Clinical attributes, treatment, and control in hypertension (CATCH)—a French and Italian longitudinal patient database study

The majority of hypertensive patients have concomitant cardiovascular disease (CVD) risk factors [1, 2], and CVD risk is higher among these hypertensive patients compared with the general population. Response to antihypertensive therapy may differ between those at high and low risk [3, 4]. For example, achieving blood pressure target may be more difficult for patients with concomitant cardiovascular risk factors or advanced age while needing more frequent therapy changes or dose adjustments [5]. Consequently, hypertension treatment guidelines have been oriented towards individual management, taking into account all concomitant risk factors rather than focusing only on blood pressure measures for determining the need and type of treatment [6]. Both the 2007 and 2013 European guidelines have indicated that diagnosis and management of hypertension should be informed by the quantification of total CVD risk and interpreted using a physician’s knowledge and experience [7, 8]. In addition to lifestyle changes, the 2013 evidence-based guidelines recommend therapeutic approaches for all patients, including the elderly and patients with diabetes, cardiovascular disease, cerebrovascular disease, or renal disease to achieve a blood pressure target of <140/90 mmHg [8]. The 2007 evidence-based guidelines recommend a lower blood pressure target of 130/80 mmHg for patients with diabetes; patients with cerebrovascular, heart, or renal disease; obese patients, and those with multiple risk factors [7].

Despite overall improvement in blood pressure treatment and control over the past decades in Europe and the USA [9, 10], a substantial proportion of patients are still not achieving their blood pressure goals [3, 11, 12]. A cross-sectional study conducted in 12 European countries showed that only 38.8 % of hypertensive patients achieved the blood pressure target of 140/90 mmHg in real-life clinical practice [11]. Belletti et al. showed that compared to patients with hypertension and no additional cardiovascular risk factors, adjusted odds ratios for attainment of target blood pressure were significantly lower in patients with associated risk factors [5]. Wong et al. showed that although treatment rates were lowest in lower risk individuals and highest in patients with cardiovascular disease, blood pressure (BP) control rates were best in lower risk patients and worst in the higher risk patients [4]. This indicates that the level of unmet medical need and suboptimal care may differ across patient populations.

To help better understand the remaining unmet needs in blood pressure treatment, we examined CVD risk profiles, treatment patterns, and blood pressure goal attainment in hypertensive patients treated in actual clinical practices in France and Italy. The specific study objectives were (1) to identify demographic characteristics and CVD risk profiles of adult hypertensive patients, (2) to examine and document antihypertension treatment patterns in segments of patient populations with and without hypertension with other risk factors, and (3) to assess blood pressure goal attainment rates in these patient segments.

The results of this analysis showed that, consistent with previous findings in the general population, more than four out five patients in France and Italy with hypertension who are already treated by general practitioners had at least one other cardiovascular disease risk factor. Yet, in this population, attainment of target blood pressure after 1 year of treatment was better in those with hypertension without other risk factors than in patients with hypertension with other risk factors [3, 5, 13]. In addition, this analysis identified that most treatment-naive patients in France and Italy were prescribed a single class of drug, and previously treated patients in both countries were being managed with combinations of drugs not considered fixed-dose combinations.

As noted in the 2013 guidelines and in other reports from industrialized countries, only a small proportion of patients with hypertension suffers from elevated BP alone [8]. In the current analysis, older age was by far the most prevalent associated risk factor, followed by dyslipidemia and isolated systolic hypertension. Our findings are consistent with other reports in which the prevalence of patients with hypertension associated with at least one risk factor ranged between ~74 % and 95 % in industrialized countries. In those studies, additional risk factors of patients with hypertension were similar to those in the present analysis including age ≥65 years and a high prevalence of obesity and dyslipidemia, especially in women [3, 5, 13]. The addition of one or more cardiovascular risk factors to BP may lead to a total CV risk profile that is greater than the sum of its individual elements. That said, among treated hypertensive patients, there are certain subgroups of hypertensive patients with other risk factors that are less optimally controlled.

In this study, the results showed that attainment of target blood pressure after 1 year of treatment was better in those with hypertension without other risk factors than in the patient segments with hypertension with other risk factors. These results substantiate those of the PRATIK study and the Wong et al. study, which showed that patients at high CVD risk were less likely to be controlled for hypertension than patients at lower CVD risk [4, 14]. In the current analysis, despite the many different treatment options available, the majority of patients in hypertension segments with additional risk factors did not achieve target blood pressure. These findings are also consistent with previous results showing poor attainment of target blood pressure using similar assessment criteria. Estimates suggest that 53.5 % of those with hypertension in the USA had inadequately controlled blood pressure [15]. Studies in Italy and Europe indicate that more than 60 % of hypertension patients treated with antihypertensive medications failed to reach blood pressure control [11, 12]. In the PRATIK and Wong studies, higher risk individuals were more likely to be treated with monotherapy than with combination therapies, which may account for the lower likelihood of attainment of BP target [4, 14].

