Systematic review of Mendelian randomization studies on antihypertensive drugs

Abstract

Background: We systematically reviewed Mendelian randomization (MR) studies and summarized evidence on the potential effects of different antihypertensive drugs on health.

Methods: We searched PubMed and Embase for MR studies evaluating the effects of antihypertensive drug classes on health outcomes until 22 May 2024. We extracted data on study characteristics and findings, assessed study quality, and compared the evidence with that from randomized controlled trials (RCTs).

Results: We identified 2643 studies in the search, of which 37 studies were included. These studies explored a wide range of health outcomes including cardiovascular diseases and their risk factors, psychiatric and neurodegenerative diseases, cancer, immune function and infection, and other outcomes. There is strong evidence supporting the protective effects of genetically proxied antihypertensive drugs on cardiovascular diseases. We found strong protective effects of angiotensin-converting enzyme (ACE) inhibitors on diabetes whereas beta-blockers showed adverse effects. ACE inhibitors might increase the risk of psoriasis, schizophrenia, and Alzheimer's disease but did not affect COVID-19. There is strong evidence that ACE inhibitors and calcium channel blockers (CCBs) are beneficial for kidney and immune function, and CCBs showed a safe profile for disorders of pregnancy. Most studies have high quality. RCT evidence supports the beneficial effects of ACE inhibitors and CCBs on stroke, diabetes, and kidney function. However, there is a lack of reliable RCTs to confirm the associations with other diseases.

Conclusions: Evidence of the benefits and off-target effects of antihypertensive drugs contribute to clinical decision-making, pharmacovigilance, and the identification of drug repurposing opportunities.

Keywords: ACE inhibitors; Antihypertensive drugs; Beta-blockers; Calcium channel blockers; Mendelian randomization; Systematic review.

Fig. 1

Flow chart of study selection process

Fig. 2

Results of major antihypertensive drugs and circulatory diseases. Units of exposure are obtained from the original studies, as shown in Table S3. Abbreviations: angiotensin-converting enzyme (ACE); beta-adrenoceptor blockers (BBs); calcium channel blockers (CCBs)

Fig. 3

Results of major antihypertensive drugs and cancer. Units of exposure are obtained from the original studies, as shown in Table S3. Abbreviations: angiotensin-converting enzyme (ACE); beta-adrenoceptor blockers (BBs); calcium channel blockers (CCBs)

Fig. 4

Results of major antihypertensive drugs and infectious diseases, mental and neurological disorders. Units of exposure are obtained from the original studies, as shown in Table S3. Angiotensin-converting enzyme (ACE); beta-adrenoceptor blockers (BBs); calcium channel blockers (CCBs)

Fig. 5

Results of major antihypertensive drugs and other diseases. Units of exposure are obtained from the original studies, as shown in Table S3. Angiotensin-converting enzyme (ACE); beta-adrenoceptor blockers (BBs); calcium channel blockers (CCBs)