Introduction

Globally, hypertension (HTN) is the leading risk factor for death and disability, contributing to 10 million deaths annually in 2019. More than 20% of adults worldwide suffer from hypertension, and 75% of them reside in Low-middle-income countries (LMICs) [1, 2]. Hypertension is a significant contributing factor in about 47% of deaths from heart disease and 54% of fatalities from stroke [3]. In addition, Nepal’s rising hypertension prevalence is another concern. Surveys carried out in different parts of Nepal between 2011 and 2016 indicated escalating prevalence of hypertension over the decades, which rose by 6% in Nepal between 2000 and 2020, according to a systematic review by Dhungana et al. in 2021 [4].

Hypertension is inadequately controlled even after its diagnosis despite the availability of effective treatment in Nepal [5]. Several studies have reported low medication adherence, irregular follow-up, a lack of uniform treatment protocols, and healthcare practitioners’ inability to convey messages as barriers to hypertension management in Nepal [4, 5]. According to World Health Organisation (WHO), at least 50% of diagnosed patients with Hypertension (HTN) do not take antihypertensive medication as prescribed [6]. Adherence to prescribed pharmacotherapies is an important predictor of optimal blood pressure (BP) control and subsequent reduction in the complication burden due to hypertension [7].

Poor medication adherence results in significant disease worsening, an increase in avoidable hospital admission rates, and extended hospital stays, which decrease treatment efficacy and increase the risk of cardiovascular events. According to several studies in clinical setting, non-adherence to anti-hypertensive treatment has also hampered drug efficiency [8–10].

Recent review provided evidence of a huge gap in the cascade of hypertension care in Nepal [11]. The study done in the community setting of Nepal reported that 37.5% [12] of hypertensive patients had a high level of adherence whereas in a hospital setting, only 23.9% [13] of hypertensive patients had a high level of adherence. The recent meta-analysis of Nepal reported that half of the hypertensive population of Nepal is non-adherent to their anti-hypertensive medications, posing a higher risk of cardiovascular events [14].

Therefore, it is crucial to identify the factors associated with adherence to antihypertensive medication to improve the control of blood pressure among patients with hypertension in Nepal [14]. Several studies have reported the presence of co-morbidity, alcohol consumption, self-purchasing of medications [7, 14], forgetfulness [13, 14], unavailability of hypertensive medicines at the nearest health facilities [15], large number of medications prescribed, irregular follow-up [16, 17], etc., were all linked to non-adherence to antihypertensive medication and all identified factors were modifiable. Although several studies have shown the prevalence of hypertension, level of medication adherence and factors associated with adherence to antihypertensive medications in some parts of Nepal [13, 15–17], there is limited evidence on medication adherence at the tertiary level hospital in Nepal.

Therefore, this study was conducted to assess the level of medication adherence and its associated factors among patients with hypertension attending Manmohan Cardiothoracic Vascular and Transplant Centre, a cardiac tertiary center hospital in Nepal, to inform the future contextual intervention design and implementation.

Materials and methods

Results

A total of 320 patients were approached for data collection; 12 patients were excluded as they did not fulfill the inclusion criteria, after excluding 12 patients, and 308 patients were included in the study. The mean age of participants was 58.1 years with standard deviation of 11.7 years. The age range of participants was between 23 to 87 years, with nearly half of them (47.4%) in the age group 60 years and above, followed by 31.5% from the age group 50–59 years, with around half (51.3%) females. More than half of the participants (52.3%) in this study were Brahmin/Chhetri, and 58.1% were literate, and the majority of them (72.0%) were self-employed, and the majority (87.3%) of the study participants were married as presented in Table 1.

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Table 1. Socio-demographic characteristics of study participants (n = 308).

https://doi.org/10.1371/journal.pone.0305941.t001

As presented in Table 2, more than half (61%) of the participants had moderate to high levels of adherence, and less than two-fifths (39%) of the study participants had low levels of adherence.

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Table 2. Level of adherence of the study participants (n = 308).

https://doi.org/10.1371/journal.pone.0305941.t002

There was no significant association of socio-demographic variables age, sex, ethnicity, education, employment status and marital status of patients with level of adherence as reported in Table 3.