Current guidelines state that diuretics, beta blockers, calcium antagonists, ACEIs, and ARBs are all appropriate medications for the initiation and maintenance of antihypertensive treatment, either as monotherapy or in some combinations [8]. More than one third of all treatment-naive patients were prescribed ARBs (France 32.8 %) and ACEIs (Italy 38.4 %). This may be related to a large proportion of patients with associated metabolic disorders and the possible contraindication of diuretics in patients with metabolic syndrome [16]. Physician prescription patterns differed for treatment-naive patients and previously treated patients in the two countries. Among treatment-naive patients in France, most patients were prescribed a single class of drug, mainly ARBs, followed by CCBs, beta blockers, ACEIs, and diuretics. Previously treated patients were mostly prescribed free combinations, a choice that might be a consequence of a previously inadequate patient response when using monotherapy or fixed-dose combinations on difficult-to-manage subpopulations of patients. In addition, the current findings can be paralleled with the lower proportion of previously treated patients who were prescribed treatment combinations in Italy. A relatively low proportion of index medication changes and discontinuations were observed among the previously treated patients compared with the treatment-naive patients in France. This might be a consequence of historic (prior to index date) therapeutic changes which made the previously treated subpopulation generally more stable with regard to their treatments during the follow-up period. Treatment-naive patients in Italy generally had more index medication discontinuations but less treatment changes than previously treated patients. Given that the majority of study patients with hypertension with other risk factors do not reach their blood pressure goal and that there is relatively little switching, it would appear that physicians were not fully utilizing recommended blood pressure targets to inform decisions about necessary changes in antihypertensive medication. Further assessment of this patient population with regard to identifying factors independently associated with achieving blood pressure goal might be an appropriate next step and could be used to better inform physicians in general clinical practice.

Factors such as age, compliance, number of concomitant medications, and disease severity, among others, all play a role in creating individual disease states. The observation that patients with cardiovascular conditions comorbid with hypertension had higher odds of attaining blood pressure target was somewhat unexpected. One can speculate that these patients had modified their lifestyle based on their current disease state and/or were being treated for their comorbid conditions, resulting in more frequent doctor visits, more aggressive treatment, and potentially better follow-up. Factors associated with lower odds of attaining blood pressure goals included increased age in males and females, and isolated systolic hypertension. Since isolated hypertension accounts for 87 % of cases in older adults, these results were not surprising [17]. Patients with other conditions, such as older age, diabetes, and obesity, may not be perceived as having a need for aggressive treatment, leading to clinical inertia. More aggressive and/or more targeted treatment options may be needed for these patients in order for them to achieve their target blood pressure.

Importantly, there may be multiple challenges present in treating patients with certain comorbidities along with hypertension. For example, despite the availability of several antihypertensive medications (including fixed-dose combinations intended to simplify dosing, reduce costs, and improve compliance [18]), prescribing multiple medications to treat comorbid conditions may lead to drug-drug interactions or compliance issues [19]; increasing age may result in a changing metabolic profile that impacts some drugs [20]; the increasing cost of medications may be overwhelming for some patients, causing them to stop taking medications; and/or fixed-dose combinations may not provide the appropriate dose of one of the component medications to meet an individual’s needs. The potential challenges of using combination therapies for the management of some hypertensive patients with additional risk factors might indicate the need for future innovative drugs specialized for such subpopulations. Bearing this in mind, one must treat the individual, not the individual symptoms.

Due to the period of study, the renin inhibitor drug class was not considered in this study and, consequently, no assessment can be made with regard to this drug class. Furthermore, these study results are subject to the quality and availability of the EMR data collected by the participating physicians. Only one BP measurement closest to the end of the follow-up period was used, which may have created some challenges in determining BP control. However, most patients would have been treated for an extended period of time at the end of follow-up, and BP control should have been established. An additional limitation of this study was that a relatively imbalanced proportion of patients were lost to follow-up in the two populations (about 25 % in the French and 60 % in the Italian), and it is difficult to tell if the data were randomly or systematically lost. However, this is a reflection of the real-world environment in which the study was conducted and indicates a greater need for adherence to guidelines, better quality of control and recording of patient data regardless of outcome, and greater follow-up with patients. Given the limitations of the clinical settings where these data were collected, generalization of these findings to the wider population should be made with caution.

This study confirms that the majority of treated hypertensive patients in France and Italy have at least one associated additional CVD risk factor. Despite many treatment options available, attainment of blood pressure targets was substantially less optimal in patients with at least one associated CVD risk factor compared with patients without any associated CVD risk factors. The findings from this study can be used by health care providers to help identify gaps in quality of care for patients being treated for hypertension and to review appropriate interventions and follow-up patterns.