Treatment of hypertension in patients with diabetes

At least 17 million people in the United States have diabetes mellitus, and another 50 million have hypertension. These chronic diseases increasingly coexist in our aging population. Both diseases are important predisposing factors for the development of cardiovascular disease (CVD) and renal disease, and the coexistence of these risk factors is a very powerful promoter of CVD and renal disease. There is accumulating evidence that the rigorous treatment of hypertension and other risk factors such as dyslipidemia and hyperglycemia considerably lessens the burden of CVD and renal disease in patients with diabetes mellitus. There is considerable evidence that strategies addressing diet and exercise reduce the development of diabetes and are an important component of treatment in persons who have established diabetes. There are also considerable data suggesting that the treatment strategies that interrupt the renin-angiotensin system have special benefits in patients with diabetes and may prevent the development of clinical diabetes in hypertensive patients with impaired glucose tolerance. Data from a recent study indicate that the control of systolic blood pressure, using a diuretic agent as part of antihypertensive therapy, reduces the risk of stroke and other CVD end points. Recent reports indicate that angiotensin receptor-blocking agents decrease the rate of development of proteinuria and diabetic renal disease. These observations will likely have a significant impact on treatment of hypertension in patients with type 2 diabetes mellitus.     

Implications of recent heart failure trials for patients with hypertension

There are two major reasons why hypertension is an important risk factor for heart failure. The first is that an elevated blood pressure increases the wall stress in the left ventricle. The second is that hypertension, in a complex manner, contributes to the development of atheromatous vascular disease. Among the more common causes of heart failure are the sequelae of coronary heart disease. The treatment of hypertension modifies the progression to heart failure and the occurrence of coronary events. In patients who have heart failure, hypotension rather than hypertension is a predictor of a poor outcome, likely because low blood pressure is a consequence of damage to the myocardium. The clinical message is that hypertension should be treated aggressively. Where heart failure is a likely outcome, or where hypertension occurs in the presence of heart failure, there is a strong case for using drugs that have been shown to be beneficial in the treatment of both hypertension and heart failure.     

Treatment of hypertension in metabolic syndrome: Implications of recent clinical trials

Metabolic syndrome represents a constellation of hypertension, abdominal obesity, impaired fasting glucose, and dyslipidemia, and it has been shown to be a risk factor for cardiovascular disease. The components of metabolic syndrome are rapidly emerging as epidemics of the twenty-first century, and reduction of these underlying causes, such as obesity, physical inactivity, and atherogenic diet, is first-line therapy. Treatment of hypertension and other cardiometabolic risk factors of the syndrome is also required. Evidence demonstrates a relationship between hypertension, type 2 diabetes mellitus, and several vascular and metabolic abnormalities that are components of metabolic syndrome. Hypertension associated with metabolic syndrome has pathophysiologic characteristics that provide clinical challenges as well as opportunities for successful therapeutic interventions. This article reviews the treatment of hypertension as a metabolic and vascular disease and also opens a new paradigm for the treatment of metabolic syndrome, which affects nearly one quarter of the world’s population.     

Prevention of sudden cardiac death: lessons from recent controlled trials.

Sudden cardiac death (SCD), presumably because of ventricular tachyarrhythmias, remains one of the major challenges of contemporary cardiology. Major randomized controlled trials conducted in patients with coronary artery disease (CAD) with the aim of primary prevention of SCD are providing insights. Several large-scale studies have demonstrated that treatment with beta-blockers, angiotensin-converting enzyme inhibitors, aldosterone antagonists, and statins results not only in a reduction in all-cause mortality but specifically also in SCD. On top of this optimized pharmacological therapy, implantable cardioverter-defibrillators (ICD) further decrease the risk of overall and SCD mortality in carefully selected patient groups. The sum of these trials indicates, however, that the benefit associated with ICD therapy is most prominent in patients with chronic stable CAD. In contrast, patients early after myocardial infarction derive less benefit from ICD treatment, presumably because of a high competing risk of non-arrhythmic cardiovascular death. Optimized pharmacological therapy, together with the ICD, can substantially improve the prognosis of high-risk CAD patients.     

