Caring for Australians with Renal Impairment. BP lowering and CVD

Transcription

1 Caring for Australians with Renal Impairment BP lowering and CVD

2 Questions: Conflicts of Interest: RH, TN, HHL- no conflict VP- level II conflict Speakers fees: Abbott, Astra Zeneca, Roche, Servier Grant review board: Baxter Steering Committees: Abbott (employer paid), J&J (unpaid) Unrestricted grants: Baxter, Amgen

3 Questions asked : In people with CKD, 1. Is BP lowering effective at preventing CV events? 2. Do any treatment regimens have greater or lesser efficacy at preventing CV events? 3. What BP target should clinicians aim for in treating patients?

4 Guideline: 1. Evidence from large randomised controlled trials indicates that blood pressure lowering in individuals with early chronic kidney disease reduces the risk of cardiovascular mortality and morbidity and total death. Blood pressure lowering should therefore be attempted in individuals with chronic kidney disease who have suboptimal blood pressure levels (II).

5 Context: BPLTTC 2003

6 Context: BPLTTC 2003

7 Is BP lowering effective in CKD? ACEI vs placebo or control CKD only trials: PREVEND-IT Subgroups of trials: HOPE EUROPA PEACE PROGRESS ADVANCE ARB vs placebo or control CKD only trials: IDNT RENAAL Subgroups of trials: Val-HEFT CCB vs placebo or control CKD only trials: IDNT

8 BP lowering: ACE inhibitors Trial Populn CKD pts Rx Effect. PREVEND-IT microalb pts 864 Fos vs plac 0.6 (0.33 to 1.10, p= 0.09) SUBGROUPS HOPE creat > Ram vs plac 0.80 ( ) high vasc risk vs 0.79 ( ) p hetero > 0.2 EUROPA egfr < 75 Per vs plac 0.84 ( ) vs 0.79 ( ) p hetero =0.47 PEACE egfr < trand vs plac no difference primary CAD greater benefit mortality PROGRESS CrCl < per/ind vs plac 0.70 ( ) CVD vs 0.74 ( ) p hetero >0.2 ADVANCE egfr < per/ind vs plac 0.87 ( ) High risk DM p hetero = 0.51

9 BP lowering: Other classes Trial Populn CKD pts Rx Effect. ARB IDNT HT, DM Nx 1715 irb vs plac 0.91 ( ) RENAAL DM Nx 1513 los vs plac 0.90, p=0.26 Val-HEFT Heart failure 2890 val vs plac 0.86 ( ) egfr < 60 on ACEI vs 0.91 ( ) p hetero =0.23 CCB IDNT HT, DM Nx 1715 amlo vs plac 0.88 ( )

10 Guideline 2: Much less data is available for individuals with chronic kidney disease receiving dialysis, however the available evidence suggests similar cardiovascular benefits are achieved with blood pressure lowering in dialysis patients to those observed in the general population. While more studies are required, the possible benefits and risks of blood pressure lowering should be considered for all patients receiving dialysis (II).

11 Is BP lowering effective in dialysis? Heerspink et al, Lancet 2009

12 Is BP lowering effective in dialysis? Aggarwal, Hypertension 2009

13 Transplantation SECRET trial Prevalent Tx pts 1-10 yrs out, any BP, CrCl > 25 Candesartan vs placebo Primary outcome: death or graft failure Stopped after 502 of 700 planned pts enrolled for futility only 26 events, no difference between arms

14 Guideline 3 There is evidence that angiotensin-converting enzyme inhibitors are efficacious at reducing blood pressure and subsequent cardiovascular disease and all-cause mortality in patients with mild, moderate and severe renal impairment (level II). There is currently little evidence about the effectiveness of other blood pressure lowering agents in preventing cardiovascular mortality and morbidity in this patient population, mainly due to the smaller amount of data available. However, comparative studies have demonstrated similar cardiovascular outcomes among most classes of blood pressure lowering agents in chronic kidney disease (level II). In the absence of data demonstrating benefits for any particular class over any other, the choice of blood pressure lowering agent should be made on the grounds of individual patient variables, tolerability and side-effect profiles.

15 Head to head comparisons ALLHAT trial No difference between chlorthalidone, lisinopril or amlodipine for CV events in CKD subgroups Less heart failure for chlorthalidone IDNT: No difference between irbesartan or amlodipine AASK trial No difference amlodipine vs metoprolol vs ramipril

16 Suggestions for clinical care 1. There is limited evidence, due mainly to the lack of data that lower BP targets in patients with renal impairment reduce the risk of cardiovascular disease (CVD). As a result it would seem reasonable to extrapolate BP targets from high-risk patients with normal renal function, namely less than 130/80 mmhg. EVIDENCE: HOT subgroups- underpowered but not different to main results AASK- similar CV events in intensive BP lowering group

17 Suggestions for clinical care 2. Post-hoc analysis of angiotensin-converting enzyme inhibitors (ACEi) trials have shown that the treatment effects of ACEi on cardiovascular outcomes are consistent in patients with and without CKD. Angiotensin-converting enzyme inhibitors appear therefore a reasonable first choice for prevention of CVD in this population. 3. The evidence about the cardiovascular protective effects of angiotensin receptor blockers in CKD patients is scarce. However, they have been shown to confer renal protection in patients with diabetic nephropathy and are therefore a sensible alternative if ACEi are not tolerated in this population.

18 Suggestions for clinical care 4. Head to head studies have reported similar CV outcomes with different classes of agents in people with CKD, although the power to detect meaningful differences was limited. ACEi, ARBs, calcium channel blockers (CCB) and diuretics are therefore all reasonable choices for people with CKD. RAS blockade is likely to have renal benefits in people with proteinuria and should therefore be preferred in this population (see separate guideline) 5. Since many patients with CKD will not achieve BP targets with monotherapy, a combination of BP lowering drugs is needed. There is little evidence about the efficacy in preventing CVD of different combinations of BP lowering drugs in this population. If BP targets are not met, the choice of a second agent should be based on individual patient factors, tolerability, and side effects.

19 Caring for Australians with Renal Impairment BP lowering and CVD