Prevention Of Cardiovascular Outcomes Research Articles

Race and ethnicity in trials of antihypertensive therapy to prevent cardiovascular outcomes: a systematic review.

We wanted to systematically review (1) the participation of racial and ethnic minorities in clinical trials of antihypertensive drug therapy and (2) racial differences in the efficacy of these therapies for the prevention of cardiovascular outcomes. MEDLINE, EMBASE, LILACS, African Index Medicus, and the Cochrane Library were searched from their inception to December 2005 for randomized controlled trials testing the efficacy of antihypertensive drug therapy in preventing myocardial infarction, stroke, revascularization, or cardiovascular death. MEDLINE was also searched from 2005 through 2006. The 2 authors independently assessed studies for inclusion and quality. Twenty-eight studies met inclusion criteria. Eight trials reported results by racial subgroup. Trials with black and Hispanic participants (ALLHAT, INVEST, VALUE) found similar primary outcomes, but ALLHAT found a greater magnitude of benefit for blacks on diuretic therapy compared with nonblacks. One trial (PROGRESS) compared Asians with non-Asians, reporting that angiotensin-converting enzyme inhibitors (vs placebo) were equally effective for preventing stroke in both groups. In the LIFE trial, post hoc analyses showed different outcomes for blacks and nonblacks, raising questions about the usefulness of angiotensin-receptor blockers as first-line antihypertensive agents in blacks. In 3 studies conducted exclusively in Asians (JMIC-B, FEVER, NICS-EH), calcium channel blockers were effective in preventing cardiovascular outcomes. No trials described cardiovascular outcomes in Native Americans. Five trials made interethnic group comparisons; 4 had similar primary outcomes for ethnic minorities and whites. Increased minority participation in future studies is needed to determine optimal prevention therapies, especially in outcome-driven trials comparing multidrug antihypertensive treatment regimens.

The effect of baseline physical activity on cardiovascular outcomes and new‐onset diabetes in patients treated for hypertension and left ventricular hypertrophy: the LIFE study

Physical activity (PA) is a preventive strategy for cardiovascular disease and for managing cardiovascular risk factors. There is little information on the effectiveness of PA for the prevention of cardiovascular outcomes once cardiovascular disease is present. Thus, we studied the relationship between PA at baseline and cardiovascular events in a high-risk population. A prespecified analyses of observational data in a prospective, randomized hypertension study. Losartan Intervention For Endpoint reduction in hypertension (LIFE) study. Hypertension and left ventricular hypertrophy (LVH) (n = 9,193). Losartan versus atenolol. Reported level of PA: never exercise, exercise <or=30 min twice per week, or exercise >30 min twice per week at baseline and after a mean of 4.8 years of treatment with losartan- versus atenolol-based therapy. Risk reductions were calculated by level of PA for the primary composite end-point and its components cardiovascular death, stroke and myocardial infarction, and also all-cause mortality and new-onset diabetes. A modest level of PA (>30 min twice per week) was associated with significant reductions in risk for the primary composite end-point [adjusted hazard ratio (aHR) 0.70, P < 0.001) and its components, all-cause mortality (aHR 0.65, P < 0.001), and new-onset diabetes (aHR 0.66, P < 0.001). A modest level of self-reported PA (>30 min twice per week) in patients with hypertension and LVH in the LIFE study was associated with significant reductions in risk for the primary composite end-point and its components of cardiovascular death, stroke, and myocardial infarction, all-cause mortality, and new-onset diabetes.

Angiotensin II antagonists: clinical experience in the treatment of hypertension, prevention of cardiovascular outcomes and renal protection in diabetic nephropathy and proteinuria

Angiotensin II antagonists (AIIAs) were introduced to treat hypertension about 10 years ago. During this period they were evaluated not only in terms of efficacy and safety but also in several large studies with clinical outcomes. They are efficacious in all clinical forms of hypertension and are effective also in all ethnic groups. Cardiovascular and renal protection in proteinuric diabetic nephropathy beyond blood pressure reduction was proved in major clinical studies: Losartan Intervention For Endpoint reduction in hypertension study (LIFE), Reduction of Endpoint in Non-Insulin dependent Diabetes Mellitus with the AII Antagonist Losartan (RENAAL) and Irbesartan Type 2 Diabetic Nephropathy Trial (IDNT). Their blood pressure independent protective effect is also mentioned by the blockade of AT1 receptor. As a class AIIs have a tolerability profile similar to placebo.

Ramipril

Ramipril is an oral, non-sulfhydryl ACE inhibitor thought to act in the renin-angiotensin-aldosterone system to decrease vasopressor activity, aldosterone secretion, and bradykinin degradation. Ramipril is generally well tolerated and effective in the treatment of patients aged > or =55 years at high risk for the development of cardiovascular (CV) events, in whom the risk of myocardial infarction (MI), stroke, and CV death can be significantly reduced. The risk of these CV outcomes may also be reduced with ramipril therapy in various subgroups; these include patients with diabetes mellitus, peripheral arterial disease (PAD) or renal insufficiency, and women. Thus, ramipril, in addition to lifestyle interventions, should be considered an important therapy in the prevention of CV outcomes in high-risk patients.

