Calcium antagonists, currently widely used in cardiological practice, are one of five classes of antihypertensive drugs, whose effectiveness has been proven in both placebo-controlled and comparative studies with end-point studies. The first study where calcium antagonists showed comparable efficacy with diuretics and BB in reducing the incidence and mortality from CVD was the Swedish study STOP Hypertension-2 (Swedish Trial in Old Patients with Hypertension). In 6614 patients who received either a dihydropyridine calcium antagonist (felodipine or isradipine), or a diuretic and / or BB, or an ACE inhibitor (enalapril or lisinopril), the effectiveness of these antihypertensive drugs was comparable.In general, no differences were established between them in terms of their impact on mortality from CVD [18]. Similarly, in a large-scale randomized study INSIGHT (Intervention as a Goal in Hypertension Treatment), in which 6321 patients with moderate and high AH for 4 years studied the effectiveness of prolonged nifedipine and diuretics (25 mg of hydrochlorothiazide in combination with 2.5 mg of amiloride), there were no significant differences between the groups by the primary end points (MI + stroke + death from CVD) and total mortality. In the same study, the most important data on the beneficial effects of nifedipine-GITS on metabolism were obtained. In the treatment group with this drug, the incidence of type 2 diabetes was significantly lower than in patients treated with diuretics.in a large-scale randomized study INSIGHT (Intervention as a Goal in Hypertension Treatment), in which 6321 patients with moderate and high AH for 4 years studied the effectiveness of prolonged nifedipine and diuretics (25 mg of hydrochlorothiazide in combination with 2.5 mg of amiloride ), there were no significant differences between groups on the primary endpoints (MI + stroke + death from CVD) and total mortality. In the same study, the most important data on the beneficial effects of nifedipine-GITS on metabolism were obtained. In the treatment group with this drug, the incidence of type 2 diabetes was significantly lower than in patients treated with diuretics.in a large-scale randomized study INSIGHT (Intervention as a Goal in Hypertension Treatment), in which 6321 patients with moderate and high AH for 4 years studied the effectiveness of prolonged nifedipine and diuretics (25 mg of hydrochlorothiazide in combination with 2.5 mg of amiloride ), there were no significant differences between groups on the primary endpoints (MI + stroke + death from CVD) and total mortality. In the same study, the most important data on the beneficial effects of nifedipine-GITS on metabolism were obtained. In the treatment group with this drug, the incidence of type 2 diabetes was significantly lower than in patients treated with diuretics.in which 6321 patients with moderate and high AH over 4 years studied the effectiveness of prolonged nifedipine and diuretics (25 mg of hydrochlorothiazide in combination with 2.5 mg of amiloride), no significant differences were found between the groups on the primary end points (MI + stroke + death from CVD) and total mortality. In the same study, the most important data on the beneficial effects of nifedipine-GITS on metabolism were obtained. In the treatment group with this drug, the incidence of type 2 diabetes was significantly lower than in patients treated with diuretics.in which 6321 patients with moderate and high AH over 4 years studied the effectiveness of prolonged nifedipine and diuretics (25 mg of hydrochlorothiazide in combination with 2.5 mg of amiloride), no significant differences were found between the groups on the primary end points (MI + stroke + death from CVD) and total mortality. In the same study, the most important data on the beneficial effects of nifedipine-GITS on metabolism were obtained. In the treatment group with this drug, the incidence of type 2 diabetes was significantly lower than in patients treated with diuretics.In the same study, the most important data on the beneficial effects of nifedipine-GITS on metabolism were obtained. In the treatment group with this drug, the incidence of type 2 diabetes was significantly lower than in patients treated with diuretics.In the same study, the most important data on the beneficial effects of nifedipine-GITS on metabolism were obtained. In the treatment group with this drug, the incidence of type 2 diabetes was significantly lower than in patients treated with diuretics.
Calcium antagonists are one of the most effective classes in terms of prevent the development of cerebral strokes. This is evidenced by a meta-analysis of large-scale studies. In this respect, the study of NORDIL stands out. This is the only study that demonstrated a statistically significant reduction in MI against the background of the use of a calcium antagonist compared with BB and diuretics. In the indicated randomized prospective study, which lasted 5 years and included 10881 previously untreated patients with hypertension aged 50- 74 years, compared the effectiveness of diltiazem (180-360 mg per day) and BB or diuretics. The frequency of the primary endpoints (total, including strokes, myocardial infarction, and death from other cardiovascular causes) was the same in both treatment groups. At the same time, the frequency of fatal and nonfatal MI was significantly lower in the diltiazem group (–20%, p = 0,04), despite the fact that the degree of blood pressure reduction in this group was slightly less than in the BB group or diuretics (–20.3 / 18.7 mm Hg vs. –23.3 / 18.7 mm Hg). Art.), which researchers explain is not sufficiently high dosage of diltiazem [21]. A possible explanation for the effectiveness of diltiazem in the prevention of stroke is the anti-atherogenic effect of the drug and the ability to reduce the activity of the SNA. Thus, in the VHAS study (Verapamil in Hypertension and Atherosclerosis Study), the same frequency of MTR was found in the treatment of Verapamil-SR and 1414 patients with hypertension with chlorthalidone. However, Verapamil-SR was superior to chlorthalidone in slowing the thickening of the carotid intima media (p <0.01) with a comparable decrease in blood pressure.3 / 18.7 mm Hg Art. against –23.3 / 18.7 mm Hg Art.), which researchers explain is not sufficiently high dosage of diltiazem [21]. A possible explanation for the effectiveness of diltiazem in the prevention of stroke is the anti-atherogenic effect of the drug and the ability to reduce the activity