Distribution of antihypertensive drug classes
The most commonly prescribed antihypertensive drug classes were ARBs and diuretics, a finding in agreement with another Swiss study [4]. The prescription rate for ARBs at follow-up was considerably higher than reported in other countries (51.7% vs. 18-36%) [12] but in accordance with the guidelines of the Swiss Society of Hypertension [13] and others [12]. Indeed, the Swiss guidelines recommend that ACEIs, ARBs, CCBs and diuretics be first line antihypertensives, BBs being considered second line drugs. A possible reason could be the choice of practitioners to prescribe an antihypertensive class with the lowest side effects but just as effective as the others [4]; further, the fact that antihypertensive medication is reimbursed by the Swiss health system might also induce practitioners to choose better tolerated, albeit more expensive antihypertensive drugs. Conversely, the low rate of ACE inhibitor prescriptions was not strictly in keeping with the guideline recommendations at baseline [11, 12], which consider ACEIs as first-line antihypertensive drugs. This can be explained by the fact that the guidelines recommend not to combine ACE inhibitors with ARBs for the treatment of hypertension [12]. As ARBs are the most commonly prescribed drug in our study, this might have led to a decrease in the number of ACE inhibitor prescriptions.
The recent 2013 ESH/ESC guidelines on management of arterial hypertension indicate that diuretics, beta-blockers, calcium antagonists, ACEI and ARBs are all suitable for the initiation and maintenance of antihypertensive treatment [13]. Still, after an approximate follow-up of five years, our results show that diuretics were more frequently replaced and ARBs were more frequently prescribed. Thus, our results suggest that practitioners on everyday’s practice tend to switch from diuretics to ARB treatment.
Changes in antihypertensive drug treatment
Almost four out of ten participants (39.6%) changed their antihypertensive drug regimen during an approximately 5.4 year follow-up (26.9% combination and 12.7% switching), a value higher than reported previously (18%) [4]. Conversely, the rate of discontinuers was very low compared to other studies (Additional file 1: Table S2). Possible reasons include more motivated, health-conscious participants, the prescription of better tolerated antihypertensive drugs, and the reimbursement of any type of antihypertensive drug by the Swiss health insurances. Further, it has been shown that a high proportion of patients discontinuing treatment are returning on therapy within 1 year [6]. Hence, it is possible that the high discontinuation rates reported in other studies [7, 14] might be overestimated due to a short follow-up time. Overall, our results suggest that, contrary to other countries, antihypertensive drug treatment maintenance is very high in Switzerland when assessed over a period of years.
Discontinuation of diuretics was higher than all other antihypertensive drugs. This is likely to be associated with the well described side effects such as hypotension and/or sodium or potassium abnormalities and/or metabolic disturbance. All side effects known to be associated with ARBs, ACEI, CCB or BB were not specifically recorded for this large population-based study but the discontinuation rate is strictly in agreement with other studies [15, 16] (Additional file 1: Table S3; for a review, see [3]) and in accordance with adverse effects well established in several studies [3, 7–19].
Factors associated with changes in antihypertensive drug treatment
Presence of uncontrolled hypertension was positively associated with antihypertensive drug combination, a finding also reported elsewhere [7]. These findings are in agreement with the guidelines of the Swiss Society of Hypertension [13] and others [20] which indicate that combination therapy should be prescribed if monotherapy fails to control blood pressure levels.
Being treated by ARBs was negatively associated with switching or discontinuing antihypertensive drug treatment, a finding in agreement with the literature [7]. The most likely explanation is the lower rate of adverse effects of ARBs relative to the other antihypertensive drugs [19].
Being on a one pill, single drug regimen was positively associated with combining or discontinuing treatment. Indeed, the single drug regimen might favor discontinuation because of fewer co-morbidities and the fact that most patients are symptom-free and might experience more side effects from the treatment than the disease itself [7].
Women had a lower risk of discontinuing antihypertensive drug treatment, a finding in agreement with some studies [21, 22] but not with others [23]. Contrary to previous studies [14, 24], no association was found between antihypertensive drug changes and smoking, physical activity, marital status, educational level, personal history of cardiovascular diseases. These findings suggest that changes in anti-hypertensive drug treatment are mainly due to factors related to blood pressure and/or to possible side effects of antihypertensive drug treatment rather than to the socio-economic status of the patients.
Impact of changes in antihypertensive drug treatment on blood pressure status
Unlike larger studies [7, 14, 25], our study was able to assess the impact of antihypertensive drug treatment on blood pressure control. Overall, our results confirm that adjusting the antihypertensive drug regimen leads to favorable changes in blood pressure status. Conversely, discontinuing treatment leads to a deleterious increase in blood pressure levels, which could partly explain the greater incidence of CVD events among discontinuers [25].
Continuers with uncontrolled blood pressure at follow-up were more frequently men, with uncontrolled blood pressure and on diuretics at baseline. These findings suggest that diuretics might be less effective in controlling blood pressure than the other antihypertensive drugs, or that their side effects might lead to a lower compliance and thus worse BP control. Indeed, diuretics have been shown to have the lowest persistence rate of all antihypertensive drugs (Additional file 1: Table S3). They also indicate that practitioners should be more aggressive towards uncontrolled hypertension, as continuing the same treatment will not improve blood pressure control.
Strengths and limitations
The main strength of this study is that it is population-based and used a representative sample of subjects with hypertension. Hence, the conclusions are applicable to the general population and to daily clinical practice compared to those from randomized controlled trials. This study also allowed the analysis of a considerable number of factors associated with antihypertensive drug changes. Further, several studies that assessed changes in antihypertensive drug treatment used only two [1, 26, 27] or three categories such as “continuers”, “switchers” and “discontinuers” [14]. In this study, we opted for a four-category classification as suggested by Mazzaglia and colleagues [7] because it reflected more accurately the behavior of a practitioner when managing a patient with hypertension. Indeed, our results suggest that the factors associated with combining antihypertensive drugs are different from those associated with maintenance of the antihypertensive drug regimen.
This study has also some limitations. Generalization might be limited by the modest participation rate (41%), but this rate is comparable to other epidemiological studies as reported by Wolff and colleagues [28]. It is also possible that the CoLaus participants are more health-conscious than the general population, thus biasing the observed prevalence of discontinuers and data on past medical history and clinical features. Unlike other studies [29], no record of adverse effects was available; hence, the impact of adverse effects of antihypertensive drugs could not be assessed. Further, it was not possible to objectively assess adherence to treatment. Compared to other studies [14, 25], our sample size was rather small but blood pressure data was available while in the other studies it was not. Hence, the effect of antihypertensive drug changes could be objectively assessed, while the other studies lacked such information or relied on administrative data only. Participants might present with outdated prescription boxes or may forget to bring a box with them. This may have led to misclassification of the patient’s baseline drug therapy status. No information was available regarding dosage of antihypertensive drugs at baseline; thus, no analysis of possible dosage escalation could be performed. Similarly, for logistic and economic reasons no yearly follow-up of the cohort could be performed, so it is possible that therapy adjustments and interventions may have been missed. Although incidence of CVD events was available, it was not possible to establish whether the changes in antihypertensive drug treatment occurred before or after the occurrence of the CVD event. The next follow-up of the cohort will start in April 2014 and will allow evaluating the impact of antihypertensive drug treatment changes in preventing CVD events Finally, we do not know the precise reason(s) for discontinuation, namely if it was a patient or practitioner decision.
