Dapagliflozin might perchance presumably perchance perchance also minimize the possibility for ventricular arrhythmias and sudden loss of life in sufferers with coronary heart failure and diminished ejection fragment (HFrEF), a post hoc evaluation of the DAPA-HF trial suggests.
The addition of dapagliflozin to same outdated therapy diminished the relative possibility for the most well-known composite endpoint of any serious ventricular arrhythmia, resuscitated cardiac arrest, or sudden loss of life by 21%, when in contrast with placebo (hazard ratio [HR], 0.79; 95% CI, 0.63 – 0.99). Absolutely the possibility discount used to be 1.5% (5.9% vs 7.4%).
The profit used to be consistent in a competing-risks evaluation that integrated all-trigger mortality (HR, 0.80; P = .043) and across the person parts of the composite final consequence, James Curtain, MD, Cardiovascular Research Centre of Glasgow, United Kingdom, mentioned at the digital European Society of Cardiology Congress 2021.
As beforehand reported from the most well-known trial, therapy with the sodium-glucose cotransporter 2 (SGLT2) inhibitor decrease the most well-known endpoint of cardiovascular loss of life or worsening coronary heart failure by 26% amongst 4744 sufferers with HFrEF and in New York Coronary heart Affiliation functional class 2 to 4.
Cochair of the unhurried-breaking science session, Lars Lund, MD, Karolinska Institute, Stockholm, pointed out that dapagliflozin diminished sudden cardiac deaths and associated events to an extent fair like that noticed for cardiovascular deaths, total mortality, and the most well-known trial’s most well-known endpoint.
“So does that mean it has any explicit enact on arrhythmic events or does it mean, equivalent to a beta-blocker, as an illustration, [it] reduces calcium transience and improves facing of calcium, or does it personal an enact merely by bettering coronary heart failure?” he asked.
Curtain spoke back they are restful attempting to realise the implications of this fresh class of drug but that examine personal proven dapagliflozin and assorted SGLT2 inhibitors personal favorable results on detrimental cardiac reworking, which contributes to sudden loss of life and ventricular arrhythmia. They’ve also been proven to gash support cardiac chamber size, left ventricular hypertrophy, and N-terminal pro-B-form natriuretic peptide (NT-proBNP) phases over time, in step with a discount in in myocardial wall stress. “So it might perchance well probably presumably perchance perchance certainly be one of plenty of mechanisms in which they’ll also exert a truly helpful cardiac enact.”
Talking with theheart.org | Medscape Cardiology, Curtain pointed out that the Kaplan-Meier curves for the composite final consequence began to separate early on, but that the clearest separation used to be after 9 months, suggestive of a undeniable circulation on detrimental cardiac reworking over time.
“This would pork up the sufferers’ coronary heart failure bother, but additionally thick ventricles are a key possibility ingredient for the incidence of sudden loss of life and ventricular arrhythmias,” he mentioned. “The outcomes on detrimental cardiac reworking, given its plausibility via our Kaplan-Meier curves, are one [mechanism] that I’d advise to in the first event but I’m sure there are extra than one actions at play.”
In accordance with the fresh evaluation, the most well-known final consequence happened in 315 (6.6%) sufferers; there were 203 adjudicated sudden deaths (64%), 104 investigator-reported ventricular arrhythmias (33%), and eight resuscitated cardiac arrests (3%).
|Parts of the Composite in the Two Groups|
|Dapagliflozin, n (%)||Placebo, n (%)||Hazard Ratio (95% CI)|
|Ventricular arrhythmia||50 (2.1)||65 (2.7)||0.76 (0.53–1.10)|
|Resuscitated cardiac arrest||5 (0.2)||3 (0.1)||n/a|
|Sudden loss of life||93 (3.9)||113 (4.8)||0.81 (0.62–1.07)|
Just predictors of the most well-known final consequence were elevated NT-proBNP phases (odds ratio [OR], 1.54), old ventricular arrhythmia (OR, 1.93), old myocardial infarction (OR, 1.42), male intercourse (OR, 1.53), and elevated physique mass index (OR, 1.03).
The enact of dapagliflozin on the most well-known final consequence used to be consistent in plenty of sensitivity analyses and “normally consistent” across key subgroups, Curtain mentioned.
For the length of a dialogue of the implications, session cochair Mitja Lainscak, MD, Total Sanatorium Murska Sobota, Slovenia, known as out two exceptions. “With regards to sufferers with implanted ICDs, the enact used to be just, and in the sufferers without diabetes, the profit used to be not as much as in diabetic sufferers. Any explanations for that?”
Curtain replied that “or not it is important to designate that in the subgroup analyses, the level estimates were all on the side favoring dapagliflozin and the interplay test used to be not most well-known in that subgroup. The numbers of sufferers who were in the defibrillator group were modest and there used to be a somewhat smaller selection of events, so it might perchance well probably presumably perchance perchance even be more difficult to designate profit in that group.”
Within the dapagliflozin and placebo groups, the event charges per 100 particular person-years were 3.9 and 5.8, respectively, in sufferers with diabetes, and 4.1 and 4.7, respectively, in these without diabetes (P for interplay = .273).
Match charges per 100 particular person-years were 5.8 and 5.9, respectively, in sufferers with a defibrillator at baseline, and 3.5 and 4.9, respectively, in these and not utilizing a defibrillator (P for interplay = .174).
Requested to commentary on the peek, which used to be simultaneously printed in the European Coronary heart Journal, Milton Packer, MD, Baylor University Medical Center, Dallas, mentioned he had “very diminutive self perception” in the findings.
“This used to be fully post hoc and the investigators combined events — with markedly assorted phases of medical significance — in discuss in confidence to assemble a P label not as much as 0.05,” he instructed theheart.org | Medscape Cardiology. “If one takes asymptomatic ventricular arrhythmias out of the evaluation, the enact shouldn’t be any longer statistically most well-known. Moreover, half of sudden deaths in sufferers with coronary heart failure are not associated to a ventricular arrhythmia.”
The authors designate of their file that the evaluation used to be not prespecified and the findings needs to be thought to be “hypothesis producing and require affirmation,” but additionally designate that a current meta-evaluation showed that SGLT2 inhibitor employ used to be associated to a decrease possibility for ventricular tachycardia. Other obstacles to the post hoc evaluation are that detrimental-event reporting probably underestimated the lawful incidence of ventricular arrhythmias, and that these events weren’t adjudicated.
DAPA-HF used to be funded by AstraZeneca. Curtain reviews no associated monetary relationships. Disclosures for the coauthors are listed in the paper.
Eur Coronary heart J. Printed online August 27, 2021. Elephantine textual lisp
European Society of Cardiology (ESC) Congress 2021. Offered August 27, 2021.