of the SNA. Thus, in the VHAS study (Verapamil in Hypertension and Atherosclerosis Study), the same frequency of MTR was found in the treatment of Verapamil-SR and 1414 patients with hypertension with chlorthalidone. However, Verapamil-SR was superior to chlorthalidone in slowing the thickening of the carotid intima media (p <0.01) with a comparable decrease in blood pressure.3 / 18.7 mm Hg Art. against –23.3 / 18.7 mm Hg Art.), which researchers explain is not sufficiently high dosage of diltiazem [21]. A possible explanation for the effectiveness of diltiazem in the prevention of stroke is the anti-atherogenic effect of the drug and the ability to reduce the activity of the SNA. Thus, in the VHAS study (Verapamil in Hypertension and Atherosclerosis Study), the same frequency of MTR was found in the treatment of Verapamil-SR and 1414 patients with hypertension with chlorthalidone. However, Verapamil-SR was superior to chlorthalidone in slowing the thickening of the carotid intima media (p <0.01) with a comparable decrease in blood pressure.A possible explanation for the effectiveness of diltiazem in the prevention of stroke is the anti-atherogenic effect of the drug and the ability to reduce the activity of the SNA. Thus, in the VHAS study (Verapamil in Hypertension and Atherosclerosis Study), the same frequency of MTR was found in the treatment of Verapamil-SR and 1414 patients with hypertension with chlorthalidone. However, Verapamil-SR was superior to chlorthalidone in slowing the thickening of the carotid intima media (p <0.01) with a comparable decrease in blood pressure.A possible explanation for the effectiveness of diltiazem in the prevention of stroke is the anti-atherogenic effect of the drug and the ability to reduce the activity of the SNA. Thus, in the VHAS study (Verapamil in Hypertension and Atherosclerosis Study), the same frequency of MTR was found in the treatment of Verapamil-SR and 1414 patients with hypertension with chlorthalidone. However, Verapamil-SR was superior to chlorthalidone in slowing the thickening of the carotid intima media (p <0.01) with a comparable decrease in blood pressure.01) with a comparable decrease in blood pressure.01) with a comparable decrease in blood pressure.
In the above-mentioned INSIGHT study among patients receiving nifedipine, there was a more pronounced slowing down of the intimal thickening of the carotid arteries than among patients treated with diuretics . In turn, the antiatherogenic effect attributable to calcium antagonists is associated with the ability of this class to correct endothelial dysfunction. This is evidenced by numerous clinical studies, including those performed at a high methodological level in the evaluation of the endothelial function .
The antiatherogenic effect of calcium antagonists is reflected in the new European guidelines for the diagnosis and treatment of hypertension: one of the most important niches for the use of calcium antagonists (both dihydropyridine and non-dihydropyridine) is associated with atherosclerosis of various localization vessels , including coronary . In addition, general indications for the use of all calcium antagonists are hypertension of various origins, arresting hypertensive crises, as well as prevention and relief of angina attacks of various nature (including vasopasmodic angina).
In conclusion, I would like to draw the attention of practitioners to one of the most important aspects of the use of calcium antagonists in clinical practice: the division of this class of drugs into two large subgroups based on their impact on the SNA, dysregulation of which plays an important role not only in raising and maintaining arterial levels – but also in the occurrence of a number of other negative effects , which significantly increase the risk of cardiovascular complications. . The first subgroup is the so-called pulse-reducing calcium antagonists (Verapamil and Diltiazem). These drugs reduce myocardial contractility, reduce the heart rate, and also have an anti-arrhythmic effect and slow down atrioventricular conductivity. Due to these properties, the drugs improve the function of the autonomic nervous system, restoring the balance between the sympathetic and parasympathetic nervous systems and reduce the myocardial oxygen demand . The second subgroup is pulse rate-increasing calcium antagonists, or dihydropyridines. In these drugs, the ability to cause dilatation of peripheral arteries prevails, as a result of which the SNS reflexively increases and the heart rate increases. . According to the results of numerous studies, on the basis of this, there are differences in the efficacy of dihydropyridine and non-dihydropyridine AK in different clinical situations. Pulse-reducing non-dihydropyridine calcium antagonists are effective and safe for treating various forms of coronary artery disease, whereas dihydropyridine calcium antagonists cause undesirable effects in acute conditions such as unstable angina and acute myocardial infarction, most likely due to SNA activation. . For example, in the HINT study (Holland Inter-University Nifedipine Trial), it was shown that intravenous administration of the short-range dihydropyridine calcium antagonist nifedipine resulted in a rate of adverse outcomes (recurrent ischemia and myocardial infarction) during the first 48 hours.(from the moment of hospitalization) was significantly higher than at using metoprolol . Another study demonstrated an increase in early mortality in these patients during therapy with nifedipine compared with nitrates and / or BB . In contrast, the diltiazem administered intravenously non-dihydropyridine calcium antagonist significantly reduced the incidence of some adverse outcomes (angina attacks, ischemic changes in the myocardium on the ECG) during the first two days and exceeded intravenous nitroglycerin in its efficacy . The use of dihydropyridine calcium antagonists (prolonged preparations) should be limited to cases of vasospastic angina pectoris and stable exertional angina pectoris.
It is no coincidence that the European recommendations for the control of hypertension emphasize the clinical significance of the division of calcium antagonists into two groups: dihydropyridine and non-dihydropyridine . In addition to the general indications for the use of these two subgroups of drugs, non-dihydropyridine calcium antagonists have an additional indication – treatment of tachyarrhythmias, as a fact indicating the sympatolytic effect of this subclass of calcium antagonists.