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Overview
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Overview John W. Kusek, PhD, Lawrence Y. Agodoa, MD, Richard Glassock, MD, Jackson T. Wright, MD, PhD, Katharine A. Kirk, PhD, and Jeannette Y. Lee, PhD, for the AASK Pilot Study Investigators
End-stage renal disease (ESRD) is a major public health problem in the United States [l]. In 1991, treatment of ESRD cost the federal government approximately $6 billion, and an additional $2.5 billion was expended by patients and private sources [2]. According to the United States Renal Data System, over 55,000 patients started ESRD therapy in this country in 1992 [2], primarily by hemodialysis, adding to the approximately 200,000 prevalent ESRD patients receiving therapy. The number of patients on ESRD therapy has doubled during the past 8.5 years and it has been suggested that the number of ESRD patients may continue to increase rapidly in the future [3]. The African American community suffers disproportionally from ESRD. Although African Americans make up about 12% of the U.S. population, they represent nearly 30% of the ESRD patient population [2]. The incidence rate of ESRD is four times greater in African Americans than in whites 121. The disparity in ESRD incidence rates between African Americans and whites is even greater for ESRD attributed to hypertension, the most common cause of chronic renal failure in this minority population. The rate of ESRD associated with hypertension is six times greater in African Americans than whites, and for the age group 2544, the incidence rate is nearly 20 times greater in African Americans [4]. Thus, effective interventions are required if this projected trend for all-cause ESRD and the disproportionate burden of hypertensive ESRD in African Americans is to be significantly reduced in this country. Additionally, because of the high rate of progression to end-stage in African American hypertensives, this population is an excellent group to evaluate preventative therapies for chronic renal disease. Compared to the longstanding history of clinical trials to reduce mortality from cardiovascular disease and stroke, clinical trails of therapies to prevent progression of chronic renal disease have been initiated only within the past decade and the results reported within the past several years [5-81. Insights gained from several of these trials and the findings from a number of other studies are the underpinnings of the clinical trial featured in this supplement of ConMled Clinical Trials, The African American Study of Kidney Disease and Hypertension (AASK) Pilot Study. As described in the design and baseline characteristics article by Wright et al. 191 in this supplement, the AASK Pilot Study evaluated the feasibility of carrying out Controlled Clinical Trials 16:1%!S (1996) 0 EIsevier Science Inc. 1996 655 Avenue of the Americas, New York, NY 10010
0197-2456/96/$15.00 PII SO197-2456(96)0082-7
2s
Overview a long-term, multicenter clinical trial of two levels of blood pressure control (usual mean arterial blood pressure [MAP] goal of 102-107 mm Hg and a low MAP goal of s 92mm Hg) and three antihypertensive drug regimens (initial therapy with an angiotensin-converting enzyme (ACE) inhibitor, calcium channel blocker, or beta blocker) on progression of chronic renal disease attributed to hypertension (hypertensive nephrosclerosis) in African Americans with mild to moderately reduced renal function. One of the reasons for considering the low MAP goal was to test the hypothesis that reducing blood pressure to levels below the currently recommended 140/ 90 mmHg to prevent mortality from cardiovascular disease and stroke might be beneficial with regard to maintaining kidney function. The basis for evaluation of two levels of blood pressure control is derived, in part, from subgroup analyses of the Modification of Diet in Renal Disease (MDRD) Study [lo]. In African American MDRD Study participants (with kidney disease of diverse causes and similar entry requirements for level of kidney function as in the AASK Pilot Study) who were randomized to a low MAP goal (identical to that in the AASK), the decline in renal function projected over three years was about one-half the rate of decline observed in participants. randomized to the usual MAP goal (cl07 mm Hg). Because of the small number of African Americans with a diagnosis of hypertensive nephrosclerosis in the MDRD Study, it could not be determined whether a lower than usual blood pressure goal would be beneficial in these patients. The concept that certain classes of antihypertensive drugs may be more effective in preventing progression of chronic renal disease independent of the level of blood pressure control (e.g., “renoprotective”) is supported by a growing literature ill]. In a randomized clinical trial of patients with insulin-dependent diabetes and evidence of renal disease, treatment with an ACE inhibitor appeared to reduce the risk of doubling of serum creatinine concentration (a measure of renal function) by nearly 50% compared to treatment with other antihypertensive agents not including an ACE inhibitor 161. No previous study, however, has compared the major classes of antihypertensive drugs for their renoprotective properties in African Americans with hypertensive nephrosclerosis. The articles contained in this supplement report selected findings from the AASK Pilot Study including baseline characteristics of participants [9], recruitment experience [12], adherence to the antihypertensive drug regimen 1131 participant satisfaction with the trial 1141, and quality of life associated with the interventions [15]. Findings of particular interest are the relative ineffectiveness of communitybased recruitment strategies, the underrepresentation of women among randomized participants, the. relatively low economic status and high unemployment rate of participants, the difficulty in achieving blood pressure goal over the short period of follow-up, and the high level of satisfaction expressed by participants regarding study procedures. These and other findings from the Pilot Study 116,171 provided valuable information to investigators in planning the ongoing full-scale phase of AASK [la].
