Lege Artis Medicinae

[The use of carvedilol following invasive interventions]

KOVÁCS Imre

SEPTEMBER 20, 2011

Lege Artis Medicinae - 2011;21(08-09)

[The primary goals of the treatment of AMI are to rapidly open - either mechanically or by thrombolysis - the blocked blood vessel and to keep it open. Restarting of the blood flow in blocked vessels results in an increased load in volume, pressure and metabolism in the blood vessel's supply area, which triggers the activation of a pathophysiological cascade. Pathophysiological processes accompanying the opening of the blood vessel include activation of catecholamines, RAS and neutrophils and subsequent free radical production, and increases in the levels of proinflammatory citokines and intracellular CA levels, that is, the so called oxygen paradox. The above mentioned processes can be blocked by beta receptor blockers (BRB) as demonstrated by class I, type A evidence. A number of clinical studies have shown their clinical efficiency following PCI. The PAMI, StentPAMI, AirPAMI and CADILLAC studies have proved that BRBs decrease mortality and morbidity after the intervention. The third-generation BRB carvedilol, which acts as a beta and alpha blocker in patients with STEMI successfully treated with PCI, and is also a Ca-channel blocker and a free radical trap, is the firstchoice agent for both theoretical and clinical reasons. Animal studies have shown that carvedilol results in greater reductions in the levels of markers indicating postinfarction reperfusion and ventricular remodeling (MCP1, MMP2, TIMP2) compared with metoprolol. Animal studies have also showed that carvedilol is the most efficient BRB for preventing the damaging of gap junction structure in reperfusion, and for inhibiting the ventricular arrhythmias induced by reperfusion, through restoring connexin 43. The beneficial effect of this drug on the cardiovascular events and mortality following myocardial infarction have been demonstrated in a number of human studies with hard endpoints. The unique efficiency of carvedilol in vascular prevention following PCI has been demonstrated by the short-term and longterm efficiency of carvedilol-filled stents, compared with BMSE-filled stents. Information on the postintervention, long-term (3-year) efficiency of carvedilol in a large (N :7500) patient group is expected to be published in 2015 in the CAPITAL-RCT study coordinated by the University of Kyoto. In summary, the results of experimental and clinical studies on carvedilol have shown that within the BRB group, carvedilol is highly recommended for the prevention of oxygen paradox following successful PCI and preserving the myocardium.]

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[CARVEDILOL AND ITS ANTIOXIDANT EFFECT]

KOVÁCS Imre

[Carvedilol, the typical basic variant of the third generation beta blocker drugs is a complex adrenergic blocker that also has Ca channel blocking effects. It has no effect of the metabolism and has a pregnant antioxidant effect that is significant for cardiac and hypertension target organ protection. Its beneficial effect on cardiac decompensation, on target organ protection in patients with hypertension and on primary and secondary prevention of ischemic heart disease is proven by clinical studies. The effect of free radicals trapping - not shown by the majority of beta blockers - plays a major role in these beneficial effects. Inflammatory factors and free radicals (ROS) play a central role in cardiovascular diseases and can be regarded as prognostic markers of vascular damage. Elevated levels of glucose, lipids, or elevated intraluminal pressure triggers the production of various free radicals. The anti-inflammatory effect of carvedilol results out of its antioxidant (scavenger) and ROS suppressive effects. Besides its complex adrenergic blocking effect, this ability of carvedilol gives a molecular explanation for its efficiency proven by clinical trials.]

Hypertension and nephrology

[Carvedilol therapy in hypertension]

KÉKES Ede

[Author analyzed the properties and antihypertensive effect of one of the best beta blockers with vasodilative effects, the carvedilol on the base of the Hungarian and international literature . Author deals with this issue for many years and he presented his own experience. The beta blockers could never be missed on therapy of the endemic hypertension. They are equivalent to other drug family. This played a big role , that the new , strong beta-1 selective and -- especially 3. generation beta blockers (carvedilol and nebivolol) - came to the fore in the therapy of hypertension compared with conventional beta blockers. The carvedilol has many beneficial properties, as vasodilatation, antioxidant effect, beneficial effect on the vascular stiffness, regression of left ventricular hypertrophy, increasing coronary reserve. Carvedilol is able to stable success on the therapy of hypertension as monotherapy or combination with the other drugs. In Hungary the physicians applied beta blockers about 30-35% in the treatment of hypertension.]