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Table 3. Association of socio-demographic characteristics of participants with level of adherence (n = 308).

https://doi.org/10.1371/journal.pone.0305941.t003

However, there was a significant association between the presence of side effects, blood pressure status, forgetfulness, missed medicines due to high cost, regular follow up and fear of taking medicines lifelong with a level of adherence as presented in Table 4.

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Table 4. Association of clinical and behavioral characteristics of participants with level of adherence (n = 308).

https://doi.org/10.1371/journal.pone.0305941.t004

Similarly, among the total respondents having side-effects, more than half (53.3%) had low level of adherence compared to 36.5% of respondents with absence of side-effects of medications. Among the respondents with uncontrolled blood pressure, nearly half of the participants (45.8%) had low level of adherence while only 33.2% of participants with controlled blood pressure had low adherence level.

In addition, more than half (66.5%) who forgot to take medicines had low adherence levels compared to only 10% of respondents with no forgetfulness.

Similarly, the majority of the participants (83.8%) who missed medicines due to high cost had low levels of adherence compared to only 32.8% of participants who did not miss medicines due to high cost.

More than half of the participants (57.1%) who had an irregular follow-up had a low level of adherence, while only 32.9% of participants who did regular follow-up had a low adherence level. More than half of the participants (59.4%) who feared taking medications lifelong had a low level of adherence compared to only 24.4% of participants who had no fear, as presented in Table 4.

Further, those six variables found significant at 5% significance level in bivariate analyses were entered into multivariate analysis. Multi-collinearity was assessed before performing logistic regression by utilizing Variance Inflation Factor (VIF). The decisive criterion for excluding variables from the regression model was set out as those with VIF values greater than 10. Variance inflation factor (VIF) was checked using collinearity diagnostics. No collinearity problems among the explanatory variables were identified (the highest observed VIF was 1.168). The goodness of fit of the regression model was tested by the application of the Hosmer and Lemeshow Chi-square test. Hosmer Lemeshow Chi-square statistic in the model showed no significant difference between the observed and predicted probabilities (p-value 0.607). This indicated a good model fit. Also, in the model, a Nagelkerke (pseudo) R Square value of 0.566 was observed, which indicates that 56.6 per cent of the variability in the adherence level was explained by the explanatory variables. The significance level to determine the statistical significance of independent variables is P-value <0.05.

The multivariate logistic regression analysis reported that forgetfulness, missed medications due to high cost, and fear of taking medications lifelong were significantly associated with low adherence to antihypertensive medication, as presented in Table 5.

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Table 5. Factors associated with the level of adherence (n = 308).

https://doi.org/10.1371/journal.pone.0305941.t005

The participants who forgot to take antihypertensive medications were 22.5 times more likely to have a low level of adherence (AOR 22.5, 95%CI 10.56–47.86) compared to those who did not forget to take medications. Likewise, the participants who missed medicines due to high cost were 3.8 times more likely to have a low level of adherence (AOR 3.8, 95%CI 1.249–11.6) compared to those who did not miss medicines due to cost. The participants who feared taking antihypertensive medication lifelong were six times more likely to have low adherence (AOR 6.04, 95%CI 2.960–12.33) than those without fear as presented in Table 5.

Discussion

Adherence to antihypertensive medication is an important factor in controlling blood pressure among diagnosed patients with hypertension. A multinational cross-sectional study reported a significant gap in the awareness level and control of blood pressure among patients with hypertension [24].

This study revealed that 61% of patients with hypertension had moderate to high levels of adherence to antihypertensive medications. This study identified associated factors of low adherence as forgetfulness, missed medicines due to high cost, and fear of taking medicines lifelong.

