Management of CAD in DM patients with CKD Is it different

0 %
100 %
Information about Management of CAD in DM patients with CKD Is it different
Education

Published on July 24, 2015

Author: heartsense

Source: authorstream.com

Management of CAD in DM patients with CKD – Is it different?: Management of CAD in DM patients with CKD – Is it different? HeartSense Team www.heartsense.in Introduction: Introduction Both diabetes and CKD are very important CV risk factors and also considered “CAD equivalents” To reduce CV risk in DM + CKD patients, multiple risk factors (BP, glucose, lipids, eGFR ) has to be controlled simultaneously Here we discuss management of CAD in DM + CKD patients Diabetic Nephropathy : Diabetic Nephropathy Diabetes is the commonest cause of CKD (chronic kidney disease) Up to 44% of the patients with ESRD who require dialysis are diabetics 40% patients with diagnosed or undiagnosed diabetes had some degree of CKD Individuals with diabetic nephropathy have an increased risk of all-cause mortality , cardiovascular mortality and kidney failure Presence of nephropathy increases the cost of DM management by 3 times World J Diabetes 2013 December 15; 4(6): 245-255 , Mayo Clin Proc . 2011;86(5): 444-456 ESRD: End Stage Renal Disease What are Diabetics with Nephropathy Dying From?: 4 What are Diabetics with Nephropathy Dying From? Stroke Myocardial Infarction Heart Failure Sudden Death Natural History in Type 2 DM: Natural History in Type 2 DM GFR decline once proteinuria present 10-12 ml/min/year (if untreated) Patients often die of other causes (CVS disease) before ESRD Other causes of nephropathy may exist such as HTN Slower progression compared to type 1 DM CVS risk rises 2-3 times with microalbuminuria , 9-10 times with clinical proteinuria Higher rates of ESRD in T1DM than T2DM Slide 6: Stage of hyper- filtration Micro albumi- nuria Macro albumi- nuria Azotemia (Renal failure) End stage Renal disease Normo albumi- nuria NATURAL HISTORY OF NEPHROPATHY IN T1DM 15 - 20 yrs 1 yrs 4 - 5 yrs Pathogenesis of DN : Hyperglycaemia Early histological lesions reversible with normoglycaemia Hypertension Predicts microalbuminuria  proteinuria paralleled by gradual rise in BP Correlation between BP and rate of  of GFR Proteinuria Induces tubulointerstitial damage/ contributes to progression Highly selective in early disease Pathogenesis of DN Five Stages of diabetic nephropathy: Five Stages of diabetic nephropathy Stage Clinical features /Pathology Lab Findings Stage 1 Early hyperfunction and hypertrophy ( ↑GFR) ACR < 30 mg/g creatinine Stage 2 Morphologic lesions without signs of clinical disease Stage 3 Microalbuminuria ACR > 30 and < 300 mg/g creatinine Stage 4 Overt nephropathy (hypertension is common) ACR > 300 mg/g creatinine and/or persistent proteinuria with serum creatinine > 2.0 mg/dL Stage 5 End-stage renal disease with uremia On dialysis GFR: Glomerular Filtration Rate, ACR: Albumin Creatinine Ratio World J Diabetes 2013 December 15; 4(6): 245-255 CKD stages as per eGFR : CKD stages as per eGFR Proteinuria Predicts Stroke & CHD Events in T2DM: Proteinuria Predicts Stroke & CHD Events in T2DM P <0.001 40 30 20 10 0 Stroke CHD Events 80 60 40 20 0 0.5 0.6 0.7 0.8 0.9 1 Survival Curves For CV Mortality Overall: P <0.001 C B A Incidence (%) Months Miettinen H et al. Stroke . 1996;27:2033-2039. B: U-Prot 150–300 mg/L A: U-Prot <150 mg/L C: U-Prot >300 mg/L 0 U- Prot = Urinary protein concentration . CHD: Coronary heart Disease 100 Management of CAD in DM Nephropathy: Management of CAD in DM Nephropathy BP Control Glycemic control Lipid Control Revascularisation BP control in DM + CKD patients : BP control in DM + CKD patients RAAS blockers (ACEI and ARBs) are most recommended antihypertensive drugs for DM + CKD patients These drugs not only control progression of CKD, but reduce cardiovascular risk also. These CV and renal benefits are partially independent of BP control Target BP levels are generally lower in patients with heavy proteinuria Slide 13: N Engl J Med 2012; 367:2204-2213 Slide 14: No benefit of Aliskiren in those DM patients already on ACEI/ARBs N Engl J Med 2012; 367:2204-2213 ALTITUDE: Adverse Events: ALTITUDE: Adverse Events Aliskiren increased risk of hyperkalemia and hypotension in DM patients already on ACEI/ARBs N Engl J Med 2012; 367:2204-2213 2013 KDIGO guidelines for BP control in DM + CKD patients: 2013 KDIGO guidelines for BP control in DM + CKD patients ARBs in DM + CKD patients : RENAAL Study: ARBs in DM + CKD patients : RENAAL Study Population: 1,513 T2DM + CKD patients ( 31-70 years) albumin/ creatinine ratio 300 mg/g serum creatinine between 1.3–3.0 mg/dL (1.5–3.0 mg/dL for men >60 kg ) Randomized to losartan or placebo, Mean follow up: 3.4 years Primary Endpoint: Composite of a doubling of serum creatinine , end stage renal disease, or death Secondary Endpoints: MI, Stroke, First hospitalization for CHF/unstable angina, Death from CV causes, Coronary /peripheral revascularization Brenner BM, et al. N Engl J Med. 2001;345(12):861-869. RENAAL Baseline Characteristics*: *The differences between the treatment groups were not statistically significant RENAAL Baseline Characteristics* Losartan ‡ Group n=751 Placebo ‡ Group n=762 Mean Age (yrs) 60 60 Male (%) 62 65 Mean Systolic BP (mmHg) Mean Diastolic BP (mmHg) 152 82 153 82 Mean BMI (kg/m 2 ) 30 29 Median urinary albumin:creatinine ratio (mg/g) 1237 1261 Mean serum creatinine (mg/dL) 1.9 1.9 Mean glycosylated hemoglobin (%) 8.5 8.4 Brenner BM, et al. N Engl J Med. 2001;345(12):861-869. RENAAL:Primary Endpoint*: RENAAL:Primary Endpoint * Losartan ‡ Group n=751 Placebo ‡ Group n=762 P value % Risk Reduction (95% CI) n % n % Primary composite endpoint* 327 43.5 359 47.1 0.02 16 (2 to 28) Doubling of serum creatinine ESRD Death 162 147 158 21.6 19.6 21.0 198 194 155 26.0 25.5 20.3 0.006 0.002 0.88 25 (8 to 39) 28 (11 to 42) -2 (-27 to 19) ESRD or Death 255 34.0 300 39.4 0.01 20 (5 to 32) Doubling of serum creatinine and ESRD 226 30.1 263 34.5 0.01 21 (5 to 34) Brenner BM, et al. N Engl J Med. 2001;345(12):861-869. Losartan treatment reduced both renal and CV end points in DM + CKD patients RENAAL Impact of Losartan on Secondary Endpoints: RENAAL Impact of Losartan on Secondary Endpoints 32 % RRR in first CHF hospitalization (P=0.005) 35 % RRR in proteinuria ( P<0.001) 18 % RRR in the decline of renal function ( P=0.01) 15.2 % RRR in the estimated GFR decline ( P=0.01) RRR: Relative risk reduction Brenner BM, et al. N Engl J Med. 2001;345(12):861-869. NKF 2012 Glycemic control guidelines in DM + CKD: NKF 2012 Glycemic control guidelines in DM + CKD A target HbA1c of7.0% to prevent or delay progression of the microvascular complications of diabetes, including DKD . ( 1A ) Do not treat to an HbA1c target of <7.0% in patients at risk of hypoglycemia . (1B ) T arget HbA1c be extended > 7.0 % in individuals with co-morbidities or limited life expectancy and risk of hypoglycemia . (2C) Intensive glycemic control can prevent CKD progression : Intensive glycemic control can prevent CKD progression Intensive glycemic control in DM CKD patients: ACCORD 2015 data : Intensive glycemic control in DM CKD patients: ACCORD 2015 data Out of > 10,000 patients, 3636 patients in ACCORD had CKD at baseline Incidence of primary outcome, all-cause and CV mortality , risk of hypoglycemia were evaluated in CKD patients in intensive vs standard glycemic control. Kidney International (2015) 87, 649–659 Intensive glycemic control in DM CKD patients: ACCORD : Intensive glycemic control in DM CKD patients: ACCORD Kidney International (2015) 87, 649–659 Intensive glycemic control in DM CKD patients: ACCORD : Intensive glycemic control in DM CKD patients: ACCORD Tight glycemic control increased CV and all cause mortality in CKD patients with T2DM Kidney International (2015) 87, 649–659 Intensive glycemic control in DM CKD patients: ACCORD : Intensive glycemic control in DM CKD patients: ACCORD Tight glycemic control increased risk of hypoglycemia in CKD patients with T2DM Kidney International (2015) 87, 649–659 Lipid control in DM + CKD patients: Lipid control in DM + CKD patients Statin therapy can reduce CAD risk in all CKD (non-ESRD) patients ( with or without DM) Exact role of statin in patients on dialysis is still not clear Drugs like fenofibrate can further reduce eGFR , should be used carefully in DM + CKD 2013 KDIGO guidelines for lipid management in CKD : 2013 KDIGO guidelines for lipid management in CKD All DM patients with CKD > 18 yrs require statin therapy (except those on dialysis) Kidney International Supplements (2013) 3: 259-305 2013 KDIGO guidelines for lipid management in CKD : 2013 KDIGO guidelines for lipid management in CKD Effect of different statin on renal function in DM Nephropathy: PLANET I: Effect of different statin on renal function in DM Nephropathy: PLANET  I 353 DM patients on ACEI/ARB were randomized to 10 mg or 40 mg rosuvastatin or 80 