Use Of Maximal Dosage Renin-Angiotensin-Aldosterone System Inhibitors In A Real Life Population Of Complicated Type 2 Diabetes – Contraindications And Opportunities

Abstract Objective Pharmacological inhibition of the renin-angiotensin-aldosterone-system (RAASi) is the cornerstone of hypertension treatment, renoprotection and secondary prevention of cardiovascular disease in patients with type 2 diabetes. Although there is a dose-dependent effect of RAASi with optimum protection when using maximal dose, little is known on actual use of maximal dosage RAASi in clinical practice. Here we investigate prevalence of maximal dosage RAASi, and contraindications for, optimizing RAASi dosage, in patients with complicated type 2 diabetes in a real-life clinical setting.Research Design and MethodsWe performed a retrospective analysis in 668 patients included in the DIAbetes and LifEstyle Cohort Twente (DIALECT). We grouped patients according to no RAASi, submaximal RAASi and maximal RAASi use. All potassium and creatinine measurements between January 1st 2000 and date of inclusion in DIALECT were extracted from patients files. We identified determinants of maximal RAASi use vs submaximal RAASi use with multivariate logistic regression analysis. ResultsMean age was 64 ± 10 years and 61% were men. In total, 460 patients (69%) used RAASi, and 30% used maximal RAASi. Maximal RAASi use was not statistically different between different indications for RAASi (i.e. hypertension, diabetic kidney disease, coronary heart disease and cerebrovascular disease; P>0.05). Per patient, 2 [1-4] measurements of potassium and 20 [13-31] measurements of creatinine were retrieved, retrospective follow-up time was -3.0 [-1.4 to -5.7] years. Pre-baseline hyperkalemia >5.0 mmol/l and acute kidney injury were found in 151 (23%) patients and 119 patients (18%), respectively. Determinants of maximal RAASi were prior acute kidney injury (OR 0.51 (0.30-0.87)), increased albuminuria (OR 1.89 (1.17-3.08)) and total number of used antihypertensives (OR 1.66 (1.33-2.06)).ConclusionsMaximal dose RAASi is used in almost one third of complicated type 2 diabetes patients in a real-life setting. The prevalence of contraindications is considerable, but relative in nature, suggesting that it is worthwhile to explore strategies aimed at maximizing RAASi while circumventing the alleged contraindications.

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Renin Angiotensin Aldosterone System, Glucose Homeostasis, and Prevention of Type 2 Diabetes: Mechanistic Insights and Evidence from Major Clinical Trials

10.5772/intechopen.97737 ◽

2021 ◽

Author(s):

Samara Skwiersky ◽

Sandra Iwuala ◽

Seeta Chillumuntala ◽

Deborah Osafehinti ◽

Jocelyne Karam

Keyword(s):

Type 2 Diabetes ◽

Secondary Analysis ◽

Health Impact ◽

Renin Angiotensin Aldosterone System ◽

Renin Angiotensin ◽

Randomized Controlled Studies ◽

Multiple Trials ◽

Added Benefit ◽

Reduced Risk

With its alarmingly rising prevalence worldwide, type 2 diabetes has become a leading cause of morbidity and mortality around the planet. Efforts to prevent progression to diabetes in individuals at risk could have a significant positive public health impact. Multiple trials examining cardiovascular outcomes of Renin-Angiotensin-Aldosterone System (RAAS) inhibitors revealed, in secondary analysis, a significantly reduced risk of new onset diabetes in participants receiving these agents. This glycemic protective effect is attributed to the known implication of RAAS in the development of insulin resistance and type 2 diabetes. The DREAM trial and the NAVIGATOR trial were two large randomized controlled studies examining, as primary outcome, the effect of Ramipril and Valsartan respectively on the incidence of diabetes in patients with prediabetes. Their results confirmed a favorable glycemic effect of RAAS inhibition agents and suggested a possible added benefit of diabetes prevention to their other several cardiovascular and blood pressure benefits.

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