OBJECTIVE: Guidelines recommend initiation of dual combination antihypertensive therapy, preferably single-pill combination (SPC), in most patients with hypertension. Evidence on narrowing gaps in clinical practice relative to guidelines is limited.
RESULTS: Monte Carlo simulation was applied to 1.1 million patients qualifying for dual combination therapy from a previously conducted retrospective analysis of clinical practice, hospital statistics, and national statistics in the UK. We provide 10-year Kaplan-Meier event rates for the primary endpoint representing a composite of nonfatal myocardial infarction, nonfatal stroke (ischemic or hemorrhagic), nonfatal heart failure hospitalization or cardiovascular death. Cox model results from a previously conducted study were utilized to estimate baseline risk, together with evidence on risk reduction from the Blood Pressure Lowering Treatment Trialists\' Collaboration (BPLTTC) meta-analysis and published evidence on BP-lowering efficacy of antihypertensive therapies. In the overall population, estimated 10-year event rates for the primary endpoint in patients with 100% persistence in monotherapy were 17.0% for irbesartan (I) and 17.6% for ramipril (R). These rates were only modestly better than that observed in clinical practice (17.8%). In patients with 100% persistence in dual therapy, estimated event rates were 13.6% for combinations of Irbesartan + Amlodipine (ARR = 8.7% compared to untreated) and 14.3% for Ramipril + Amlodipine (ARR = 8.0% compared to untreated). The absolute risk of the primary endpoint was reduced by 15.9% in patients with ASCVD and 6.6% in those without ASCVD. Similarly, the absolute risk was reduced by 11.7% in diabetics and 7.8% in those without diabetes.
CONCLUSIONS: This study represents the first to investigate guidelines-based treatment in hypertensive patients and demonstrates the opportunity for considerable risk reduction by ensuring recommended dual therapy in clinical practice, particularly in the form of SPC with high persistence, relative to no treatment or monotherapy.

BACKGROUND: Systematic reviews suggested that the eradication efficacy of PPI-amoxicillin dual therapy is similar to that of other commonly used regimens. However, it might be affected by the medication frequency. Basic and clinical studies have shown that dual therapy administered four-times daily has a reliable pathophysiological basis and could achieve satisfactory efficacy. Therefore, a systematic review of RCTs of dual therapy and other regimens was conducted to clarify whether dual therapy is superior to guidelines recommended regimens.
METHODS: The RCTs comparing dual therapy with other regimens were subjected to meta-analysis to evaluate the eradication rate, adverse reactions, and compliance using a random-effects model.
RESULTS: Dual therapy administered four-times daily had a higher eradication rate than other regimens (intention-to-treat analysis: 89.7% vs 84.6%, OR: 1.52, 95%CI 1.08-2.14, p = 0.02; per-protocol analysis: 92.6% vs 88.2%, OR: 1.54, 95%CI 1.01-2.34, p = 0.04). In first-line therapy, according to intention-to-treat analysis, the eradication rate of dual therapy was higher than other regimens (89.8% vs 84.2%, OR: 1.63, 95%CI 1.02-2.61, p = 0.04). In per-protocol analysis, dual therapy showed better efficacy than others (92.9% vs 88.3%, OR: 1.68, 95% CI 0.98-2.89, p = 0.06), but not significantly. In salvage treatment, no significant difference was detected. The safety of dual therapy was significantly better than other regimens (19.6% vs 36.7%, p < 0.01), but no difference was observed in compliance (p = 0.58).
CONCLUSIONS: PPI-amoxicillin dual therapy administered four-times daily has better efficacy and safety in H. pylori eradication than current guidelines recommended regimens, especially in first-line therapy, and mainly in Asia.

OBJECTIVE: The American Association of Clinical Endocrinologists (AACE) recommends initiating dual therapy with antihyperglycemic agents in untreated patients with type 2 diabetes mellitus and HbA1c between 7.6% (60 mmol/mol) and 9.0% (75 mmol/mol). In practice physicians do not always follow guidelines. This study assessed why physicians do not prescribe dual therapy when treating eligible patients.
METHODS: 1235 primary care physicians (PCPs) and 290 specialists in the United States reviewed medical charts for 5995 patients whose HbA1c was between 7.6% (60 mmol/mol) and 9.0% (75 mmol/mol) at diagnosis and were being treated with metformin monotherapy. In an online survey physicians rated the relevance of 22 reasons for not initiating dual therapy using a 5-point Likert scale. Relevant reasons were compared between PCPs vs. specialists, and younger vs. older patients, using multivariate general linear regression and mixed-effect models.
RESULTS: Four relevant reasons for not following AACE guidelines were physician-related: (1) \"Metformin monotherapy is sufficient to improve glycemic control\"; (2) \"Monotherapy is easier to handle than dual therapy\"; (3) \"I believe that monotherapy and changes in lifestyle are enough for hyperglycemia control\"; and (4) \"I recommend monotherapy before considering dual therapy.\" One relevant reason was patient-related: (5) \"Patient has mild hyperglycemia.\" Regression analysis demonstrated that PCPs rated each physician-related reason as significantly more relevant than specialists. Three physician-related reasons were significantly more relevant for younger patients than older patients.
CONCLUSIONS: Physicians do not follow AACE guidelines due to physicians\' beliefs toward therapy and the perception of mild hyperglycemia in patients.