Comparison of Various Blood Pressure Lowering Treatments on the Primary Prevention of Cardiovascular Outcomes in Recent Randomised Clinical Trials

Randomised clinical trials completed over the past 8 to 10 years have provided much new evidence regarding the cardiovascular risks and benefits of treatment with newer blood pressure lowering drugs, particularly ACE inhibitors and calcium channel blockers (CCB). Trials of active treatment against placebo have now established that ACE inhibitors and CCBs reduce the risk of coronary heat disease and stroke in subjects with elevated blood pressure and that ACE inhibitors reduce the risk of heart failure but calcium antagonists do not. Clinical trials comparing active treatment regimens based on different blood pressure lowering drug classes, have provided convincing evidence that ACE inhibitors, CCBs, and "conventional treatment" with diuretics/beta-blockers are equally effective in the primary prevention of coronary heart disease, but that minor differences of the order of 5-12% favouring calcium antagonists may exist. The one area with a major difference is again for the primary prevention of heart failure where calcium antagonists are clearly inferior to diuretics/ beta-blockers and to ACE inhibitors. There is now convincing evidence that blood pressure lowering is effective in the secondary prevention of cardiovascular outcomes in subjects with established coronary heart disease, cerebrovascular disease, diabetes and chronic kidney disease, especially diabetic nephropathy. Clinical trial evidence comprising regimens based on different drug classes for the secondary prevention of cardiovascular outcomes is still very limited. It is possible that longer differences will be found between the efficacy and safety of drugs in secondary prevention than have been reported so far in primary prevention.

Spotlight on ramipril in the prevention of cardiovascular outcomes.

Ramipril (Altace)Use of tradenames is for product identification purposes only and does not imply endorsement.), an angiotensin-converting enzyme (ACE) inhibitor, is a prodrug which is rapidly hydrolyzed after absorption to the active metabolite ramiprilat. Earlier trials have shown that ACE inhibitors, when given to patients with low ejection fractions, have reduced the relative risk of myocardial infarction (MI) and other ischemic events by 14-23%. Subsequently, the double-blind, randomized, placebo-controlled, multicenter Heart Outcomes Prevention Evaluation (HOPE) study has shown that, in patients who are not known to have low ejection fraction or heart failure but are at increased risk for developing cardiovascular events, ramipril reduced the incidence of stroke, MI and death due to cardiovascular disease. Results from the HOPE study, in which 9297 patients were randomized to receive either ramipril 10 mg/day or placebo for a mean of 4.5 years, indicate that ramipril reduced the relative risk of the composite outcome of MI, stroke and cardiovascular death by 22%. The incidence of the composite outcome was significantly lower in the ramipril group than in the placebo group (14.0% vs 17.8%). Patients who received ramipril, compared with placebo recipients, had a significantly decreased incidence of stroke, MI or death due to cardiovascular disease (3.4% vs 4.9%, 9.9% vs 12.3% and 6.1% vs 8.1%, respectively). The relative risk of death from any cause was reduced among patients who received ramipril. In addition, treatment with ramipril reduced as the incidence of revascularization procedures, and, among patients with diabetes mellitus, ramipril reduced the incidence of complications related to diabetes mellitus, including the development of overt nephropathy. Moreover, in patients without a previous diagnosis of diabetes mellitus, ramipril, compared with placebo, significantly reduced the development of diabetes mellitus. Furthermore, compared with patients receiving placebo, patients receiving ramipril had a reduced rate of progression of carotid artery wall thickness. Ramipril 10 mg/day can significantly reduce the incidence of MI, stroke or death from cardiovascular causes in patients aged > or =55 years who are at increased risk for the development of ischemic cardiovascular events due to a history of stroke, coronary artery disease (with controlled blood pressure), diabetes mellitus plus at least one other risk factor or peripheral vascular disease but no heart failure or low ejection fraction. Therefore, in addition to dietary and lifestyle modifications, ramipril should be an integral part of secondary prevention therapy in patients at increased risk for the development of cardiovascular events.

Women do benefit from lipid lowering: latest clinical trial data.

Cardiovascular disease is the leading cause of morbidity and mortality among women in industrialized nations. Optimizing cardiovascular risk reduction is therefore of paramount importance, particularly among postmenopausal women, in whom the incidence of cardiovascular disease is highest. Accumulated data from a series of landmark trials unequivocally demonstrate the efficacy of statin therapy in the primary and secondary prevention of cardiovascular outcomes in both men and women. Moreover, the recently released Heart Protection Study provides substantive evidence that lowering low-density lipoprotein cholesterol below levels currently defined as optimal by National Cholesterol Educational Program guidelines is strongly associated with further cardiovascular risk reduction, and that this benefit accrues in all subgroups of patients, including women and the elderly. Despite the ability of hormone replacement therapy to improve serum lipid profiles, randomized trials of hormone therapy have demonstrated no benefit in reducing coronary outcomes among postmenopausal women. In contrast, data from over 8,000 women enrolled in the statin trials demonstrate that lipid lowering with statins is as effective at reducing cardiovascular outcomes in women as it is in men and suggest that statins should be considered standard of care for the prevention of adverse cardiovascular events in women at risk for coronary heart disease.

Seeking the optimal aspirin dose in acute coronary syndromes

V results from previous aspirin trials have underscored the uncertain relation between aspirin dose and reduction of secondary vascular events. In the largest investigation to date, the Antiplatelet Trialists’ Collaboration (ATC), a systematic overview of 11 trials of antiplatelet therapy suggested that there was no dose relation of aspirin to the secondary prevention of cardiovascular outcomes. Although there are inherent limitations and indirect comparisons in meta-analytic methods, 1 effective strategy is to accommodate the heterogeneity among trials using random effects methods. Using such models, we sought to re-examine the ATC data to evaluate optimal cardiovascular dosing of aspirin while adjusting for patient populations and time trends.