Overview John W. Kusek, PhD, Lawrence Y. Agodoa, MD, Richard Glassock, MD, Jackson T. Wright, MD, PhD, Katharine A. Kirk, PhD, and Jeannette Y. Lee, PhD, for the AASK Pilot Study Investigators
End-stage renal disease (ESRD) is a major public health problem in the United States [l]. In 1991, treatment of ESRD cost the federal government approximately $6 billion, and an additional $2.5 billion was expended by patients and private sources [2]. According to the United States Renal Data System, over 55,000 patients started ESRD therapy in this country in 1992 [2], primarily by hemodialysis, adding to the approximately 200,000 prevalent ESRD patients receiving therapy. The number of patients on ESRD therapy has doubled during the past 8.5 years and it has been suggested that the number of ESRD patients may continue to increase rapidly in the future [3]. The African American community suffers disproportionally from ESRD. Although African Americans make up about 12% of the U.S. population, they represent nearly 30% of the ESRD patient population [2]. The incidence rate of ESRD is four times greater in African Americans than in whites 121. The disparity in ESRD incidence rates between African Americans and whites is even greater for ESRD attributed to hypertension, the most common cause of chronic renal failure in this minority population. The rate of ESRD associated with hypertension is six times greater in African Americans than whites, and for the age group 2544, the incidence rate is nearly 20 times greater in African Americans [4]. Thus, effective interventions are required if this projected trend for all-cause ESRD and the disproportionate burden of hypertensive ESRD in African Americans is to be significantly reduced in this country. Additionally, because of the high rate of progression to end-stage in African American hypertensives, this population is an excellent group to evaluate preventative therapies for chronic renal disease. Compared to the longstanding history of clinical trials to reduce mortality from cardiovascular disease and stroke, clinical trails of therapies to prevent progression of chronic renal disease have been initiated only within the past decade and the results reported within the past several years [5-81. Insights gained from several of these trials and the findings from a number of other studies are the underpinnings of the clinical trial featured in this supplement of ConMled Clinical Trials, The African American Study of Kidney Disease and Hypertension (AASK) Pilot Study. As described in the design and baseline characteristics article by Wright et al. 191 in this supplement, the AASK Pilot Study evaluated the feasibility of carrying out Controlled Clinical Trials 16:1%!S (1996) 0 EIsevier Science Inc. 1996 655 Avenue of the Americas, New York, NY 10010
0197-2456/96/$15.00 PII SO197-2456(96)0082-7
2s
Overview a long-term, multicenter clinical trial of two levels of blood pressure control (usual mean arterial blood pressure [MAP] goal of 102-107 mm Hg and a low MAP goal of s 92mm Hg) and three antihypertensive drug regimens (initial therapy with an angiotensin-converting enzyme (ACE) inhibitor, calcium channel blocker, or beta blocker) on progression of chronic renal disease attributed to hypertension (hypertensive nephrosclerosis) in African Americans with mild to moderately reduced renal function. One of the reasons for considering the low MAP goal was to test the hypothesis that reducing blood pressure to levels below the currently recommended 140/ 90 mmHg to prevent mortality from cardiovascular disease and stroke might be beneficial with regard to maintaining kidney function. The basis for evaluation of two levels of blood pressure control is derived, in part, from subgroup analyses of the Modification of Diet in Renal Disease (MDRD) Study [lo]. In African American MDRD Study participants (with kidney disease of diverse causes and similar entry requirements for level of kidney function as in the AASK Pilot Study) who were randomized to a low MAP goal (identical to that in the AASK), the decline in renal function projected over three years was about one-half the rate of decline observed in participants. randomized to the usual MAP goal (cl07 mm Hg). Because of the small number of African Americans with a diagnosis of hypertensive nephrosclerosis in the MDRD Study, it could not be determined whether a lower than usual blood pressure goal would be beneficial in these patients. The concept that certain classes of antihypertensive drugs may be more effective in preventing progression of chronic renal disease independent of the level of blood pressure control (e.g., “renoprotective”) is supported by a growing literature ill]. In a randomized clinical trial of patients with insulin-dependent diabetes and evidence of renal disease, treatment with an ACE inhibitor appeared to reduce the risk of doubling of serum creatinine concentration (a measure of renal function) by nearly 50% compared to treatment with other antihypertensive agents not including an ACE inhibitor 161. No previous study, however, has compared the major classes of antihypertensive drugs for their renoprotective properties in African Americans with hypertensive nephrosclerosis. The articles contained in this supplement report selected findings from the AASK Pilot Study including baseline characteristics of participants [9], recruitment experience [12], adherence to the antihypertensive drug regimen 1131 participant satisfaction with the trial 1141, and quality of life associated with the interventions [15]. Findings of particular interest are the relative ineffectiveness of communitybased recruitment strategies, the underrepresentation of women among randomized participants, the. relatively low economic status and high unemployment rate of participants, the difficulty in achieving blood pressure goal over the short period of follow-up, and the high level of satisfaction expressed by participants regarding study procedures. These and other findings from the Pilot Study 116,171 provided valuable information to investigators in planning the ongoing full-scale phase of AASK [la].