Dapagliflozin for heart failure

The sodium-glucose cotransporter-2 (SGLT2) inhibitor group of drugs are now assuming an importance in the improvement cardiovascular outcomes a similar way that introduction HMG-CoA reductase inhibitors (statins) did 1990s. SGLT2 proteins on surface renal tubule cells responsible for 90% glucose re-absorption from glomerular filtrate with inhibition increasing loss both and sodium urine. modern have been developed phlorizin non- selective SGLT extracted root bark apple tree first tested people 1933.1 standard therapy glycaemic control diabetes also demonstrated reductions major events those type 2 diabetes. We good outcome data use defined heart failure but who do not In these patients, however, mechanism action is possibly beyond one only lowering. NICE published 24 February 2021 their technology appraisal (TA 679) dapagliflozin treating chronic reduced ejection fraction (HFrEF).2 recommendations were based acceptance by committee there remains unmet need new treatment options as many patients still symptoms such breathlessness despite current being regarded having optimised. recommends symptomatic add-on to optimised care. Its should be advice specialist primary, secondary or community care monitoring done most appropriate health professional. Optimised stated angiotensin-converting enzyme (ACE) angiotensin-2 receptor blocker (ARB) beta mineralocorticoid antagonist (MRA) if tolerated. specifically mentions alternative regimen sacubitril/valsartan, angiotensin receptor-neprilysin (ARNI), and, tolerated, MRA. A full submission adults additionally due Scottish Medicines Consortium 12 April 2021.3 Dapagliflozin Patients Heart Failure Reduced Ejection Fraction (DAPA-HF) trial randomised 4744 New York Association class II, III IV <40% receive 10mg placebo addition recommended therapy. baseline therapies well matched between two groups 96% levels receiving renin system blockers. Just over 10% taking ARNI. primary was composite worsening indicated hospitalisation urgent visit resulting intravenous death.4 Over median period 18.2 months occurred 16.3% 21.2% group. hazard ratio (HR) 0.74 95% CI 0.65–0.85; p<0.001. results death causes 9.6% 11.5% respectively. HR 0.82 0.69–0.98. There significant difference total symptom score measured Kansas City Cardiomyopathy Questionnaire (p<0.01). clinical benefit seen early after randomisation. An important finding effective 55% without mean eGFR 66ml/min/1.73m2 40.6% rate <60ml/min/1.73m2. Worsening function <8% groups. Serious adverse 1.6% 2.7% (p=0.009). 2018 national guideline NG 106 – Chronic adults: diagnosis management.5 Their pharmacological recommendation first-line offer ACE licence failure. They when deciding which drug start first, judgement used. Beta blockers introduced ‘start low, go slow’ manner. initiated at low dose titrated upwards short intervals weeks suggested. ARB licensed can used unable tolerate inhibitor. MRA next therapeutic choice patient continues Based guidance, sacubitril/valsartan option already stable ARB. However, guidance clear this started access multidisciplinary team. This ‘team’ within guideline.5 TA 679 noted innovative step change HFrEF. its basis cost effectiveness estimates felt acceptable NHS resources. committee's preferred incremental cost-effectiveness (ICER) £7264 per quality-adjusted life year gained.2 As part economic analysis ACE/ARBs, diuretics, MRAs direct comparators dapagliflozin, unlike sacubitril/valsartan. On indirect comparison less costly, least reducing risk causes. comment experts informing would depend individually patient's comorbidities. With publication NICE's 679, we different populations going It currently improve commenced <60ml/min/1.73m2 discontinued falls below 45ml/min/1.73m2.6 Before commencing physician consider any factors history predispose ketoacidosis. Awareness possible volume depletion during intercurrent illness important, strict adherence ‘sick day rules’.7 relation obtaining prior community. approach required starting what it falls: DAPA-HF went down 30ml/min. For diabetes, additional glucose-lowering considered 45ml/min. cannot 1 whereas 5mg adjunct insulin control. recent European Society Cardiology (ESC) 20168 update planned year. 2016 empagliflozin order prevent delay onset prolong life. expert consensus report ESC 2019 acknowledged time no specific established could made.9 Any evidence statement update. list 18 ongoing trials included paper. lead author paper has recently argument reconsider our sequencing HFrEF.10 Are development groups, willing adopt management? article argued commence sequence they showed last 40 years, assumes best tolerated first. fairness, does choice.5 At present titrate each target before moving dose. Low can, reduce slightly more effective. Even trials, lower than doses treatments. Some classes all. If reached take up six prescribe all drugs. comprehensive dedicated approach, scale often practice extended. may deny benefit, time, shown morbidity mortality soon initiation. suggested simultaneous initiation latter will hospitalistion mitigate short-term commenced. Within hypotension, further added serum potassium normal impaired. suitable outpatients up-titration pursued initial four-week period. ideal situation, always individualised own individual circumstances. approval management condition. robust processes place monitor use. Documenting differentiating indication disease categories paramount, yet continuing individualise Dr Begg previously received lecture advisory board fees AstraZeneca. References available Practical Diabetes online https://wchh.onlinelibrary.wiley.com.