AIMS: In the Ongoing Telmisartan Alone and in Combination with Ramipril Trial (ONTARGET), dual agent renin-angiotensin-aldosterone system (RAAS) blockade with angiotensin-converting-enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) did not reduce the risk of renal and cardiovascular outcomes compared with the single use of either agent. Dual therapy however increased the incidence of hyperkalemia. We examined risk factors for hyper- and hyokalemia and hypothesized that both would be associated with worse cardiovascular and renal outcomes. METHODS: A post-hoc analysis of the ONTARGET trial comparing dual therapy (ramipril and telmisartan) vs monotherapy (ramipril or telmisartan) was performed. The association between serum potassium at week 6 on cardiovascular and renal outcomes during the 56 months follow-up was assessed by multivariate Cox analysis. The main cardiovascular outcome was the composite of cardiovascular death, myocardial infarction, stroke, or hospitalization for heart failure. The renal outcome was defined as the composite of a doubling of serum creatinine or chronic dialysis. RESULTS: Six weeks after randomization, hyperkalemia developed in 210 (2.7%) patients on dual therapy vs. 264 (1.6%) patients on monotherapy (p < 0.001 vs. dual therapy). Hypokalemia developed in 87 (1.1%) patients on dual therapy vs. 200 (1.2%)patients on monotherapy. Serum potassium was nonlinearly associated with cardiovascular and renal events with a nadir between 4.0-5.0 mmol/l for cardiovascular and 4.0-4.5 mmol/l for renal events such that subjects above or below these values exhibited higher risks. This association was independent of age, gender, diabetes, estimated glomerular filtration rate, systolic blood pressure and diuretic use. CONCLUSIONS: With the precautions stipulated by the protocol of the ONTARGET trial, hypokalemia and hyperkalemia were infrequent events. Nevertheless, both high and low serum potassium were associated with an increased risk of cardiovascular and renal disease.
RCT Entities:
AIMS: In the Ongoing Telmisartan Alone and in Combination with Ramipril Trial (ONTARGET), dual agent renin-angiotensin-aldosterone system (RAAS) blockade with angiotensin-converting-enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) did not reduce the risk of renal and cardiovascular outcomes compared with the single use of either agent. Dual therapy however increased the incidence of hyperkalemia. We examined risk factors for hyper- and hyokalemia and hypothesized that both would be associated with worse cardiovascular and renal outcomes. METHODS: A post-hoc analysis of the ONTARGET trial comparing dual therapy (ramipril and telmisartan) vs monotherapy (ramipril or telmisartan) was performed. The association between serum potassium at week 6 on cardiovascular and renal outcomes during the 56 months follow-up was assessed by multivariate Cox analysis. The main cardiovascular outcome was the composite of cardiovascular death, myocardial infarction, stroke, or hospitalization for heart failure. The renal outcome was defined as the composite of a doubling of serum creatinine or chronic dialysis. RESULTS: Six weeks after randomization, hyperkalemia developed in 210 (2.7%) patients on dual therapy vs. 264 (1.6%) patients on monotherapy (p < 0.001 vs. dual therapy). Hypokalemia developed in 87 (1.1%) patients on dual therapy vs. 200 (1.2%)patients on monotherapy. Serum potassium was nonlinearly associated with cardiovascular and renal events with a nadir between 4.0-5.0 mmol/l for cardiovascular and 4.0-4.5 mmol/l for renal events such that subjects above or below these values exhibited higher risks. This association was independent of age, gender, diabetes, estimated glomerular filtration rate, systolic blood pressure and diuretic use. CONCLUSIONS: With the precautions stipulated by the protocol of the ONTARGET trial, hypokalemia and hyperkalemia were infrequent events. Nevertheless, both high and low serum potassium were associated with an increased risk of cardiovascular and renal disease.
Authors: Toshiaki Ohkuma; Katie Harris; Mark Cooper; Diederick E Grobbee; Pavel Hamet; Stephen Harrap; Giuseppe Mancia; Michel Marre; Anushka Patel; Anthony Rodgers; Bryan Williams; Mark Woodward; John Chalmers Journal: Clin J Am Soc Nephrol Date: 2022-07-27 Impact factor: 10.614
Authors: Csaba P Kovesdy; Kunihiro Matsushita; Yingying Sang; Nigel J Brunskill; Juan J Carrero; Gabriel Chodick; Takeshi Hasegawa; Hiddo L Heerspink; Atsushi Hirayama; Gijs W D Landman; Adeera Levin; Dorothea Nitsch; David C Wheeler; Josef Coresh; Stein I Hallan; Varda Shalev; Morgan E Grams Journal: Eur Heart J Date: 2018-05-01 Impact factor: 29.983
Authors: Hiddo J L Heerspink; Dennis L Andress; George Bakris; John J Brennan; Ricardo Correa-Rotter; Jyotirmoy Dey; Fan Fan Hou; Dalane W Kitzman; Donald Kohan; Hirofumi Makino; John McMurray; Vlado Perkovic; Sheldon Tobe; Melissa Wigderson; Hans-Henrik Parving; Dick de Zeeuw Journal: Diabetes Obes Metab Date: 2018-03-09 Impact factor: 6.577
Authors: Ahmed Al-Naher; David Wright; Mark Alexander John Devonald; Munir Pirmohamed Journal: Br J Clin Pharmacol Date: 2017-10-22 Impact factor: 4.335