Any issues combining it with Telmisartan being that Elanapril is an ACE and Telmisartan is an ARB?
Two indications for combination therapy with ACE inhibitors and ARBs are prominently cited in the literature: heart failure and CKD with proteinuria.
4,
5 In patients with heart failure, several randomized controlled trials have shown that combination therapy, compared with ACE-inhibitor monotherapy, decreases cardiovascular morbidity.
4 Conversely, ONTARGET (Ongoing Telmisartan Alone and in Combination With Ramipril Global Endpoint Trial), conducted in patients with vascular disease or diabetes with end-organ damage, suggested that combination therapy did not decrease death or cardiovascular events and also was associated with higher rates of adverse events, including hyperkalemia and acute kidney failure requiring dialysis.
6 Although there is no definitive evidence that combination therapy improves clinically meaningful outcomes in patients with proteinuria, it is speculated to be beneficial in this setting based on a meta-analysis of small trials.
5
When evidence from clinical trials is conflicting or incomplete, carefully designed observational studies can fill knowledge gaps about the comparative effectiveness of different treatment strategies. A recent study by McAlister et al,
7published in 2011 in the
Canadian Medical Association Journal, evaluated the indications for and outcomes of combination therapy in elderly patients living in Alberta, Canada.
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What does this Important Study Show?
Taking advantage of administrative data from a large provincial health care system, McAlister et al
7 identified ∼32,000 patients 66 years and older who received a new prescription for an ACE inhibitor, ARB, or both between 2002 and 2006. The investigators compared the incidence of doubling of serum creatinine level, initiation of long-term dialysis therapy, or death within 6 months of starting therapy and the incidence of hyperkalemia (serum potassium ≥6 mEq/L) in users of monotherapy versus combination therapy. Mean age of the study cohort was 76 years, and mean serum creatinine level was 1.1 mg/dL. Most patients (61%) received monotherapy with ACE inhibitors, 29% received monotherapy with ARBs, and 5% received combination therapy.
Their findings provide several useful insights about the real-world application of combination therapy. First, 86% of those prescribed combination therapy did not have heart failure or proteinuria, the 2 indications best supported by clinical trials. Prevalences of heart failure, diabetes, and albuminuria were similar between monotherapy versus combination-therapy users, although hypertension (64.4% vs 60.5%) and nephrotic-range proteinuria (6.7% vs 4.0%) were more common in combination-therapy users. Second, combination therapy was linked to a small but significantly higher risk of hyperkalemia, and there was no clear benefit in terms of mortality or progression of CKD. Specifically, combination therapy was linked to a 2-fold higher rate of the composite primary outcome of death, initiation of long-term dialysis therapy, or doubling of serum creatinine level (
Table 1), and excluding the serum creatinine end point, combination therapy tripled the risk of death or initiation of long-term dialysis therapy. Third, and perhaps most importantly, combination therapy generally was short lived; only 12% remained on combination therapy for longer than 6 months, whereas most of the remaining patients switched to monotherapy. Curiously, most patients who discontinued combination therapy did not experience hyperkalemia or decreasing kidney function, suggesting that other factors influenced the decision to curtail treatment. Because the benefits take longer to accrue than the risks or adverse events, this prescribing pattern would suggest that many patients were exposed to the small but serious risks of combination therapy without having an opportunity to experience the potential benefits
Anand S, Kurella Tamura M. Combining angiotensin receptor blockers with ACE inhibitors in elderly patients. Am J Kidney Dis. 2012 Jan;59(1):11-4. doi: 10.1053/j.ajkd.2011.09.002. Epub 2011 Oct 13. PMID: 21995968; PMCID: PMC4077711.
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