Amlodipine in hypertension: a first-line agent with efficacy for improving blood pressure and patient outcomes.

OBJECTIVES: Hypertension is well established as a major risk factor for cardiovascular disease. Although there is undeniable evidence to support the beneficial effects of antihypertensive therapy on morbidity and mortality, adequate blood pressure management still remains suboptimal. Research into the treatment of hypertension has produced a multitude of drug classes with different efficacy profiles. These agents include ß-blockers, diuretics, ACE inhibitors, angiotensin receptor blockers and calcium channel blockers. One of the oldest groups of antihypertensives, the calcium channel blockers are a heterogeneous group of medications. METHODS: This review paper will focus on amlodipine, a dihydropyridine calcium channel blockers, which has been widely used for 2 decades. RESULTS: Amlodipine has good efficacy and safety, in addition to strong evidence from large randomised controlled trials for cardiovascular event reduction. CONCLUSIONS: Amlodipine should be considered a first-line antihypertensive agent.

ß-Blockers in hypertension, diabetes, heart failure and acute myocardial infarction: a review of the literature.

ß-Blockers (BBs) are an essential class of cardiovascular medications for reducing morbidity and mortality in patients with heart failure (HF). However, a large body of data indicates that BBs should not be used as first-line therapy for hypertension (HTN). Additionally, new data have questioned the role of BBs in the treatment of stable coronary heart disease (CHD). However, these trials mainly tested the non-vasodilating ß1 selective BBs (atenolol and metoprolol) which are still the most commonly prescribed BBs in the USA. Newer generation BBs, such as the vasodilating BBs carvedilol and nebivolol, have been shown not only to be better tolerated than non-vasodilating BBs, but also these agents do not increase the risk of diabetes mellitus (DM), atherogenic dyslipidaemia or weight gain. Moreover, carvedilol has the most evidence for reducing morbidity and mortality in patients with HF and those who have experienced an acute myocardial infarction (AMI). This review discusses the cornerstone clinical trials that have tested BBs in the settings of HTN, HF and AMI. Large randomised trials in the settings of HTN, DM and stable CHD are still needed to establish the role of BBs in these diseases, as well as to determine whether vasodilating BBs are exempt from the disadvantages of non-vasodilating BBs.

Icosapent ethyl for the treatment of severe hypertriglyceridemia.

Hypertriglyceridemia is a highly prevalent lipid abnormality and it is associated with atherosclerosis, with a growing body of evidence linking elevated triglycerides (TGs) with cardiovascular disease. The current major omega-3 polyunsaturated fatty acids, eicosapentaenoic acid (EPA)/docosahexaenoic acid (DHA) combination, lowers serum TGs while often increasing levels of low-density lipoprotein cholesterol. Icosapent ethyl is an omega-3 polyunsaturated fatty acid with a 96% pure ethyl ester of EPA that has been recently approved for lowering TG levels in patients with very high TGs (≥500 mg/dL), and it does so without significantly affecting serum low-density lipoprotein cholesterol. The potential benefits of omega-3 fatty acid therapy for dyslipidemias will be discussed, including the potential pros and cons of EPA alone versus the more common and readily available EPA/DHA combination therapy.

Omega-3 fatty acids: a growing ocean of choices.

There has been increasing interest in the health benefits of supplemental and/or dietary omega-3 polyunsaturated fatty acids (PUFAs), particularly in their role in disease prevention. This interest escalated once their effects on cardiovascular health were observed from numerous observational studies in populations whose diet consisted mainly of fish. Research has since been undertaken on omega-3 PUFAs to investigate their health benefits in a vast array of medical conditions, including primary and secondary prevention. This article discusses the evidence and controversies concerning omega-3 PUFAs in various health conditions. In addition to the effects on cardiovascular health, omega-3 PUFAs have been shown to prevent the development of dementia, reduce systemic inflammatory diseases, prevent prostate cancer, and possibly have a role in the treatment of depression and bipolar disorder.

Fragmented QRS complexes-a novel but underutilized electrocardiograhic marker of heart disease.

The electrocardiogram is the mainstay approach for diagnosing a myocardial infarction (MI). The diagnosis of an old MI and the identification of myocardial scar via the electrocardiogram are difficult because there are no other specific signs for a non-Q-wave MI. In this article, we will review the fragmented QRS and its role in identifying myocardial scar and depolarization abnormalities in patients with coronary artery disease.

Meta-analysis of cilostazol versus aspirin for the secondary prevention of stroke.

