Comparative effectiveness of antihypertensive drugs in patients with diabetes.

Diabetes mellitus is a major chronic noncommunicable disease that requires continuing medical care to reduce long-term complications [1,2]. Diabetes can lead to various macrovascular and microvascular diseases, such as cardiovascular diseases, cerebrovascular diseases, nephropathy, retinopathy and neuro pathy, among others [1,3,4]. Those comorbidities contribute to a large percentage of disability and mortality in many populations, causing a great burden on healthcare expenditure in many countries [3,5]. Cardiovascular disease is the major cause of morbidity and mortality for diabetic patients; it is also the largest contributor to costs of medical care for diabetes [6]. Hypertension, a common comorbidity of diabetes, is a major risk factor for both cardiovascular and microvascular complications [7]. In Type 1 diabetes, hypertension is often the result of diabetic nephropathy, while in Type 2 diabetes, it usually coexists with other cardiometabolic risk factors [1]. Diabetic nephropathy, a major cause of end-stage renal disease, occurs in 20–40% of patients with diabetes [2,8]. The development and progression of diabetic nephropathy are closely inter-related to hypertension, and aggressive antihypertensive management is able to decrease the risk of cardiovascular mortality and the decline in renal function [8]. According to current major guidelines, renin–angiotensin system (RAS) blockers are the first-line treatment for hypertension or nephropathy in patients with diabetes, and the target of hypertension control is to reduce systolic blood pressure to 140 mmHg or less, and diastolic blood pressure to below 80–90 mmHg [1,4,6,7,9,10]. Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are the two major classes of drugs among blockers of the RAS, and are believed to have interchangeable and similarly superior cardiorenoprotective effects than other classes of antihypertensive agents [11,12]. In order to achieve appropriate control of blood pressure, many diabetic patients require additional antihypertensive agents in combination with RAS blockers. The additional drugs for combination suggested by relevant guidelines include calcium channel blockers (CCBs), diuretics and β-blockers, either prescribed in pills of single ingredient or polypills of fixed-dose combination [6,7,9,10]. While current guidelines indicate that ACEIs and ARBs have similar protective effects for diabetic patients, some guidelines prefer ACEIs as the first-line treatment on the grounds of cost, and suggest that ARBs should be substituted mainly under the condition of ACEI intolerance or when a low-cost generic ARB is available [9,10]. Besides, so far, there has been no consensus about the priority for treatments in combination with RAS blockers. Head-to-head randomized clinical trials designed to compare an ACEI with an ARB among diabetic patients are rare, so which drug should be used as the first-line treatment remains inconclusive despite of their protective effects being claimed equivalent “In Type 1 diabetes, hypertension is often the result of diabetic nephropathy, while in Type 2 diabetes, it usually coexists with other cardiometabolic risk factors. ”