Characterizing Dual Combination Therapy Use in Treatment Escalation of Hypertension: Real-World Evidence from Multinational Cohorts

Background Over one billion adults have hypertension globally, of whom approximately 70% cannot achieve blood pressure control goal with monotherapy alone. Data are lacking on patterns of dual combination therapies prescribed to patients who escalate from monotherapy in routine practice. Methods Using eleven electronic health record databases that cover 118 million patients across eight countries/regions, we characterized the initiation of antihypertensive dual combination therapies for patients with hypertension. In each database, we first constructed twelve exposure cohorts of patients who newly initiate dual combination therapy with one of the four most commonly used antihypertensive drug classes (angiotensin-converting enzyme inhibitor [ACEi] or angiotensin receptor blocker [ARB]; calcium channel blocker [CCB]; beta-blocker; and thiazide or thiazide-like diuretic) after escalating from monotherapy with one of the three alternative classes. Using these cohorts, we then described dual combination therapy utilization, stratified by age, gender, history of cardiovascular diseases (CVD), and country. Results Across data sources, we identified 980,648 patients with hypertension initiating dual combination therapy with antihypertensive agents after escalating from monotherapy: 12,541 from Australia, 6,980 from South Korea, 2,096 from Singapore, 7,008 from China, 16,663 from Taiwan, 103,994 from France, 76,082 from Italy, and 754,137 from the United States (US). Significant variations in treatment utilization existed across countries and patient subgroups. In Australia and Singapore, starting an ACEi/ARB monotherapy followed by a CCB was most common while in South Korea, China and Taiwan, starting a CCB monotherapy followed by an ACEi/ARB was most common. In Italy, France, and the US, sequential use of an ACEi/ARB monotherapy followed by a diuretic was most common. Younger patients were more likely to be prescribed ACEi/ARB followed by either a CCB or a diuretic compared with older patients. Women were more likely to be prescribed diuretics then an ACEi/ARB or a CCB compared with men. Among patients with history of CVD, ACEi/ARB followed by beta-blocker, and beta-blocker followed by ACEi/ARB were more commonly prescribed. Conclusion This is the largest and most comprehensive study characterizing the real-world utilization of dual combination therapies in treating hypertension. Large variation in the transition between monotherapy and dual combination therapy for hypertension was observed across countries. These results highlight the need for future research to identify which second-line dual combination therapy is most effective in practice.