Challenges in heart failure management Diabetes and Renal Impairment - - PowerPoint PPT Presentation

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Challenges in heart failure management Diabetes and Renal Impairment - - PowerPoint PPT Presentation

May 09, 2023 111 likes •327 views

Challenges in heart failure management Diabetes and Renal Impairment Martin R Cowie Professor of Cardiology National Heart & Lung Institute Imperial College London (Royal Brompton Hospital Campus) m.cowie@imperial.ac.uk @ProfMartinCowie

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Challenges in heart failure management

Diabetes and Renal Impairment Martin R Cowie

Professor of Cardiology National Heart & Lung Institute Imperial College London (Royal Brompton Hospital Campus) m.cowie@imperial.ac.uk @ProfMartinCowie

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Declaration of Interests

  • Research grants administered by Imperial College London from

Bayer, Boston Scientific, St Jude Medical, and ResMed

  • Consultancy and speaker fees from ResMed, Servier, Novartis,

Pfizer, Bayer, Medtronic, Boston Scientific, St Jude Medical, Alere, Daiichi-Sankyo, Bristol Myers Squibb, Roche, Amgen, MSD, Respicardia, Sorin

  • Non-Executive Director of the National Institute for Health and Care

Excellence (NICE) in England but opinions are my own

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A ‘typical’ CHF patient

76M; T2DM; CABG; LVEF 15%; CRT-D; ‘Optimal’ medical therapy Tight rope between “too dry” and “too wet”

Admitted for IV diuretics Admitted for observation “too dry” Admitted for IV diuretics

eGFR: 51 ml/min/1.73m2 eGFR: 20 ml/min/1.73m2 ACEI BB MRA

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Renal function in incident heart failure

The Hillingdon Study

Serum Creatinine Median 113 mol/l N=220 38% had [creatinine] > 125 mol/l 20% had [creatinine] > 150 mol/l Cowie et al. Eur Heart J 1999

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Renal function and prognosis in HF

Hillingdon Study (incident heart failure)

Creat < 113 mol/l Creat ≥ 113 mol/l P < 0.0005

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Worsening renal function during HF hospitalisation Prospective Outcomes Study in Heart Failure

  • 299 patients admitted with HFrEF to 8 EU centres
  • Average age 69 (74% male)
  • Median serum creatinine 137 mol/l (1.58 mg/dl)

= eCreat clearance 56ml/min [90% range 19-113 ml/min/1.73m2]

  • 29% developed WRF (rise in serum creatinine by

at least 26 mol/l (0.3mg/dl)) during admission

  • Factors independently associated with risk of

WRF:

– baseline serum creatinine – pulmonary oedema on chest x-ray – history of atrial fibrillation

  • WRF had no impact on mortality (after adjustment

for co-morbidity), but prolonged length of stay up by 2 days

Cowie & Komajda (POSH Investigators). Eur Heart J 2006; 27: 1216-22

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MAGGIC meta-analysis in Chronic HF

25 prospective studies

Finlay A. McAlister et al. Circ Heart Fail. 2012;5:309-314

N=15 962 N= 4 792

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8

Kidney disease and diabetes mellitus are common co-morbidities in patients with cardiovascular disease

Prevalence of CKD and diabetes mellitus in patients in the USA with STEMI (n = 19 029) and NSTEMI (n = 30 462)2

30,5 22,5 42,9 33,9 10 20 30 40 50

CKD Diabetes Prevalence (%)

STEMI NSTEMI 41 29 10 20 30 40 50

CKD Diabetes Prevalence (%) Prevalence of CKD and diabetes mellitus in patients in Europe with heart failure (N = 3226)1

CKD, chronic kidney disease; NSTEMI, non ST-segment elevation myocardial infarction; STEMI, ST-segment elevation myocardial infarction Data from 1. van Deursen VM et al. Eur J Heart Fail 2014;16:103–11; 2. Fox CS et al. Circulation 2010;121:357–65 8

Diabetes mellitus Diabetes mellitus Diabetes mellitus

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DM prevalence in HF admissions

Euroheart Survey

21% 26% 23% 18% 35% 23% 18% 36% 37% 29% 32% 23%

EHJ 2003; 24: 442 – 463

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More facts and figures

Diabetes and heart failure

  • Framingham: DM increases risk of HF by 1.82 ♂ and 3.15 ♀
  • CV Health Study (retired population): 33% of diabetic men

and 45% of diabetic women develop HF in 5.5 years

  • Hospitalisation databases suggest that 11.8% of patients with

diabetes have HF (vs. 4.5% of non-diabetics)

  • 44% of acute HF admissions (USA) are coded as diabetic

Voors AA and van der Horst ICC. Heart 2011; 97: 774 – 780 Cleland JGF et al. Eur Heart J 2003; 24: 442 – 463

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Recent CHF trials

Trial HF type Year Drug Hx of DM Pts enrolled PARADIGM HFrEF 2014

“Entresto” Sacubitril valsartan

35% N=8442

TOPCAT HFnEF 2013

Spironolactone

32% N=3445

EMPHASIS HFrEF 2011

Eplerenone

31% N=2737

SHIFT HFrEF 2010

Ivabradine

30% N=6558

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HF risk is related to diabetic control

10 1 0.5 5 6 7 8 9 10 Updated Mean HbA1C Concentration (%) Hazard Ratio

p=0.021

16% decrease per 1% reduction in HbA1C

Heart Failure

Based on UKPDS Study. BMJ 2000; 321: 405 – 412

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Is better TIDM control associated with lower HF risk?

