Combination therapy of hypertension in general clinical practice. The results of the KOHYBA study

Summary

Introduction:
The aim of hypertension treatment is to achieve blood pressure target values; in the majority of patients this is achieved with combination therapy. ACE inhibitors and imidazoline receptor agonists have neutral effect on lipid metabolism and positive effect on glucose metabolism. They thus may significantly improve long‑term prognosis of patients with hypertension and metabolic syndrome or hypertension and diabetes mellitus. The aim of our research was to evaluate physicians’ approach to hypertension treatment and to ascertain the proportion of patients in general clinical practice who require combination treatment to control their hypertension. The study also aimed to assess the knowledge of the type and frequency of adverse events associated with the administered agents.

Materials and methodology:
The 12‑week evaluation (two 6‑week visits) included 993 patients with mild to moderate hypertension above 18 years of age (20– 92; mean 57; median 56) with proportional distribution of men and women (48% and 51%, respectively). Data were collected using a standard instrument and blood pressure measured in a standard manner according to guidelines. Hypertension was newly identified in 609 patients (61%), insufficiently controlled hypertension in 363 patients (37%) and data on hypertension were missing in 21 patients (2%). The initial therapy was imidapril (Tanatril^®) 10 mg. On the first follow up visit, it was on the physician’s discretion to increase the dose (increase –  imidapril 20 mg) or to prescribe a combination of lower doses [low dose combination –  imidapril 10 mg + moxonidin (Cynt^®) 0.2 or 0.3 mg, respectively]. The second visit, scheduled at 12 weeks post study entry, was attended by 965 patients (97%).

Results:
Eleven (1.1%) patients discontinued the treatment prematurely. Dry irritant cough, occurring in 4, i.e. only 0.4%, patients was the most frequent cause of treatment discontinuation. Over the 12 weeks of treatment, systolic blood pressure declined from 154 mm Hg to 132 mm Hg (p < 0.001); diastolic blood pressure declined from 92 mm Hg to 80 mm Hg (p < 0.001). By the second visit, normal blood pressure was achieved by 718 (74%) patients. Overweight and obese patients have profited from the treatment significantly more than patients with BMI ≤ 25. This held true for the reduction of systolic blood pressure (p = 0.022 at the first follow up and p = 0.037 at the second follow up, respectively) as well as the reduction of diastolic blood pressure (p = 0.003 at the first follow up and p = 0.001 at the second follow up, respectively). After the first follow up visit, the majority of patients continued to take 10 mg of imidapril (610; 61%). At the second follow up visit, 808 (84%) patients continued on the study medication, 79% of patients were on imidapril (5, 10 or 20mg) and 21% on imidapril + moxonidin combination. Imidapril monotherapy (no other antihypertensive) was prescribed to 258 (27%) patients.

Conclusion:
Imidapril is an ACE inhibitor with one of the lowest incidences (less than 1% of patients) of dry irritant cough. It thus may become an alternative treatment modality in patients who experienced cough while taking other ACE inhibitors. A significant reduction of blood pressure can be expected in the majority of patients at a dose as low as 10 mg.

Key words:
hypertension –  combination therapy –  imidapril –  cough