Algorithm for differential administration of combination antihypertensive therapy in patients with Type 2 diabetes mellitus

Aim. To compare the effectiveness of three variants of long-term combination antihypertensive therapy (AHT), based on two methods of renin-angiotensinaldosterone system (RAAS) inhibition (angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II receptor antagonists (ARAII)) or on calcium channel blockade with a dihydropyridine calcium channel blocker (CCB), all of which were administered in order to achieve target levels of blood pressure (BP). To develop an algorithm for differential administration of combination AHT in patients with arterial hypertension (AH) and Type 2 diabetes mellitus (DM-2). 

Material and methods. The study included 71 patients (mean age 56,8±6,5 years) with AH and DM-2, but without clinically manifested nephroangopathy. The therapy course (30–32 weeks) was completed by 69 patients. All participants were randomised into three groups. The ACEI+CCB group (n=22) received perindopril (5–10 mg/d), indapamide SR (1,5 mg/d), and amlodipine (5–10 mg). The ARAII+CCB group (n=25) was administered valsartan (80–160 mg/d), indapamide SR, and amlodipine. The CCB+BAB group (n=22) received amlodipine (5–10 mg/d), indapamide SR, and metoprolol succinate (50–100 mg/d). The doses of AHT were

increased stepwise. At baseline and after 30–32 weeks of the treatment, 24-hour BP monitoring (BPM), renal artery ultrasound and Doppler ultrasound, carbohydrate and lipid metabolism assessment, and 24-hour albumin excretion measurement were performed. 

Results. Target BP levels were achieved in the majority of patients from all three groups. For the two-component combination AHT, target BP levels were achieved more often with the combination of RAAS inhibitors and indapamide SR, compared to the combination of CCB and indapamide SR. Most patients receiving the latter combination required additional administration of a third medication, in order to achieve adequate BP control. The combination of CCB and BAB increased intrarenal vascular resistance and less effectively controlled night-time systolic AH, compared to the combination of RAAS inhibitors and CCB. The combination of ACEI and CCB, compared to the ARAII+CCB combination, was associated with improved glycemic control, effective reduction of the duration of night-time diastolic AH and night-time heart rate, and normalisation of initially elevated intrarenal vascular resistance at the level of segmental intrarenal arteries. These findings were used for the development of the algorithm for differential administration of combination AHT in patients with AH and DM-2. 

Conclusion. In DM-2 patients, long-term combination AHR with ACEI and CCB demonstrates more beneficial effects on the metabolic and neurohumoral regulation processes, compared to the combination of ARAII and CCB. These benefits are particularly pronounced in patients with inadequate glycemic control and increased intrarenal vascular resistance. The combination of CCB and BAB inadequately controls night-time systolic AH and does not improve renal hemodynamics.

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