Swedish National Registry

Lind M et al. Lancet 2011; 378: 140 – 146

  • 20 985 adults with

T1DM

  • Mean age 38.6 yrs
  • Median FU 9 yrs
  • Endpoint: HF

admission

  • HR 3.98

[2.23-7.14] for those with HbA1c ≥ 10.5% cf. HbA1c < 6.5%

20 15 10 5 40 30 20 10

Adjusted Incidence per 1000 Patients (yrs) Updated Mean HbA1C (%)

6 7 8 9 10 11

A. B.

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What is associated with HF risk in T1DM?

Multivariable analysis from national Swedish Registry

Hazard Ratio (95% CI) P-value HbA1c (1% increase) 1.30 (1.21–1.40) <0.0001 Men vs women 1.14 (0.97–1.35) 0.10 Age (10 yr increase) 1.64 (1.46–1.83) <0.0001 DM duration (10 yr increase) 1.34 (1.21–1.49) <0.0001 Smoking (across dose)

  • <0.0001

BMI (1 kg/m2 increase) 1.05 (1.03–1.08) <0.0001 SBP (10 mmHg increase) 1.15 (1.09–1.22) <0.0001 DBP (10 mmHg increase) 1.10 (0.98–1.24) 0.10 AF 1.89 (1.42–2.50) <0.0001 Myocardial infarction 6.42 (5.41–7.62) <0.0001 Ischaemic heart disease 2.9 (1.53–5.45) 0.001

Lind M et al. Lancet 2011; 378: 140 – 146

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Trials

  • No. of Events (annual event rate, %)

ΔHbA1C (%) Favors More Intensive Favors Less Intensive Hazard Ratio (%% CI) More Intensive Less intensive MAJOR CARDIOVASCULAR EVENTS ACCORD 352 (2.11) 371 (2.29)

  • 1.01

0.90 (0.78-1.04) ADVANCE 557 (2.15) 590 (2.28)

  • 0.72

0.94 (0.84-1.06) UKPDS 169 (1.30) 87 (1.60)

  • 0.66

0.80 (0.62-1.04) VADT 116 (2.68) 128 (2.98)

  • 1.16

0.90 (0.70-1.16) OVERALL 1.194 1.176

  • 0.88

0.91 (0.84-0.99) STROKE ACCORD 73 (0.43) 70 (0.42)

  • 1.01

1.00 (0.72-1.39) ADVANCE 238 (0.91) 246 (0.94)

  • 0.72

0.97 (0.81-1.16) UKPDS 35 (0.26) 17 (0.31)

  • 0.66

0.85 (0.48-1.52) VADT 32 (0.71) 37 (0.82)

  • 1.16

0.87 (0.54-1.39) OVERALL 378 370

  • 0.88

0.96 (0.83-1.10) MYOCARDIAL INFARCTION ACCORD 198 (1.18) 245 (1.51)

  • 1.01

0.77 (0.64-0.93) ADVANCE 310 (1.18) 337 (1.28)

  • 0.72

0.92 (0.79-1.07) UKPDS 150 (1.20) 76 (1.40)

  • 0.66

0.81 (0.62-1.07) VADT 72 (1.65) 87 (1.99)

  • 1.16

0.83 (0.61-1.13) OVERALL 730 745

  • 0.88

0.85 (0.76-0.94) HOSPITALISED/FATAL HEART FAILURE ACCORD 152 (0.90) 124 (0.75)

  • 1.01

1.18 (0.93-1.49) ADVANCE 220 (0.83) 231 (0.88)

  • 0.72

0.95 (0.79-1.14) UKPDS 8 (0.06) 6 (0.11)

  • 0.66

0.55 (0.19-1.60) VADT 79 (1.80) 85 (1.94)

  • 1.16

0.92 (0.68-1.25) OVERALL 459 446

  • 0.88

1.00 (0.86-1.16)

Does improving T2DM control reduce the HF risk?

0.5 1.0 2.0 Hazard Ratio (95% CI)

(Q=1.32, p=0.72, I2=0.0%) (Q=0.40, p=0.94, I2=0.0%) (Q=2.25, p=0.52, I2=0.0%) (Q=3.59, p=0.31, I2=16.4%)

Turnbull FM et al. Diabetologia 2009; 52: 2288 – 2298

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American Diabetes Association 2017 Standards of Care. Diabetes Care 2017; 40 (Suppl 1)

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https://www.nice.org.uk/guidance/ng28/resources/algorithm-for-blood-glucose-lowering-therapy-in-adults-with-type-2-diabetes-2185604173

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EMPA-REG OUTCOME

Zinman B et al. N Engl J Med 2015; 373: 2117 – 28

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Zinman B et al. N Engl J Med 2015; 373: 2117 – 28

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Conclusions

  • Diabetes (and renal dysfunction) are VERY common

in patients with heart failure

  • Strong association between poorer diabetic control

and poorer micro- and macro-vascular outcome, including heart failure

  • Until recently tightening up diabetic control appears

to have had only modest effects on CV outcome

  • The game may have changed with EMPA-REG