Journal of hypertension. Supplement : official journal of the International Society of Hypertension最新文献

In addition to the prevention and treatment of macro- and microvascular complications, management goals for patients with type 2 diabetes include reducing the risk of cardiovascular events with a view to improving quality of life. A number of epidemiological and observational cohort studies have been published in Italy and France in an effort to determine the patient profile of individuals with type 2 diabetes in these countries and to gather data on current clinical practice and prescribing patterns. The results of the studies confirm that cardiovascular risk factors, such as hypertension and elevated cholesterol, commonly occur in patients with type 2 diabetes and that these co-morbid conditions are not well controlled. As a consequence, both macro- and microvascular complications are prevalent in this patient population. It is clear that the management of type 2 diabetes in France and Italy is suboptimal. In both primary and specialist care, treatment guidelines need to be reinforced and a more aggressive approach needs to be adopted in the treatment of modifiable cardiovascular risk factors and in particular hypertension. Collectively, the available data highlight the importance of managing global cardiovascular risk within the context of diabetes care. Greater adherence to therapeutic targets recommended in guidelines will ensure that greater proportions of patients attain these treatment goals thereby reducing diabetes-related morbidity and mortality.

Objectives: The ADVANCE trial was designed to determine the effects of routine blood pressure lowering using a fixed combination of perindopril-indapamide on major vascular outcomes in patients with type 2 diabetes, regardless of initial blood pressure levels or the use of other blood pressure-lowering drugs, including angiotensin-converting enzyme inhibitors.

Methods: After a 6-week run-in period, 11,140 high-risk individuals with type 2 diabetes were randomized to fixed combination perindopril-indapamide or matching placebo, in addition to current therapy. The two primary outcomes were composites of major macrovascular and major microvascular events, analysed jointly and separately by intention to treat.

Results: The reduction in blood pressure in participants assigned to active treatment was 5.6/2.2 mmHg greater than that observed in the control group. Active treatment reduced the risk of the combined primary outcome, a major macrovascular or microvascular event by 9% (P = 0.041) and resulted in a 14% (P = 0.025) reduction in all-cause mortality and an 18% (P = 0.027) reduction in cardiovascular mortality. There were reductions of 14% (P = 0.02) in total coronary events and 21% (P < 0.0001) in total renal events. The treatment was well tolerated, with 73% and 74% of patients in the active treatment and placebo groups still adherent to randomized therapy after an average of 4.3 years of follow-up.

Conclusions: Routine treatment with the fixed combination of perindopril and indapamide was well tolerated and reduced the risk of death and major vascular events, regardless of the initial blood pressure level or concomitant treatments received. The results suggest that for every 79 patients treated in this manner, one death would be avoided over 5 years.

Hypertension is a major co-morbidity for type 2 diabetes, and an important modifiable risk factor for vascular events. Therefore, treatment of diabetes and its risk factors is important to minimize complications, and much progress has been made over the past 30 years. The UKPDS trial showed that intensive glycaemic and blood pressure control reduced the risk of vascular events. In the HOT study, the addition of aspirin to patients with diabetes and controlled hypertension decreased the risk of myocardial infarction. Blood pressure control with angiotensin-converting enzyme inhibitors in MICRO-HOPE also showed significant reductions in the risk of vascular complications, and blockers of the renin-angiotensin system produced substantial renal protective effects in patients with hypertension and diabetes. Statin therapy in the HPS and CARDS studies was effective in the primary prevention of cardiovascular disorders. Finally, an intensive multifactorial intervention achieved sustained reduction in the risk of vascular complications and death in patients with type 2 diabetes in the Steno-2 study. Nevertheless, the major coronary event risk remains high in type 2 diabetes patients, and the results of the ADVANCE trial provided a step forward in treatment.

Chronic hypertension and diabetes produce both macrovascular and microvascular pathophysiological changes. Greater arterial stiffness increases central systolic and pulse pressure, which raises left ventricular afterload and reduces coronary perfusion. Resistance arteries remodelling and capillary rarefaction increase peripheral resistance, thereby contributing to hypertension and amplifying the detrimental haemodynamic effects of arterial stiffening. The result is target organ impairment, such as left ventricular hypertrophy, decreased coronary perfusion pressure, reduced coronary reserve and further vascular remodelling, culminating in coronary artery disease and stroke. Therapeutic intervention is possible and necessary to stop these vascular changes. Vasodilating antihypertensive drugs, such as the perindopril/indapamide combination, have been shown to modify both arterial and arteriolar remodelling, leading to reduced central systolic blood pressure and enhancing vascular bed perfusion. These effects probably underpin the benefits of these agents in reducing cardiovascular morbidity and mortality.

Blood pressure is an important determinant of the risk of macro- and microvascular vascular complications in patients with type 2 diabetes. Current European guidelines for the management of hypertension recommend lowering blood pressure in patients with type 2 diabetes to reduce the risk of cardiovascular events. The Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) trial (n = 11,140), is the first trial designed to address the issue of whether routine blood pressure lowering with the fixed combination of perindopril/indapamide is beneficial in patients with diabetes with a broad range of baseline blood pressure values. In addition, it aimed to determine if clinical benefit is achieved over and above that observed with background angiotension-converting enzyme inhibitor therapy. In the perindopril/indapamide arm, the reduction in blood pressure led to significant clinical benefits in patients with type 2 diabetes, irrespective of baseline blood pressure values, and subsequently improved mortality rates, and macro- and microvascular outcomes, beyond the improvements associated with patients' existing antihypertensive therapies. ADVANCE is a robust well-designed trial, the results of which are directly applicable to current clinical practice. The ADVANCE study defines the relevant blood pressure goals for patients with type 2 diabetes who are at high risk of cardiovascular events and underscores the benefits of aggressive blood pressure reduction even in normotensive patients with diabetes. It is likely that these findings will have a significant impact on the management of patients with type 2 diabetes. In view of the evidence indicating that clinical benefits obtained with the perindopril/indapamide combination can be expected even in patients who are normotensive, vascular risk rather than initial blood pressure should be employed to determine appropriate treatment protocols in patients with type 2 diabetes.