1,721,746 research outputs found
Calcium-channel blockers for the prevention of stroke: From scientific evidences to the clinical practice
No full textThe present review aims to analyze the role of calcium-channel blockers, and particularly newer molecules, as first-line therapy for cerebrovascular disease. BACKGROUND: Stroke is the leading cause of disability in the general population. Among traditional cardiovascular risk factors, hypertension has a key role in the genesis of both hemorrhagic and ischemic stroke and a direct correlation exists between blood pressure values and the risk of stroke. Moreover, blood pressure reduction has been demonstrated to be the most important route to reduce stroke incidence and recurrence. However, the mere reduction of blood pressure values does not normalize the cardiovascular risk of the hypertensive patient. It is therefore necessary to use drug classes that beyond their blood pressure-lowering effect have also an additional effect in terms of organ protection. Among these, calcium-channel blockers have a crucial profile. Firstly, they are effective in inducing left ventricular hypertrophy regression, with a strength at least equal to that of ACE-inhibitors. Secondly, they have an antithrombotic and an endothelium-protecting effect, mediated by their antioxidant activity. Finally, calcium-channel blockers are the most powerful drugs in preventing vascular remodeling. For these reasons this drug class has probably the strongest antiatherosclerotic effect, and it is the first-choice treatment mainly for cerebrovascular disease. Among different available calcium-channel blockers, the newer ones seem to possess pharmacokinetic characteristics allowing a more homogeneous 24 hours coverage as compared to older molecules, and preliminary data seem to suggest a greater beneficial effect also on left ventricular hypertrophy and lower incidence of side effects. CONCLUSIONS: Although blood pressure reduction is the main tool to reduce cerebrovascular risk in hypertensive patients, some drug classes, such as calcium-channel blockers, seem to provide a protective action beyond the mere antihypertensive effect, and represent a key element in the prevention of atherosclerosis
RAS inhibitors' dose-dependent efficacy: Myth or reality?
No full textObjective: Treatment of hypertension remains challenging in clinical practice. One major problem is incorrect utilization of the principal drug classes. Drugs from each class are currently used in accordance with an assumption that the blood pressure (BP) lowering effect is dose dependent. While this is true for most drugs, it is not appropriate for all drugs that block the renin-angiotensin system (RAS). Methods: This review is based on a PubMed/Cochrane database search for articles on the dose-dependent effect of RAS blockers on BP and cardiovascular protection. Results: Of the RAS blockers, most angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) have a flat dose-response curve for BP decrease, meaning an increase in dose prolongs duration of action, but does not yield greater potency. Perindopril is the only ACE inhibitor to show a real dose-response curve for BP decrease. While the effectiveness of RAS blockers on target organ damage is dose dependent and at least partially unrelated to BP control, there is evidence that the only way to obtain a beneficial effect is to use them at full dose. Thus, RAS blockers need to be used at the correct dose, based on the results of controlled clinical trials and meta-analysis. Furthermore, for all-cause mortality, ACE inhibitors have been shown to be better than ARBs, a specific efficacy supported by perindopril-based studies including ASCOT-BPLA (the Anglo-Scandinavian Cardiac Outcomes Trial-BP Lowering Arm), ADVANCE (the Action in Diabetes and Vascular disease: PreterAx and DiamicroN-MR Controlled Evaluation trial) and HYVET (HYpertension in the Very Elderly Trial). Conclusion: In hypertensive patients, a strategy based on ACE inhibitors with dose-dependent efficacy such as perindopril as optimal treatment should lead both to improved BP control and to a better protection from target organ damage, thereby reducing the incidence of cardiovascular events
Blood pressure through aging and menopause
No full textTogether with the aging process, hypertension is the main risk factor contributing to the increase in cardiovascular morbidity and mortality in postmenopausal women, with a prevalence of around 60% in women older than 65 years. Considering that hypertension is a modifiable risk factor, the understanding of its epidemiology and pathophysiology and the development of appropriate therapeutic strategies are conceivably crucial in reducing cardiovascular risk. The high prevalence of hypertension in older women is largely due to the progressive stiffening of the arterial structure which accompanies the aging process in both sexes. However, the abrupt fall in circulating estrogen levels might independently contribute to the rise in blood pressure, through partly unknown mechanisms, such as a direct effect on the arterial wall, the activation of the renin-angiotensin system and of the sympathetic nervous system. Postmenopausal hypertension fosters the development of left ventricular hypertrophy and is the main factor contributing to coronary artery disease, chronic heart failure and stroke in older women. Recent analysis demonstrates that men and women receive a similar benefit from antihypertensive therapy in terms of reduction of cardiovascular morbidity and mortality and, considering that generally the response to different drugs is not different between the sexes, currently there is no need to use specific antihypertensive drug classes after menopause. Finally, although observational studies have shown that hormone replacement therapy is associated with lower cardiovascular risk and lower blood pressure values, randomized clinical trials have conversely denied this benefit and demonstrated rather that this therapeutical approach increases the risk of cardiovascular events
The pharmacotherapy of arterial hypertension and the prevention of cardiovascular events. From evidence-based medicine to the new therapeutic opportunities.
