Okay, moving on to the next common question, “should I add an ARB to the ACE inhibitor?” Read more..
It’s been shown that angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARB) reduce both proteinuria as well as renal risk (loss of GFR and need for dialysis). What remains unclear, however, is whether a combination of these classes of drugs has an additive effect on renal risk reduction, and whether the effects of ARB and ACE inhibitors are equivalent. Several previous studies have shown that combination therapy reduces proteinuria; however, these trials were limited by their small sample size, short duration of therapy, and did not report on major renal outcomes. The current investigation, the ONTARGET study, published in this week’s Lancet, is a large multi-center, randomized controlled trial that took place over 6 years. Participants were 55 years or older and had established atherosclerotic vascular disease or diabetes with end-organ damage (the baseline mean creatinine was about 83mmol/l). Over 25,000 patients were assigned to ramipril 10 mg daily, telmisartan 80 mg daily, or to a combination of both drugs. The primary outcome was a composite of dialysis, doubling of serum creatinine and death; the secondary outcome was a composite of dialysis and doubling of serum creatinine. The results of this trial may surprise you. Combination therapy reduced proteinuria to a greater degree than either therapy alone. However, both the primary outcome as well as secondary outcome were similar for telmisartan and ramipril but were increased with combination therapy. The study raises interesting questions regarding the relationship between proteinuria and kidney damage and asks if the reduction in proteinuria by itself can be taken as a definitive marker of improved renal function; these questions will no doubt require further investigation. Study limitations include a population that, at baseline, was well-treated with regards to standard cardiovascular therapy and only included a small subgroup with overt diabetic nephropathy. So this population may not represent the majority of patients we treat in our clinic. Overall, this trial suggests that while monotherapy with either an ARB or ACE inhibitor confers similar beneficial effects on major renal outcomes, combination blockade of the renin-angiotensin system may not be the way to go.
It’s been shown that angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARB) reduce both proteinuria as well as renal risk (loss of GFR and need for dialysis). What remains unclear, however, is whether a combination of these classes of drugs has an additive effect on renal risk reduction, and whether the effects of ARB and ACE inhibitors are equivalent. Several previous studies have shown that combination therapy reduces proteinuria; however, these trials were limited by their small sample size, short duration of therapy, and did not report on major renal outcomes. The current investigation, the ONTARGET study, published in this week’s Lancet, is a large multi-center, randomized controlled trial that took place over 6 years. Participants were 55 years or older and had established atherosclerotic vascular disease or diabetes with end-organ damage (the baseline mean creatinine was about 83mmol/l). Over 25,000 patients were assigned to ramipril 10 mg daily, telmisartan 80 mg daily, or to a combination of both drugs. The primary outcome was a composite of dialysis, doubling of serum creatinine and death; the secondary outcome was a composite of dialysis and doubling of serum creatinine. The results of this trial may surprise you. Combination therapy reduced proteinuria to a greater degree than either therapy alone. However, both the primary outcome as well as secondary outcome were similar for telmisartan and ramipril but were increased with combination therapy. The study raises interesting questions regarding the relationship between proteinuria and kidney damage and asks if the reduction in proteinuria by itself can be taken as a definitive marker of improved renal function; these questions will no doubt require further investigation. Study limitations include a population that, at baseline, was well-treated with regards to standard cardiovascular therapy and only included a small subgroup with overt diabetic nephropathy. So this population may not represent the majority of patients we treat in our clinic. Overall, this trial suggests that while monotherapy with either an ARB or ACE inhibitor confers similar beneficial effects on major renal outcomes, combination blockade of the renin-angiotensin system may not be the way to go.
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