Drug Safety and Effectiveness Network Report: A Systematic Review with Network Meta-Analyses and Economic Evaluation Comparing Therapies for Hypertension in Non-Diabetic Patients

Background: \nHypertension has been cited as the most common attributable risk factor for death worldwide, and an independent predictor of stroke mortality and ischemic heart disease mortality. Hypertension is a chronic yet modifiable condition which places increased stress on the heart for circulation of blood in the body, and it has been documented as a critical risk factor for clinically significant events including myocardial infarction, heart failure, stroke, peripheral artery disease, kidney disease, and death. It represents a preventable cause of early death in many countries. Reduction of elevated blood pressure is associated with reduction of clinically significant events such as those noted above. Evidence suggests there is a direct correlation between the magnitude of blood pressure reduction and the occurrence rate of such events. In addition to implementation of lifestyle changes including increased exercise, weight reduction, reduced alcohol consumption and dietary changes, there exists a number of classes of antihypertensive pharmacotherapies for use in clinical practice to manage elevated blood pressure. These include thiazide diuretics (TZD), angiotensin-converting enzyme (ACE) inhibitors, calcium channel blockers (CCB), beta blockers (BB), alpha blockers, and angiotensin receptor blockers (ARB). Furthermore, data from randomized trials suggests more than 66% of patients with hypertension cannot have their blood pressure adequately lowered using monotherapy, and so addition of a second agent (and sometimes third) may be required. Of primary importance in clinical practice is thus about the choice of therapies, and the sequence of interventions to minimize the risk of undesirable outcomes. The drugs are associated with different mechanisms of action, different harm profiles, and different costs. As such, the choice of agent is important. The optimal choice of first line agent is unclear. Several systematic reviews have explored the benefits and harms of pharmacotherapies for hypertension. However, the co-presence of comorbidities such as dyslipidemia, diabetes and so forth increase the risk of cardiovascular events, and a review comparing multiple treatments for patients free of diabetes has not been performed.. There remains a need to explore their properties in the sub-population of patients without diabetes.\n\nResearch Questions\n1.\tHow does monotherapy with a thiazide diuretic compare to monotherapy with other pharmacotherapeutic agents (i.e. ACE inhibitors, CCBs, BBs, ARBs, etc) in patients without diabetes with hyptertension?\n2.\tHow do combination treatments involving a thiazide diuretic compare to combination treatments not involving a thiazide diuretic in patients without diabetes with moderate/severe hypertension or cardiovascular risk?\n3.\tWhat is the relative cost effectiveness of monotherapies and combination therapies used to manage non-diabetic patients with hypertension?