3234 individuals with a baseline mean age of 51 years (68% women) and with a mean fasting blood insulin level of 160 pmol/L, were followed for a median of 21 years and of whom, 1073 were assigned to placebo, 1082 metformin and 1079 a lifestyle intervention.

During the period of follow-up, 310 individuals experienced an adverse cardiovascular event; 101 for patients assigned to metformin and 111 to the lifestyle intervention. These events did not differ significantly compared with placebo (hazard ratio, HR = 1.03, 95% CI 0.78 – 1.37, p = 0.81, metformin vs placebo) and a hazard ratio of 1.14 (95% CI 0.87 – 1.40, p = 0.34) for lifestyle vs placebo.

When considering non-fatal myocardial infarctions and strokes separately, there no significant differences for either intervention compared to placebo.

The authors concluded that despite the value of each intervention to reduce the risk of developing overt type 2 diabetes, neither was associated with a reduced risk of cardiovascular events in pre-diabetic patients.

Citation
Goldberg RB et al. Effects of Long-term Metformin and Lifestyle Interventions on Cardiovascular Events in the Diabetes Prevention Program and Its Outcome Study Circulation 2022

SGLT-2 inhibitors and metformin have similar cardiovascular outcomes in type 2 diabetes

31st May 2022

SGLT-2 inhibitors and metformin have similar CV outcomes in type 2 diabetes though SGLT-2 inhibitors slightly lower heart failure mortality

SGLT-2 inhibitors and metformin when initiated for patients with type 2 diabetes have been shown to have the same cardiovascular outcomes such as myocardial infarction, stroke and death although use of SFLT-2 inhibitors is associated with a slightly lower risk of both hospitalisation and death due to heart failure.

These were the key findings from a cohort study analysis by a team based at Harvard University, Boston, USA.

Sodium-glucose cotransporter-2 inhibitors (SGLT-2i) such as empagliflozin, although primarily used in the management of type 2 diabetes, have also been shown to reduce cardiovascular events when added to standard care.

In addition, evidence from the UK Prospective Diabetes Study showed that patients assigned to metformin had risk reductions of 32% for any diabetes-related endpoint, 42% for diabetes-related death and 36% for all-cause mortality.

Thus, although SGLT-2 inhibitors and metformin are primarily diabetic treatments, it is apparent that both are associated with cardiovascular benefits in diabetic patients. Furthermore, using SGLT-2 inhibitors and metformin as a first-line combination therapy for patients with type 2 diabetes has been suggested as a cost-effective strategy for the management of both type2 diabetes and cardiovascular disease.

However, what remains uncertain, is the relative cardiovascular benefits of using either a SGLT-2 inhibitor or metformin as mono-therapy in patients with type 2 diabetes.

In the present study, the US team used information held within two large commercial health insurance databases to compare the incidence of cardiovascular events when either treatment was initiated as mono-therapy.

The researchers focused on adults (> 18 years of age) with a diagnosis of type 2 diabetes and those who had new prescription for SGLT-2 inhibitors or metformin. Individuals were followed-up until the occurrence of a study outcome, death or discontinuation of treatment.

There were two primary outcomes of interest; a composite of acute myocardial infarction, stroke or all-cause mortality (referred to as ‘mortality’) and a composite of hospitalisation for heart failure or all-cause mortality (HHF).

For secondary outcomes, the authors individually assessed the effect of either treatment on different components of the two composites. Individuals were propensity-matched 1:2 (SGLT-2i: metformin).

SGLT-2 inhibitors and metformin

A total of 8,613 first-time SGLT-2i patients were matched to 17,226 metformin users, with a mean age of 60 years (approximately 51% male). Individuals prescribed SGLT-2i were followed for a mean of 10.7 months and metformin users for 12.2 months.

The risk of the composite mortality outcome was not significantly different between the two treatments (hazard ratio, HR = 0.96, 95% CI 0.77 – 1.19). However, SGLT-2i inhibitor use was associated with a lower risk of HHF (HR = 0.80, 95% CI 0.66 – 0.97).