Aspirin is the most widely prescribed antiplatelet agent for the secondary prevention of stroke. Cilostazol, an antiplatelet and vasodilating agent, has shown promise for the secondary prevention of stroke. A systematic review and meta-analysis of randomized controlled trials using Ovid MEDLINE, PubMed, and Excerpta Medica (EMBASE) was searched up to October 2012. Four trials, in 3,917 patients, comparing cilostazol with aspirin were identified. Compared with aspirin, cilostazol was associated with a 73% reduction in hemorrhagic stroke (relative risk [RR] 0.27, 95% confidence interval [CI] 0.13 to 0.54, p = 0.0002), 28% reduction in the composite end point of stroke, myocardial infarction, or vascular death (RR 0.72, 95% CI 0.57 to 0.89, p = 0.003), and 48% reduction in total hemorrhagic events (RR 0.52, 95% CI 0.34 to 0.79, p = 0.002), with trend for lesser gastrointestinal bleeds (RR 0.60, 95% CI 0.34 to 1.06, p = 0.08). In conclusion, compared with aspirin, cilostazol is associated with significantly less hemorrhagic stroke, the combined end point of stroke, myocardial infarction, and vascular death, and total hemorrhagic events, with numerically fewer gastrointestinal bleeds when used for the secondary prevention of stroke.

L-carnitine in the secondary prevention of cardiovascular disease: systematic review and meta-analysis.

OBJECTIVE: To evaluate the effects of L-carnitine compared with placebo or control on morbidity and mortality in the setting of acute myocardial infarction. METHODS: A systematic review and meta-analysis of 13 controlled trials (N=3629) was conducted to determine the effects of L-carnitine vs placebo or control on mortality, ventricular arrhythmias (VAs), angina, heart failure, and reinfarction. These trials were identified via searches of the Ovid MEDLINE, PubMed, and Excerpta Medica (Embase) databases between May 1, 2012, and August 31, 2012. RESULTS: Compared with placebo or control, L-carnitine was associated with a significant 27% reduction in all-cause mortality (odds ratio, 0.73; 95% CI, 0.54-0.99; P=.05; risk ratio [RR], 0.78; 95% CI, 0.60-1.00; P=.05), a highly significant 65% reduction in VAs (RR, 0.35; 95% CI, 0.21-0.58; P<.0001), and a significant 40% reduction in the development of angina (RR, 0.60; 95% CI, 0.50-0.72; P<.00001), with no reduction in the development of heart failure (RR, 0.85; 95% CI, 0.67-1.09; P=.21) or myocardial reinfarction (RR, 0.78; 95% CI, 0.41-1.48; P=.45). CONCLUSION: Compared with placebo or control, L-carnitine is associated with a 27% reduction in all-cause mortality, a 65% reduction in VAs, and a 40% reduction in anginal symptoms in patients experiencing an acute myocardial infarction. Further study with large randomized controlled trials of this inexpensive and safe therapy in the modern era is warranted.

Meta-analysis of carvedilol versus beta 1 selective beta-blockers (atenolol, bisoprolol, metoprolol, and nebivolol).

Because carvedilol is a unique vasodilating ß blocker (BB) exerting antioxidant activity and pleiotropic effects, it was theorized that it may confer more potent beneficial effects on cardiovascular mortality and morbidity in acute myocardial infarction (AMI) and heart failure (HF) settings. A systematic review and meta-analysis was performed of randomized, controlled, direct-comparison trials that included adults receiving atenolol, bisoprolol, metoprolol, nebivolol, or carvedilol to evaluate the effects of carvedilol compared to other BBs on mortality, cardiovascular events, and hospital readmissions in the setting of AMI or systolic HF. Compared to ß(1)-selective BBs used in HF (8 trials, n = 4,563), carvedilol significantly reduced all-cause mortality (risk ratio 0.85, 95% confidence interval 0.78 to 0.93, p = 0.0006). In 3 trials of patients with AMI (n = 644), carvedilol significantly reduced all-cause mortality by 45% (fixed-effects model: risk ratio 0.55, 95% confidence interval 0.32 to 0.94, p = 0.03, random-effects model: risk ratio 0.56, 95% confidence interval 0.26 to 1.12, p = 0.10), with no reduction in non-fatal MI (risk ratio 0.61, 95% confidence interval 0.31 to 1.22, p = 0.16). In conclusion, carvedilol, as compared against atenolol, bisoprolol, metoprolol and nebivolol in randomized direct comparison trials, significantly reduced all-cause mortality in systolic HF patients. Additionally, carvedilol significantly reduced all-cause mortality compared with ß(1)-selective BBs in AMI patients using the fixed-effects model but not using the random-effects model.

Telmisartan prevents excess-salt-induced exacerbated (malignant) hypertension in spontaneously hypertensive rats.

