Given the lack of robust evidence, the benefits and risks of adding additional drugs for reducing blood pressure to treat people with thickening of the heart muscle and high blood pressure are unclear.
It is unclear if adding drugs for reducing blood pressure causes more serious harms in patients than placebo (dummy treatment) or no treatment; however, it may increase treatment discontinuation due to unwanted effects.
There is a need for future studies to better understand the benefits and harms of adding drugs for reducing blood pressure in people with thickening of the heart muscle caused by high blood pressure.
What is thickening of the heart muscle?
Thickening of the heart muscle is a condition where the muscle gets bigger and affects the function of the heart. This can happen when the heart has worked too hard over time and is mainly caused by high blood pressure. People with thickening of the heart muscle can experience shortness of breath, fatigue, chest pain, heart palpitations, and dizziness or fainting.
How is thickening of the heart muscle treated?
Thickening of the heart muscle can be treated with drugs for reducing blood pressure.
What did we want to find out?
We wanted to find out if adding drugs for reducing blood pressure was better than placebo or no drug treatment at preventing illness and death in people with thickening of the heart muscle and high blood pressure.
We also wanted to learn if the addition of drugs for reducing blood pressure was associated with any unwanted or harmful effects.
What did we do?
We searched for studies that investigated the addition of drugs for reducing blood pressure compared with placebo or no drug treatment.
We compared and summarised the results of the studies and rated our confidence in the evidence, based on factors such as methods and sizes of participant groups.
What did we find?
We found 3 studies that involved 930 people with thickening of the heart muscle and high blood pressure. The largest study was in 692 people, and the smallest study was in 15 people. Study participants were of both genders and on average between 66 and 75 years old. Participants were followed for between three and four years. The studies were conducted in several countries in Europe, Asia, and North and South America. One study received pharmaceutical industry funding.
It is uncertain if adding drugs for reducing blood pressure has an effect on death, development of heart and blood vessel diseases, or on hospitalisation for heart failure. It is unclear if adding drugs for reducing blood pressure causes more serious harms than placebo or no drug treatment, but it may increase treatment discontinuations due to unwanted effects. It is unclear if adding drugs for reducing blood pressure has an effect on heart muscle mass.
What are the limitations of the evidence?
Our confidence in the evidence is lacking because of the small number of identified studies. The available evidence is based on a small percentage of people with thickening of the heart muscle and high blood pressure identified from larger populations in the included studies. Further evidence may change our results.
How up-to-date is the evidence?
The evidence is current to September 2020.
We are uncertain about the effects of adding additional antihypertensive drug therapy on the morbidity and mortality of participants with LVH and hypertension compared to placebo. Although the incidence of serious adverse events was similar between study arms, additional antihypertensive therapy may be associated with more withdrawals due to adverse events. Limited and low-certainty evidence requires that caution be used when interpreting the findings. High-quality clinical trials addressing the effect of antihypertensives on clinically relevant variables and carried out specifically in individuals with hypertension-induced LVH are warranted.
Hypertension is the leading preventable risk factor for cardiovascular disease and premature death worldwide. One of the clinical effects of hypertension is left ventricular hypertrophy (LVH), a process of cardiac remodelling. It is estimated that over 30% of people with hypertension also suffer from LVH, although the prevalence rates vary according to the LVH diagnostic criteria. Severity of LVH is associated with a higher prevalence of cardiovascular disease and an increased risk of death.
The role of antihypertensives in the regression of left ventricular mass has been extensively studied. However, uncertainty exists regarding the role of antihypertensive therapy compared to placebo in the morbidity and mortality of individuals with hypertension-induced LVH.
To assess the effect of antihypertensive pharmacotherapy compared to placebo or no treatment on morbidity and mortality of adults with hypertension-induced LVH.
Cochrane Hypertension’s Information Specialist searched the following databases for studies: Cochrane Hypertension Specialised Register (to 26 September 2020), the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library; 2020, Issue 9), Ovid MEDLINE (1946 to 22 September 2020), and Ovid Embase (1974 to 22 September 2020). We searched the World Health Organization International Clinical Trials Registry Platform and the ClinicalTrials.gov for ongoing trials. We also searched Epistemonikos (to 19 February 2021), LILACS BIREME (to 19 February 2021), and Clarivate Web of Science (to 26 February 2021), and contacted authors and funders of the identified trials to obtain additional information and individual participant data. There were no language restrictions.
Randomised controlled trials (RCTs) with at least 12 months’ follow-up comparing antihypertensive pharmacological therapy (monotherapy or in combination) with placebo or no treatment in adults (18 years of age or older) with hypertension-induced LVH were eligible for inclusion. The trials must have analysed at least one primary outcome (all-cause mortality, cardiovascular events, or total serious adverse events) to be considered for inclusion.
Two review authors screened the search results, with any disagreements resolved by consensus amongst all review authors. Two review authors carried out the data extraction and analyses. We assessed risk of bias of the included studies following Cochrane methodology. We used the GRADE approach to assess the certainty of the body of evidence.
We included three multicentre RCTs. We selected 930 participants from the included studies for the analyses, with a mean follow-up of 3.8 years (range 3.5 to 4.3 years). All of the included trials performed an intention-to-treat analysis. We obtained evidence for the review by identifying the population of interest from the trials' total samples. None of the trials provided information on the cause of LVH. The intervention varied amongst the included trials: hydrochlorothiazide plus triamterene with the possibility of adding alpha methyldopa, spironolactone, or olmesartan. Placebo was administered to participants in the control arm in two trials, whereas participants in the control arm of the remaining trial did not receive any add-on treatment.
The evidence is very uncertain regarding the effect of additional antihypertensive pharmacological therapy compared to placebo or no treatment on mortality (14.3% intervention versus 13.6% control; risk ratio (RR) 1.02, 95% confidence interval (CI) 0.74 to 1.40; 3 studies; 930 participants; very low-certainty evidence); cardiovascular events (12.6% intervention versus 11.5% control; RR 1.09, 95% CI 0.77 to 1.55; 3 studies; 930 participants; very low-certainty evidence); and hospitalisation for heart failure (10.7% intervention versus 12.5% control; RR 0.82, 95% CI 0.57 to 1.17; 2 studies; 915 participants; very low-certainty evidence). Although both arms yielded similar results for total serious adverse events (48.9% intervention versus 48.1% control; RR 1.02, 95% CI 0.89 to 1.16; 3 studies; 930 participants; very low-certainty evidence) and total adverse events (68.3% intervention versus 67.2% control; RR 1.07, 95% CI 0.86 to 1.34; 2 studies; 915 participants), the incidence of withdrawal due to adverse events may be significantly higher with antihypertensive drug therapy (15.2% intervention versus 4.9% control; RR 3.09, 95% CI 1.69 to 5.66; 1 study; 522 participants; very low-certainty evidence). Sensitivity analyses limited to blinded trials, trials with low risk of bias in core domains, and trials with no funding from the pharmaceutical industry did not change the results of the main analyses. Limited evidence on the change in left ventricular mass index prevented us from drawing any firm conclusions.