Hypertension is an elevation in systolic and/or diastolic blood pressure. The standard definition of hypertension is a persistent, resting elevation above 130/80 bpm. Under the new guidelines of the American Heart Association (AHA), some 14% more Americans will be diagnosed with hypertension (AHA, 2018). However, most of these adults will not need pharmacologic treatment (AHA, 2018). In the UK, approximately 15 million adults have been diagnosed with hypertension, but less than half of these cases are properly controlled (British Heart Foundation, 2020).
Uncontrolled hypertension leads to potentially life-threatening diseases, including heart attack, stroke, aneurysm and renal failure. When lifestyle alterations are not successful in lowering blood pressure, pharmacologic therapy is implemented. The most common classes of antihypertensive medications include diuretics, angiotensin-converting enzyme (ACE) inhibitors, angiotensin-receptor blockers (ARBS), beta-blockers and calcium channel blockers (Musini et al, 2019).
The standard definition of hypertension is a resting persistent elevation above 130/80 bpm
Diuretics, most commonly from the thiazide class, inhibit sodium and chloride (and, therefore, water) reabsorption from the kidneys. When used over a long term, they also lower peripheral resistance. ACE inhibitors act to lower arteriolar resistance and increase venous capacity. ARBs reduce the secretion of vasopressin and aldosterone. Beta-blockers prevent the stimulation of receptors that secrete catecholamines, such as epinephrine and nor-epinephrine. Lastly, calcium channel blockers cause vasodilation and decrease the strength of myocardial contraction (Musini et al, 2019).
Objectives
Musini et al (2019) undertook a review to quantify the effects of antihypertensive pharmacologic treatment compared with placebo or no treatment in adults aged 60 years and older. Outcomes of interest included all-cause mortality, cardiovascular and cerebrovascular morbidity or mortality and treatment withdrawal due to adverse effects.
Intervention/methods
The authors of this review extensively searched various electronic databases, including the Cochrane Registers, Medline Ovid, Embase Ovid, ClinicalTrials.gov and the WHO Clinical Trials Registry, through November 2017 (Musini et al, 2019). No language or publications barriers were imposed. Reference lists of included studies were reviewed, and field experts were contacted to identify any missed trials.
Randomised controlled trials (RCTs) included in the review had to have included study participants at least 60 years of age who were on antihypertensive drug therapy for at least 1 year and who were compared against placebo or no treatment. Individual trials lasted from 1 to 6 years. For inclusion purposes, hypertension was defined as blood pressure>140/90 bpm. A subgroup analysis by patient age was planned, separating those aged 60–79 years and those aged 80 years and greater. Cardiovascular and cerebrovascular morbidity included stroke, congestive heart failure, ruptured aneurysm and myocardial infarction. Transient ischemic attack (TIA) was not included in the reporting of cardiovascular mortality or morbidity, as the authors felt it to be subjective and less serious (Musini et al, 2019).
Results
Sixteen RCTs were included in this review involving a total of 26 795 patients (Musini et al, 2019). While the authors reported that most patients were healthy adults, individual study data reported the baseline existence of stroke (4.2%), myocardial infarction (1.8%), diabetes (3.4%), hyperlipidaemia (1.7%) and smoking (10.5%). The authors pointed out that, despite accepting any trial that included participants with baseline blood pressure>140/90 bpm, most of the patients in the trials had moderate to severe hypertension (mean baseline blood pressure=182/95 bpm).
Thiazide diuretics were used as a first-line treatment in more than 70% of the trials. Four trials maintained patients on the first-line treatment alone throughout the study, while the remainder maintained the first-line drug and added other drugs if blood pressure was not controlled on the initial medication.
At a 95% confidence interval, antihypertensive drug therapy for a mean duration of 3.8 years was found to decrease all-cause mortality (relative risk (RR)=0.91, I2=8%, with an absolute risk reduction of 1%); cardiovascular morbidity or mortality (RR=0.72, I2=65%, with an absolute risk reduction of 3.8%); and both cerebrovascular mortality or morbidity (RR=0.66, I2=0%, with an absolute risk reduction of 1.8%) and coronary heart disease morbidity or mortality (RR=0.78, I2=0%, with an absolute risk reduction of 1.1%). Mortality was reduced to a greater extent in the 60–79 year subgroup than in the 80 years and older subgroup.
Conclusions
Musini et al's (2019) review suggested that antihypertensive therapy does reduce morbidity and mortality in hypertensive adults aged 60 years and older. Most of the evidence of benefit pertains to primary prevention in the population with moderate to severe hypertension using a thiazide diuretic as first-line treatment. Overall, the absolute decrease in all-cause mortality was 1%, and the absolute reduction in cardiovascular and cerebrovascular morbidity or mortality was 4% over a 4-year duration.
Implications for practice
This review provides clinicians with an evidence-based justification for antihypertensive drug treatment of adults aged 60 years and over with moderate to severe hypertension (Musini et al, 2019). The observed reduction in mortality suggests that there is a net health benefit when using this approach. Trials are needed in people with mild hypertension (resting blood pressure=130–140/80–90 bpm). Unfortunately, the results of this review demonstrated considerable reporting bias and a lack of generalisability to different patient populations. The authors reported that approximately 50% of the trials could have reporting bias (Musini et al, 2019). Indeed, the authors themselves reported that their primary and secondary outcomes were for healthy patients with mild to moderate hypertension and then included multiple studies involving patients with pre-existing comorbidities and moderate to severe hypertension.
While antihypertensive treatment does seem successful, it remains unclear which antihypertensive drug to use first. Future reviews should focus on studies that are more directly aligned with primary and secondary outcome goals and should seek to identify particular drug classes for first-line management of hypertension in this population.