THE IMPACT OF CCB AND RAS INHIBITOR COMBINATION THERAPY TO PREVENT CKD INCIDENCE IN HYPERTENSION AND ADVANCED ATHEROSCLEROSIS

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1 THE IMPACT OF CCB AND RAS INHIBITOR COMBINATION THERAPY TO PREVENT CKD INCIDENCE IN HYPERTENSION AND ADVANCED ATHEROSCLEROSIS Daisuke MAEBUCHI, Yasuyuki SHIRAISHI, Hiroaki TANAKA, Yumiko INUI, Makoto TAKEI, Yuumi SUTOH, Yukinori IKEGAMI, Jun FUSE, Munehisa SAKAMOTO, Yukihiko MOMIYAMA Department of Cardiology, National Hospital Organization Tokyo Medical Center, Tokyo, Japan

2 Background Chronic kidney disease (CKD) progression relate to atherosclerosis and hypertension. On the other hand, angiotensin-converting enzyme inhibitor (ACEI) or angiotensin Ⅱ receptor blocker (ARB), antihypertensive drugs, are known to prevent CKD incidence, however the efficacy of combination with calcium channel blocker (CCB) was controversial.

3 Previous report ACCOMPLISH (2010) ACEI *1 +CCB *2 vs ACEI *1 +diuretics *3 Hazard Ratio * (95%CI ) REIN-2 (2005) ACEI *5 +CCB *6 vs ACEI *5 Hazard Ratio * (95%CI ) *1, benazepril ; *2, amlodipine; *3, hydrochlorothiazide; *4, HR for CKD progression in hypertensive patients ; *5, ramipril; *6, felodipine; *7, HR for end- stage renal disease progression in non-diabetic hypertensive patients

4 Object We investigated the high risk population in hypertensive patients and examined the efficacy of CCB and renin-angiotensin system (RAS) inhibitor combination therapy, to prevent CKD incidence in high risk patients.

5 Methods Subjects Follow-up Exclusion criteria Index of atherosclerosis Estimated GFR (egfr) CKD definition Consecutive 577 hypertensive patients undergoing CAVI from 2006 to months (29±10months) Estimated GFR < 60 ml/min/1.73m 2 ABI < 0.9 Cardio Ankle Vascular Index (CAVI) egfr=194 scr age (0.739 if female) (modified MDRD formula) egfr<60 ml/min/1.73m 2 or proteinuria

6 CAVI(Cardio-Ankle Vascular Index) CAVI=In(Ps/Pd) (PWV) 2 /(ΔP/2ρ) (Ps: systolic blood pressure, Pd: diastolic blood pressure, ΔP: pulse pressure, ρ: blood density) PWV= L T T = t + tc Tibial arterial pressure Brachial arterial pressure Heart sound Electrocardiogram Shirai et al. J Atheroscler Thromb, 2006; 13:

7 Baseline Charactaristics (N=145) (=146) CAVI (N=143) (N=143) Age (y.o) 58±11 64±9 68±8 73±8 Male (%) BMI Systolic BP (mmhg) 130±18 133±20 135±19 137±21 Diastolic BP (mmhg) 79±13 81±11 81±11 82±12 Diabetes (%) Dyslipidemia (%) egfr (ml/min/1.73m 2 ) 82±20 78±15 77±15 74±13 BMI, body mass index; BP blood pressure; egfr estimated glome

8 Odds ratios Odds Ratios for CKD incidence according to CAVI quartile 3.0 *P >0.05 v.s reference * 1.0 reference CAVI Adjusted for age, sex, systolic BP, dyslipidemia, diabetes and baseline egfr

9 ROC curve for CAVI to predict CKD incidence AUC = Cut Off value = 9.0

10 Baseline Characteristics 2 Single therapy *1 (N=115) Combination therapy *2 (N=121) Age (y) 69 ±10 70±6 Male (%) BMI Systolic blood pressure (mmhg) 133±22 139±19 Diastolic blood pressure (mmhg) 81±12 82±11 egfr (ml/min/1.73m 2 ) 75±14 75±13 CAVI Dyslipidemia (%) Statin (%) Diabetes (%) SU (%) *1, RAS inhibitor single therapy; *2, CCB and RAS inhibitor combination therapy

11 Incidence rate for CKD Kaplan-Meiyer curve for CKD incidence 0,5 45 CKD incidences (39.1%) in 115 patients with single therapy 37 CKD incidences (30.6%) in 121 patients with combination therapy 0,4 0,3 Single Therapy Combination Therapy 0,2 0,1 P= (log-rank test) 0, (months)

12 Hazard ratio for CKD incidence of combination therapy vs single therapy Hazard Ratio 95% C.I P value Univariate Age- and sexadjusted Multivariate* adjusted *adjusted for age, sex, systolic blood pressure, BMI, egfr, statin and SU

13 Discussion CKD stage Ⅰ Ⅱ Ⅲ Ⅳ Ⅴ High risk population population CKD ESRD According to previous 2 reports, the efficacy of CCB and ACEI combination therapy to prevent ESRD in non ESRD population is controversial. Our result showed CCB and RAS inhibitor combination therapy is effective to prevent CKD in non CKD high risk patients, even though this group had higher blood pressure and BMI compared to single therapy population.

14 Discussion CAVI reflect arterial stiffness and is known to be one of an index of atherosclerosis for the whole body. In our study, CAVI is an useful tool to know the risk of CKD progression. Additionally, we showed CCB and RAS inhibitor combination therapy was effective to prevent CKD in non CKD hypertensive patients with advanced atherosclerosis.

15 Conclusion We found that high CAVI level hypertensive patients were high risk for CKD progression and suggest that CCB and RAS inhibitor combination therapy is effective to prevent CKD incidence compared to RAS inhibitor single therapy in such high risk patients without CKD.

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