High-density lipoprotein and coronary heart disease: lessons from recent intervention trials

Epidemiologic studies have consistently implicated low plasma high-density lipoprotein cholesterol as an important, independent risk factor for the development of coronary heart disease. However, clinical trials specifically designed to evaluate the role of lipid therapy in patients with low high-density lipoprotein cholesterol have only been recently reported. They include two trials with angiographic end points, the Lopid Coronary Angiography Trial and the Bezafibrate Coronary Atherosclerosis Intervention Trial, and three clinical end points trials, the Air Force/Texas Coronary Atherosclerosis Prevention study, the Department of Veterans Affairs High-Density Lipoprotein Intervention Trial, and the Bezafibrate Infarction Prevention study. These and other trials clearly indicate that persons with coronary heart disease and high low-density lipoprotein cholesterol (>130 mg/dL [3.36 mmol/L]), with or without low high-density lipoprotein cholesterol, benefit from statin therapy. The Air Force/Texas Coronary Atherosclerosis Prevention study showed that persons at high risk of coronary heart disease but without known disease, who have moderate levels of low-density lipoprotein cholesterol as well as low levels of high-density lipoprotein cholesterol, also appear to benefit from statin therapy although the cost effectiveness of this approach is unclear. The results from the Department of Veterans Affairs High Density Lipoprotein Intervention Trial provide convincing evidence that patients without high low-density lipoprotein cholesterol and with established coronary heart disease and low high-density lipoprotein cholesterol benefit from gemfibrozil. This drug may be particularly beneficial for patients who, in addition to low high-density lipoprotein cholesterol, present with other features of the metabolic syndrome, such as obesity, glucose intolerance, and high triglycerides. Whether other fibrates, niacin, or statins lower coronary heart disease risk in persons with low high-density lipoprotein cholesterol in the absence of high or moderately high low-density lipoprotein cholesterol is unknown. (c)2000 by CHF, Inc.     

Optimizing glycoprotein IIb/IIIa inhibition: lessons from recent randomized controlled trials

Recent randomized clinical trials with intravenous glycoprotein IIb/IIIa inhibition have provided unanticipated results, thereby questioning their role as empirical medical management for acute coronary syndromes. The lack of benefit with abciximab observed in Global Utilization of Strategies to Open Occluded Coronary Arteries IV is somewhat inconsistent with the benefits seen with this agent in coronary intervention, and the benefits of an early invasive approach incorporating tirofiban seen within Treat Angina with Aggrastat and determine Cost of Therapy with an Invasive or Conservative Strategy Thrombolysis in Myocardial Infraction 18. Additionally, a direct 'head-to-head' comparative study of abciximab and tirofiban within the setting of percutaneous coronary intervention demonstrates clinically relevant superiority with abciximab with respect to 30-day outcomes. in the setting of coronary instability and mechanical plaque disruption is more complex than initially perceived. Hence, although an abundance of evidence details the efficacy of these agents, their optimal clinical application remains somewhat challenging in light of these recent data. However, within the context of previous trial experience, the current evidence highlights several key aspects of glycoprotein IIb/IIIa inhibitor therapy that may be associated with improved patient outcomes. In particular, these trials indicate: (i) the importance of selecting high-risk patients in whom substantial clinical benefit is evident, (ii) the incorporation of these agents into an early invasive strategy, thereby matching the timing of vascular injury with maximal platelet inhibition and (iii) optimal dosing to achieve the high levels of platelet inhibition that appear to be required for efficacy with these agents.     

