Materials and methods

Results

We identified 103,624 patients affiliated with the SGSSS being treated with lipid-lowering drugs continuously during the study period. The average age was 67.5 ± 12.1 years (range: 18-105 years), and the sex distribution showed that 60,098 (58.0%) were women. People aged 65 years and older represented 49.8% (n=51,615) of the population (figure 1).

Figure 1. Distribution of 103,624 patients treated with lipid-lowering drugs, by age and sex, Colombia, 2017 

Of the population, 93.5% (n=96,910) received treatment with some statin, with atorvastatin being the most used (n=80,812; 78.0% of the total population), followed by lovastatin with 12,621 patients (12.2%). The main presentations dispensed were atorvastatin tablets 20 mg (n=42,389; 52.4% of those with atorvastatin) and 40 mg (n=39,724; 49.2%), but 3,210 (4.0%) received 10 mg, and 634 received 80 mg (0.8%). All lovastatin was prescribed as 20 mg. Only 4 patients received pitavastatin, and no formulations of cerivastatin, fluvastatin and pravastatin were found.

A total of 9,258 (8.9%) patients received fibrates, mainly gemfibrozil (n=8,242; 8.0% of the total subjects). Seven hundred eighty patients (0.8%) used some form of ezetimibe. Table 1 shows the prescription patterns of each of these drug groups.

The relationship between the average dose administered and the DDD varied greatly, with values from 0.44 for lovastatin to 2.53 for rosuvastatin (table 1). A total of 40,358 patients with atorvastatin (38.9% of the total population and 49.9% of those with atorvastatin) were receiving presentations of 40 mg or more, while 5,274 patients received rosuvastatin 20 mg or more (5.1% of all patients and 94.0% of rosuvastatin users).

Monotherapy versus combination therapy

A total of 98,355 patients (94.9%) used a single lipid-lowering drug during the study period, while 5,190 (5.0%) used a combination of two drugs, and 79 cases received three medications. Figure 2 shows the distribution of the main lipid-lowering agents used by monotherapy or combination therapy.

Figure 2. Frequency of prescription of the main lipid-lowering drugs used, alone or in combination therapy, Colombia, 2017 

The most frequent association was atorvastatin plus gemfibrozil (n=1,986 patients, 1.9% of all patients). Multivariate analysis of the relationship between the use of combination lipid-lowering therapy and other variables showed that the concomitant use of antidiabetics, thiazide diuretics, minoxidil and proton pump inhibitors increased the probability of receiving therapy with more than one lipid-lowering drug. In contrast, being 65 years of age or older and using apixaban reduced this probability (table 2).

Table 2 Variables associated with combined lipid-lowering therapy in binary logistic regression models, Colombia, 2017 

Variables	Sig.	OR	95% CI
			Lower	Upper
Age ≥65 years	<0.01	0.75	0.70	0.80
Male sex	0.10	1.05	0.99	1.12
Use of:
Antidiabetics	<0.01	1.12	1.05	1.20
Thiazide diuretics	<0.01	1.18	1.10	1.27
Alpha-blockers	0.09	0.87	0.74	1.02
Minoxidil	0.04	2.41	1.03	5.68
Apixaban	0.04	0.48	0.24	0.96
Proton pump inhibitors	<0.01	1.16	1.09	1.24
Living in Cali city	<0.01	1.43	1.30	1.57
Constant	0.00	0.05

Sig.: Significance; OR: Odds ratio; 95 % CI: 95 % confidence Interval

Discussion

In the present work, the utilization profile of the main lipid-lowering drugs used in an insured population of the Colombian health system was described, finding large differences from data previously reported in the country.

The average age of those who use these medications is consistent with the profile of dyslipidemia and cardiovascular disease ^2,10. The predominance of females attracts attention because men experience greater mortality and more years of life potentially lost due to this group of pathologies ², although in Colombia, mixed dyslipidemia has been described as the most common and that it presents more frequently in women ¹⁰.

During the study period, the most used drug group was the statins, encompassing over 90% of the total prescriptions, while fibrates only accounted for approximately 9%. This shows an important change regarding the 2008 data, where statins, despite also being the most consumed, only encompassed 71% of total prescriptions and fibrates comprised 27% ⁶. As mentioned above, for 2008, the dominant statin was lovastatin because it was the only one included on the SGSSS benefit plan’s drug list. The change in the prescription pattern to atorvastatin, until now the dominant drug, was likely due to its inclusion in the benefit plan ⁹ and because higher doses can be achieved, which improves the therapy’s intensity and therefore the expected efficacy ^11-13.

