Comparative Effectiveness of Novel Combination Therapies for Simultaneous Management of Hypertension and Hypercholesterolemia: A Systematic Review and Meta-Analysis

Hypertension and hypercholesterolemia are the two most common modifiable risk factors for cardiovascular disease (CVD). Current guidelines recommend treating these risk factors simultaneously rather than in isolation. One prominent way to simultaneously treat the risk factors is by concurrently administering blood pressure (BP) lowering and lipid-lowering drugs (statins). However, there is still a controversy on which antihypertensive drugs to combine with statins for effective treatment. Therefore, the present meta-analysis assessed the efficacy of various antihypertensive agents combined with statins on BP and low-density lipoprotein cholesterol (LDL-C). PubMed, MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), and Google Scholar databases were searched thoroughly for records published in English up to February 2024. According to the PICOS (Patients, Intervention, Comparison, Outcomes, and Study design) criteria, randomized controlled trials (RCTs) evaluating the effectiveness of combination therapy of antihypertensives and statins in treating hypertension and hypercholesterolemia were eligible for inclusion. Furthermore, statistical analyses were performed using Review Manager software (RevMan version 5.4.1), and quality assessment was performed using the Cochrane risk of bias tool. Eight RCTs comprising 1,182 patients with hypertension and hypercholesterolemia were included. Compared to statin monotherapy, no significant difference in the change of LDL-C levels was observed in patients receiving combination therapy of angiotensin receptor blockers (ARBs) with statins (MD, -3.98; P = 0.56) and BBs with statins (mean difference [MD], -0.47; P = 0.90). However, calcium channel blockers (CCBs) combined with statins showed a significantly greater reduction in LDL-C levels than statins alone (MD, -8.0; P = 0.0008). Similarly, patients treated with CCBs and statins had a considerable decrease in diastolic blood pressure (DBP) than those treated with antihypertensives only (MD, -6.37; P = 0.04). On the other hand, patients receiving antihypertensive drugs only demonstrated significantly better reductions in systolic blood pressure (SBP) than patients treated with combination therapy of ARBs and statins (MD, 2.88; P < 0.00001). Furthermore, we found that triple combination therapy was associated with better BP-lowering effects than double combination therapy of antihypertensive and statin (MD, -15.15; P < 0.00001 for SBP; and MD, -10.28; P < 0.00001, for DBP). No significant difference was recorded in the incidence of treatment-emergent adverse events. Concurrent administration of antihypertensives and statins has similar effects on BP and LDL-C as the use of either drug alone. Furthermore, triple combination therapy (two antihypertensives and a statin) is associated with better BP-lowering effects than double combination therapy (one antihypertensive and a statin).