Adhering to the principles of clinical pharmacology - the correct fixed combinations of antihypertensive drugs

Abstract

Hypertension is one of the primary modifiable risk factor for cardiac and renal diseases with the prevalence around 30-45% of the general population, with a steep increase with ageing. The administration of blood pressure-lowering drugs is to reduce the risk of major clinical cardiovascular outcomes. Hypertension guidelines recommend combination therapy in patients with high cardiovascular risk and with subclinical organ damage as well as when monotherapy fails. Areas covered: As the etiology of essential hypertension is multifactorial, combination therapy using different classes of antihypertensive agents have greater effect than each on its own (synergistic effect), may have better tolerability (two components minimizing each other's side effects) and lead to improved patient compliance. Several studies assess the hypotensive efficacy on drug combination; there are also studies on triple drug combination. Expert commentary: At present, dual and triple combination therapy is available to hypertensive patients with good clinical outcomes, compliance and low profile of side effects. It is critical as patients' adherence to the pharmacological therapy significantly decreases the risk of long-term adverse events including mortality. It appears that combinations not only of hypotensive drugs but also with statins (as well as antidiabetics) will be widely used.

An expert opinion paper on statin adherence and implementation of new lipid-lowering medications by the ESC Working Group on Cardiovascular Pharmacotherapy: Barriers to be overcome

“…Combination therapies present different advantages as elsewhere reviewed (33). First, they have a synergistic effect, thus the efficacy is thought to be higher compared to the sum of single drugs.…”

Association of masked uncontrolled hypertension and cardiovascular diseases in treated hypertensive patients

“…It is well known that the diagnosis of hypertension is traditionally defined by the clinic BP [22][23][24]. Prior randomized clinical trials and metaanalysis have consistently demonstrated that reducing clinic BP can improve cardiovascular outcomes [25][26][27][28][29]. With the advent and advancement of 24 h ABPM, out-of-clinic BP can be captured and used for evaluating daytime and nighttime BP changes [30,31].…”

Is type 2 diabetes mellitus a coronary heart disease equivalent or not? Do not just enjoy the debate and forget the patient!

“…Similar results were obtained with losartan in T2DM patients with LVH (but without known CVD) in the Losartan Intervention For Endpoint reduction (LIFE) study [68]. Of note, fixed combinations of antihypertensive drugs and/or polypills containing aspirin, statin and one or more antihypertensive medication may represent a cost-effective strategy for CVD prevention, also improving patients’ adherence to treatment and thus achievement of therapeutic goals [69–71].…”