mg atorvastatin Primary End Point: Change in urine protein/ creatinine ratio Secondary End Point: change in eGFR Follow up: 1 yr Slide 31: de  Zeeuw D. 2010European Renal Association-European Dialysis and Transplant Association Congress; June 27, 2010; Munich, Germany. Effect of different statin on renal function in DM Nephropathy: PLANET  I : Adverse event Rosuvastatin 10 mg/day (n = 116) Rosuvastatin 40 mg/day (n = 123) Atorvastatin 80 mg/day (n = 110) p Any renal adverse event 7.8 9.8 4.5 NS Acute renal failure 0.0 4.1 0.9 <0.05 Serum creatinine doubling 0.0 4.9 0.0 <0.01 Serum creatinine doubling or acute renal failure 0.0 7.3 0.9 <0.01 Atorvastatin is safer than rosuvastatin in DM patients with protrinuria Statin/Ezetimibe in DM Nephropathy patients: SHARP study: Statin/ Ezetimibe in DM Nephropathy patients: SHARP study This randomised double-blind trial included 9270 patients with CKD (3023 on dialysis and 6247 not on dialysis) without CVD Out of these 23% (n=2093) were diabetics Patients were randomly assigned to simvastatin 20mg mg plus ezetimibe 10 mg daily versus matching placebo. Follow up: 4.9 yrs The key pre-specified outcome: first major atherosclerotic event (non-fatal myocardial infarction or coronary death, non- haemorrhagic stroke, or any arterial revascularisation procedure). SHARP: Study of Heart and Renal Protection Lancet . 2011 Jun 25;377(9784):2181-92 SHARP study: Primary outcome: SHARP study: Primary outcome Statin + Ezetimibe Statin/ Ezetimibe reduced CV events by 17% Lancet. 2011 Jun 25;377(9784):2181-92 SHARP study: Primary outcome: SHARP study: Primary outcome HR: 0.78 P< 0.05 Lancet. 2011 Jun 25;377(9784):2181-92 Statin/ Ezetimibe reduced CV events by 22% in patients with DM Prevention and management of DM nephropathy: Summary: Prevention and management of DM nephropathy: Summary Parameter Goals Therapy Glycemic Control < 7% (if no comorbidity, to prevent nephropathy) > 7% if comorbidities or nephropathies already present) Metformin (if GFR > 30 ml/min) BP < 130/80 mm Hg (if proteinuria is present) < 140/90 mm Hg if proteinuria is absent ARBs or ACEIs CCBs/diuretics as 2 nd choice LDL-C < 70 mg/dl Statin alone or statin+ Ezetimbe Challenges in CKD patients for revascularization (with or without DM): Challenges in CKD patients for revascularization (with or without DM) Greater underlying comorbidities Coronary lesion calcification and complexity Increased thrombotic and bleeding risk Tendency for restenosis with bare-metal stents Relatively less data for such patient groups for both DES and CABG Circ Cardiovasc Interv . 2015;8:e001973 PCI vs CABG in DM + CKD patients: 2015 study: PCI vs CABG in DM + CKD patients: 2015 study A 1786 propensity-matched patients from 4006 patients with CKD undergoing index revascularization for multi-vessel disease with either DES or isolated CABG (n=893 each) were analyzed in a Canadian study Follow up: 3 yrs Early 30-day and late clinical outcomes after revascularization were measured 43% patients had diabetes, a sub-analysis was done for DM patients Circ Cardiovasc Interv . 2015;8:e001973 Independent Predictors of Late Mortality and Late MACCE: Independent Predictors of Late Mortality and Late MACCE In DM + CKD patients, mortality and MACCE associated with revascularization is significantly increased Circ Cardiovasc Interv . 2015;8:e001973 PCI vs CABG in DM + CKD patients: PCI vs CABG in DM + CKD patients Circ Cardiovasc Interv . 2015;8:e001973 In DM + CKD patients, MACCE are lower in CABG compared to PCI Management of CAD in DM + CKD: Summary: Management of CAD in DM + CKD: Summary Parameter Goals Therapy Glycemic Control < 7% (if no comorbidity,) > 7% if comorbidities or nephropathies already present) Metformin (if GFR > 30 ml/min) BP < 130/80 mm Hg (if proteinuria is present) < 140/90 mm Hg if proteinuria is absent ARBs or ACEIs CCBs/diuretics as 2 nd choice LDL-C All patients not on dialysis with eGFR < 60 ml/min should be treated Statin alone or statin+ Ezetimbe Revascularization CABG is preferred Take Home Message: Take Home Message Patients with DM + CKD are at very high risk of CAD Control of multiple risk factor (BP and lipid) can reduce risk of CAD in such patients Tight glycemic control does not provide any CV benefit, though it may prevent progression of CKD Statins, ACEI/ARB are preferred drugs for reducing CAD risk in DM + CKD patients Specific clinical trials are required to further evaluate exact role of revascularisation in DM + CKD