When each of the outcomes were analysed separately, only hospitalisation for heart failure was significantly lower (HR = 0.78, 95% CI 0.62 – 0.97) in those prescribed a SGLT-2i.

Based on these findings, the authors concluded that first-line treatment of type 2 diabetes with SGLT-2i or metformin was associated with a similar risk of adverse cardiovascular outcomes although SGLT-2i use was linked to a lower risk of hospitalisation and mortality due to heart failure. However, they called for a randomised trial to provide more robust evidence to confirm these findings.

Citation
Shin JH et al. Cardiovascular Outcomes in Patients Initiating First-Line Treatment of Type 2 Diabetes With Sodium–Glucose Cotransporter-2 Inhibitors Versus Metformin. A Cohort Study Ann Intern Med 2022

Higher avocado intake linked with a reduced risk of cardiovascular disease

27th April 2022

A higher avocado intake has been found to be associated with a lower risk of cardiovascular disease in two large prospective studies

A higher avocado intake reduces the risk of cardiovascular disease according to the findings from two large prospective studies reported by researchers from Harvard T.H. Chan School of Public Health, Boston, USA.

Cardiovascular disease (and which also includes coronary heart disease) represents the leading cause of death globally. Interestingly, studies suggest that there is a valid association between several dietary factors and patterns with coronary heart disease.

One healthy food is avocado, which contains a large amount (71%) of monounsaturated fatty acids and helps to promote healthy blood lipid profiles, enhancing the bioavailability of fat soluble vitamins and phyto-chemicals from the avocado or other fruits and vegetables.

In fact, there are data showing how avocado consumption is associated with a reduced risk of metabolic syndrome and other work has indicated that eating at least one avocado each day provides a beneficial effect on cardio-metabolic risk factors that extended beyond their heart-healthy fatty acid profile.

Furthermore, a recent systematic review found that avocado intake increased serum HDL-cholesterol concentrations, prompting the authors to suggest that the association between avocado intake and cardiovascular risk should be confirmed by well-conducted prospective observational studies or long-term trials.

For the present study, the US team examined the association between a higher avocado intake and cardiovascular outcomes. They turned to data held in both the Nurse’s Health Study (NHS) and the Health Professionals Follow-up Study (HPFS), which are two prospective cohort studies which were initiated in the 1970’s and 1980’s respectively.

In both of these cohort studies, participants were asked to complete validated questionnaires asking about lifestyle and diet every 2 years and from this information, the researchers were able to determine how much avocado was consumed. This was then categorised as never or less than once a month, 1 – 3 times per month, weekly and > twice a week.

The primary outcome of interest was incident cases of total cardiovascular disease, which was a composite of several adverse cardiovascular outcomes e.g., fatal coronary heart disease. The main secondary outcome related to strokes.

Higher avocado intake and adverse cardiovascular outcomes

A total of 68,786 women from the NHS and 41,701 men from the HPFS who were free of cardiovascular disease and stroke at baseline were included and followed for 30 years (median for men was 13.3 years and 14.2 for women). During follow-up there were a total of 14,274 cases of cardiovascular disease (CVD) in both NHS and HPFS.

After adjustments were made for dietary and lifestyle factors, compared to those who did not eat avocados, individuals with a higher avocado intake (> twice/week) week had a 16% lower risk of CVD (hazard ratio, HR = 0.84, 95% CI 0.75 – 0.95) and a 21% lower risk of coronary heart disease (HR = 0.79, 95% CI 0.68 – 0.91). However, there was no significant reduction for stroke.

The authors calculated that for each half serving/day increase in avocado intake, the pooled hazard ratio for CVD was 0.80. In fact, the authors added that by replacing half a serving/day of margarine, butter, egg, yoghurt, cheese or processed meats with the equivalent amount of avocado would be associated with a 16 to 22% lower risk of CVD.

Citation
Pacheco LS et al. Avocado Consumption and Risk of Cardiovascular Disease in US Adults J Am Heart Assoc 2022

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