Cardiovascular protection in type 2 diabetes: Insights from recent outcome trials

This review examines recent randomized controlled cardiovascular (CV) outcome trials of glucose-lowering therapies in type 2 diabetes and their impact on the treatment of patients with type 2 diabetes. The trials were designed to comply with regulatory requirements to confirm that major adverse cardiac events (MACE) are not detrimentally affected by such therapies. Trials involving dipeptidyl peptidase-4 (DPP-4) inhibitors did not alter a composite MACE outcome comprising CV deaths, non-fatal myocardial infarction and non-fatal stroke; however, the possibility that some members of this class might incur a small increased risk or worsening of heart failure cannot be excluded. Some studies on glucagon-like peptide-1 receptor agonists (liraglutide: LEADER trial; semaglutide: SUSTAIN-6 trial) found significant benefits for MACE, while treatment with sodium-glucose co-transporter-2 inhibitors (empagliflozin: EMPA-REG OUTCOME trial; canagliflozin: CANVAS trial) also significantly reduced MACE and reduced hospitalization for heart failure. Comparisons among trials are complicated by variance in the populations recruited, particularly CV status at randomization, and differences in trial design, data collection and analyses. A large proportion of patients recruited into these trials have previously experienced adverse CV events; thus, the therapies are mostly assessing secondary prevention of a further event. This contrasts with the overall type 2 diabetes population receiving glucose-lowering therapies, of whom the majority will not have had MACE and will be regarded as primary prevention. Overall, the trials provide reassuring evidence that new glucose-lowering medications do not adversely affect CV events and some of these agents may offer CV protection.     

Treatment of hypertension in the elderly—What have we learned from the recent trials?

Summary Treatment of hypertension in the elderly has so far mainly been based on clinical judgment and very few large controlled trials. During the last year several large new trials have been published, the so-called STOP-Hypertension, SHEP, and MRC trials. All have shown that drug treatment of hypertension in the elderly (65–85 years) with permanent diastolic hypertension or isolated systolic hypertension reduces stroke incidence. Most patients have needed combined drug treatment with diuretics and beta-blockers. When thiazide diuretics are used, serum postassium should be followed very closely and most likely amiloride should be added to the thiazide therapy, since this was done both in the STOP and the MRC trials. Since many elderly patients with hypertension suffer from other diseases that might represent contraindications to thiazide diuretics or beta-blockers, the choice of drug must be made after careful clinical evaluation. With the newer classes of antihypertensive agents (calcium antagonists, ACE inhibitors and alpha-blockers) side effects are probably seen less often, but long-term data on morbidity and mortality are still lacking.     

Development of heart failure in recent hypertension trials

BACKGROUND: Heart failure represents a major cause of disease burden worldwide and is expected to further rise in the coming decades. Hypertension is the clinical condition most frequently associated to heart failure. OBJECTIVE: To systematically review the incidence of heart failure compared to coronary heart diseases and stroke in recent hypertension trials. METHODS: We identified 23 trials concluded within the last decade including 193,424 patients with hypertension or at 'high' cardiovascular risk with a predominant presence of hypertensive patients, and reported incidence of major cardiovascular events, including heart failure, coronary heart disease and stroke. RESULTS: A total of 24 837 major cardiovascular events were recorded in trials performed between 1997 and 2007, of which 7171 (28.9%) were cases of heart failure, 10,223 (41.1%) of coronary heart disease and 7443 (30.0%) of stroke. The rate of heart failure was comparable with that of stroke, accounting for 8.5 and 9.1 events per 1000 patients (P = NS), respectively. Heart failure development was more prevalent in older subjects (>65 years) [odds ratio: 3.08, confidence interval 95% (2.88-3.31); P < 0.0001], in black versus nonblack individuals [odds ratio 1.90, (1.76-2.06); P < 0.0001], in diabetic versus nondiabetic patients [odds ratio 4.91, 95% confidence interval (4.40-5.43); P < 0.0001] and in patients with 'very high' risk versus those with a 'high' risk profile [odds ratio 1.29, 95% confidence interval (1.23-1.36); P < 0.0001]. CONCLUSION: Our analysis shows that heart failure development remains a major problem in hypertension. In recent trials on hypertension, the development of heart failure was found comparable with that of stroke: it is more prevalent in older, black, diabetic and 'very high' risk individuals. These findings highlight the relevance of heart failure development in hypertension and support the need for optimizing antihypertensive strategies aimed at preventing the progression to overt heart failure, thus reducing the growing burden of disease associated with hypertension.