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Renal outcomes with telmisartan, ramipril, or both, in people at high vascular risk (the ONTARGET study): a
Johannes F E Mann1, Roland E Schmieder, Matthew McQueen
1Schwabing General Hospital, and KfH Kidney Centre, Ludwig Maximilians University Munchen, Germany.
Background:
Angiotensin receptor blockers (ARB) and angiotensin converting enzyme (ACE) inhibitors are known to reduce proteinuria. Their combination might be more effective than either treatment alone, but long-term data for comparative changes in renal function are not available. We investigated the renal effects of ramipril (an ACE inhibitor), telmisartan (an ARB), and their combination in patients aged 55 years or older with established atherosclerotic vascular disease or with diabetes with end-organ damage.
Methods:
The trial ran from 2001 to 2007. After a 3-week run-in period, 25 620 participants were randomly assigned to ramipril 10 mg a day (n=8576), telmisartan 80 mg a day (n=8542), or to a combination of both drugs (n=8502; median follow-up was 56 months), and renal function and proteinuria were measured. The primary renal outcome was a composite of dialysis, doubling of serum creatinine, and death. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00153101.
Findings:
784 patients permanently discontinued randomised therapy during the trial because of hypotensive symptoms (406 on combination therapy, 149 on ramipril, and 229 on telmisartan). The number of events for the composite primary outcome was similar for telmisartan (n=1147 [13.4%]) and ramipril (1150 [13.5%]; hazard ratio [HR] 1.00, 95% CI 0.92-1.09), but was increased with combination therapy (1233 [14.5%]; HR 1.09, 1.01-1.18, p=0.037). The secondary renal outcome, dialysis or doubling of serum creatinine, was similar with telmisartan (189 [2.21%]) and ramipril (174 [2.03%]; HR 1.09, 0.89-1.34) and more frequent with combination therapy (212 [2.49%]: HR 1.24, 1.01-1.51, p=0.038). Estimated glomerular filtration rate (eGFR) declined least with ramipril compared with telmisartan (-2.82 [SD 17.2] mL/min/1.73 m(2)vs -4.12 [17.4], p<0.0001) or combination therapy (-6.11 [17.9], p<0.0001). The increase in urinary albumin excretion was less with telmisartan (p=0.004) or with combination therapy (p=0.001) than with ramipril.
Interpretation:
In people at high vascular risk, telmisartan's effects on major renal outcomes are similar to ramipril. Although combination therapy reduces proteinuria to a greater extent than monotherapy, overall it worsens major renal outcomes.
Insights
Combination therapy with angiotensin receptor blockers (ARB) and angiotensin converting enzyme (ACE) inhibitors worsened major renal outcomes in high-risk patients. While effective in reducing proteinuria, the combination therapy showed increased risks compared to monotherapy.
Area of Science:
- Nephrology
- Cardiology
- Pharmacology
Background:
- Angiotensin receptor blockers (ARB) and angiotensin converting enzyme (ACE) inhibitors are established treatments for reducing proteinuria.
- Long-term comparative renal function data for combined ARB and ACE inhibitor therapy are limited.
- This study evaluated the renal effects of ramipril (ACE inhibitor), telmisartan (ARB), and their combination in elderly patients with vascular disease or diabetes with end-organ damage.
Purpose of the Study:
- To compare the long-term renal effects of ramipril, telmisartan, and their combination in high-risk patients.
- To assess the impact of monotherapy versus combination therapy on major renal outcomes.
- To evaluate changes in proteinuria and estimated glomerular filtration rate (eGFR).
Main Methods:
- A randomized controlled trial involving 25,620 participants aged 55 years or older.
- Participants were assigned to ramipril 10 mg/day, telmisartan 80 mg/day, or a combination of both drugs.
- Primary renal outcome: composite of dialysis, doubling of serum creatinine, or death; median follow-up was 56 months.
Main Results:
- Combination therapy increased the risk of the primary composite renal outcome (14.5%) compared to telmisartan (13.4%) or ramipril (13.5%).
- The incidence of dialysis or doubling of serum creatinine was also higher with combination therapy.
- Ramipril showed the least decline in eGFR, while combination therapy resulted in the greatest decline; telmisartan and combination therapy reduced urinary albumin excretion more than ramipril.
Conclusions:
- Telmisartan demonstrated similar major renal outcomes compared to ramipril in patients at high vascular risk.
- Combination therapy, while superior in reducing proteinuria, led to worse major renal outcomes.
- The findings suggest caution when using combined ARB and ACE inhibitor therapy in this patient population.
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