This change towards increased atorvastatin prescriptions is also supported by previous national study results, which found that patients treated with lovastatin were less likely to achieve metabolic control (although it was used at doses lower than those recommended, similar to the present study) ⁸. In addition, atorvastatin has been identified as the most cost-effective option for patients with dyslipidemia in the Colombian health context when moderate to high intensity treatments are required ¹⁴. When comparing these results with studies from other countries, atorvastatin has also been the most prescribed in Taiwan, but only at 37% ¹⁵, whereas research in Italy and Brazil found a predominance of simvastatin ^16,17.

In the present study, more than a third of the population was receiving statins at high intensity doses by international standards (atorvastatin 40-80 mg, rosuvastatin 20-40 mg) ¹². In a sample of Colombian patients receiving lipid-lowering drugs, according to the Framingham scale, 94% of these patients had a moderate to high cardiovascular risk ¹⁰, which is why it would be expected that more patients in the study were receiving high doses of these drugs in addition to the indications of national and international management guidelines ^12,13.

Lipid-lowering drug use in combination therapy was 5%, which is similar to previous national reports ⁸ and works published in France ¹⁸ and the United States ¹⁹. Concomitantly using statins with fibrates is usually avoided due to the increased risk of adverse reactions, which has been documented in pharmacoepidemiological studies ¹⁹; therefore, the high monotherapy frequency seems appropriate, although in adequately selected patients with residual cardiovascular risk, combination therapy may be a therapeutic option of interest to achieve goals ²⁰ with fibrates as well as ezetimibe ²¹, and more recently with new therapeutic options such as PCSK9 inhibitors ³.

The comorbidities and co-medications found in the study population are consistent with the profile associated with patients requiring lipid-lowering drugs. Therefore, antihypertensive, antiplatelet and antidiabetic agents were the dominant co-medications, as has been described in other studies ⁸. It is striking that in this patient group, antiplatelet agents reached a usage near 60%, much higher than the value of 3.8% reported in 2008, indicating an improvement in preventing cardiovascular risk among this type of patients ⁶.

The worldwide tendency is to increase prescriptions of lipid-lowering drugs in patients with diabetes mellitus ²², because the recommended use of statins is growing in patients with this comorbidity as a routine step for prevention of cardiovascular events, which was also identified in this study (increasing from 20% in 2008 to 32% in 2017) ⁶. The high use of antiulcerative drugs has been described previously, especially in chronic disease populations, often without a clear indication ²³, although in this case, it can be explained by the high prescription of antiplatelet agents in elderly patients.

Another interesting aspect is the relationship found between ezetimibe use and the lower probability of having co-medications, especially because ezetimibe has been described as a useful medication to achieve goals in patients with dyslipidemia who also have multiple comorbidities ²⁴. Residual confounders not considered during the study may explain this relationship, such as the patient’s educational levels or socioeconomic statuses ²⁵, aspects of health and insurance services, preferences of prescribing physicians or the presence of clinical inertia to reach goals in dyslipidemia in patients with multiple pathologies ²⁶.

Differences between prescription profiles in different cities (for example, variations in the prevalence of rosuvastatin use) are frequent in pharmacoepidemiological studies ⁶ and have been associated with local differences in health services, medical training or inhabitants’ characteristics ²⁷.

This research has some limitations. Because the results came from dispensing databases, and clinical records were not consulted, variables such as patients’ cardiovascular risk, lipid profiles, efficacy or the presence of adverse reactions were not analyzed. Likewise, the patterns found are applicable only to populations with insurance characteristics similar to the study subjects. New research is required to determine detailed aspects of using these drugs, for example, by the indication of treatment in the field of primary and secondary cardiovascular disease prevention.

The prescription patterns identified in this study highlight that the main lipid-lowering drug dispensed in Colombia is atorvastatin, especially in monotherapy and at doses close to DDD.

Regarding previous analyses, the prescriptions differed considerably, likely due to modifications in the drugs included in the benefit plans and the evidence presented in different clinical guides, highlighting the increase in useful co-medications for cardiovascular prevention such as antiplatelet drugs.

These data may be useful for professionals and health administrators to define behaviors related to managing cardiovascular risk in the Colombian population, since there seems to be an opportunity for improvement related to a probable underuse of statins at high doses in patients who require them. The adequate management of dyslipidemias can have a long-term impact on public health by reducing cardiovascular risk, morbidity and mortality secondary to ischemic events, heart failure and, in addition, the costs derived from their attention.