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Review
. 2024 Oct 19;16(10):e71876.
doi: 10.7759/cureus.71876. eCollection 2024 Oct.

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

Apurva Popat  1 , Sweta Yadav  1
Affiliations
Review

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

Apurva Popat et al. Cureus. .

Abstract

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).

Keywords: angiotensin receptor blockers; beta blockers; calcium channel blockers; combination therapy; hypercholesterolemia; hypertension; primary care; statins.

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Conflict of interest statement

Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.

Figures

Figure 1
Figure 1. PRISMA flowchart for study selection.
PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses
Figure 2
Figure 2. Risk-of-bias summary using the Cochrane Risk-of-Bias tool.
The green color indicates low risk of bias, the red color indicates a high risk of bias, and no color was assigned for unclear risk of bias [9].
Figure 3
Figure 3. Change in LDL-C levels between combination therapies versus statin only.
LDL-C, low-density lipoprotein cholesterol; CI, confidence interval; ARB, angiotensin receptor blocker; CCB, calcium channel blocker; BB, beta-blocker
Figure 4
Figure 4. Change in LDL-C levels between combination therapies versus antihypertensives only.
LDL-C, low-density lipoprotein cholesterol; CI, confidence interval; ARB, angiotensin receptor blocker; CCB, calcium channel blocker; BB, beta-blocker
Figure 5
Figure 5. Change in SBP levels between combination therapies versus statin only.
SBP, systolic blood pressure; CI, confidence interval; ARB, angiotensin receptor blocker; CCB, calcium channel blocker; BB, beta-blocker
Figure 6
Figure 6. Change in SBP levels between combination therapies versus antihypertensives.
SBP, systolic blood pressure; CI, confidence interval; ARB, angiotensin receptor blocker; CCB, calcium channel blocker; BB, beta-blocker
Figure 7
Figure 7. Change in DBP levels between combination therapies versus statin only.
DBP, diastolic blood pressure; CI, confidence interval; ARB, angiotensin receptor blocker; CCB, calcium channel blocker; BB, beta-blocker
Figure 8
Figure 8. Change in DBP levels between combination therapies versus antihypertensives only.
DBP, diastolic blood pressure; CI, confidence interval; ARB, angiotensin receptor blocker; CCB, calcium channel blocker; BB, beta-blocker
Figure 9
Figure 9. Comparison of percentage change in LDL-C between triple combination and double combination therapies.
LDL-C, low-density lipoprotein cholesterol; CI, confidence interval
Figure 10
Figure 10. Comparison of least mean change in SBP between triple combination and double combination therapies.
SBP, systolic blood pressure; CI, confidence interval
Figure 11
Figure 11. Comparison of least mean change in DBP between triple combination and double combination therapies.
DBP, diastolic blood pressure; CI, confidence interval
Figure 12
Figure 12. Comparison of incidences of treatment-emergent adverse events between combination therapy and antihypertensive or statin alone.
CI, confidence interval
Figure 13
Figure 13. Comparison of incidences of treatment-emergent adverse events between triple combination therapy and double combination therapy.
CI, confidence interval
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