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Combination Therapy in Hypertension: What Are the Best Options According to Clinical Pharmacology Principles and Controlled Clinical Trial Evidence?
No full textDespite extensive debate about the first choice for treating essential hypertension, monotherapy effectively normalizes blood pressure (BP) values in only a limited number of hypertensive patients. Thus, the aim of combination therapy should always be to both improve BP control and to reduce cardiovascular events. Antihypertensive drugs can be effectively combined if they have different and complementary mechanisms of action. This is crucial to obtain additive BP-lowering effects without impacting on tolerability. One typical combination is the association of drugs blocking and stimulating the renin–angiotensin system (RAS) (angiotensin-converting enzyme [ACE] inhibitor or angiotensin receptor blocker and calcium antagonist or diuretic, respectively). In contrast, some combinations (e.g., calcium antagonists plus diuretics or beta-blockers plus RAS blockers) have no additive BP-lowering effects, while other combinations (e.g., clonidine plus alpha-1 receptor blockers) can have a negative interaction. Regardless, BP reduction is not the only mechanism that reduces cardiovascular risk. Scientific evidence indicates that some drug classes are better than others in this respect, and therefore some drug combinations are also better than others. The results of the ASCOT-BPLA and ACCOMPLISH trials suggested that an ACE inhibitor/calcium antagonist combination had better cardioprotective effects than beta-blocker/diuretic or ACE inhibitor/diuretic combinations. It is worth noting that no controlled clinical trials have used hard endpoints when investigating the effects of an angiotensin receptor blocker/calcium antagonist combination. In conclusion, combination therapy is needed for optimal antihypertensive management, with the first choice being an ACE inhibitor plus a calcium antagonist. This approach should improve BP control and provide better cardiovascular protection
Fixed-dose combination therapy in hypertension: pros.
No full textEffective treatment of high blood pressure represents a key strategy for reducing the burden of hypertension-related cardiovascular diseases, mostly myocardial infarction and stroke. Despite these well established concepts, however, hypertension remains poorly controlled, worldwide. In addition, treated hypertensive patients often remain at higher risk compared with the normotensive population, even when a satisfactory blood pressure control is achieved, due to the high or very high added cardiovascular risk profile observed in these patients. An emerging strategy to improve blood pressure control and achieve this unmet target for cardiovascular disease prevention in hypertensive patients is represented by a more extensive use of rational and effective combination therapies with respect to monotherapy. Such an approach has been recently proposed even as first-line strategy in hypertensive patients at high added cardiovascular risk or in those in whom strict blood pressure control is required. Within the possible antihypertensive drug combinations currently available for the clinical management of hypertension, those based on the association of drugs inhibiting the renin-angiotensin system and thiazide diuretics or calcium channel blockers have demonstrated to be effective and safe in lowering both systolic and diastolic blood pressure levels with a good tolerability profile. In addition, these strategies have provided evidence for effective cardiovascular protection compared with conventional antihypertensive therapies. Among the antihypertensive drugs able to counteract the deleterious effects of abnormal activation of the renin-angiotensin system, angiotensin II receptor blockers have demonstrated to provide better tolerability profile and greater cardiovascular protection on hypertension-related organ damage compared with ACE inhibitors in randomized controlled clinical trials, in the presence of similar antihypertensive efficacy and safety. In particular, these drugs are characterized by lower rates of drug-related side effects, better compliance and adherence to prescribed antihypertensive regimens, and use in synergistic and rational combination therapies, all factors that may contribute to improve blood pressure control and reduce discontinuations from antihypertensive therapy in treated hypertensive patients
Evolving the concept of regulation of vascular tone in humans.
No full textElucidation of mechanisms regulating microcirculatory vascular tone is a key issue in the knowledge of human pathophysiology. Anandamide is an endogenous lipidic cannabinoid (CB) characterized by potent vasodilator activity acting mainly through the activation of CB receptors, located on the vessel walls, and the vanilloid receptor 1, located on sensory peptidergic nerve endings within the external layers of vessel walls. In humans, cutaneous anandamide administration causes forearm skin vasodilation by activating vanilloid receptor 1 presumably on primary sensory nerves, while intrabrachial infusion of the same compound is devoid of effect on forearm muscle microcirculation. Taken together, these results indicate that, apart from a possible distrectual difference, the effect of anandamide is specific for the abluminal, but not for the endoluminal, part of the vessel wall. Thus, it is conceivable that, at least in the peripheral microcirculation, this compound could act as an autocrine/paracrine agent and not as a circulating hormone. In line with this possibility, it has been demonstrated that anandamide can be produced by macrophages and therefore its biological effect might increase in clinical conditions characterized by augmented activity of this cell line, including cardiogenic, hemorrhagic and endotoxic shock and even in atherosclerosis, inflammation and ischemia. Moreover, increased serum values of anandamide have been found in patients with endotoxic shock. However, decisive information concerning the role of anandamide in humans will be obtained when specific antagonists or inhibitors will be available. In that case, the anandamide system might represent a potential target for the treatment of important cardiovascular conditions, including severe shock
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