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ABSTRACT
Introduction
Arterial hypertension represents the leading modifiable risk factor for all-cause death and early development of cardiovascular disease in women. Current clinical guidelines for the treatment of hypertension noted that women respond to antihypertensive drugs similarly to men and, therefore, treatment recommendations remain the same for both sexes. However, clinical evidence suggests the existence of sex- and gender-related differences (SGRD) in the prevalence, pathophysiology, pharmacodynamics (efficacy and safety) and pharmacokinetics of antihypertensive drugs.
Areas covered
This review summarizes SGRD in the prevalence of hypertension, hypertension-mediated organ damage and blood pressure control, prescription patterns, and pharmacokinetics/ pharmacodynamics and doses of antihypertensive drugs.
Expert opinion
There is limited information on SGRD in antihypertensive drug efficacy because of the underrepresentation of women in randomized clinical trials and, more important, because few trials reported results stratified by sex or performed sex-specific analyses. However, there are SGRD in hypertension-mediated organ damage, drug pharmacokinetics and, particularly, in drug safety. Prospective trials specifically designed to better understand the basis for SGRD in the pathophysiology of hypertension and in the efficacy and safety of antihypertensive drugs are needed to achieve a more personalized treatment of hypertension and hypertension-mediated organ damage in women.
Article highlights
Arterial hypertension is the leading modifiable risk factor for all-cause death and early development of cardiovascular disease in women and uncontrolled hypertension remains more common in older women than in men.
Despite clinical guidelines make no specific recommendations based on patient’s sex/gender, there is evidence of sex- and gender-related differences (SGRD) in the prevalence, pathophysiology, efficacy and safety and optimal dosing of some antihypertensive drugs.
The limited information on SGRD in antihypertensive drug efficacy and safety can be related to the underrepresentation of women in clinical trials and because most trials did not perform a prospective sex/gender-specific analyses of clinical results and outcomes.
SGRD in the pharmacokinetics of some antihypertensive drugs may lead to higher drug exposure and incidence of ADRs in women, but dose modifications for women are not recommended.
Women present a higher incidence of adverse drug reactions than men which directly impact antihypertensive drug choice and reduces therapeutic adherence and blood pressure control.
Further prospective clinical trials specifically designed to uncover potential SGRD in the response to antihypertensive drugs, understand the pathophysiological mechanisms involved, and its clinical relevance are needed.
Abbreviations
| ACEIs | = | angiotensin-converting-enzyme inhibitors |
| ADRs | = | adverse drug reactions |
| AF | = | atrial fibrillation |
| ARBs | = | angiotensin receptor blockers |
| AUC | = | area under the plasma drug concentration-time curve |
| BP | = | blood pressure |
| CCBs | = | calcium channel blockers |
| CHD | = | coronary heart disease |
| CKD | = | chronic kidney disease |
| Cmax | = | peak plasma levels |
| CV | = | cardiovascular |
| CVD | = | cardiovascular disease |
| DBP | = | diastolic blood pressure |
| DM | = | diabetes mellitus |
| GFR | = | glomerular filtration rate |
| HCTZ | = | hydrochlorothiazide |
| HF | = | heart failure |
| HFrEF | = | heart failure with reduced ejection fraction |
| HMOD | = | hypertension-mediated organ damage |
| HR: | = | hazard ratio |
| HTN | = | arterial hypertension |
| IMT | = | intima-media thickness |
| LV | = | left ventricle |
| LVH | = | LV hypertrophy |
| MI | = | myocardial infarction |
| PAD | = | peripheral artery disease |
| P-gp | = | P-glycoprotein |
| PK | = | pharmacokinetics |
| RAAS | = | renin-angiotensin-aldosterone system |
| RCTs | = | randomized clinical trials |
| SBP | = | systolic blood pressure |
| SGRD | = | sex/gender-related differences |
| TD | = | thiazide diuretics |
| Vd | = | volume of distribution |
Declaration of interest
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
Reviewer disclosures
Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.