Add a comment

Related presentations

Related pages

The Association between Kidney Function, Coronary Artery ...

... severity of coronary artery disease (CAD), ... significant across patients in different CKD ... management of the increased ...
Read more

The Management of Diabetic Neuropathy in CKD and Dialysis ...

... state make the management of coronary artery disease (CAD) ... patients is different from ... peripheral neuropathy in patients with CKD or ...
Read more

Antiplatelet Therapy in the Management of Cardiovascular ...

Table 1 lists different ... dose in patients with CKD and CAD was based on extrapolation ... is available to guide management in CKD ...
Read more

Overview of the management of chronic kidney disease in adults

All patients with renal disease ... An overview of the general issues involved in the management of the patient with ... these different manifestations are ...
Read more

Diabetes and CKD - Kidney Health Australia

For Patients ... Management> Diabetes and CKD ... About 10% of people with diabetes develop early signs of CKD in the first 10 years after diagnosis.
Read more

Dilemmas in the Management of Atrial Fibrillation in ...

... introduced in 2002 a systematic classification for different stages of CKD on ... CKD, ATRIAL FIBRILLATION, ... the management of patients ...
Read more

Evaluate Patients with Chronic Kidney Disease (CKD ...

Identification of the etiology may help guide management. ... Patients with CKD. ... with an eGFR of 55 may be different than that for a 45 ...
Read more

Educate Your Patients: Kidney Disease Education Lesson ...

Patient and Professional Education. Effective management of ... CKD patients, NKDEP has developed ... to patients, including patient education ...
Read more

Effect of Statin Therapy on Outcomes in Patients With CKD

... suggests that therapy with statin reduces the risk of cardiovascular events across different ... no CVD or DM: CKD ... Hyperlipidaemia and CKD patients:
Read more