The effects of angiotensin receptor blocker, diuretic, a calcium antagonist, and their combination were evaluated on the progression of cardiovascular and renal damage in spontaneously hypertensive rats (SHRs) given excess salt. To this end, 8-week male SHRs were divided into 7 groups. The control group (C) received normal NaCl (0.6%) diet. All other groups were given 8% NaCl rat chow. In addition, group 2 was given placebo (tap water alone), group 3 the angiotensin receptor antagonist telmisartan (10 mg/kg per d), group 4 received the diuretic chlorothiazide (80 mg/kg per d), group 5 was given telmisartan plus the diuretic, group 6 was given the calcium antagonist amlodipine (10 mg/kg per d), and group 7 was given telmisartan plus amlodipine. All treatments lasted for 8 weeks. Compared with controls, mean arterial pressure (MAP), renal blood flow, coronary flow reserve, minimal coronary vascular resistance, diastolic time constant, and maximal rate of ventricular pressure fall were all adversely affected by salt loading. Increased left ventricular mass with marked cardiac fibrosis was also found in the salt-overloaded SHR group. Telmisartan normalized all indices except MAP, whereas diuretic and amlodipine only partially restored cardiac functional and mass indexes. Combination therapy with telmisartan and either diuretic or amlodipine also normalized all indices including arterial pressure. These data suggest that (1) cardiovascular  damage induced by excess salt in the SHRs was not pressure dependent; (2) compared with the calcium antagonist and diuretic, blockade of angiotensin receptors  was extremely effective in this model.

Nebivolol prevents myocardial fibrosis and diastolic dysfunction in salt-loaded spontaneously hypertensive rats.

BACKGROUND: We have demonstrated previously that a high-salt diet (HS) produces myocardial fibrosis, left ventricular (LV) dysfunction, and renal insufficiency in adult spontaneously hypertensive rats (SHR), and that blockade of the renin-angiotensin system prevented those adverse effects of HS. METHODS AND RESULTS: Eight-week-old male SHR were divided into four groups: controls received regular rat chow (0.6 NaCl); the other three were given HS. The second group was given placebo; the third, nebivolol (2 × 10 mg/kg/day) orally; and, the fourth, the same dose of nebivolol by osmotic minipump. Rats received respective treatments for 8 weeks. The data demonstrated that the HS induced increased cardiac mass (2.85 ± 0.05 vs. 5.36 ± 0.22 mg/g; P < .05 in control and HS groups, respectively); LV fibrosis as indicated by higher hydroxyproline concentration; further increase in arterial pressure (161 ± 7 vs. 184 ± 8 mm Hg; P < .05); myocardial ischemia; and LV diastolic dysfunction. Nebivolol ameliorated the adverse cardiac effects of HS, demonstrated by decreased LV mass and fibrosis and improved coronary hemodynamics and LV function. CONCLUSIONS: The effects of nebivolol were independent of arterial pressure. The results of this study provide important laboratory data that support a rationale for nebivolol in the treatment of patients with hypertension having diastolic dysfunction with preserved ejection fraction.

Vasodilating versus first-generation ß-blockers for cardiovascular protection.

The utility of ß-blockers in the treatment of hypertension has created much speculation as to their efficacy in patients with comorbid conditions, and there are concerns regarding their adverse metabolic effects. It is important to note that these findings were observed with traditional ß-blockers, such as atenolol and metoprolol. The newer generation of ß-blockers, namely carvedilol and nebivolol, is changing the manner in which ß-blockers are viewed in hypertension management. Their ability to inhibit A1 adrenoreceptors and influence nitric oxide leads to vasodilation, which traditional ß-blockers fail to do. These agents have been shown to have favorable metabolic effects while maintaining the beneficial cardiovascular effects of this drug class in post-myocardial infarction patients and the heart failure population.

Salt, arterial pressure, and cardiovascular and renal damage.

This brief review deals with some novel developments regarding the possible role of salt in the pathogenesis of cardiovascular and renal disorders. Studies in both humans and experimental animals are discussed. Increased salt intake is usually associated with an increase in arterial pressure although some controversies still exist. Salt sensitivity of arterial pressure (defined as an increase in arterial pressure on dietary salt overload) was demonstrated in many animal species as well as in humans. However, findings in rats, the most often used animal model, also demonstrated that this salt sensitivity was not uniform; some strains are salt sensitive, while other strains are salt resistant. Salt sensitivity of arterial pressure in humans is also not uniform; less than one-third of normotensive individuals and less than one-half of hypertensive individuals are salt sensitive. Of great importance are findings that excessive salt intake may damage target organs (cardiovascular system and kidneys) irrespective of arterial pressure. Together with an ever-growing consensus that sodium intake in acculturated societies is high, these findings also emphasize the need for reduction in salt intake. Therefore, the adverse cardiovascular and renal effects of salt continue to be a subject of intense study. Current data indicate that a reduction in salt intake should ameliorate, if not prevent, cardiovascular and renal morbidity and mortality, particularly among individuals with hypertension.