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BackgroundThe incidence of hypertension and clinical complications (e.g., heart, cerebrovascular and kidney injury) is increasing worldwide. It is widely known that a relatively large dose of valsartan (320 mg) could alleviate clinical complications. The current network meta-analysis assessed which drug could be combined with a relatively large dose of valsartan to control blood pressure (BP) more effectively. And which combination therapy with different dosages of valsartan did not induce excessive BP reduction with increasing dosages of valsartan.MethodsThe PubMed, Embase, Medline, Cochrane Library, CNKI, Wanfang, and CSTJ databases were searched from inception to October 2022 for relevant randomized controlled trials (RCTs). The search strategies included concepts related to hypertension and two-drug combination therapy of different doses of valsartan, and there were no language or data restrictions. The outcomes included adverse effects and changes in systolic BP and diastolic BP. Permanent discontinuations related to treatment were the most accurate and objective measure of adverse effects. The common adverse effects of most studies (i.e., dizziness, headache, nasopharyngitis, asthenia and urticaria) were also included. A Bayesian network meta-analysis was performed, and mean differences with 95% confidence intervals were calculated. ADDIS and STATA were used for Bayesian model network meta-calculation.ResultsThirty-four RCTs were included involving 26,752 patients, and the interventions included different doses of valsartan combined with various types and doses of drugs. Among many combination therapies, the combination of valsartan 320 mg with amlodipine 10 mg (p p > 0.05) did not further reduce BP and was not shown to increase the incidence of adverse effects.ConclusionsCombination therapy with a relatively large dose of valsartan could control BP and improve clinical complications effectively. However, for hypertensive patients with different treatment requirements, specific choices should be made regarding whether to control BP, treat clinical complications, or both.

Abstract licence: CC BY

Dihydropyridine calcium channel blockers (DHPCCBs) are widely used to treat hypertension and chronic coronary artery disease. One common adverse effect of DHPCCBs is peripheral edema, particularly of the lower limbs. The side effect could lead to dose reduction or discontinuation of the medication. The combination of DHPCCBs and renin-angiotensin system blockers has shown to reduce the risk of DHPCCBs-associated peripheral edema compared with DHPCCBs monotherapy. We performed the current systematic review and network meta-analysis of randomized controlled trials (RCTs) to estimate the rate of peripheral edema with DHPCCBs as a class and with individual DHPCCBs and the ranking of the reduction of peripheral edema. The effects of renin-angiotensin system blockers on DHPCCBs network meta-analysis were created to analyze the ranking of the reduction of peripheral edema. A total of 3312 publications were identified and 71 studies with 56,283 patients were included. Nifedipine ranked highest in inducing peripheral edema (SUCRA 81.8%) and lacidipine (SUCRA 12.8%) ranked the least. All DHPCCBs except lacidipine resulted in higher relative risk (RR) of peripheral edema compared with placebo. Nifedipine plus angiotensin receptor blocker (SUCRA: 92.3%) did not mitigate peripheral edema and amlodipine plus angiotensin-converting enzyme inhibitors (SUCRA: 16%) reduced peripheral edema the most. Nifedipine ranked the highest and lacidipine ranked the lowest amongst DHPCCBs for developing peripheral edema when used for cardiovascular indications. The second or higher generation of DHPCCBs combination with ACEIs or ARBs or diuretics lowered the chance of peripheral edema development compared to single DHPCCB treatment.

Abstract licence: CC BY-NC