Thomopoulos et al. (2015) did not evaluate differences in adverse events.[135] However, the Work Group determined that the benefits of the reduction in composite cardiovascular outcomes outweighed the harms, including both the AEs associated with pharmacologic therapy (e.g., orthostatic hypotension, increases in serum creatinine, hyperkalemia, other metabolic concerns) and the alternative of not receiving drug treatment. Although the four main drug classes for initial therapy were supported by the evidence base, there is still some variation, as individual patients may show differences in personal choices, including tablet burden and frequency of medication administration. Additionally, patient-to-patient variation in tolerability of AEs can be a factor when choosing a particular antihypertensive drug class. This variability was also supported by the patient focus group, during which some of the patients indicated that providers focused on pharmacological therapies, rather than providing information and education on non-pharmacologic treatments. An important implication in terms of resource use is cost. Drug copayments for VA and TRICARE beneficiaries vary depending on factors such as dispensing venue (e.g., military treatment facilities [MTF] versus mail order) and whether a generic versus branded formulation is dispensed. Cost may be less of an issue for active duty personnel, who receive their medications at no cost. The Work Group agreed on a Strong for recommendation due to the robust and extensive body of evidence from RCTs, meta-analyses, and SRs supporting use of the four main antihypertensive drug classes.[135] This is considered a Reviewed, New-replaced recommendation, as new evidence from the SR focused on composite cardiovascular outcomes, in contrast to the 2014 VA/DoD HTN CPG recommendation for which the primary literature was evaluated to recommend thiazide-type diuretics as first-line. 