The prevalence of moderate to high adherence in our study was 61%, at 95%CI (0.55–0.66). However, the community-based study [17] from the Eastern part of Nepal reported that among 154 hypertensive patients, 56.5% of patients were adherent to antihypertensive medications. This could be due to the measurement of adherence based on different criteria, along with variation in the subset of the population that served as the study sample. In addition, the previous study was community based, whereas ours is a hospital-based study. The results of our study is higher than what has been reported from Malaysia (53.4%) [25], Taiwan (47.5%) [26] and Bangladesh (41%) [27]. The adherence rate in this study is also higher than the study from the western part of Nepal, Pokhara (35.4%) [28]. However, more people of LMICs in Pakistan [29], 77%, were adherent to their medication than in this study. This may be due to differences in measurement criteria of adherence and difference in socio-demographic characteristics. MMAS 4 tool was used to assess the level of adherence in most of the studies, whereas we used MMAS-8 in our study. The MMAS-4 is a generic self-reported medication-taking behavior scale which consists of four items with a scoring scheme of “Yes” = 0 and “No” = 1. The items are summed to give a range of scores from 0 to 4 [30]. However, this study used the MMAS-8 which consists of 8 items containing question about medication adherence. Low adherence is 0 to <6, moderate adherence is from 6 to <8 and high adherence is 8. Nevertheless, it is important to have an optimum level of adherence for blood pressure control, so the findings of our study are crucial to address the issue of non-adherence.

The study found forgetfulness as one of the determinants of low levels of adherence to antihypertensive medications. The participants who forgot to take antihypertensive medications were 22.5 times more likely to have a low level of adherence compared to those who did not forget to take medicines. In a study conducted in a multispecialty tertiary care teaching hospital in India [31], it was reported that forgetfulness, the presence of side effects, and not taking medication timely are the reasons for low adherence. Forgetfulness was the top reported cause (72%) of unintended non-adherence, similar to our findings. It is also consistent with the findings from a hospital-based study done in five centres in Nepal [13] that reported 56% of the participants were non-adherent to antihypertensive therapy due to forgetfulness. These demand strategies to address forgetfulness, such as text or voice messages, and personalized reminders that can remind patients to improve their adherence to medications [32, 36].

This study found that those who missed medications due to high cost were 3.8 times more likely to have a low adherence than those who did not miss medicines due to cost. The findings of the study are similar to the findings from the National health survey from a nationally representative sample of US citizens [33], which reported that antihypertensive medication adherence and hypertension control are significantly associated with the inability to obtain antihypertensive medication due to financial constraints. The findings of the study are also consistent with the study done in eastern Nepal [17], which identified missed medicines due to high cost as one of the predictors of low level of adherence. It demands the strategies to reduce the high out of pocket expenditure in health such as increasing the coverage of national health insurance [34].

Further, this study identified fear of taking e lifelong antihypertensive medicines as the associated factors of a low level of adherence. The participants who feared taking antihypertensive medication lifelong were 6 times more likely to have a low level of adherence than those without fear. The findings of the study are consistent with the study done by Shrestha et al. [35] in 2019, which reported fear of taking medication for a lifetime was the most common reason for non-adherence. These fears could be due to a lack of enough information to clarify their misconceptions [35]. Hence, those disease misconceptions can be overcome with adequate information from reliable sources to patients.

Different measures, like a reminder messaging alarm to reduce forgetfulness, counselling to reduce misconceptions about medications, and improving patient education, have been found to be effective improving adherence to antihypertensive medications among patients with hypertension [32, 34–36]. However, the effectiveness and feasibility of those interventions in addressing the issue of non-adherence in this context should be explored in future studies.

Conclusion

Although the study found that more than half of the participants had moderate to high adherence levels, it remains concerning that two-fifths of the participants had low levels of adherence to antihypertensive medications. To improve the medication adherence level among patients with hypertension, the identified factors, such as forgetfulness, missed medicines due to high cost, and fear of taking medicines lifelong, should be addressed.

Supporting information

Acknowledgments

We would like to express our deep gratitude to Prof. Dr. Amod Kumar Poudyal and Mr Susan Man Shrestha for their valuable support and suggestions. We would also like to acknowledge two data enumerators Ms. Aarati Neupane and Mr. Aashish Rana for their effort and contribution during data collection. Further, we would like to express our sincere thanks to Manmohan Cardiothoracic Vascular and Transplant Centre for providing us permission for data collection, and hospital administration for coordinating with staff members for data collection at the Out Patient Department of Cardiology unit. Finally, we would like to acknowledge Dr. Arnold Morisky for granting formal permission to use MMAS-8 scale in our study.

The MMAS-8© Scale, content, name, and trademarks are protected by US copyright and trademark laws. Permission for use of the scale and its coding is required. A license agreement is available from MMAR, LLC., www.moriskyscale.com.