Hypertension and nephrology

[Role of β-blockers, especially carvedilol in the treatment of hypertension]

PÁLL Dénes, MARODA László, ZRÍNYI Miklós

[Changes in hypertension guidelines in the past years have affected the clinical thinking about β-blockers. Authors reviewed the development of β-blockers emphasizing the differences across various active pharmaceutical agents. Different hemodynamic and metabolic effects are being discussed in details for the third ge - neration vasodilatator carvedilol. Carvedilol has no effect on cardiac output but decreases peripheral vascular resistance which results in lower blood pressure values. However, carvedilol, opposite to unfavorable effects of traditional β-blockers, has a neutral impact on both carbohydrate and lipid metabolisms. Its more advanced cardiac effects include decreased left ventricular hypertrophy and increased coronary flow reserve. Vasodilatator type β-blockers (carvedilol, nebivolol) are indicated in the combi - nation treatment of hypertension, especially when the patient has heart failure, coronary disease or suffered from a previous heart attack.]

Lege Artis Medicinae

[Carvedilol and its antioxidant effect]

KOVÁCS Imre

[Carvedilol, the typical basic variant of the third generation beta blocker drugs is a complex adrenergic blocker that also has Ca channel blocking effects. It has no effect of the metabolism and has a pregnant antioxidant effect that is significant for cardiac and hypertension target organ protection. Its beneficial effect on cardiac decompensation, on target organ protection in patients with hypertension and on primary and secondary prevention of ischemic heart disease is proven by clinical studies. The effect of free radicals trapping - not shown by the majority of beta blockers - plays a major role in these beneficial effects. Inflammatory factors and free radicals (ROS) play a central role in cardiovascular diseases and can be regarded as prognostic markers of vascular damage. Elevated levels of glucose, lipids, or elevated intraluminal pressure triggers the production of various free radicals. The anti-inflammatory effect of carvedilol results out of its antioxidant (scavenger) and ROS suppressive effects. Besides its complex adrenergic blocking effect, this ability of carvedilol gives a molecular explanation for its efficiency proven by clinical trials.]

Hypertension and nephrology

[The use of beta-blockers in Hungary 2007-2014 based on data from National Health Insurance]

BARNA István, GYURCSÁNYI András

[disease, various rhythm disturbances, migraine, essential tremor case, addition to the treatment of endocrine disorders caused tachycardia and also may be used in the treatment of systolic and diastolic heart failure. Using the National Health Insurance Fund (NHIF) database, we analyzed changes in the turnover of beta-blockers used domestically between 2007 and 2014. At the beginning of the period more than 50% was metoprolol as the used active ingredient, the end of the period, nebivolol became the most frequently assigned active agent betablocker (29%). Besides nebivolol the use of bisoprolol and carvedilol increased, among the “old” beta-blockers the use of pindolol, bopindolol continuously decreases, propranolol and sotalolol consumption stagnant after the initial small decrease. Metabolic syndrome, disorders of carbohydrate metabolism, in case of sleep apnea the advantage of nebivolol is accompanied by the status of enhanced sympathetic activity and consequent reduction of RAS activation. Vasodilation, inhibition of plaque formation, reduction of platelet aggregation and anti-proliferative effects of nebivolol are its unique characteristics in the beta-blocker group. Improves insulin sensitivity, thus it is not characterized by a long-term side effects that cause diabetes. Effective reduction in the central blood pressure with nebivolol is likely to reduce the risk of complications in stroke and other related central blood pressure. Therefore, if the recommendations of the international and domestic support for considering it is not surprising that the use of metoprolol reduced such a large extent and how nebivolol covered the significant majority of the entire domestic beta-blockers market. Carvedilol was before the second and currently has become the 3rd or 4th most frequently used beta blocker. The decrease in the use of metoprolol undoubtedly caused by change in the recommendations, getting out of the subsidized products, and the appearance of the above known, new effective drugs.]